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Psychiatrist, Geriatric Specialist (elderly care)
21 years of experience
Accepting new patients
Video profile

Credentials

Education ?

Medical School Score Rankings
Duke University (1991)
  •  
Top 25%

Awards & Distinctions ?

Awards  
One of America's Leading Experts on:
Clinical Depression (Major Depressive Disorder)
Patients' Choice Award (2014)
Compassionate Doctor Recognition (2014)
On-Time Doctor Award (2014)
Appointments
New York-presbyterian Hospital
Columbia University College Of Physicians And Surgeons, Ny, Ny (1995 - Present)
Associations
American Board of Psychiatry and Neurology

Affiliations ?

Dr. Lisanby is affiliated with 5 hospitals.

Hospital Affiliations

Score

Rankings

  • Duke University Hospital
    2301 Erwin Rd, Durham, NC 27710
    •  
    Top 25%
  • New York Presbyterian Hospital / Columbia
    630 W 168th St, New York, NY 10032
    •  
    Top 25%
  • NewYork-PresbyterianColumbia
  • New York State Psychiatric Institute
    1051 Riverside Dr, New York, NY 10032
  • New York Presbyterian HospitalColumbia Presbyterian Center
  • Publications & Research

    Dr. Lisanby has contributed to 100 publications.
    Title Repetitive Transcranial Magnetic Stimulator with Controllable Pulse Parameters.
    Date November 2011
    Journal Journal of Neural Engineering
    Excerpt

    The characteristics of transcranial magnetic stimulation (TMS) pulses influence the physiological effect of TMS. However, available TMS devices allow very limited adjustment of the pulse parameters. We describe a novel TMS device that uses a circuit topology incorporating two energy storage capacitors and two insulated-gate bipolar transistor (IGBT) modules to generate near-rectangular electric field pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable pulse parameter TMS (cTMS) device can induce electric field pulses with phase widths of 10-310 µs and positive/negative phase amplitude ratio of 1-56. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation up to 82% and 57% and decreases coil heating up to 33% and 41%, respectively. We demonstrate repetitive TMS trains of 3000 pulses at frequencies up to 50 Hz with electric field pulse amplitude and width variability less than the measurement resolution (1.7% and 1%, respectively). Offering flexible pulse parameter adjustment and reduced power consumption and coil heating, cTMS enhances existing TMS paradigms, enables novel research applications and could lead to clinical applications with potentially enhanced potency.

    Title Transcranial Magnetic Stimulation in the Presence of Deep Brain Stimulation Implants: Induced Electrode Currents.
    Date March 2011
    Journal Conference Proceedings : ... Annual International Conference of the Ieee Engineering in Medicine and Biology Society. Ieee Engineering in Medicine and Biology Society. Conference
    Excerpt

    The safety of transcranial magnetic stimulation (TMS) in patients with an implanted deep brain stimulation (DBS) systems has not been thoroughly investigated. One potential safety hazard is the induction of significant voltages in the subcutaneous leads in the scalp that could result in unintended electrical currents in the DBS electrode contacts. We measured ex-vivo the TMS-induced voltages and currents in DBS electrodes with the implantable pulse generator (IPG) set in various modes of operation. We show that voltages as high as 100 V resulting in currents as high as 83 mA can be induced in the DBS leads by a TMS pulse in all IPG modes. These currents are an order of magnitude higher than the normal DBS pulses, and could result in tissue damage. When the IPG is turned off, electrode currents flow only if the TMS-induced voltage exceeds 5 V.

    Title Durability of Clinical Benefit with Transcranial Magnetic Stimulation (tms) in the Treatment of Pharmacoresistant Major Depression: Assessment of Relapse During a 6-month, Multisite, Open-label Study.
    Date March 2011
    Journal Brain Stimulation
    Excerpt

    Although transcranial magnetic stimulation (TMS) can be an effective acute antidepressant treatment, few studies systematically examine persistence of benefit.

    Title Self-specific Processing in the Default Network: a Single-pulse Tms Study.
    Date February 2011
    Journal Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
    Excerpt

    In examining neural processing specific to the self, primarily by contrasting self-related stimuli with non-self-related stimuli (i.e., self vs. other), neuroimaging studies have activated a consistent set of regions, including medial prefrontal cortex (MPFC), precuneus, and right and left inferior parietal cortex. However, criticism has arisen that this network may not be specific to self-related processing, but instead reflects a more general aspect of cortical processing. For example, it is almost identical to the active network of the resting state, the "default" mode, when the subject is free to think about anything at all. We tested the self-specificity of this network by using transcranial magnetic stimulation (TMS) to briefly disrupt local cortical processing while subjects rated adjectives as like or unlike themselves or their best friend. Healthy volunteers show a self-reference effect (SRE) in this task, in which performance with self-related items is superior to that with other-related items. As individual adjectives appeared on a monitor, single-pulse TMS was applied at five different times relative to stimulus onset (SOA: stimulus onset asynchrony) ranging from 0 to 480 ms. In 18 subjects, TMS to left parietal cortex suppressed the SRE from 160 to 480 ms. SRE suppression occurred at later SOA with TMS to the right parietal cortex. In contrast, no effects were seen with TMS to MPFC. Together with our previous work, these results provide evidence for a self-specific processing system in which midline and lateral inferior parietal cortices, as elements of the default network, play a role in ongoing self-awareness.

    Title Electroconvulsive Therapy Stimulus Parameters: Rethinking Dosage.
    Date December 2010
    Journal The Journal of Ect
    Excerpt

    In this article, we review the parameters that define the electroconvulsive therapy (ECT) electrical stimulus and discuss their biophysical roles. We also present the summary metrics of charge and energy that are conventionally used to describe the dose of ECT and the rules commonly deployed to individualize the dose for each patient. We then highlight the limitations of these summary metrics and dosing rules in that they do not adequately capture the roles of the distinct stimulus parameters. Specifically, there is strong theoretical and empirical evidence that stimulus parameters (pulse amplitude, shape, and width, and train frequency, directionality, polarity, and duration) exert unique neurobiological effects that are important for understanding ECT outcomes. Consideration of the distinct stimulus parameters, in conjunction with electrode placement, is central to further optimization of ECT dosing paradigms to improve the risk-benefit ratio. Indeed, manipulation of specific parameters, such as reduction of pulse width and increase in number of pulses, has already resulted in dramatic reduction of adverse effects, while maintaining efficacy. Furthermore, the manipulation of other parameters, such as current amplitude, which are commonly held at fixed, high values, might be productively examined as additional means of targeting and individualizing the stimulus, potentially reducing adverse effects. We recommend that ECT dose be defined using all stimulus parameters rather than a summary metric. All stimulus parameters should be noted in treatment records and published reports. To enable research on optimization of dosing paradigms, we suggest that ECT devices provide capabilities to adjust and display all stimulus parameters.

    Title Effects of Pulse Width and Electrode Placement on the Efficacy and Cognitive Effects of Electroconvulsive Therapy.
    Date October 2010
    Journal Brain Stimulation
    Excerpt

    While electroconvulsive therapy (ECT) in major depression is effective, cognitive effects limit its use. Reducing the width of the electrical pulse and using the right unilateral electrode placement may decrease adverse cognitive effects, while preserving efficacy.

    Title Decreasing Procedural Pain over Time of Left Prefrontal Rtms for Depression: Initial Results from the Open-label Phase of a Multi-site Trial (opt-tms).
    Date October 2010
    Journal Brain Stimulation
    Excerpt

    There is much interest in whether daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) over several weeks may become a clinically useful antidepressant treatment. Although rTMS appears largely safe, many patients report that this procedure is somewhat painful, which may restrict its ultimate appeal and utility. We analyzed interim results from the open-label phase of a multi-site randomized trial of rTMS as a treatment for depression to investigate whether the procedural pain of left prefrontal rTMS changes over time.

    Title Separating Hope from Hype: Some Ethical Implications of the Development of Deep Brain Stimulation in Psychiatric Research and Treatment.
    Date July 2010
    Journal Cns Spectrums
    Title Functional Magnetic Resonance Imaging Guided Transcranial Magnetic Stimulation in Obsessive-compulsive Disorder.
    Date June 2010
    Journal Biological Psychiatry
    Title Daily Left Prefrontal Transcranial Magnetic Stimulation Therapy for Major Depressive Disorder: a Sham-controlled Randomized Trial.
    Date May 2010
    Journal Archives of General Psychiatry
    Excerpt

    Daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) has been studied as a potential treatment for depression, but previous work had mixed outcomes and did not adequately mask sham conditions.

    Title Lateral Prefrontal Cortex and Self-control in Intertemporal Choice.
    Date May 2010
    Journal Nature Neuroscience
    Excerpt

    Disruption of function of left, but not right, lateral prefrontal cortex (LPFC) with low-frequency repetitive transcranial magnetic stimulation (rTMS) increased choices of immediate rewards over larger delayed rewards. rTMS did not change choices involving only delayed rewards or valuation judgments of immediate and delayed rewards, providing causal evidence for a neural lateral-prefrontal cortex-based self-control mechanism in intertemporal choice.

    Title Fda Considers Classification of Ect.
    Date May 2010
    Journal Cns Spectrums
    Title Randomized Sham-controlled Trial of Repetitive Transcranial Magnetic Stimulation in Treatment-resistant Obsessive-compulsive Disorder.
    Date April 2010
    Journal The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (cinp)
    Excerpt

    In open trials, 1-Hz repetitive transcranial magnetic stimulation (rTMS) to the supplementary motor area (SMA) improved symptoms and normalized cortical hyper-excitability of patients with obsessive-compulsive disorder (OCD). Here we present the results of a randomized sham-controlled double-blind study. Medication-resistant OCD patients (n=21) were assigned 4 wk either active or sham rTMS to the SMA bilaterally. rTMS parameters consisted of 1200 pulses/d, at 1 Hz and 100% of motor threshold (MT). Eighteen patients completed the study. Response to treatment was defined as a > or = 25% decrease on the Yale-Brown Obsessive Compulsive Scale (YBOCS). Non-responders to sham and responders to active or sham rTMS were offered four additional weeks of open active rTMS. After 4 wk, the response rate in the completer sample was 67% (6/9) with active and 22% (2/9) with sham rTMS. At 4 wk, patients receiving active rTMS showed on average a 25% reduction in the YBOCS compared to a 12% reduction in those receiving sham. In those who received 8-wk active rTMS, OCD symptoms improved from 28.2+/-5.8 to 14.5+/-3.6. In patients randomized to active rTMS, MT measures on the right hemisphere increased significantly over time. At the end of 4-wk rTMS the abnormal hemispheric laterality found in the group randomized to active rTMS normalized. The results of the first randomized sham-controlled trial of SMA stimulation in the treatment of resistant OCD support further investigation into the potential therapeutic applications of rTMS in this disabling condition.

    Title Effect of Anatomical Variability on Neural Stimulation Strength and Focality in Electroconvulsive Therapy (ect) and Magnetic Seizure Therapy (mst).
    Date April 2010
    Journal Conference Proceedings : ... Annual International Conference of the Ieee Engineering in Medicine and Biology Society. Ieee Engineering in Medicine and Biology Society. Conference
    Excerpt

    We present a quantitative comparison of two metrics-neural stimulation strength and focality-in electrocon-vulsive therapy (ECT) and magnetic seizure therapy (MST) using finite-element method (FEM) simulation in a spherical head model. Five stimulation modalities were modeled, including bilateral ECT, unilateral ECT, focal electrically administered seizure therapy (FEAST), and MST with circular and double-cone coils, with stimulation parameters identical to those applied in clinical practice. We further examine the effect on the stimulation metrics of individual-, sex- and age-related variability in tissue layer thickness and conductivity. Neural stimulation by MST is shown to be more focal and superficial than ECT. This result suggests that it may be advantageous to reduce the current used in ECT. The stimulation strength in MST is also less sensitive to variations in head geometry and tissue conductivity than in ECT. Individualization of pulse amplitude in both ECT and MST could compensate for anatomical variability, which could lead to more consistent clinical outcomes.

    Title Unaltered Neuronal and Glial Counts in Animal Models of Magnetic Seizure Therapy and Electroconvulsive Therapy.
    Date February 2010
    Journal Neuroscience
    Excerpt

    Anatomical evidence of brain damage from electroconvulsive therapy (ECT) is lacking; but there are no modern stereological studies in primates documenting its safety. Magnetic seizure therapy (MST) is under development as a less invasive form of convulsive therapy, and there is only one prior report on its anatomical effects. We discerned no histological lesions in the brains of higher mammals subjected to electroconvulsive shock (ECS) or MST, under conditions that model closely those used in humans. We sought to extend these findings by determining whether these interventions affected the number of neurons or glia in the frontal cortex or hippocampus. Twenty-four animals received 6 weeks of ECS, MST, or anesthesia alone, 4 days per week. After perfusion fixation, numbers of neurons and glia in frontal cortex and hippocampus were determined by unbiased stereological methods. We found no effect of either intervention on volumes or total number or numerical density of neurons or glia in hippocampus, frontal cortex, or subregions of these structures. Induction of seizures in a rigorous model of human ECT and MST therapy does not cause a change in the number of neurons or glia in potentially vulnerable regions of brain. This study, while limited to young, healthy, adult subjects, provides further evidence that ECT and MST, when appropriately applied, do not cause structural damage to the brain.

