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Andrew Kozel

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Gulhane Military Medical Academy

Raffaella Ricci

Università degli Studi di Torino

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University of Trento

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Papers by Andrew Kozel

Safety and benefits of distance-adjusted prefrontal transcranial magnetic stimulation in depressed patients 55-75 years of age: A pilot study

by Mark George, F. Daro, and Andrew Kozel

Depression and Anxiety, 2004

In contrast to the effects seen in younger adults, depressed elderly subjects have shown more mod... more In contrast to the effects seen in younger adults, depressed elderly subjects have shown more modest antidepressant responses to transcranial magnetic stimulation (TMS). We theorized that higher stimulation intensities in older depressed subjects with prefrontal atrophy might be needed to stimulate underlying cortex. In an open design with patients on stable baseline medications, we treated 18 treatment-resistant elderly depressed subjects (mean age 61.277.3) with 15 rTMS sessions over 3 weeks. We adjusted the delivered TMS intensity to account for MRI measured prefrontal atrophy. The skull to prefrontal cortex distance increased with age, whereas the skull to motor cortex distance did not. All subjects tolerated the higher doses well. The average intensity used was 114% of motor threshold (MT) with a range from 103-141% MT. There was an average 35% decline over the 3 weeks in HRSD scores. After 3 weeks of treatment, 27% (5/18) met response criteria (450% improvement), with four of these five also meeting criteria for remission (exit Hamilton Depression Score o8). These initial pilot findings support the need for blinded studies using prefrontal TMS in an elderly population, testing whether TMS, delivered at stimulation intensities calculated to overcome atrophy, is more effective than TMS without adjusting for atrophy.

Fractional anisotropy changes after several weeks of daily left high-frequency repetitive transcranial magnetic stimulation of the prefrontal cortex to treat major depression

The Journal of Ect, Mar 1, 2011

Objectives-As part of a sham controlled treatment trial using daily left rTMS, brain changes asso... more Objectives-As part of a sham controlled treatment trial using daily left rTMS, brain changes associated with four to six weeks of treatment were examined using diffusion tensor imaging (DTI) in order to non-invasively evaluate prefrontal white matter microstructure. A decrease in fractional anisotropy (FA) values of the left prefrontal white matter could indicate damage to the region.

Developing a Neuropsychiatric Functional Brain Imaging Test

Neurocase, 2008

A number of critical issues must be addressed in order to develop and properly apply a functional... more A number of critical issues must be addressed in order to develop and properly apply a functional brain imaging test. Diagnostic tests involve making a judgment for a single person. As a result, functional brain imaging tests must also be evaluated at the individual level. The population examined in determining the evidence for the accuracy of the test and the specific question being tested should be clearly described so that the test can be applied appropriately. The accuracy of the test must also be established in order to know the degree of confidence to accord a result. Incorporating what has been learned with medical diagnostic test development will enable legitimate and significant neuropsychiatric functional brain imaging tests to be developed in the future.

Improvement of depression following transcranial magnetic stimulation

Current Psychiatry Reports, 1999

Potential mechanisms of action of vagus nerve stimulaiton for depression

Vagus nerve stimulation alters pain perception in depressed adults

Pain research & management: the journal of the Canadian Pain Society = journal de la societe canadienne pour le traitement de la douleur

ABSTRACT

Using imaging to target the prefrontal cortex for transcranial magnetic stimulation studies in treatment-resistant depression

Dialogues in clinical neuroscience

ABSTRACT

Roper v. Simmons: An fMRI Perspective Study

by Andrew Kozel and Markus Kruesi

<title>Credibility assessments: operational issues and technology impact for law enforcement applications</title>

Sensors, and Command, Control, Communications, and Intelligence (C3I) Technologies for Homeland Defense and Law Enforcement II, 2003