    Title Neurophysiological Characterization of High-dose Magnetic Seizure Therapy: Comparisons with Electroconvulsive Shock and Cognitive Outcomes.
    Date November 2009
    Journal The Journal of Ect
    Excerpt

    Magnetic seizure therapy (MST) is under development as a means of improving cognitive outcomes with convulsive therapy through achieving better control over therapeutic seizure induction than is possible with conventional electroconvulsive therapy. In this investigation, we present the first neurophysiological characterization of high-dose MST (HD-MST, 6x seizure threshold) to see if a higher dose that is often used in human trials retains differential expression relative to electroconvulsive shock (ECS) and to explore the relationship between seizure expression and cognitive outcomes. To this end, rhesus monkeys received 4 weeks of daily treatment with ECS, HD-MST, and anesthesia-alone sham in counterbalanced order, with an interposed recovery period. Two channels of electroencephalogram were recorded during and immediately after the ictal period. Electroencephalogram power within delta, theta, alpha, and beta frequency bands was calculated. Electroconvulsive shock showed significantly more ictal power in all frequency bands than HD-MST (P < 0.01). Electroencephalogram power during the postictal period was significantly different among conditions only for the delta band. Higher ictal expression with ECS was associated with slowed completion time for an orientation task given immediately after the treatments. Our results support earlier findings demonstrating that MST- and ECS-induced seizures elicit differential patterns of ictal expression, consistent with the relatively more superficial stimulation achieved via magnetic induction in comparison with conventional electroconvulsive therapy. These results demonstrate that MST, even at high dose, results in seizures that differ neurophysiologically from ECS. It further suggests that some of the differences in ictal expression may relate to the improved cognitive outcomes seen with MST.

    Title Safety of Radial Arterial Catheterization in Pet Research Subjects.
    Date November 2009
    Journal Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
    Title Differential Heart Rate Response to Magnetic Seizure Therapy (mst) Relative to Electroconvulsive Therapy: a Nonhuman Primate Model.
    Date October 2009
    Journal Neuroimage
    Excerpt

    Electroconvulsive therapy (ECT) is an effective treatment for severe depression; however, the induced therapeutic seizure acts on the autonomic nervous system and results in significant cardiac effects. This is an important consideration particularly in the elderly. Magnetic seizure therapy (MST) is in development as a less invasive alternative, but its effects on cardiac function have not been studied. We sought to model those effects in nonhuman primates to inform the development of safer neurostimulation interventions. Twenty four rhesus monkeys were randomly assigned to receive 6 weeks of daily treatment with electroconvulsive stimulation (ECS), magnetic seizure therapy (MST) or anesthesia-alone sham. Digitally acquired ECG and an automated R-wave and inter-R interval (IRI) sampling were used to measure intervention effects on heart rate (HR). Significant differences between experimental conditions were found in the HR as evidenced by changes in the immediate post-stimulus, ictal and postictal epochs. Immediate post-stimulus bradycardia was seen with ECS but not with MST. ECS induced significantly more tachycardia than MST or sham in both the ictal and postictal periods. MST resulted in a small, but statistically significant increase in HR during the postictal period relative to baseline. HR was found to increase by 25% and 8% in the ECS and MST conditions, respectively. MST resulted in significantly less marked sympathetic and parasympathetic response than did ECS. This differential physiological response is consistent with MST having a more superficial cortical site of action with less impact on deeper brain structures implicated in cardiac control relative to ECT. The clinical relevance of the topographical seizure spread of MST and its associated effects on the autonomic nervous system remain to be determined in human clinical trials.

    Title Translational Development Strategy for Magnetic Seizure Therapy.
    Date September 2009
    Journal Experimental Neurology
    Excerpt

    Electroconvulsive therapy (ECT) has unparalleled antidepressant efficacy, but its cognitive side effects may be persistent. Research suggests that the side effects may be at least partially dissociable from the therapeutic effects of ECT, suggesting that distinct cortical networks may underlie them and introducing a role for focal seizure induction as a means of minimizing side effects. In magnetic seizure therapy (MST), magnetic fields avoid tissue impedance and induce electrical currents confined to superficial cortex, facilitating focal seizure induction. The translational development strategy for MST has included: (1) device development, (2) feasibility in animals and initial human trials, (3) testing in nonhuman primates on safety and mechanisms of action (with neuroanatomical, neurophysiological and cognitive endpoints), (4) safety testing in patients, (5) initial efficacy testing in patients, (6) dosage optimization, and (7) randomized comparison with ECT. These stages have been iterative, with results of early clinical testing prompting device enhancements that were, in turn, tested in nonhuman primates prior to human trials. Safety testing was aided by development of a nonhuman primate model of human ECT, and the validation of a cognitive battery for the monkey that is sensitive to the range of effects of ECT on human memory. Human testing has been facilitated by the development of an international consortium of centers addressing various aspects of technique and dose/response relationships. Challenges facing MST are common to other device-based therapies: characterizing dose/response relationships, optimizing efficacy, and developing efficient and reliable methods to induce lasting therapeutic change in the circuitry underlying depression.

    Title Focal Electrically Administered Seizure Therapy: a Novel Form of Ect Illustrates the Roles of Current Directionality, Polarity, and Electrode Configuration in Seizure Induction.
    Date September 2009
    Journal Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
    Excerpt

    Electroconvulsive therapy (ECT) is a mainstay in the treatment of severe, medication-resistant depression. The antidepressant efficacy and cognitive side effects of ECT are influenced by the position of the electrodes on the head and by the degree to which the electrical stimulus exceeds the threshold for seizure induction. However, surprisingly little is known about the effects of other key electrical parameters such as current directionality, polarity, and electrode configuration. Understanding these relationships may inform the optimization of therapeutic interventions to improve their risk/benefit ratio. To elucidate these relationships, we evaluated a novel form of ECT (focal electrically administered seizure therapy, FEAST) that combines unidirectional stimulation, control of polarity, and an asymmetrical electrode configuration, and contrasted it with conventional ECT in a nonhuman primate model. Rhesus monkeys had their seizure thresholds determined on separate days with ECT conditions that crossed the factors of current directionality (unidirectional or bidirectional), electrode configuration (standard bilateral or FEAST (small anterior and large posterior electrode)), and polarity (assignment of anode and cathode in unidirectional stimulation). Ictal expression and post-ictal suppression were quantified through scalp EEG. Findings were replicated and extended in a second experiment with the same subjects. Seizures were induced in each of the 75 trials, including 42 FEAST procedures. Seizure thresholds were lower with unidirectional than with bidirectional stimulation (p<0.0001), and lower in FEAST than in bilateral ECS (p=0.0294). Ictal power was greatest in posterior-anode unidirectional FEAST, and post-ictal suppression was strongest in anterior-anode FEAST (p=0.0008 and p=0.0024, respectively). EEG power was higher in the stimulated hemisphere in posterior-anode FEAST (p=0.0246), consistent with the anode being the site of strongest activation. These findings suggest that current directionality, polarity, and electrode configuration influence the efficiency of seizure induction with ECT. Unidirectional stimulation and novel electrode configurations such as FEAST are two approaches to lowering seizure threshold. Furthermore, the impact of FEAST on ictal and post-ictal expression appeared to be polarity dependent. Future studies may examine whether these differences in seizure threshold and expression have clinical significance for patients receiving ECT.

    Title Non-invasive Brain Stimulation in the Detection of Deception: Scientific Challenges and Ethical Consequences.
    Date July 2009
    Journal Behavioral Sciences & the Law
    Excerpt

    Tools for noninvasive stimulation of the brain, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have provided new insights in the study of brain-behavior relationships due to their ability to directly alter cortical activity. In particular, TMS and tDCS have proven to be useful tools for establishing causal relationships between behavioral and brain imaging measures. As such, there has been interest in whether these tools may represent novel technologies for deception detection by altering a person's ability to engage brain networks involved in conscious deceit. Investigation of deceptive behavior using noninvasive brain stimulation is at an early stage. Here we review the existing literature on the application of noninvasive brain stimulation in the study of deception. Whether such approaches could be usefully applied to the detection of deception by altering a person's ability to engage brain networks involved in conscious deceit remains to be validated. Ethical and legal consequences of the development of such a technology are discussed.

    Title Regional Cerebral Blood Flow and Metabolic Rate in Persistent Lyme Encephalopathy.
    Date May 2009
    Journal Archives of General Psychiatry
    Excerpt

    There is controversy regarding whether objective neurobiological abnormalities exist after intensive antibiotic treatment for Lyme disease.

    Title Coil Design Considerations for Deep-brain Transcranial Magnetic Stimulation (dtms).
    Date May 2009
    Journal Conference Proceedings : ... Annual International Conference of the Ieee Engineering in Medicine and Biology Society. Ieee Engineering in Medicine and Biology Society. Conference
    Excerpt

    Deep-brain transcranial magnetic stimulation (dTMS) could provide new, non-invasive therapeutic options for various psychiatric and neurological disorders. Figures of merit (FoMs) are proposed to evaluate and compare dTMS coil designs. These FoMs characterize the depth of electric field penetration, scalp stimulation, focality, and energy. Two coil configurations potentially suitable for dTMS are analyzed: circular crown coil and C-core coil. These coils have significantly less attenuation of the electric field strength in depth, compared to conventional TMS coils. In the limiting case as the coil dimensions become large relative to the head, the electric field decay in depth becomes linear, which indicates that, at best, the electric field attenuation is directly proportional to the depth of the target. The charge density and heating induced in the brain are at safe levels, but the risk of unintended neuromodulation and seizures with dTMS has to be evaluated further. Preliminary simulation results suggest that the crown coil has the best overall performance for dTMS. Finally, synchronous firing of all TMS coil elements appears more effective at stimulating deep neurons than is sequential firing.

    Title Differential Neurophysiological Effects of Magnetic Seizure Therapy (mst) and Electroconvulsive Shock (ecs) in Non-human Primates.
    Date October 2008
    Journal Clinical Eeg and Neuroscience : Official Journal of the Eeg and Clinical Neuroscience Society (encs)
    Excerpt

    Magnetic seizure therapy (MST) is under development as a means of reducing the side effects of electroconvulsive therapy (ECT) through enhanced control over patterns of seizure induction and spread. We previously reported that chronic treatment with MST resulted in less impairment in cognitive function than electroconvulsive shock (ECS) in a non-human primate model of convulsive therapy. Here we present quantitative analyses of ictal expression and post-ictal suppression following ECS, MST, and anesthesia-alone sham in the same model to test whether differential neurophysiological characteristics of the seizures could be identified. Rhesus monkeys received 4 weeks of daily treatment with ECS, MST, and anesthesia-alone sham in a counterbalanced order separated by a recovery period. Both ECS and MST were given bilaterally at 2.5 x seizure threshold. Neurophysiological characteristics were derived from two scalp EEG electrode recording sites during and immediately following the ictal period, and were compared to sham treatment. EEG power within four frequencies (delta, theta, alpha and beta) was calculated. Our results support earlier findings from intracerebral electrode recordings demonstrating that MST- and ECS- induced seizures elicit differential patterns of EEG activation. Specifically, we found that ECS shows significantly more marked ictal expression, and more intense post-ictal suppression than MST in the theta, alpha, and beta frequency bands (Ps < .05). However, the ECS and MST were indistinguishable in the delta frequency band during both ictal and post-ictal periods. These results demonstrate that magnetic seizure induction can result in seizures that differ in some neurophysiological respects compared with ECS, but that these modalities share some aspects of seizure expression. The clinical significance of these similarities and differences awaits clinical correlation.

    Title Differential Effects of High-dose Magnetic Seizure Therapy and Electroconvulsive Shock on Cognitive Function.
    Date August 2008
    Journal Biological Psychiatry
    Excerpt

    BACKGROUND: Magnetic seizure therapy (MST) is under investigation as an alternative form of convulsive therapy that induces more focal seizures and spares cortical regions involved in memory. With a newly expanded version of the Columbia University Primate Cognitive Profile, we compared the cognitive effects of high-dose MST delivered at 100 Hz (6 x seizure threshold) with electroconvulsive shock (ECS) delivered at 2.5 x seizure threshold. METHODS: Daily high-dose MST, ECS, and sham (anesthesia-only) were administered for 4 weeks each in a within-subject crossover design. Rhesus macaques (n = 3) were trained on five cognitive tasks assessing automatic memory, anterograde learning and memory, combined anterograde and retrograde simultaneous chaining, and spatial and serial working memory. Acutely after each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-hour retention interval. RESULTS: Subjects were slower to complete criterion tasks (p values < .0001) after ECS, compared with sham and high-dose MST. Moreover, time to task-completion after high-dose MST did not differ from sham. Of six measures of accuracy, treatment effects were found in four; in all of these, ECS but not MST fared worse than sham. On all accuracy and time to completion measurements, subjects performed as well after high-dose MST as subjects from a previous study on moderate-dose MST. CONCLUSIONS: These findings provide evidence that high-dose MST results in benign acute cognitive side-effect profile relative to ECS and are in line with our previous studies.

    Title Rtms Strategies for the Study and Treatment of Schizophrenia: a Review.
    Date August 2008
    Journal The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (cinp)
    Excerpt

    Transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS) have been used increasingly over the past few years to study both the pathophysiology of schizophrenia as well as the utility of focal neuromodulation as a novel treatment for schizophrenia. rTMS treatment studies to date have explored its effect on both positive and negative symptoms by targeting cortical regions thought to underlie these symptom clusters. Studies on auditory hallucinations have been largely positive, while efficacy for negative symptoms is equivocal. A better understanding of the functional abnormalities that accompany symptoms may facilitate the development of rTMS as a treatment modality. Furthermore, schizophrenia patients appear to have abnormal cortical inhibition, consistent with GABA and dopamine abnormalities in schizophrenia. The effect of TMS on GABA and dopamine neurotransmission has not been clearly delineated. Given the variability in cortical response to rTMS in schizophrenia, methods to optimize dosage are essential. Consideration of these factors among others may broaden the scope of utility of TMS for schizophrenia as well as enhance its efficacy.

    Title The Efficacy of Acute Electroconvulsive Therapy in Atypical Depression.
    Date May 2008
    Journal The Journal of Clinical Psychiatry
    Excerpt

    OBJECTIVE: This study examined the characteristics and outcomes of patients with major depressive disorder (MDD), with or without atypical features, who were treated with acute bilateral electroconvulsive therapy (ECT). METHOD: Analyses were conducted with 489 patients who met DSM-IV criteria for MDD. Subjects were identified as typical or atypical on the basis of the Structured Clinical Interview for DSM-IV obtained at baseline prior to ECT. Depression symptom severity was measured by the 24-item Hamilton Rating Scale for Depression (HAM-D(24)) and the 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR(30)). Remission was defined as at least a 60% decrease from baseline in HAM-D(24) score and a total score of 10 or below on the last 2 consecutive HAM-D(24) ratings. The randomized controlled trial was performed from 1997 to 2004. RESULTS: The typical (N = 453) and atypical (N = 36) groups differed in several sociodemographic and clinical variables including gender (p = .0071), age (p = .0005), treatment resistance (p = .0014), and age at first illness onset (p < .0001) and onset of current episode (p = .0008). Following an acute course of bilateral ECT, a considerable portion of both the typical (67.1%) and the atypical (80.6%) groups reached remission. The atypical group was 2.6 (95% CI = 1.1 to 6.2) times more likely to remit than the typical group after adjustment for age, psychosis, gender, clinical site, and depression severity based on the HAM-D(24). CONCLUSION: Acute ECT is an efficacious treatment for depressed patients with typical or atypical symptom features. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000375.

    Title Transcranial Magnetic Stimulation in the Acute Treatment of Major Depressive Disorder: Clinical Response in an Open-label Extension Trial.
    Date May 2008
    Journal The Journal of Clinical Psychiatry
    Excerpt

    BACKGROUND: This report describes the results of an open-label extension study of active trans-cranial magnetic stimulation (TMS) in medication-resistant patients with major depressive disorder who did not benefit from an initial course of therapy in a previously reported 6-week, randomized controlled study of active versus sham TMS. METHOD: Patients with DSM-IV-defined major depressive disorder were actively enrolled in the study from February 2004 through September 2005 and treated with left prefrontal TMS administered 5 times per week at 10 pulses per second, at 120% of motor threshold, for a total of 3000 pulses/session. The primary outcome was the baseline to endpoint change score on the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: In those patients who received sham in the preceding randomized controlled trial (N = 85), the mean reduction in MADRS scores after 6 weeks of open-label active TMS was -17.0 (95% CI = -14.0 to -19.9). Further, at 6 weeks, 36 (42.4%) of these patients achieved response on the MADRS, and 17 patients (20.0%) remitted (MADRS score < 10). For those patients who received and did not respond to active TMS in the preceding randomized controlled trial (N = 73), the mean reduction in MADRS scores was -12.5 (95% CI = -9.7 to -15.4), and response and remission rates were 26.0% and 11.0%, respectively, after 6 weeks of additional open-label TMS treatment. CONCLUSIONS: This open-label study provides further evidence that TMS is a safe and effective treatment of major depressive disorder. Furthermore, continued active TMS provided additional benefit to some patients who failed to respond to 4 weeks of treatment, suggesting that longer courses of treatment may confer additional therapeutic benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00104611.

    Title Classical Conditioned Learning Using Transcranial Magnetic Stimulation.
    Date April 2008
    Journal Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
    Excerpt

    This study examined whether brain responses to transcranial magnetic stimulation (TMS) would be amenable to classical conditioning. Motor cortex in human participants was stimulated with TMS pulses, which elicited a peripheral motor response in the form of a motor evoked potential (MEP). The TMS pulses were paired with audio-visual cues that served as conditioned stimuli. Over the course of training, MEPs following the conditioned stimuli decreased in amplitude. Two experiments demonstrated that the attenuated response only occurred when the TMS was preceded by the conditioned stimulus. Unsignaled TMS and TMS preceded by a cue that was not previously paired did not attenuate the response. The experiments demonstrate that the modulation of the motor response depended on the prior pairings of the conditioned stimuli and TMS and that the effects were stimulus specific. Thus we demonstrate here, for the first time, that TMS can serve as the unconditioned stimulus in Pavlovian conditioning.

    Title Transcranial Magnetic Stimulation in the Treatment of Major Depressive Disorder: a Comprehensive Summary of Safety Experience from Acute Exposure, Extended Exposure, and During Reintroduction Treatment.
    Date April 2008
    Journal The Journal of Clinical Psychiatry
    Excerpt

    BACKGROUND: Transcranial magnetic stimulation (TMS) has demonstrated efficacy in the treatment of major depressive disorder; however, prior studies have provided only partial safety information. We examined the acute efficacy of TMS in a randomized sham-controlled trial, under open-label conditions, and its durability of benefit. METHOD: Aggregate safety data were obtained from a comprehensive clinical development program examining the use of TMS in the treatment of major depressive disorder. There were 3 separate clinical protocols, including 325 patients from 23 clinical sites in the United States, Australia, and Canada. Active enrollment occurred between January 2004 and August 2005. Adverse events were assessed at each study visit by review of spontaneous reports with separate reporting of serious adverse events. Safety assessments were also completed for cognitive function and auditory threshold. Assessment of disease-specific risk included the potential for worsening of depressive symptoms. Finally, the time course and accommodation to the most commonly appearing adverse events were considered. RESULTS: TMS was administered in over 10,000 cumulative treatment sessions in the study program. There were no deaths or seizures. Most adverse events were mild to moderate in intensity. Transient headaches and scalp discomfort were the most common adverse events. Auditory threshold and cognitive function did not change. There was a low discontinuation rate (4.5%) due to adverse events during acute treatment. CONCLUSIONS: TMS was associated with a low incidence of adverse events that were mild to moderate in intensity and demonstrated a largely predictable time course of resolution. TMS may offer clinicians a novel, well-tolerated alternative for the treatment of major depressive disorder that can be safely administered in an outpatient setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00104611.

    Title A Transcranial Magnetic Stimulator Inducing Near-rectangular Pulses with Controllable Pulse Width (ctms).
    Date February 2008
    Journal Ieee Transactions on Bio-medical Engineering
    Excerpt

    A novel transcranial magnetic stimulation (TMS) device with controllable pulse width (PW) and near-rectangular pulse shape (cTMS) is described. The cTMS device uses an insulated gate bipolar transistor (IGBT) with appropriate snubbers to switch coil currents up to 6 kA, enabling PW control from 5 micros to over 100 micros. The near-rectangular induced electric field pulses use 2%-34% less energy and generate 67%-72% less coil heating compared to matched conventional cosine pulses. CTMS is used to stimulate rhesus monkey motor cortex in vivo with PWs of 20 to 100 micros, demonstrating the expected decrease of threshold pulse amplitude with increasing PW. The technological solutions used in the cTMS prototype can expand functionality, and reduce power consumption and coil heating in TMS, enhancing its research and therapeutic applications.

    Title Repetitive Transcranial Magnetic Stimulation of the Supplementary Motor Area in the Treatment of Tourette Syndrome: Report of Two Cases.
    Date November 2007
    Journal Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology
    Title Electroconvulsive Therapy for Depression.
    Date November 2007
    Journal The New England Journal of Medicine
    Title Revisiting the Backward Masking Deficit in Schizophrenia: Individual Differences in Performance and Modeling with Transcranial Magnetic Stimulation.
    Date October 2007
    Journal Biological Psychiatry
    Excerpt

    BACKGROUND: Deficits in backward masking have been variably reported in schizophrenia patients, but individual differences in the expression of these deficits have not been explicitly investigated. In addition, increased knowledge of the visual system has opened the door for new techniques such as transcranial magnetic stimulation (TMS) to explore these deficits physiologically. METHODS: Patients with schizophrenia and healthy controls were tested using a backward masking paradigm. In order to examine the functionality of visual pathways involved in backward masking, subjects were retested on a backward masking paradigm using single pulse TMS applied to occipital cortex in lieu of the masking stimuli. RESULTS: Compared with controls, patients had significantly delayed recovery from visual backward masking. However, 23.5% of patients (compared to 5% of controls) never recovered to levels approaching unmasked performance. When these subjects were segregated from the analysis, group differences vanished. In addition, stimulus masking with occipital TMS followed the same pattern in both patients and controls. CONCLUSIONS: Observations of individual differences in visual masking performance may identify a subgroup of schizophrenia patients. The TMS data suggest that this deficit may not localize to the occipital cortex. However, TMS can be a useful tool for localizing processing deficits in schizophrenia.

    Title Repetitive Transcranial Magnetic Stimulation (rtms) in the Treatment of Panic Disorder (pd) with Comorbid Major Depression.
    Date October 2007
    Journal Journal of Affective Disorders
    Excerpt

    BACKGROUND: Studies suggest that the dorsolateral prefrontal cortex (DLPFC) participates in neural circuitry that is dysregulated in Panic Disorder (PD) and Major Depressive Disorder (MDD). We tested whether low-frequency repetitive Transcranial Magnetic Stimulation (rTMS) could normalize the overactivity of right frontal regions and thereby improve symptoms. METHODS: Six patients with PD and comorbid MDD were treated with daily active 1-Hz rTMS to the right DLPFC for 2 weeks in this open-label trial. RESULTS: Clinical improvements were apparent as early as the first week of treatment. After the second week, 5/6 of patients showed improvements in panic and anxiety, and 4/6 showed a decrease in depression, with sustained improvement at 6 months of follow-up. Right hemisphere resting motor threshold increased significantly after rTMS. LIMITATIONS: Limitations of this study are the open design and the small sample size. CONCLUSIONS: Slow rTMS to the right DLPFC resulted in significant clinical improvement and reduction of ipsilateral motor cortex excitability. Replications in larger sample will help to clarify the relevance of this preliminary data and to define the potential role of right DLPFC rTMS in panic with major depression.

    Title Neuropathologic Examination After 91 Ect Treatments in a 92-year-old Woman with Late-onset Depression.
    Date August 2007
    Journal The Journal of Ect
    Excerpt

    Whereas pathological seizure states, such as temporal lobe epilepsy, are commonly associated with cell loss and glial scarring in the hippocampus, seizures induced via electroconvulsive therapy (ECT) have not been associated with histological evidence of neuronal damage. We present a case report including the late-life medical history and postmortem histology of an elderly woman with major depression who received 91 sessions of ECT during the last 22 years of her life. Given the large number of ECT sessions, and her advanced age, this case provides a strong test of whether ECT causes detectable evidence of neuronal damage. We examined the gross morphology of the hippocampus, hippocampal cytoarchitecture, and measures of neuropathology. We found no pathological changes that could be attributed to ECT. Only expected, age-related features were present. Corpora amylacea and rare neurofibrillary tangles were evident, but we failed to detect any obvious evidence of cell loss or gliosis. Cognition in this patient was intact as indicated by a perfect score on a Mini-Mental Status Examination administered 6 days before death at the age of 92. This case adds to the considerable evidence for the safety of ECT.

    Title Motor Cortex Excitability After Vagus Nerve Stimulation in Major Depression.
    Date July 2007
    Journal Journal of Clinical Psychopharmacology
    Excerpt

    Recent data suggest that inhibitory pathways may be involved in the pathophysiology of depression and in the mode of action of some antidepressant interventions. The aim of the present study was to test whether vagus nerve stimulation (VNS) can affect motor cortex excitability. Measures of motor cortical excitability were probed by using single-pulse and paired-pulse transcranial magnetic stimulation at baseline, after 10 weeks of left VNS, and additionally, in an on-off paradigm in 10 patients with treatment-resistant unipolar depression. Ten weeks of VNS was associated with a selective and pronounced increase in intracortical inhibition, whereas no changes occurred in the on-off paradigm. These results suggest that VNS is capable of changing motor cortical excitability in patients with depression.

    Title Neocortical and Hippocampal Neuron and Glial Cell Numbers in the Rhesus Monkey.
    Date June 2007
    Journal Anatomical Record (hoboken, N.j. : 2007)
    Excerpt

    The rhesus monkey is widely used as an experimental animal model in the study of brain function and disease. While previous quantitative studies have provided knowledge of regional numbers, little is known of the total neocortical neuron and glial cell numbers in this species. The aim of this study is to establish quantitative norms. We use the optical fractionator and Cavalieri principle to examine the right hemisphere of eight young rhesus monkeys taken from the control group of an ongoing study. Applying these methods to agar-embedded and vibratome-sectioned tissue, we generate estimates of cell numbers and regional volumes of neocortical and hippocampal regions with coefficients of variance (CV) around 10%. The mean unilateral neocortical neuron number is 1.35 x 10(9) (CV +/- 0.10) and the mean unilateral neocortical glial cell number is 0.78 x 10(9) (CV +/- 0.17). Mean unilateral neocortical volume is found to be 8.5 (CV +/- 0.10) cm(3) after processing, or 19 cm(3) when correcting for shrinkage. The neuron/glia ratio is 1.77. The neurons are distributed with 18% in the frontal cortex, 57% in the temporal and parietal cortices, and 25% in the occipital cortex. In the hippocampal subregions, we found unilateral neuron number of 1.72 x 10(6) (CV +/- 0.13) and glial number of 2.25 x 10(6) (CV +/- 0.17) in CA1, and 0.80 x 10(6) (CV +/- 0.27) neurons and 1.05 x 10(6) (CV +/- 0.26) glial cells in CA2-3. Comparisons with related studies show quantitative variation, but also variations in methods and applications. The results are phylogenetically consistent, apart from the neuron/glia ratio, which is remarkably higher than what is found in other species.