Law Enforcement personnel are faced with new challenges to rapidly assess the credibility of stat... more Law Enforcement personnel are faced with new challenges to rapidly assess the credibility of statements made by individuals in airports, border crossings, and a variety of environments not conducive to interviews. New technologies may offer assistance to law enforcement personnel in the interview and interrogation process. Additionally, homeland defense against terrorism challenges scientists to develop new methods of assessing truthfulness

Regional Brain Activation During Meditation Shows Time and Practice Effects: An Exploratory FMRI Studyy

Meditation involves attentional regulation and may lead to increased activity in brain regions as... more Meditation involves attentional regulation and may lead to increased activity in brain regions associated with attention such as dorsal lateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Using functional magnetic resonance imaging, we examined whether DLPFC and ACC were activated during meditation. Subjects who meditate were recruited and scanned on a 3.0 Tesla scanner. Subjects meditated for four sessions

Neural correlates of successful response inhibition in unmedicated patients with late-life depression

by Andrew Kozel and Kimberly Mapes

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2012

Accumulating evidence implicates a strong association between abnormal frontostriatal-limbic brai... more Accumulating evidence implicates a strong association between abnormal frontostriatal-limbic brain circuits, executive dysfunction, and late-life depression (LLD). The stop signal task (SST) was designed by Rubia et al. for use with functional magnetic resonance imaging (fMRI) to identify the neural correlates of motor response inhibition, a well-characterized executive function. In this study, we compared brain activation between a group of unmedicated participants with LLD and an unmedicated healthy cohort during SST performance. Participants 55-85 years of age were screened, clinically evaluated, and entered into either the LLD (n = 15) or healthy comparison group (n = 13). Both groups underwent neuroimaging while performing the SST under similar conditions. The brain circuitry of successful motor inhibition was evaluated by contrasting the condition of correctly inhibiting responses with the condition of correctly responding to Go signals. Differential areas of brain activation ...

Treatment outcomes for older depressed patients with earlier versus late onset of first depressive episode: a Sequenced Treatment Alternatives to Relieve Depression (STAR*D) report

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2008

Controversy exists whether age at onset of the first depressive episode predicts chance of respon... more Controversy exists whether age at onset of the first depressive episode predicts chance of response and remission or the timing of such outcome. In this study of older depressed outpatients, the authors evaluated whether the age at onset of the first major depressive episode (MDE) was related to clinical outcomes. Post-hoc dataset analysis for older participants treated with citalopram in the Sequenced Treatment Alternatives to Relieve Depression trial was performed. Side effects, remission rates, and baseline characteristics were compared for participants whose first MDE began at or before age 55 (earlier onset) versus those with their first MDE after age 55 (late onset). Participants were enrolled from 23 psychiatric and 18 primary care settings. There were 574 treatment-seeking outpatients (age range: 55-75 years) with nonpsychotic major depressive disorder who had a baseline 17-item Hamilton Rating Scale for Depression score of > or =14. Participants received citalopram treat...

Conditioning of transcranial magnetic stimulation: Evidence of sensory-induced responding and prepulse inhibition

Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating the human cortex... more Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating the human cortex. Classical conditioning is a phenomenon of developed associations between stimuli. Our primary objective was to determine whether TMS effects could be conditioned. Prepulse inhibition represents another relationship between two stimuli, and a secondary assessment was performed to explore this relationship. An auditory-visual conditioning stimulus (CS) was paired with the TMS unconditioned stimulus (US) over motor cortex producing a motor-evoked potential (MEP) unconditioned response (UR). Two versions of the CS-US pairing paradigms were tested, one with a short intertrial interval (ITI) and another with a long ITI. The short ITI paradigm had more CS-US pairings and shorter session duration than the long ITI paradigm. Tests for conditioned responses (CRs) were performed following CS-US pairing (CS+/US+), by presenting the CS alone (CS+/US-). Reverse testing was also performed after CS-US pairing (CS+/US+) in separate sessions, by presenting the US alone (CS-/US+). Evidence for CRs was found only with the short ITI paradigm. The magnitudes of CRs were smaller than TMS-induced MEPs, and the CRs were found only in a percentage of tests. Prepulse inhibition was robustly evident for the long ITI paradigm, but not for the short ITI paradigm. We have found evidence that classical conditioning principles can be applied to brain stimulation in humans. These findings provide a method for exploring brain and behavioral relationships in humans, as well as suggesting approaches to enhance therapeutic uses of TMS or other forms of brain stimulation.