    Title Antidepressant-induced Neurogenesis in the Hippocampus of Adult Nonhuman Primates.
    Date June 2007
    Journal The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
    Excerpt

    New neurons are generated in the adult hippocampus of many species including rodents, monkeys, and humans. Conditions associated with major depression, such as social stress, suppress hippocampal neurogenesis in rodents and primates. In contrast, all classes of antidepressants stimulate neuronal generation, and the behavioral effects of these medications are abolished when neurogenesis is blocked. These findings generated the hypothesis that induction of neurogenesis is a necessary component in the mechanism of action of antidepressant treatments. To date, the effects of antidepressants on newborn neurons have been reported only in rodents and tree shrews. This study examines whether neurogenesis is increased in nonhuman primates after antidepressant treatment. Adult monkeys received repeated electroconvulsive shock (ECS), which is the animal analog of electroconvulsive therapy (ECT), the most effective short-term antidepressant. Compared with control conditions, ECS robustly increased precursor cell proliferation in the subgranular zone (SGZ) of the dentate gyrus in the monkey hippocampus. A majority of these precursors differentiated into neurons or endothelial cells, while a few matured into glial cells. The ECS-mediated induction of cell proliferation and neurogenesis was accompanied by increased immunoreactivity for the neuroprotective gene product BCL2 (B cell chronic lymphocytic lymphoma 2) in the SGZ. The ECS interventions were not accompanied by increased hippocampal cell death or injury. This study demonstrates that ECS is capable of inducing neurogenesis in the nonhuman primate hippocampus and supports the possibility that antidepressant interventions produce similar alterations in the human brain.

    Title Facilitation of Performance in a Working Memory Task with Rtms Stimulation of the Precuneus: Frequency- and Time-dependent Effects.
    Date March 2007
    Journal Brain Research
    Excerpt

    Although improvements in performance due to TMS have been demonstrated with some cognitive tasks, performance improvement has not previously been demonstrated with working memory tasks. In the present study, a delayed match-to-sample task was used in which repetitive TMS (rTMS) at 1, 5, or 20 Hz was applied to either left dorsolateral prefrontal or midline parietal cortex during the retention (delay) phase of the task. Only 5 Hz stimulation to the parietal site resulted in a significant decrease in reaction time (RT) without a corresponding decrease in accuracy. This finding was replicated in a second experiment, in which 5 Hz rTMS at the parietal site was applied during the retention phase or during presentation of the recognition probe. Significant speeding of RT occurred in the retention phase but not the probe phase. This finding suggests that TMS may improve working memory performance, in a manner that is specific to the timing of stimulation relative to performance of the task, and to stimulation frequency.

    Title Repetitive Transcranial Magnetic Stimulation (rtms) in the Treatment of Obsessive-compulsive Disorder (ocd) and Tourette's Syndrome (ts).
    Date September 2006
    Journal The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (cinp)
    Excerpt

    There is evidence that motor and premotor cortex are hyperexcitable in obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). We tested whether low-frequency repetitive transcranial magnetic stimulation (rTMS) could normalize overactive motor cortical regions and thereby improve symptoms. Subjects with OCD or TS were treated with active rTMS to the supplementary motor area (SMA) for 10 daily sessions at 1 Hz, 100% of motor threshold, 1200 stimuli/day. Suggestions of clinical improvement were apparent as early as the first week of rTMS. At the second week of treatment, statistically significant reductions were seen in the YBOCS, YGTSS, CGI, HARS, HDRS, SAD, BDI, SCL-90, and SASS. Symptoms improvement was correlated with a significant increase of the right resting motor threshold and was stable at 3 months follow-up. Slow rTMS to SMA resulted in a significant clinical improvement and a normalization of the right hemisphere hyperexcitability, thereby restoring hemispheric symmetry in motor threshold.

    Title Randomized Controlled Trial of the Cognitive Side-effects of Magnetic Seizure Therapy (mst) and Electroconvulsive Shock (ecs).
    Date September 2006
    Journal The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (cinp)
    Excerpt

    Magnetic seizure therapy (MST) is under development as a means of improving the cognitive side-effect profile of electroconvulsive therapy (ECT) by inducing more spatially delimited seizures that spare cortical regions involved in memory. We tested whether MST had a cognitive side-effect profile distinct from electroconvulsive shock (ECS) in a non-human primate model, using the Columbia University Primate Cognitive Profile, which has been shown to be sensitive to the cognitive effects of ECS. Using a within-subject cross-over design, daily ECS, MST, and sham (anaesthesia-only) interventions were administered in 5-wk blocks. Rhesus macaques (n = 2) were trained on a long-term memory task, an anterograde learning and memory task, and a combined anterograde and retrograde task where learning and memory were evaluated for new and previously learned 3-item lists. Acutely following each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-h retention interval. Overall, monkeys were least accurate following ECS (p's < 0.05) compared to sham and MST. This effect was most marked for long-term memory of a constant target, short-term memory of a variable target and recall of previously learned 3-item lists. Monkeys were slowest to complete all tasks following ECS (p's = 0.0001). Time to task completion following MST did not differ from sham. These findings suggest that MST results in a more benign acute cognitive side-effect profile than ECS in this model, consistent with initial observations with human MST.

    Title Anesthetic Considerations for Magnetic Seizure Therapy: a Novel Therapy for Severe Depression.
    Date August 2006
    Journal Anesthesia and Analgesia
    Excerpt

    Electroconvulsive therapy (ECT) is a highly effective treatment for severe depression. However, its use is associated with significant posttreatment cognitive impairment. Magnetic seizure therapy (MST) was developed as an alternative therapy that could reduce postseizure side effects through the induction of more "focal" seizure activity. Using an open-parallel study design, we compared 20 case-matched patients undergoing a series of either ECT or MST procedures with respect to their anesthetic, muscle relaxant, and cardiovascular drug requirements, effects on cardiovascular and electroencephalographic bispectral index (BIS) values, and early recovery times. We found that MST was associated with a reduced time to orientation (4 +/- 1 versus 18 +/- 5 min; P < 0.01) compared with ECT. To minimize residual muscle paralysis after MST, a reduction in the succinylcholine dosage (38 +/- 17 versus 97 +/- 2 mg; P < 0.01) was required. The BIS values were higher before, and lower immediately after, the stimulus was applied in the MST (versus ECT) group. The Hamilton depression rating scale score was significantly reduced from the baseline value in both treatment groups; however, the posttreatment score was lower after the series of ECT treatments (6 +/- 6 versus 14 +/- 10; P < 0.05). We conclude that MST was associated with a decreased requirement for muscle relaxants, reduced variability in the BIS values after seizure induction, and a more rapid recovery of cognitive function compared with ECT. Further studies are required to evaluate the antidepressant efficacy of MST versus ECT when they are administered at comparable levels of cerebral stimulation.

    Title Evidence for Impaired Cortical Inhibition in Patients with Unipolar Major Depression.
    Date May 2006
    Journal Biological Psychiatry
    Excerpt

    BACKGROUND: Several lines of evidence suggest that central cortical inhibitory mechanisms, especially associated with gamma-aminobutyric acid (GABA) neurotransmission, may play a role in the pathophysiology of major depression. Transcranial magnetic stimulation is a useful tool for investigating central cortical inhibitory mechanisms associated with GABAergic neurotransmission in psychiatric and neurological disorders. METHODS: By means of transcranial magnetic stimulation, different parameters of cortical excitability, including motor threshold, the cortical silent period, and intracortical inhibition/facilitation, were investigated in 20 medication-free depressed patients and 20 age- and gender-matched healthy volunteers. RESULTS: Silent period and intracortical inhibition were reduced in depressed patients, consistent with a reduced GABAergic tone. Moreover, patients showed a significant hemispheric asymmetry in motor threshold. CONCLUSIONS: This study provides evidence of reduced GABAergic tone and motor threshold asymmetry in patients with major depression.

    Title Two-year Outcome of Vagus Nerve Stimulation (vns) for Treatment of Major Depressive Episodes.
    Date December 2005
    Journal The Journal of Clinical Psychiatry
    Excerpt

    BACKGROUND: Vagus nerve stimulation (VNS) had antidepressant effects in an initial open, acute phase pilot study of 59 participants in a treatment-resistant major depressive episode (MDE). We examined the effects of adjunctive VNS over 24 months in this cohort. METHOD: Adult outpatients (N = 59) with chronic or recurrent major depressive disorder or bipolar (I or II) disorder and experiencing a treatment-resistant, nonpsychotic MDE (DSM-IV criteria) received 2 years of VNS. Changes in psychotropic medications and VNS stimulus parameters were allowed only after the first 3 months. Response was defined as > or = 50% reduction from the baseline 28-item Hamilton Rating Scale for Depression (HAM-D-28) total score, and remission was defined as a HAM-D-28 score < or = 10. RESULTS: Based on last observation carried forward analyses, HAM-D-28 response rates were 31% (18/59) after 3 months, 44% (26/59) after 1 year, and 42% (25/59) after 2 years of adjunctive VNS. Remission rates were 15% (9/59) at 3 months, 27% (16/59) at 1 year, and 22% (13/59) at 2 years. By 2 years, 2 deaths (unrelated to VNS) had occurred, 4 participants had withdrawn from the study, and 81% (48/59) were still receiving VNS. Longer-term VNS was generally well tolerated. CONCLUSION: These results suggest that patients with chronic or recurrent, treatment-resistant depression may show long-term benefit when treated with VNS.

    Title Cortical Excitability in Cocaine-dependent Patients: a Replication and Extension of Tms Findings.
    Date July 2005
    Journal Journal of Psychiatric Research
    Excerpt

    Cortical excitability can be assessed by transcranial magnetic stimulation (TMS). Previously we observed that TMS motor threshold (MT) was elevated in abstinent cocaine-dependent subjects. In the current study we aimed at replicating our initial finding, exploring other TMS-based measures of excitability, and examining association with personality characteristics. Nineteen cocaine-dependent and 12 healthy control subjects were examined. Resting and activated motor thresholds (RMT and AMT) and duration of the cortical silent period (CSP) were examined. The Cocaine Experience Questionnaire (CEQ) was administered to assess cocaine-induced psychotic symptoms. The relationship between Minnesota Multiphasic Personality Inventory (MMPI) scales and cortical excitability measures was also examined. AMT was significantly elevated in cocaine-dependent subjects on both hemispheres. RMT was also significantly elevated on the right hemisphere. No CSP changes were noted. Patients with cocaine-induced paranoia had longer CSPs on the right hemisphere compared to subjects reporting no paranoid experiences. The patients displayed significantly elevated scores on several MMPI scales, though the scale scores did not correlate with cortical excitability measures. These data support our initial finding of decreased cortical excitability in abstinent cocaine-dependent subjects. We interpret this finding as a compensatory mechanism against the stimulating and epileptogenic effects of cocaine.

    Title Neurogenesis and Depression.
    Date July 2005
    Journal Journal of Psychiatric Practice
    Excerpt

    The recognition that the brain continues to generate new neurons well into adulthood has made a marked impact on the field of neuroscience in general and specifically on neurobiological models of the pathogenesis of major depression. Stress, neuroendocrine activation, neurotransmitter systems, and other factors can down-regulate the process of neurogenesis and may contribute to certain morphological changes seen in depression. Evidence is emerging that antidepressant treatments may mitigate these effects by stimulating neurogenesis in particular regions of the brain. This review introduces the reader to recent literature on neurogenesis as it relates to the understanding and treatment of depression.

    Title Protein Kinase a in Major Depression: the Link Between Hypothalamic-pituitary-adrenal Axis Hyperactivity and Neurogenesis.
    Date May 2005
    Journal Cns Spectrums
    Excerpt

    The latest and most generative biological theories of major depression center on two major hypotheses. The first focuses on the concept that hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis leads to many of the pathological changes in the brain that accompany major depression. The second posits that neurogenesis leads to the repair of depression-related injuries. These two hypotheses are complementary: the former alludes to the etiology or consequences of depression, while the latter suggests mechanisms of antidepressant action. Significant crosstalk occurs between these two systems at many levels. Protein kinase A (PKA) may play an important role in this crosstalk at the intracellular level of signaling cascades. PKA is involved in the formation of long-term potentiation and fear conditioning in response to stress. Chronic stress leads to the suppression of hippocampal activity, which may cause the hyperactivity of the HPA axis during melancholic depression. PKA is also involved in the stimulation of hippocampal neurogenesis after antidepressant treatment. In theory, neurogenesis may lead to the restoration of hippocampal function, and this may be the mechanism that leads to antidepressant-mediated normalization of HPA hyperactivity. Thus, PKA is active during processes that potentially lead to depression and other processes that lead to the resolution of the illness. These opposing processes may be mediated by separate PKA isozymes that activate two distinct pathways. This review highlights the dual role of this enzyme in two biological hypotheses pertaining to depression and its treatment.

    Title Electroconvulsive Therapy and Repetitive Transcranial Magnetic Stimulation in Children and Adolescents: a Review and Report of Two Cases of Epilepsia Partialis Continua.
    Date January 2005
    Journal Child and Adolescent Psychiatric Clinics of North America
    Excerpt

    Brain stimulation for the treatment of psychiatric disorders has received increasing attention over the past decade. The introduction of experimental means to stimulate the brain noninvasively with magnetic fields not only has raised interest in these novel means of modulating brain activity but also has refocused attention on a mainstay in the treatment of severe major depression and other disorders (electroconvulsive therapy). This article reviews the current state of knowledge concerning the use electroconvulsive therapy, repetitive transcranial magnetic stimulation, and magnetic seizure therapy in children and adolescents. Two cases of medically intractable epilepsia partialis continua are presented to add to the limited literature on the use of repetitive transcranial magnetic stimulation in children and adolescents and illustrate the concept of using functional neuroimaging results to target the application of a focal intervention in an attempt to dampen hyperactive regions of the cortex.

    Title Parietal Cortex and Representation of the Mental Self.
    Date July 2004
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    For a coherent and meaningful life, conscious self-representation is mandatory. Such explicit "autonoetic consciousness" is thought to emerge by retrieval of memory of personally experienced events ("episodic memory"). During episodic retrieval, functional imaging studies consistently show differential activity in medial prefrontal and medial parietal cortices. With positron-emission tomography, we here show that these medial regions are functionally connected and interact with lateral regions that are activated according to the degree of self-reference. During retrieval of previous judgments of Oneself, Best Friend, and the Danish Queen, activation increased in the left lateral temporal cortex and decreased in the right inferior parietal region with decreasing self-reference. Functionally, the former region was preferentially connected to medial prefrontal cortex, the latter to medial parietal. The medial parietal region may, then, be conceived of as a nodal structure in self-representation, functionally connected to both the right parietal and the medial prefrontal cortices. To determine whether medial parietal cortex in this network is essential for episodic memory retrieval with self-representation, we used transcranial magnetic stimulation over the region to transiently disturb neuronal circuitry. There was a decrease in the efficiency of retrieval of previous judgment of mental Self compared with retrieval of judgment of Other with transcranial magnetic stimulation at a latency of 160 ms, confirming the hypothesis. This network is strikingly similar to the network of the resting conscious state, suggesting that self-monitoring is a core function in resting consciousness.

    Title A Primate Model of Anterograde and Retrograde Amnesia Produced by Convulsive Treatment.
    Date June 2004
    Journal The Journal of Ect
    Excerpt

    A nonhuman primate model of the key cognitive effects of convulsive treatment was developed and tested. Rhesus macaques were trained on 3 tasks: a long-term memory task that required selection of a constant target from a background of distracters, an anterograde task that involved learning a new target each day against a variable number of distracters, and a task that assessed learning and memory for new and previously trained 3-item serial lists. This battery samples a range of cognitive functions, including orientation, working memory, retrograde amnesia for temporally graded stimuli, and anterograde amnesia. Using a within-subject, sham-controlled design, the amnestic effects of electroconvulsive shock (ECS) were evaluated in 2 monkeys. Significant effects of the interventions (sham and ECS) were seen on all tasks. The degree of impairment varied across tasks and as a function of task difficulty. ECS did not impair accuracy on the less difficult tasks (memory for an overlearned item and acquisition of a new item) but did increase the amount of time required to complete the tasks, consistent with a period of disorientation acutely after the intervention. This effect was progressive across the treatments. ECS impaired the acquisition and memory of new lists compatible with an anterograde memory deficit, whereas recall for old lists was relatively spared. This study developed and validated a cognitive battery to assess amnesia in nonhuman primates, providing new experimental paradigms for evaluating the cognitive effects of convulsive treatment.

    Title Absence of Histological Lesions in Primate Models of Ect and Magnetic Seizure Therapy.
    Date April 2004
    Journal The American Journal of Psychiatry
    Excerpt

    OBJECTIVE: The authors present preliminary findings from the first nonhuman primate neuropathological study of ECT to use perfusion fixation and adequate controls and the first to compare ECT with magnetic seizure therapy, to their knowledge. METHOD: Twelve Macaca mullata received 6 weeks of daily ECT, magnetic seizure therapy, or anesthesia alone. After perfusion fixation, their brains were examined while masked to intervention. RESULTS: No identified lesions were attributable to the interventions. Cortical and hippocampal immunoreactivity for glial fibrillary acidic protein (an astrocytic marker) was most intense in the group that received ECT. CONCLUSIONS: This small but rigorous primate study supports the view that ECT does not produce histological lesions in the brain and provides the first comparable safety data on magnetic seizure therapy.

    Title Optimization of Golgi Methods for Impregnation of Brain Tissue from Humans and Monkeys.
    Date February 2004
    Journal Journal of Neuroscience Methods
    Excerpt

    Golgi impregnation is unique in its ability to display the dendritic trees of large numbers of individual neurons. However, its reputation for inconsistency leaves many investigators reluctant to embrace this methodology, particularly for the study of formalin-fixed human brain tissue. After reviewing the literature, testing a variety of technical variations, and discussing the procedure with experienced practitioners, we have concluded that much of the unpredictability can be removed by matching the Golgi technique to the conditions that were used for fixation of the tissue. Briefly fixed tissues worked best with the rapid Golgi technique, which includes osmium during the initial chromation step, and with the Golgi-Cox method, which includes mercuric chloride during chromation. For tissues that have been fixed for several years or even for several decades, superior results are obtained with the Golgi-Kopsch technique, using multiple changes of a chromation solution that contains paraformaldehyde. In the Golgi-Kopsch technique, pH should be used to monitor the reduction of Cr6+ to Cr3+, which is a crucial determinant of successful chromation. With any Golgi technique, agitation throughout the impregnation helps to avoid precipitates and to improve the quality of impregnation. When the appropriate method is chosen, Golgi impregnation is a useful technique for the neuropathologist.

    Title Magnetic Seizure Therapy Improves Mood in Refractory Major Depression.
    Date January 2004
    Journal Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
    Excerpt

    This report describes the successful treatment of a patient suffering from an episode of drug-resistant major depression using magnetic seizure therapy (MST). The patient suffered from recurrent major depression since adolescence. MST is a novel brain stimulation method using transcranial magnetic stimulation at convulsive parameters in order to induce therapeutic seizures under general anesthesia in the same setting used for electroconvulsive therapy (ECT). The first use of therapeutic magnetic seizure induction in a psychiatric patient took place at the University Hospital in Bern, Switzerland, in May 2000. Results of a recent randomized, within-subject, double-masked trial comparing ECT and MST in 10 patients indicate that MST appears to have less subjective and objective side effects, is associated with faster recovery of orientation, and is superior to ECT on measures of attention, retrograde amnesia, and category fluency. ECT has an unparalleled and well-documented efficacy in severe depression but is associated with cognitive side effects. MST is currently under study in several centers with respect to its antidepressant efficacy. We report here on the treatment of a patient with refractory major depression (DSM IV-R), who underwent a series of 12 sessions of MST in an inpatient setting. Baseline Hamilton Depression Rating Scale (HRSD-21) of 33 and Beck Depression Inventory (BDI) of 40 decreased to 6 and 11 respectively, 1 week after completion of the MST trial. Measures of cognitive functions support the hypothesis that MST is associated with a less severe profile of cognitive side effects. [(99m)Tc]-HMPAO SPECT studies (baseline and 4 days after the completion of the MST trial) point to a raise of blood flow at baseline in the left fronto-parietal region and the brainstem. Our preliminary data support the prospect of antidepressant efficacy of MST and point to a benign cognitive side-effect profile in a patient suffering from severe treatment-resistant major depression.

    Title Neurophysiological Characterization of Magnetic Seizure Therapy (mst) in Non-human Primates.
    Date January 2004
    Journal Supplements to Clinical Neurophysiology
    Title Neuropsychiatric Applications of Transcranial Magnetic Stimulation: a Meta Analysis.
    Date December 2003
    Journal The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (cinp)
    Excerpt

    Transcranial magnetic stimulation (TMS) is a technology that allows for non-invasive modulation of the excitability and function of discrete brain cortical areas. TMS uses alternating magnetic fields to induce electric currents in cortical tissue. In psychiatry, TMS has been studied primarily as a potential treatment for major depression. Most studies indicate that slow-frequency repetitive TMS (rTMS) and higher frequency rTMS have antidepressant properties. A meta-analysis of controlled studies indicates that this effect is fairly robust from a statistical viewpoint. However, effect sizes are heterogeneous, and few studies have shown that rTMS results in substantial rates of clinical response or remission, and the durability of antidepressant effects is largely unknown. We review in detail rTMS studies in the treatment of depression, as well as summarize treatment studies of mania, obsessive-compulsive disorder, post-traumatic stress disorder, and schizophrenia. We also review the application of TMS in the study of the pathophysiology of psychiatric disorders and summarize studies of the safety of TMS in human subjects.

    Title Safety and Feasibility of Magnetic Seizure Therapy (mst) in Major Depression: Randomized Within-subject Comparison with Electroconvulsive Therapy.
    Date December 2003
    Journal Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
    Excerpt

    Magnetic seizure therapy (MST) is a novel means of performing convulsive therapy using rapidly alternating strong magnetic fields. MST offers greater control of intracerebral current intensity than is possible with electroconvulsive therapy (ECT). These features may result in a superior cognitive side effect profile for MST, while possibly retaining the efficacy of ECT. The objective of this study was to determine whether MST and ECT differ in seizure characteristics, and acute objective and subjective cognitive side effects. A total of 10 inpatients in a major depressive episode referred for ECT were enrolled in this randomized, within-subject, double-masked trial. Seizure threshold was determined with MST and ECT in the first two sessions of a course of convulsive therapy, with order randomized. The remaining two sessions consisted of suprathreshold stimulation with MST and ECT. A neuropsychological battery and side effect rating scale were administered by a masked rater before and after each session. Tonic-clonic seizures were elicited with MST in all patients. Compared to ECT, MST seizures had shorter duration, lower ictal EEG amplitude, and less postictal suppression. Patients had fewer subjective side effects and recovered orientation more quickly with MST than ECT. MST was also superior to ECT on measures of attention, retrograde amnesia, and category fluency. Magnetic seizure induction in patients with depression is feasible, and appears to have a superior acute side effect profile than ECT. Future research will be needed to establish whether MST has antidepressant efficacy.

    Title A Magnetic Resonance Spectroscopic Imaging Study of Adult Nonhuman Primates Exposed to Early-life Stressors.
    Date October 2003
    Journal Biological Psychiatry
    Excerpt

    BACKGROUND: Long-term behavioral, immunologic, and neurochemical alterations have been found in primates exposed to adverse early rearing. METHODS: Bonnet macaque (Macaca radiata) mother-infant dyads were exposed to uncertain requirements for food procurement (variable foraging demand, VFD) for a few months. Ten years later, these offspring and age- and gender-matched control subjects were studied using proton magnetic resonance spectroscopic imaging (MRSI). RESULTS: In anterior cingulate, VFD-reared subjects displayed significantly decreased N-acetylaspartate (NAA) resonance and significantly increased glutamate-glutamine-gamma-aminobutyric acid (Glx) resonance relative to the stable neurometabolite creatine (Cr). Across all subjects, NAA/Cr and Glx/Cr ratios in the anterior cingulate were negatively correlated (r = -.638, p =.014). In the medial temporal lobe, the ratio of choline-containing compounds to Cr was significantly increased in VFD subjects. CONCLUSIONS: These findings indicate that adverse early rearing in primates has an enduring impact on adult MRSI measures considered reflective of neuronal integrity and metabolism, membrane structure and glial function, and cerebral glutamate content, and that these alterations occur in the same brain regions implicated in trauma-related psychiatric disorders.

    Title Managing the Risks of Repetitive Transcranial Stimulation.
    Date October 2003
    Journal Cns Spectrums
    Title New Developments in Electroconvulsive Therapy and Magnetic Seizure Therapy.
    Date October 2003
    Journal Cns Spectrums
    Excerpt

    New findings regarding the mechanisms of action of electro-convulsive therapy (ECT) have led to novel developments in treatment technique to further improve this highly effective treatment for major depression. These new approaches include novel placements, optimization of electrical stimulus parameters, and new methods for inducing more targeted seizures(eg, magnetic seizure therapy [MST]). MST is the use of transcranial magnetic stimulation to induce a seizure. Magnetic fields pass through tissue unimpeded, providing more control over the site and extent of stimulation than can be achieved with ECT. This enhanced control represents a means of focusing the treatment on target cortical structures thought to be essential to antidepressant response and reducing spread to medial temporal regions implicated in the cognitive side effects of ECT. MST is at an early stage of development. Preliminary results suggest that MST may have some advantages over ECT in terms of subjective side effects and acute cognitive functioning. Studies designed to address the antidepressant efficacy of MST are underway. As with all attempts to improve convulsive therapy technique, the clinical value of MST will need to be established through controlled clinical trials. This article reviews the experience to date with MST, and places this work in the broader context of other means of optimizing convulsive therapy in the treatment of depression.

    Title Transcranial Magnetic Stimulation.
    Date August 2003
    Journal Neurosurgery Clinics of North America
    Excerpt

    TMS is a powerful new tool with extremely interesting research and therapeutic potentials. Further understanding of the ways by which TMS changes neuronal function, especially as a function of its use parameters, will improve its ability to answer neuroscience questions as well as to treat diseases. Because of its noninvasiveness, it does not readily fit under the umbrella of neurosurgery. Nevertheless, it is important for neurosurgeons to be aware of TMS, because findings from TMS studies will have implications for neurosurgical approaches like DBS and VNS. Indeed, it is possible to think of using TMS as a potential noninvasive initial screening tool to identify whether perturbation of a circuit has short-term clinical effects. In the example of chronic refractory depression or OCD, which is generally a chronic illness, it might then follow that rather than having daily or weekly TMS for the rest of their lives, patients would have DBS electrodes implanted in the same circuit. Whatever road the future takes, TMS is an important new tool that will likely be of interest to neurosurgeons over the next 20 years and perhaps even longer.