Novel treatments of mood disorders based on brain circuitry (ECT, MST, TMS, VNS, DBS)

Seminars in clinical neuropsychiatry, 2002

Advances in understanding the functional and structural anatomy of depression outlined in this is... more Advances in understanding the functional and structural anatomy of depression outlined in this issue set the stage for attempting to manipulate implicated brain regions as potential antidepressant therapies. On the one hand, these circuit- and device-based approaches to treating depression are not new. Electroconvulsive therapy (ECT) dates back to the beginning of modern biologic psychiatry with the discovery and rapid increase of first chemical (around 1910), and then later ECT. On the other hand, this area represents an important paradigm shift with treatments that are radical and different. A dizzying array of diverse technologies now allows researchers to stimulate the brain in undreamed of ways. However, the approaches described in this article are still considered experimental and are not approved for use in the United States by the Food and Drug Administration (FDA), except ECT, which predates the FDA. These device-based approaches to brain stimulation offer promise as potent...

Transcranial magnetic stimulation

Neurosurgery clinics of North America, 2003

TMS is a powerful new tool with extremely interesting research and therapeutic potentials. Furthe... more 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. What...

Decision analysis of the cost-effectiveness of repetitive transcranial magnetic stimulation versus electroconvulsive therapy for treatment of nonpsychotic severe depression

CNS spectrums, 2004

Repetitive transcranial magnetic stimulation (rTMS) is a new treatment with promise for resistant... more Repetitive transcranial magnetic stimulation (rTMS) is a new treatment with promise for resistant depression. We tested the economic feasibility of this new method compared with electroconvulsive therapy (ECT). An economic decision analysis was used to compare the costs of three different treatment strategies for nonpsychotic severe depression. The strategies were: ECT alone; rTMS alone; and rTMS followed by ECT for nonresponders (rTMS-to-ECT). We calculated 12-month costs and quality adjusted life years (QALYs) for the three treatment options for all nonpsychotic, severely depressed United States patients who would have otherwise undergone ECT. A sensitivity analysis was performed to test the degree of change in outcome with various parameter changes. The additional cost of using ECT alone compared with rTMS alone was 460,031 US dollars per quality adjusted year of life gained. For ECT versus rTMS-to-ECT, there was both an increased cost and a loss of 1,538 QALYs with ECT alone. Th...

<title>Bilateral responses of prefrontal and motor cortices to repetitive transcranial magnetic stimulation as measured by functional near infrared spectroscopy</title>

by Andrew Kozel and Kimberly Mapes

Photonic Therapeutics and Diagnostics V, 2009

Simultaneously acquiring cortical functional Near Infrared Spectroscopy (fNIRS) during repeated T... more Simultaneously acquiring cortical functional Near Infrared Spectroscopy (fNIRS) during repeated Transcranial Magnetic Stimulation (rTMS) offers the possibility of directly investigating the effects of rTMS on brain regions without quantifiable behavioral changes. In this study, the left motor cortex and subsequently the left prefrontal cortex were stimulated at 1 Hz while fNIRS data was simultaneously acquired. Changes in hemodynamic signals were measured on both ipsilateral and contralateral sides. In each cortex, a significantly larger decrease in the concentration of oxygenated hemoglobin and a smaller increase in the concentration of deoxygenated hemoglobin during the stimulation periods were observed in both the motor and prefrontal cortices. The ipsilateral and contralateral changes showed high temporal consistency. Same experiment was repeated for each subject 2 or 3 days later. The hemodynamic responses associated with the stimulation showed good reproducibility in two sessions. To our knowledge, this is the first report of simultaneous fNIRS measurement of ipsilateral and contralateral changes of either the motor or prefrontal cortex during rTMS stimulation.