    Title Update on Magnetic Seizure Therapy: a Novel Form of Convulsive Therapy.
    Date May 2003
    Journal The Journal of Ect
    Excerpt

    Magnetic seizure therapy (MST) refers to the use of transcranial magnetic stimulation to induce a seizure for therapeutic purposes. MST is under investigation as a means of improving the safety profile of electroconvulsive therapy (ECT). Although both MST and ECT induce seizures through electrical stimulation of the brain, the electric field induced by MST is more focal and limited than that induced by ECT. Because magnetic fields pass through tissue unimpeded, there is greater control over the site and extent of stimulation with MST than can be achieved with ECT. This enhanced control represents a means of focusing the treatment on target cortical structures thought to be essential to antidepressant response and of reducing spread to medial temporal regions implicated in the cognitive side effects of ECT. MST is currently at an early stage of development. This article reviews the experience with MST in animal models and initial human investigations. Preliminary results have demonstrated the feasibility of performing MST in the clinical setting, and there are suggestions that MST may have advantages over ECT in terms of subjective side effects and some measures of acute cognitive functioning. The antidepressant efficacy of MST is not yet known, but studies designed to address that critical issue are underway. As with all attempts to refine convulsive therapy techniques (such as modifications in stimulation parameter configurations and electrode placement), the ultimate clinical value of MST will need to be established through controlled clinical trials.

    Title Focal Brain Stimulation with Repetitive Transcranial Magnetic Stimulation (rtms): Implications for the Neural Circuitry of Depression.
    Date April 2003
    Journal Psychological Medicine
    Title Applications of Tms to Therapy in Psychiatry.
    Date January 2003
    Journal Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society
    Excerpt

    Transcranial magnetic stimulation (TMS) has been applied to a growing number of psychiatric disorders as a noninvasive probe to study the underlying neurobiologic processes involved in psychiatric disorders and as a putative treatment. Transcranial magnetic stimulation is unparalleled in its ability to test the hypotheses generated by functional neuroimaging studies by modulating activity in selected neural circuits. As a focal intervention that may in some cases exert lasting effects, TMS offers the hope of targeting and ameliorating the circuitry underlying psychiatric disorders. The ultimate success of such an approach depends on our knowledge of the neural circuitry underlying these disorders, of how TMS exerts its effects, and of how to control the application of TMS to exert the desired effects. Although most clinical trials have focused on the treatment of major depression, increasing attention has been paid to schizophrenia and anxiety disorders. Many of these trials have supported a significant effect of TMS, but in some studies the effect is small and short lived. Current challenges in the field include determining how to enhance the efficacy of TMS in these disorders and how to identify patients for whom TMS may be efficacious.

    Title Vagus Nerve Stimulation (vns) for Major Depressive Episodes: One Year Outcomes.
    Date May 2002
    Journal Biological Psychiatry
    Excerpt

    BACKGROUND: Vagus nerve stimulation has shown promising results in an open, acute phase pilot study of adults in a treatment-resistant major depressive episode. This open, naturalistic follow-up study was conducted to determine whether the initial promising effects were sustained, and whether changes in function would be observed. METHODS: Thirty adult outpatients in a treatment-resistant, nonpsychotic major depressive episode received an additional 9 months of vagus nerve stimulation treatment following exit from the 3-month acute study. Changes in psychotropic medications and vagus nerve stimulation stimulus parameters were allowed during this longer-term follow-up study. A priori definitions were used to define response (> or = 50% reduction in baseline Hamilton Rating Scale for Depression total score) and remission (Hamilton Rating Scale for Depression < or = 10). RESULTS: The response rate was sustained [40% (12/30) to 46% (13/28); p =.317] and the remission rate significantly increased [17% (5/30) to 29% (8/28); p =.045] with an additional 9 months of long-term vagus nerve stimulation treatment after exit from the acute study (1 year total vagus nerve stimulation treatment). Significant improvements in function between acute study exit and the 1-year follow-up assessment as measured by the Medical Outcomes Study Short Form-36 were observed. CONCLUSIONS: Longer-term vagus nerve stimulation treatment was associated with sustained symptomatic benefit and sustained or enhanced functional status in this naturalistic follow-up study.

    Title Transcranial Magnetic Stimulation Differentially Affects Speed and Direction Judgments.
    Date December 2001
    Journal Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
    Excerpt

    This study was conducted to determine whether humans' judgments about the speed and direction of moving stimuli was differentially affected by transcranial magnetic stimulation (TMS). Subjects viewed two successively presented moving stimuli that differed from each other both in speed and direction of motion. Single-pulse TMS was applied either medially (approximately 2 cm above the inion) or laterally (approximately 5 cm lateral to and 4 cm above the inion), while subjects judged the speed and direction differences. The physical stimulation (visual and TMS) was identical on the two tasks, as was discriminability (d') when TMS was not applied. We found significant criterion (beta) shifts on the speed discrimination task at both stimulation sites. Specifically, on TMS trials the proportion of "slower" judgments increased significantly, consistent with subjective reports that stimuli often appeared to slow when TMS was applied. The subjective reports indicated no corresponding change in perceived direction. We also found that speed discriminability was impaired significantly more than direction discriminability, but only when TMS was applied medially. Indeed, after controlling for TMS-related changes in reaction time, speed discriminability was impaired significantly, while direction discriminability remained largely intact. This dissociation suggests that the sensory response constraining speed discrimination is at least partially independent from the sensory response constraining direction discrimination. Combined with previous psychophysical data, the present data suggest a double dissociation between speed and direction discrimination in humans.

    Title Focal Prefrontal Seizures Induced by Bilateral Ect.
    Date October 2001
    Journal The Journal of Ect
    Excerpt

    INTRODUCTION: It has been proposed that the greater efficacy of bilateral (BL) over right unilateral (RUL) electroconvulsive therapy (ECT) at low stimulus intensity is due to differences in site of seizure initiation. We hypothesized that focal prefrontal seizures are more common with BL than RUL administration. METHOD: Records were reviewed of the 1,007 ECT treatments of 84 consecutive patients randomized to RUL or BL electrode placement. RESULTS: Eight events were identified in which there was an electroencephalographic seizure without motor manifestation. All of these events occurred at titration sessions and with BL stimuli (p = 0.002). These events were more likely to occur later in the course of treatment. DISCUSSION: We suggest that BL ECT may induce focal seizures in prefrontal areas and that these seizures are more likely to occur later in the treatment course.

    Title Ect in the Treatment of Status Epilepticus.
    Date October 2001
    Journal The Journal of Ect
    Excerpt

    INTRODUCTION: Owing to its potent anticonvulsant actions, electroconvulsive therapy (ECT) has been proposed as an intervention for treatment-resistant seizure disorders. METHOD: We review the literature on the use of ECT in treatment-resistant epilepsy and status epilepticus (SE) and present a case of a patient who was in nonconvulsive SE for 26 days and then treated with ECT after all standard pharmacological strategies were exhausted. Because of skull defects, a novel electrode placement was used. RESULTS: Owing to massively elevated seizure threshold attributable to concomitant anticonvulsant medications, extraordinarily high electrical dosage was needed for ECT to elicit generalized seizures. Status was terminated after three successful ECT-induced seizures. However, the long-term functional outcome of the patient was poor. DISCUSSION: The role of ECT in the treatment algorithm for SE is discussed.

    Title Treatment of the Modal Patient: Does One Size Fit Nearly All?
    Date October 2001
    Journal The Journal of Ect
    Title Ect in Bipolar and Unipolar Depression: Differences in Speed of Response.
    Date September 2001
    Journal Bipolar Disorders
    Excerpt

    OBJECTIVES: There is sparse evidence for differences in response to electroconvulsive therapy (ECT) between patients with bipolar or unipolar major depression, with virtually no information on speed of response. We contrasted a large sample of bipolar (BP) and unipolar (UP) depressed patients in likelihood and rapidity of clinical improvement with ECT. METHODS: Over three double-blind treatment protocols, 228 patients met Research Diagnostic Criteria for UP (n = 162) or BP depression (n = 66). Other than lorazepam PRN (3 mg/day), patients were withdrawn from psychotropics prior to the ECT course and until after post-ECT assessments. Patients were randomized to ECT conditions that differed in electrode placement and stimulus intensity. Symptomatic change was evaluated at least twice weekly by a blinded evaluation team, which also determined treatment length. RESULTS: Patients with BP and UP depression did not differ in rates of response or remission following the ECT course, or in response to unilateral or bilateral ECT. Degree of improvement in Hamilton Rating Scale for Depression scores following completion of ECT was also comparable. However, BP patients received significantly fewer ECT treatments than UP patients, and this effect was especially marked among bipolar ECT responders. Both BP I and BP II patients showed especially rapid response to ECT. CONCLUSIONS: The BP/UP distinction had no predictive value in determining ECT outcome. In contrast, there was a large effect for BP patients to show more rapid clinical improvement and require fewer treatments than unipolar patients. The reasons for this difference are unknown, but could reflect a more rapid build up of anticonvulsant effects in BP patients.

    Title Therapeutic Application of Repetitive Transcranial Magnetic Stimulation: a Review.
    Date August 2001
    Journal Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology
    Excerpt

    Transcranial magnetic stimulation (TMS), a non-invasive means of electrically stimulating neurons in the human cerebral cortex, is able to modify neuronal activity locally and at distant sites when delivered in series or trains of pulses. Data from stimulation of the motor cortex suggest that the type of effect on the excitability of the cortical network depends on the frequency of stimulation. These data, as well as results from studies in rodents, have been generalized across brain areas and species to provide rationales for using repetitive TMS (rTMS) to treat various brain disorders, most notably depression. Research into clinical applications for TMS remains active and has the potential to provide useful data, but, to date, the results of blinded, sham-controlled trials do not provide clear evidence of beneficial effects that replace or even match the effectiveness of conventional treatments in any disorder. In this review, we discuss the clinical and scientific bases for using rTMS as treatment, and review the results of trials in psychiatric and neurological disorders to date.

    Title Elevated Motor Threshold in Drug-free, Cocaine-dependent Patients Assessed with Transcranial Magnetic Stimulation.
    Date June 2001
    Journal Biological Psychiatry
    Excerpt

    BACKGROUND: Transcranial magnetic stimulation (TMS) provides a noninvasive method of examining cortical inhibitory and excitatory processes and cortical excitability in awake subjects. There is evidence from clinical and electroencephalographic (EEG) data that cortical excitability may be abnormal in some psychiatric populations. Chronic cocaine abuse influences a number of neurotransmitters that are involved in the excitatory/inhibitory balance of the cerebral cortex. This pilot study was conducted to ascertain the possible utility of TMS in examining cortical excitability in a population of chronic cocaine abusers. METHODS: The right and left motor thresholds of ten cocaine-dependent subjects, according to DSM-IV, and ten normal control subjects were examined using single pulse TMS. RESULTS: The resting motor thresholds resulting from stimulation of the right or the left motor cortical regions were significantly elevated in cocaine-dependent subjects compared with matched control subjects. CONCLUSIONS: These pilot data suggest that chronic cocaine use significantly alters cortical excitability in the direction of increased inhibition or decreased excitability. We hypothesize that this observation reflects adaptation to those effects of cocaine intoxication that promote cortical excitability and seizures.

    Title Sham Tms: Intracerebral Measurement of the Induced Electrical Field and the Induction of Motor-evoked Potentials.
    Date June 2001
    Journal Biological Psychiatry
    Excerpt

    Testing the therapeutic potential of transcranial magnetic stimulation (TMS) in controlled trials requires a valid sham condition. Sham TMS is typically administered by tilting the coil 45--90 degrees off the scalp, with one or two wings of the coil touching the scalp. Lack of cortical effects has not been verified. We compared sham manipulations in their thresholds for eliciting motor-evoked potentials (MEPs) in human volunteers and in intracerebral measurements of voltage induced in the prefrontal cortex of a rhesus monkey. Three types of sham (one-wing 45 degrees and 90 degrees and two-wing 90 degrees tilt) induced much lower voltage in the brain than active TMS (67--73% reductions). However, the two-wing 45 degrees sham induced values just 24% below active TMS. This sham was about half as potent in inducing MEPs over the motor cortex as active TMS. Some sham TMS conditions produce substantial cortical stimulation, making it critical to carefully select the sham manipulation for clinical trials.

    Title The Effects of Vagus Nerve Stimulation on Cognitive Performance in Patients with Treatment-resistant Depression.
    Date May 2001
    Journal Neuropsychiatry, Neuropsychology, and Behavioral Neurology
    Excerpt

    BACKGROUND: Chronic vagus nerve stimulation (VNS) is effective in the management of treatment-resistant epilepsy. Open-trial evidence suggests that VNS has clinically significant antidepressant effects in some individuals who experience treatment-resistant major depressive episodes. However, limited information regarding the effects of VNS on neurocognitive performance exists. OBJECTIVE: The primary aim of this study was to determine whether VNS leads to neurocognitive deterioration. METHOD: A neuropsychological battery was administered to 27 patients with treatment-resistant depression before and after 10 weeks of VNS. Thirteen neurocognitive tests sampled the domains of motor speed, psychomotor function, language, attention, memory, and executive function. RESULTS: No evidence of deterioration in any neurocognitive measure was detected. Relative to baseline, improvement in motor speed (finger tapping), psychomotor function (digit-symbol test), language (verbal fluency), and executive functions (logical reasoning, working memory, response inhibition, or impulsiveness) was found. For some measures, improved neurocognitive performance correlated with the extent of reduction in depressive symptoms, but VNS output current was not related to changes in cognitive performance. CONCLUSIONS: Vagus nerve stimulation in treatment-resistant depression may result in enhanced neurocognitive function, primarily among patients who show clinical improvement. Controlled investigation is needed to rule out the contribution of practice effects.