Mechanisms of action of vagus nerve stimulation (VNS)

Clinical Neuroscience Research, 2004

In 1992, Dr Jake Zabara discovered in a canine model that repeated stimulation of the vagus nerve... more In 1992, Dr Jake Zabara discovered in a canine model that repeated stimulation of the vagus nerve in the neck could stop seizures. Since that time, repeated stimulation of the vagus nerve has been FDA approved as an anticonvulsant. Zabara's work is built on a 50-year-old theme in the literature where scientists had sought to exploit the fact that the vagus nerve is composed of 80% afferent fibers. Thus vagus stimulation might potentially provide a 'window' into the brain. This manuscript reviews the basic science and brain imaging work done to date with VNS, attempting to understand how VNS affects the brain. This research is crucial to perfecting VNS as an anticonvulsant, and for determining other neuropsychiatric conditions that might be helped by VNS. q

Functional Connectivity of Brain Structures Correlates with Treatment Outcome in Major Depressive Disorder

by Andrew Kozel and Kimberly Mapes

Frontiers in Psychiatry, 2011

Identifying biosignatures to assess the probability of response to an antidepressant for patients... more Identifying biosignatures to assess the probability of response to an antidepressant for patients with major depressive disorder (MDD) is critically needed. Functional connectivity MRI (fcMRI) offers the promise to provide such a measure. Previous work with fcMRI demonstrated that the correlation in signal from one region to another is a measure of functional connectivity. In this pilot work, a baseline non-task fcMRI was acquired in 14 adults with MDD who were free of all medications. Participants were then treated for 8 weeks with an antidepressant and then clinically re-evaluated. Probabilistic anatomic regions of interest (ROI) were defined for 16 brain regions (eight for each hemisphere) previously identified as being important in mood disorders. These ROIs were used to determine mean time courses for each individual's baseline non-task fcMRI. The correlations in time courses between 16 brain regions were calculated. These calculated correlations were considered to signify measures of functional connectivity. The degree of connectivity for each participant was correlated with treatment outcome. Among 13 participants with 8 weeks follow-up data, connectivity measures in several regions, especially the subcallosal cortex, were highly correlated with treatment outcome. These connectivity measures could provide a means to evaluate how likely a patient is to respond to an antidepressant treatment. Further work using larger samples is required to confirm these findings and to assess if measures of functional connectivity can be used to predict differential outcomes between antidepressant treatments.

Replication of Functional MRI Detection of Deception

by Andrew Kozel and Kimberly Mapes

The Open Forensic Science Journal, 2009

Background-Several studies support the use of fMRI for detecting deception. There have been, howe... more Background-Several studies support the use of fMRI for detecting deception. There have been, however, no reported replications on different scanners or at different locations. In a previous study, deception was accurately detected in at least 90% of the participants in two independent cohorts. This study attempted to replicate those findings using a different scanner and location.

Safety and benefits of distance-adjusted prefrontal transcranial magnetic stimulation in depressed patients 55-75 years of age: A pilot study

by Mark George, F. Daro, and Andrew Kozel

Depression and Anxiety, 2004

In contrast to the effects seen in younger adults, depressed elderly subjects have shown more mod... more In contrast to the effects seen in younger adults, depressed elderly subjects have shown more modest antidepressant responses to transcranial magnetic stimulation (TMS). We theorized that higher stimulation intensities in older depressed subjects with prefrontal atrophy might be needed to stimulate underlying cortex. In an open design with patients on stable baseline medications, we treated 18 treatment-resistant elderly depressed subjects (mean age 61.277.3) with 15 rTMS sessions over 3 weeks. We adjusted the delivered TMS intensity to account for MRI measured prefrontal atrophy. The skull to prefrontal cortex distance increased with age, whereas the skull to motor cortex distance did not. All subjects tolerated the higher doses well. The average intensity used was 114% of motor threshold (MT) with a range from 103-141% MT. There was an average 35% decline over the 3 weeks in HRSD scores. After 3 weeks of treatment, 27% (5/18) met response criteria (450% improvement), with four of these five also meeting criteria for remission (exit Hamilton Depression Score o8). These initial pilot findings support the need for blinded studies using prefrontal TMS in an elderly population, testing whether TMS, delivered at stimulation intensities calculated to overcome atrophy, is more effective than TMS without adjusting for atrophy.

Fractional anisotropy changes after several weeks of daily left high-frequency repetitive transcranial magnetic stimulation of the prefrontal cortex to treat major depression

The Journal of Ect, Mar 1, 2011

Objectives-As part of a sham controlled treatment trial using daily left rTMS, brain changes asso... more Objectives-As part of a sham controlled treatment trial using daily left rTMS, brain changes associated with four to six weeks of treatment were examined using diffusion tensor imaging (DTI) in order to non-invasively evaluate prefrontal white matter microstructure. A decrease in fractional anisotropy (FA) values of the left prefrontal white matter could indicate damage to the region.

Developing a Neuropsychiatric Functional Brain Imaging Test

Neurocase, 2008

A number of critical issues must be addressed in order to develop and properly apply a functional... more A number of critical issues must be addressed in order to develop and properly apply a functional brain imaging test. Diagnostic tests involve making a judgment for a single person. As a result, functional brain imaging tests must also be evaluated at the individual level. The population examined in determining the evidence for the accuracy of the test and the specific question being tested should be clearly described so that the test can be applied appropriately. The accuracy of the test must also be established in order to know the degree of confidence to accord a result. Incorporating what has been learned with medical diagnostic test development will enable legitimate and significant neuropsychiatric functional brain imaging tests to be developed in the future.

Improvement of depression following transcranial magnetic stimulation

Current Psychiatry Reports, 1999

Potential mechanisms of action of vagus nerve stimulaiton for depression

Vagus nerve stimulation alters pain perception in depressed adults

Pain research & management: the journal of the Canadian Pain Society = journal de la societe canadienne pour le traitement de la douleur

ABSTRACT

Using imaging to target the prefrontal cortex for transcranial magnetic stimulation studies in treatment-resistant depression

Dialogues in clinical neuroscience

ABSTRACT

Roper v. Simmons: An fMRI Perspective Study

by Andrew Kozel and Markus Kruesi

<title>Credibility assessments: operational issues and technology impact for law enforcement applications</title>

Sensors, and Command, Control, Communications, and Intelligence (C3I) Technologies for Homeland Defense and Law Enforcement II, 2003

Law Enforcement personnel are faced with new challenges to rapidly assess the credibility of stat... more Law Enforcement personnel are faced with new challenges to rapidly assess the credibility of statements made by individuals in airports, border crossings, and a variety of environments not conducive to interviews. New technologies may offer assistance to law enforcement personnel in the interview and interrogation process. Additionally, homeland defense against terrorism challenges scientists to develop new methods of assessing truthfulness

Regional Brain Activation During Meditation Shows Time and Practice Effects: An Exploratory FMRI Studyy

Meditation involves attentional regulation and may lead to increased activity in brain regions as... more Meditation involves attentional regulation and may lead to increased activity in brain regions associated with attention such as dorsal lateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Using functional magnetic resonance imaging, we examined whether DLPFC and ACC were activated during meditation. Subjects who meditate were recruited and scanned on a 3.0 Tesla scanner. Subjects meditated for four sessions

Neural correlates of successful response inhibition in unmedicated patients with late-life depression

by Andrew Kozel and Kimberly Mapes

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2012

Accumulating evidence implicates a strong association between abnormal frontostriatal-limbic brai... more Accumulating evidence implicates a strong association between abnormal frontostriatal-limbic brain circuits, executive dysfunction, and late-life depression (LLD). The stop signal task (SST) was designed by Rubia et al. for use with functional magnetic resonance imaging (fMRI) to identify the neural correlates of motor response inhibition, a well-characterized executive function. In this study, we compared brain activation between a group of unmedicated participants with LLD and an unmedicated healthy cohort during SST performance. Participants 55-85 years of age were screened, clinically evaluated, and entered into either the LLD (n = 15) or healthy comparison group (n = 13). Both groups underwent neuroimaging while performing the SST under similar conditions. The brain circuitry of successful motor inhibition was evaluated by contrasting the condition of correctly inhibiting responses with the condition of correctly responding to Go signals. Differential areas of brain activation ...