    Title Vagus Nerve Stimulation. A Potential Therapy for Resistant Depression?
    Date April 2001
    Journal The Psychiatric Clinics of North America
    Excerpt

    VNS builds on a long history of investigating the relationship of autonomic signals to limbic and cortical function and is one of the newest methods to physically alter brain function. VNS is a clinically useful anticonvulsant therapy in treatment resistant patients with epilepsy, and pilot data suggest that it has potential as an antidepressant therapy. The known anatomic projections of the vagus nerve suggest that VNS also might have other neuropsychiatric applications. Additional research is needed to clarify the mechanisms of action of VNS and the potential clinical utility of this intriguing new somatic portal into the CNS.

    Title Magnetic Seizure Therapy of Major Depression.
    Date March 2001
    Journal Archives of General Psychiatry
    Title Repetitive Transcranial Magnetic Stimulation to Sma Worsens Complex Movements in Parkinson's Disease.
    Date March 2001
    Journal Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology
    Excerpt

    OBJECTIVES: To evaluate the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) for Parkinson's disease (PD) by delivering stimulation at higher intensity and frequency over longer time than in previous research. Promising beneficial effects on movement during or after rTMS have been reported. METHODS: Ten patients with idiopathic PD were enrolled in a randomized crossover study comparing active versus sham rTMS to the supplementary motor area (SMA). Assessments included reaction and movement times (RT/MT), quantitative spiral analysis, timed motor performance tests, United Parkinson's Disease Rating Scale (UPDRS), patient self-report and guess as to stimulation condition. RESULTS: Two of 10 patients could not tolerate the protocol. Thirty to 45 min following stimulation, active rTMS as compared with sham stimulation worsened spiral drawing (P=0.001) and prolonged RT in the most affected limb (P=0.030). No other significant differences were detected. CONCLUSIONS: We sought clinically promising improvement in PD but found subclinical worsening of complex and preparatory movement following rTMS to SMA. These results raise safety concerns regarding the persistence of dysfunction induced by rTMS while supporting the value of rTMS as a research tool. Studies aimed at understanding basic mechanisms and timing of rTMS effects are needed.

    Title Ect and Tms: Past, Present, and Future.
    Date March 2001
    Journal Depression and Anxiety
    Title Animal Models of the Mechanisms of Action of Repetitive Transcranial Magnetic Stimulation (rtms): Comparisons with Electroconvulsive Shock (ecs).
    Date March 2001
    Journal Depression and Anxiety
    Excerpt

    Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive means of brain stimulation with a broad range of basic neuroscience and potential future clinical applications. Recent animal studies have shed some light on the mechanisms of action of rTMS, and broadened our understanding of how this intervention affects brain functioning acutely and chronically. Differences in the physical properties of magnetic and electrical stimulation result in marked disparities in the amount and distribution of electrical current induced in the brain; nevertheless, rTMS shares many of the behavioral and biochemical actions of electroconvulsive shock (ECS) and other antidepressant treatments. rTMS reduces immobility in the Porsolt swim task and enhances apomorphine-induced stereotypy, as does ECS. Although rTMS can induce a seizure when given at high enough doses, most studies have found subconvulsive levels of rTMS to be anticonvulsant. rTMS acutely modulates dopamine and serotonin content and turnover rates. Chronic rTMS modulates cortical beta-adrenergic receptors, reduces frontal cortex 5-HT2 receptors, increases 5-hydroxytryptamine1A receptors in frontal cortex and cingulate, and increases N-methyl-D-aspartate receptors in the ventromedial hypothalamus, basolateral amygdala, and parietal cortex. More work will be needed to clarify and explore the mechanism behind the early suggestions that rTMS may exert long-term-potentiation-like or long-term-depression-like action on hippocampal activity. Finally, rTMS is emerging as yet another intervention, like ECS and other antidepressants, that can regulate gene expression and may have an impact on neuronal viability and synaptic plasticity.

    Title Deliberate Seizure Induction with Repetitive Transcranial Magnetic Stimulation in Nonhuman Primates.
    Date March 2001
    Journal Archives of General Psychiatry
    Title The Effects of Electroconvulsive Therapy on Memory of Autobiographical and Public Events.
    Date June 2000
    Journal Archives of General Psychiatry
    Excerpt

    BACKGROUND: Retrograde amnesia is the most persistent cognitive adverse effect of electroconvulsive therapy (ECT); however, it is not known whether ECT has differential effects on autobiographical vs impersonal memories. This study examined the short- and long-term effects of differing forms of ECT on memory of personal and impersonal (public) events. METHODS: Fifty-five patients with major depression were randomly assigned to right unilateral (RUL) or bilateral (BL) ECT, each at either low or high electrical dosage. The Personal and Impersonal Memory Test was administered by blinded raters at baseline, during the week after ECT, and at the 2-month follow-up. Normal controls were tested at matched intervals. RESULTS: Shortly after ECT, patients recalled fewer events and event details than controls, with the deficits most marked for impersonal compared with personal events. Bilateral ECT caused more marked amnesia for events and details than RUL ECT, and especially for impersonal memories. These effects were independent of electrical dosage and clinical outcome. At the 2-month follow-up, patients had reduced retrograde amnesia, but continued to show deficits in recalling the occurrence of impersonal events and the details of recent impersonal events. CONCLUSIONS: The amnestic effects of ECT are greatest and most persistent for knowledge about the world (impersonal memory,) compared with knowledge about the self (personal memory), for recent compared with distinctly remote events, and for less salient events. Bilateral ECT produces more profound amnestic effects than RUL ECT, particularly for memory of impersonal events.

    Title A Prospective, Randomized, Double-blind Comparison of Bilateral and Right Unilateral Electroconvulsive Therapy at Different Stimulus Intensities.
    Date May 2000
    Journal Archives of General Psychiatry
    Excerpt

    BACKGROUND: Controversy persists about the use of right unilateral (RUL) and bilateral (BL) electroconvulsive therapy (ECT). While RUL ECT results in less severe short-term and long-term cognitive effects, there is concern that it is less efficacious than BL ECT. METHODS: In a double-blind study, 80 depressed patients were randomized to RULECT, with electrical dosages 50%, 150%, or 500% above the seizure threshold, or BL ECT, with an electrical dosage 150% above the threshold. Depression severity and cognitive functioning were assessed before, during, immediately after, and 2 months after ECT. Compared with baseline, responders had at least a 60% reduction in symptom scores 1 week after ECT, and were monitored for relapse for 1 year. RESULTS: High-dosage RUL and BL ECT were equivalent in response rate (65%) and approximately twice as effective as low-dosage (35%) or moderate-dosage (30%) unilateral ECT. During the week after the randomized phase, BL ECT resulted in greater impairment than any dosage of unilateral ECT in several measures of anterograde and retrograde memory. Two months after ECT, retrograde amnestic deficits were greatest among patients treated with BL ECT. Thirty-three (53%) of the 62 patients who responded to ECT relapsed, without treatment group differences. The relapse rate was greater in patients who had not responded to adequate pharmacotherapy prior to ECT and who had more severe depressive symptoms after ECT. CONCLUSION: Right unilateral ECT at high dosage is as effective as a robust form of BL ECT, but produces less severe and persistent cognitive effects.

    Title Determinants of Seizure Threshold in Ect: Benzodiazepine Use, Anesthetic Dosage, and Other Factors.
    Date May 2000
    Journal The Journal of Ect
    Excerpt

    The electrical dosage of the ECT stimulus impacts on efficacy and cognitive side effects, yet seizure threshold (ST) may vary as much as 50-fold across patients. It would be desirable to predict ST on the basis of patient and treatment characteristics. In particular, concerns have been raised that benzodiazepine use and higher dosage of barbiturate anesthetics elevate ST. In a three-site study, ST was quantified at the first ECT session using an identical empirical titration procedure in 294 patients who met RDC and DSM-IIIR criteria for a major depressive episode. ST varied over a 35-fold range across patients treated with right unilateral (RUL) (n = 267) and bilateral (BL) (n = 27) ECT. Higher ST was associated with BL electrode placement (p = 0.001). Among patients treated with RUL ECT, univariate analyses indicated that higher ST was associated with advanced age (p < 0.001), male gender (p < 0.001), greater burden of medical illness (p < 0.001), weight (p < 0.01), duration of mood disorder (p < 0.01), and history of previous ECT (p < 0.05). Average lorazepam dose in the 48 hours prior to ECT was not associated with ST, but was associated with decreased seizure duration (p < 0.01). Absolute, but not weight-adjusted, methohexital dose was associated with ST (p < 0.01). Multivariate analyses in patients treated with unilateral ECT showed that only 27.6% of the variance in ST (p < 0.0001) could be predicted. In the multivariate analyses, only age (p = 0.0001), gender (p = 0.01), and methohexital dose (p = 0.0001) were independently related to ST. Low dosage of lorazepam and methohexital dosage below 1 mg/kg are unlikely to impact on ST. Given the limited capacity to predict ST, empirical titration remains the only accurate method to determine electrical dosage in RUL ECT.

    Title Transcranial Magnetic Stimulation: Applications in Neuropsychiatry.
    Date April 1999
    Journal Archives of General Psychiatry
    Excerpt

    In the 1990s, it is difficult to open a newspaper or watch television and not find someone claiming that magnets promote healing. Rarely do these claims stem from double-blind, peer-reviewed studies, making it difficult to separate the wheat from the chaff. The current fads resemble those at the end of the last century, when many were falsely touting the benefits of direct electrical and weak magnetic stimulation. Yet in the midst of this popular interest in magnetic therapy, a new neuroscience field has developed that uses powerful magnetic fields to alter brain activity--transcranial magnetic stimulation. This review examines the basic principles underlying transcranial magnetic stimulation, and describes how it differs from electrical stimulation or other uses of magnets. Initial studies in this field are critically summarized, particularly as they pertain to the pathophysiology and treatment of neuropsychiatric disorders. Transcranial magnetic stimulation is a promising new research and, perhaps, therapeutic tool, but more work remains before it can be fully integrated in psychiatry's diagnostic and therapeutic armamentarium.

    Title The Relative Efficiency of Altering Pulse Frequency or Train Duration when Determining Seizure Threshold.
    Date March 1999
    Journal The Journal of Ect
    Excerpt

    In 12 depressed inpatients referred for bilateral electroconvulsive therapy (ECT), each patient was titrated at the first treatment session by using an ascending method-of-limits procedure with a step-wise increase in pulse frequency (frequency titration) or train duration (duration titration). At the second treatment session, seizure threshold was redetermined by using the method (frequency or duration titration) not used at the first treatment. Frequency or duration was maintained at the lowest level when the other parameter was titrated. Seizure threshold was significantly lower with duration titration (mean, 90 mC; SD, 27.3) than frequency titration (mean, 114 mC; SD, 35.6; p = 0.03). On average, patients in the duration-titration group required 1.2 (SD, 0.6) subconvulsive stimulations before a seizure was elicited, and patients in the frequency-titration group required 1.7 (SD, 0.9) subconvulsive stimulations before a seizure was elicited, a nonsignificant difference. These findings suggest that to elicit a seizure during ECT, increasing train duration may be slightly more efficient than increasing frequency. Basic and other clinical research findings indicate that increasing pulse width may be an inefficient way to elicit a seizure. Therefore the following sequence in the determination of seizure threshold is worth considering when using dose-titration or related techniques: the train duration should be increased first before increasing pulse frequency, and the decision to increase pulse width should be reserved for patients who do not seize at the maximal duration and frequency settings. Further empiric research is needed to establish the utility of this approach.

    Title Prolactin Response to Electroconvulsive Therapy: Effects of Electrode Placement and Stimulus Dosage.
    Date April 1998
    Journal Biological Psychiatry
    Excerpt

    BACKGROUND: It is unclear whether the serum prolactin (PRL) surge following electroconvulsive therapy (ECT) is a marker of optimal ECT administration. We investigated the relations among PRL surge, stimulus parameters, and outcome in major depressive disorder (MDD). METHODS: Seventy-nine patients with MDD were randomized in a double-blind trial to right unilateral (RUL) or bilateral (BL), and to low-dose (just above seizure threshold) or high-dose (2.5 x threshold) ECT. RESULTS: Change in PRL (delta PRL) varied among treatment groups, with significant effects of electrode placement (BL > RUL, p < .006), electrical dosage (high > low, p < .04), and gender (female > male, p < .005). There was no evidence that clinical improvement was associated with greater PRL surge. CONCLUSIONS: Although delta PRL varied with parameters impacting on response rates, these data indicate the PRL surge cannot serve as a useful index of clinically effective treatment. This finding does not support the view that diencephalic seizure propagation is necessary for ECT to exert therapeutic effects.

    Title Exceptionally High Seizure Threshold: Ect Device Limitations.
    Date January 1997
    Journal Convulsive Therapy
    Excerpt

    Three patients had exceptionally high seizure threshold, as determined by an empirical titration procedure. Initial seizure threshold was 896 mC in two of the patients. The third patient had an initial threshold of 336 mC that increased to 840 mC at the end of the course of electroconvulsive therapy (ECT), and remained elevated during a second course of ECT. All three patients were elderly men with complicated medical histories and ongoing low-dose benzodiazepine use. Each patient had an excellent response to ECT delivered with a custom modified device, capable of delivering more than twice the charge of ECT devices presently commercially available in the United States. Implications for the administration of ECT in patients with exceptionally high seizure threshold and the limitations of current device output are discussed.