Treatment outcomes for older depressed patients with earlier versus late onset of first depressive episode: a Sequenced Treatment Alternatives to Relieve Depression (STAR*D) report

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2008

Controversy exists whether age at onset of the first depressive episode predicts chance of respon... more Controversy exists whether age at onset of the first depressive episode predicts chance of response and remission or the timing of such outcome. In this study of older depressed outpatients, the authors evaluated whether the age at onset of the first major depressive episode (MDE) was related to clinical outcomes. Post-hoc dataset analysis for older participants treated with citalopram in the Sequenced Treatment Alternatives to Relieve Depression trial was performed. Side effects, remission rates, and baseline characteristics were compared for participants whose first MDE began at or before age 55 (earlier onset) versus those with their first MDE after age 55 (late onset). Participants were enrolled from 23 psychiatric and 18 primary care settings. There were 574 treatment-seeking outpatients (age range: 55-75 years) with nonpsychotic major depressive disorder who had a baseline 17-item Hamilton Rating Scale for Depression score of > or =14. Participants received citalopram treat...

Conditioning of transcranial magnetic stimulation: Evidence of sensory-induced responding and prepulse inhibition

Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating the human cortex... more Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating the human cortex. Classical conditioning is a phenomenon of developed associations between stimuli. Our primary objective was to determine whether TMS effects could be conditioned. Prepulse inhibition represents another relationship between two stimuli, and a secondary assessment was performed to explore this relationship. An auditory-visual conditioning stimulus (CS) was paired with the TMS unconditioned stimulus (US) over motor cortex producing a motor-evoked potential (MEP) unconditioned response (UR). Two versions of the CS-US pairing paradigms were tested, one with a short intertrial interval (ITI) and another with a long ITI. The short ITI paradigm had more CS-US pairings and shorter session duration than the long ITI paradigm. Tests for conditioned responses (CRs) were performed following CS-US pairing (CS+/US+), by presenting the CS alone (CS+/US-). Reverse testing was also performed after CS-US pairing (CS+/US+) in separate sessions, by presenting the US alone (CS-/US+). Evidence for CRs was found only with the short ITI paradigm. The magnitudes of CRs were smaller than TMS-induced MEPs, and the CRs were found only in a percentage of tests. Prepulse inhibition was robustly evident for the long ITI paradigm, but not for the short ITI paradigm. We have found evidence that classical conditioning principles can be applied to brain stimulation in humans. These findings provide a method for exploring brain and behavioral relationships in humans, as well as suggesting approaches to enhance therapeutic uses of TMS or other forms of brain stimulation.

Novel treatments of mood disorders based on brain circuitry (ECT, MST, TMS, VNS, DBS)

Seminars in clinical neuropsychiatry, 2002

Advances in understanding the functional and structural anatomy of depression outlined in this is... more Advances in understanding the functional and structural anatomy of depression outlined in this issue set the stage for attempting to manipulate implicated brain regions as potential antidepressant therapies. On the one hand, these circuit- and device-based approaches to treating depression are not new. Electroconvulsive therapy (ECT) dates back to the beginning of modern biologic psychiatry with the discovery and rapid increase of first chemical (around 1910), and then later ECT. On the other hand, this area represents an important paradigm shift with treatments that are radical and different. A dizzying array of diverse technologies now allows researchers to stimulate the brain in undreamed of ways. However, the approaches described in this article are still considered experimental and are not approved for use in the United States by the Food and Drug Administration (FDA), except ECT, which predates the FDA. These device-based approaches to brain stimulation offer promise as potent...