    Title Diminished Subcortical Nuclei Volumes in Parkinson's Disease by Mr Imaging.
    Date March 1994
    Journal Journal of Neural Transmission. Supplementum
    Excerpt

    Parkinson's disease (PD) is associated with changes in the substantia nigra, which communicates with subcortical nuclei. This study investigates subcortical nuclei volume in PD in vivo by magnetic resonance (MR) imaging. Caudate, putaminal, and thalamic nuclei were measured on axial MR images using a point counting method and systematic sampling. PD patients (n = 21) had significantly smaller subcortical nuclei than age- and sex-matched controls (p < 0.001) and depressed patients (p < 0.01). The decline in PD was not correlated with age, sex, or cortical volume. Depressed patients had significantly smaller caudate and putaminal nuclei than controls (p < 0.05 and 0.01, respectively) but thalamic nuclei were not significantly different. Caudate, putaminal, and thalamic nuclei volumes of controls were significantly negatively correlated with age (r = -0.58, p < 0.01; r = -0.77, p < 0.001; r = -0.57, p < 0.01, respectively). Depressed subjects demonstrated a negative trend. Volumetric measurements by MR imaging may be a useful in investigating the role of the basal ganglia in neurological disorders.

    Title Psychosis Secondary to Brain Tumor.
    Date
    Journal Seminars in Clinical Neuropsychiatry
    Excerpt

    Brain tumors may present with psychotic symptoms that resemble schizophrenia. Although psychosis secondary to brain tumor is relatively rare, the frequent lack of neurological findings can lead to misdiagnosis. Psychosis secondary to brain tumor is more common and also harder to accurately diagnose in the elderly. Key aspects of the epidemiology, clinical spectrum, diagnostic evaluation, and treatment are reviewed. The case of a 26-year old woman with psychosis secondary to a meningioma of the right lateral ventricle with extension into the corpus callosum and periventricular white matter is presented. Symptoms completely resolved after surgical excision of the tumor and remain in remission at 2(1/2) year follow-up on no medications. The clinician should maintain a high degree of vigilance for clinical features suggestive of this potentially reversible cause of psychosis.

    Title Transcranial Magnetic Stimulation: Applications in Basic Neuroscience and Neuropsychopharmacology.
    Date
    Journal The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (cinp)
    Excerpt

    Introduced 15 years ago, transcranial magnetic stimulation (TMS) is a non-invasive means of stimulating the cortex that has proved to be a unique tool for probing brain-behaviour relationships. While a therapeutic role for TMS in neuropsychiatry is uncertain, the utility of TMS in studying brain function has been demonstrated in diverse neuroscience applications. We review studies in animals on the mechanisms of action of TMS, and present a summary of the applications of TMS in basic neuroscience. TMS is still a relatively young technique, and unanswered questions remain regarding its acute and chronic impact on neural excitability and various aspects of brain function. Nonetheless, recent work with TMS has demonstrated its unique role in complementing other tools for studying brain function. As a brain intervention tool, TMS holds the promise of moving beyond correlative studies to help define the functional role of cortical regions in selected cognitive and affective processes.

    Title Remediation of Sleep-deprivation-induced Working Memory Impairment with Fmri-guided Transcranial Magnetic Stimulation.
    Date
    Journal Cerebral Cortex (new York, N.y. : 1991)
    Excerpt

    Repetitive transcranial magnetic stimulation (rTMS) was applied to test the role of selected cortical regions in remediating sleep-deprivation-induced deficits in visual working memory (WM) performance. Three rTMS targets were chosen using a functional magnetic resonance imaging (fMRI)-identified network associated with sleep-deprivation-induced WM performance impairment: 2 regions from the network (upper left middle occipital gyrus and midline parietal cortex) and 1 nonnetwork region (lower left middle occipital gyrus). Fifteen participants underwent total sleep deprivation for 48 h. rTMS was applied at 5 Hz during a WM task in a within-subject sham-controlled design. The rTMS to the upper-middle occipital site resulted in a reduction of the sleep-induced reaction time deficit without a corresponding decrease in accuracy, whereas stimulation at the other sites did not. Each subject had undergone fMRI scanning while performing the task both pre- and postsleep deprivation, and the degree to which each individual activated the fMRI network was measured. The degree of performance enhancement with upper-middle occipital rTMS correlated with the degree to which each individual failed to sustain network activation. No effects were found in a subset of participants who performed the same rTMS procedure after recovering from sleep deprivation, suggesting that the performance enhancements seen following sleep deprivation were state dependent.

    Title Quick Recovery of Orientation After Magnetic Seizure Therapy for Major Depressive Disorder.
    Date
    Journal The British Journal of Psychiatry : the Journal of Mental Science
    Excerpt

    BACKGROUND: Magnetic seizure therapy, in which seizures are elicited with a high-frequency magnetic field, is under development as a new treatment for major depressive disorder. Its use may be justified if it produces the antidepressant effects of electroconvulsive therapy (ECT), coupled with limited cognitive side-effects. AIMS: To evaluate the usefulness of a new 100 Hz magnetic seizure therapy device. METHOD: We induced seizures with 100 Hz magnetic transcranial stimulation in 11 patients with major depressive disorder during one session of a regular course of ECT. Recovery times after seizures induced by magnetic seizure therapy and ECT were compared. RESULTS: Seizures could be elicited in 10 of the 11 patients. Stimulation over the vertex produced tonic-clonic activity on 9 out of 11 occasions. Stimulation over the prefrontal midpoint elicited seizures on 3 out of 7 occasions. The mean duration of magnetically induced seizures was 31.3 s, ranging from 10 to 86 s. All patients had an exceptionally quick recovery of orientation: mean of 7 min 12 s (s.d.=2 min 7 s, range 4 min 20 s to 9 min 41 s). The recovery times were on average 15 min 35 s shorter with magnetic seizure therapy than with ECT in the same patients (paired-samples t-test: P<0.0001). Patients reported feeling less confused after magnetic seizure therapy. Side-effects were confined to myoclonic movements, associated with the use of etomidate. CONCLUSIONS: The new 100 Hz magnetic stimulator elicits seizures in the majority of patients when administered over the vertex. Magnetic seizure therapy was associated with shorter recovery times and less confusion following treatment. Subsequent work will be required to assess the safety and effectiveness of magnetic seizure therapy in the treatment of depression.

    Title Daily Left Prefrontal Repetitive Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: Clinical Predictors of Outcome in a Multisite, Randomized Controlled Clinical Trial.
    Date
    Journal Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
    Excerpt

    Randomized controlled trials support the antidepressant efficacy of transcranial magnetic stimulation (TMS); however, there is individual variability in the magnitude of response. Examination of response predictors has been hampered by methodological limitations such as small sample sizes and single-site study designs. Data from a multisite sham-controlled trial of the antidepressant efficacy of TMS provided an opportunity to examine predictors of acute outcome. An open-label extension for patients who failed to improve provided the opportunity for confirmatory analysis. Treatment was administered to the left dorsolateral prefrontal cortex at 10 pulses per second, 120% of motor threshold, for a total of 3000 pulses per day. Change on the Montgomery-Asberg Depression Rating Scale after 4 weeks was the primary efficacy outcome. A total of 301 patients with nonpsychotic unipolar major depression at 23 centers were randomized to active or sham TMS. Univariate predictor analyses showed that the degree of prior treatment resistance in the current episode was a predictor of positive treatment outcome in both the controlled study and the open-label extension trial. In the randomized trial, shorter duration of current episode was also associated with a better outcome. In the open-label extension study, absence of anxiety disorder comorbidity was associated with an improved outcome, but duration of current episode was not. The number of prior treatment failures was the strongest predictor for positive response to acute treatment with TMS. Shorter duration of current illness and lack of anxiety comorbidity may also confer an increased likelihood of good antidepressant response to TMS.Neuropsychopharmacology advance online publication, 13 August 2008; doi:10.1038/npp.2008.118.

    Title Toward Individualized Post-electroconvulsive Therapy Care: Piloting the Symptom-titrated, Algorithm-based Longitudinal Ect (stable) Intervention.
    Date
    Journal The Journal of Ect
    Excerpt

    OBJECTIVES: Effective strategies to prolong remission after electroconvulsive therapy (ECT) are urgently needed. Fixed schedules for continuation ECT (C-ECT) cannot adapt to early signs of impending relapse. Symptom-Titrated, Algorithm-Based Longitudinal ECT (STABLE) is proposed as a novel patient-focused approach to individualize the ECT schedule. In STABLE, the ECT schedule adapts to symptom fluctuations to prevent overtreatment of those who do not need it and to recapture response in those who might have otherwise relapsed with a rigid dosing schedule. Here we back-test STABLE to optimize the algorithm for subsequent testing in a prospective trial. METHODS: Three variations of the STABLE algorithm, differing in cutoff points to trigger or withhold additional ECT, were back-tested in a data set of 89 patients randomized to the C-ECT arm in the CORE (Consortium for Research on ECT) Study comparing C-ECT with combination pharmacotherapy. RESULTS: The selected algorithm identified 100% of patients who ultimately relapsed as requiring additional ECT at an average of 2.2 weeks before relapse, while exposing 20% of sustained remitters to additional ECT. Other variations either failed to capture impending relapse or exposed an unacceptably large percentage of patients to potentially unnecessary ECT. CONCLUSIONS: This patient-focused approach to relapse prevention is an attempt to provide the first operationalized guidance to the field regarding how to conduct C-ECT. The effectiveness of this approach should be tested in a randomized controlled trial.

    Title Flexible Dosing Schedules for Continuation Electroconvulsive Therapy.
    Date
    Journal The Journal of Ect
    Title High-frequency Prefrontal Repetitive Transcranial Magnetic Stimulation for the Negative Symptoms of Schizophrenia: a Case Series.
    Date
    Journal The Journal of Ect
    Excerpt

    : The negative symptoms of schizophrenia are difficult to treat and are predictors of poor outcome. New somatic treatments are needed to reverse these symptoms and improve function. One promising approach is repetitive transcranial magnetic stimulation (rTMS), although results to date have been mixed. This pilot study assessed higher doses of rTMS and assessed particular demographic factors that may influence treatment response.

    Title Repetitive Transcranial Magnetic Stimulator with Controllable Pulse Parameters (ctms).
    Date
    Journal Conference Proceedings : ... Annual International Conference of the Ieee Engineering in Medicine and Biology Society. Ieee Engineering in Medicine and Biology Society. Conference
    Excerpt

    We describe a novel transcranial magnetic stimulation (TMS) device that uses a circuit topology incorporating two energy-storage capacitors and two insulated-gate bipolar transistors (IGBTs) to generate near-rectangular electric field E-field) pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable-pulse-parameter TMS (cTMS) device can induce E-field pulses with phase widths of 5-200 µs and positive/negative phase amplitude ratio of 1-10. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation by 78-82% and 55-57% and decreases coil heating by 15-33% and 31-41%, respectively. We demonstrate repetitive TMS (rTMS) trains of 3,000 pulses at frequencies up to 50 Hz with E-field pulse amplitude and width variability of less than 1.7% and 1%, respectively. The reduced power consumption and coil heating, and the flexible pulse parameter adjustment offered by cTMS could enhance existing TMS paradigms and could enable novel research and clinical applications with potentially enhanced potency.

    Title Regional Electric Field Induced by Electroconvulsive Therapy: a Finite Element Simulation Study.
    Date
    Journal Conference Proceedings : ... Annual International Conference of the Ieee Engineering in Medicine and Biology Society. Ieee Engineering in Medicine and Biology Society. Conference
    Excerpt

    The goal of this study is to investigate the regional distribution of the electric field (E-field) strength induced by electroconvulsive therapy (ECT), and to contrast clinically relevant electrode configurations through finite element (FE) analysis. An FE human head model incorporating tissue heterogeneity and white matter anisotropy was generated based on structural magnetic resonance imaging (MRI) and diffusion tensor MRI (DT-MRI) data. We simulated the E-field spatial distributions of three standard ECT electrode placements [bilateral (BL), bifrontal (BF), and right unilateral (RUL)] and an investigational electrode configuration [focal electrically administered seizure therapy (FEAST)]. A quantitative comparison of the E-field strength was subsequently carried out in various brain regions of interests (ROIs) that have putative role in the therapeutic action and/or adverse side effects of ECT. This study illustrates how the realistic FE head model provides quantitative insight in the biophysics of ECT, which may shed light on the differential clinical outcomes seen with various forms of ECT, and may guide the development of novel stimulation paradigms with improved risk/benefit ratio.

    Title Electroconvulsive Therapy in the Presence of Deep Brain Stimulation Implants: Electric Field Effects.
    Date
    Journal Conference Proceedings : ... Annual International Conference of the Ieee Engineering in Medicine and Biology Society. Ieee Engineering in Medicine and Biology Society. Conference
    Excerpt

    The safety of electroconvulsive therapy (ECT) in patients who have deep brain stimulation (DBS) implants represents a significant clinical issue. A major safety concern is the presence of burr holes and electrode anchoring devices in the skull, which may alter the induced electric field distribution in the brain. We simulated the electric field using finite-element method in a five-shell spherical head model. Three DBS electrode anchoring techniques were modeled, including ring/cap, microplate, and burr-hole cover. ECT was modeled with bilateral (BL), right unilateral (RUL), and bifrontal (BF) electrode placements and with clinically-used stimulus current amplitude. We compared electric field strength and focality among the DBS implantation techniques and ECT electrode configurations. The simulation results show an increase in the electric field strength in the brain due to conduction through the burr holes, especially when the burr holes are not fitted with nonconductive caps. For typical burr hole placement for subthalamic nucleus DBS, the effect on the electric field strength and focality is strongest for BF ECT, which runs contrary to the belief that more anterior ECT electrode placements are safer in patients with DBS implants.

    Title The Structure of the Lived Experience for Persons Having Undergone Rtms for Depression Treatment.
    Date
    Journal Journal of the American Psychiatric Nurses Association
    Excerpt

    This phenomenological research study reports preliminary findings about experiences of persons undergoing repeated transcranial magnetic stimulation (rTMS) for depression treatment.

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