Transcranial magnetic stimulation

Neurosurgery clinics of North America, 2003

TMS is a powerful new tool with extremely interesting research and therapeutic potentials. Furthe... more 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. What...

Decision analysis of the cost-effectiveness of repetitive transcranial magnetic stimulation versus electroconvulsive therapy for treatment of nonpsychotic severe depression

CNS spectrums, 2004

Repetitive transcranial magnetic stimulation (rTMS) is a new treatment with promise for resistant... more Repetitive transcranial magnetic stimulation (rTMS) is a new treatment with promise for resistant depression. We tested the economic feasibility of this new method compared with electroconvulsive therapy (ECT). An economic decision analysis was used to compare the costs of three different treatment strategies for nonpsychotic severe depression. The strategies were: ECT alone; rTMS alone; and rTMS followed by ECT for nonresponders (rTMS-to-ECT). We calculated 12-month costs and quality adjusted life years (QALYs) for the three treatment options for all nonpsychotic, severely depressed United States patients who would have otherwise undergone ECT. A sensitivity analysis was performed to test the degree of change in outcome with various parameter changes. The additional cost of using ECT alone compared with rTMS alone was 460,031 US dollars per quality adjusted year of life gained. For ECT versus rTMS-to-ECT, there was both an increased cost and a loss of 1,538 QALYs with ECT alone. Th...

<title>Bilateral responses of prefrontal and motor cortices to repetitive transcranial magnetic stimulation as measured by functional near infrared spectroscopy</title>

by Andrew Kozel and Kimberly Mapes

Photonic Therapeutics and Diagnostics V, 2009

Simultaneously acquiring cortical functional Near Infrared Spectroscopy (fNIRS) during repeated T... more Simultaneously acquiring cortical functional Near Infrared Spectroscopy (fNIRS) during repeated Transcranial Magnetic Stimulation (rTMS) offers the possibility of directly investigating the effects of rTMS on brain regions without quantifiable behavioral changes. In this study, the left motor cortex and subsequently the left prefrontal cortex were stimulated at 1 Hz while fNIRS data was simultaneously acquired. Changes in hemodynamic signals were measured on both ipsilateral and contralateral sides. In each cortex, a significantly larger decrease in the concentration of oxygenated hemoglobin and a smaller increase in the concentration of deoxygenated hemoglobin during the stimulation periods were observed in both the motor and prefrontal cortices. The ipsilateral and contralateral changes showed high temporal consistency. Same experiment was repeated for each subject 2 or 3 days later. The hemodynamic responses associated with the stimulation showed good reproducibility in two sessions. To our knowledge, this is the first report of simultaneous fNIRS measurement of ipsilateral and contralateral changes of either the motor or prefrontal cortex during rTMS stimulation.

Mechanisms of action of vagus nerve stimulation (VNS)

Clinical Neuroscience Research, 2004

In 1992, Dr Jake Zabara discovered in a canine model that repeated stimulation of the vagus nerve... more In 1992, Dr Jake Zabara discovered in a canine model that repeated stimulation of the vagus nerve in the neck could stop seizures. Since that time, repeated stimulation of the vagus nerve has been FDA approved as an anticonvulsant. Zabara's work is built on a 50-year-old theme in the literature where scientists had sought to exploit the fact that the vagus nerve is composed of 80% afferent fibers. Thus vagus stimulation might potentially provide a 'window' into the brain. This manuscript reviews the basic science and brain imaging work done to date with VNS, attempting to understand how VNS affects the brain. This research is crucial to perfecting VNS as an anticonvulsant, and for determining other neuropsychiatric conditions that might be helped by VNS. q

Functional Connectivity of Brain Structures Correlates with Treatment Outcome in Major Depressive Disorder

by Andrew Kozel and Kimberly Mapes

Frontiers in Psychiatry, 2011

Identifying biosignatures to assess the probability of response to an antidepressant for patients... more Identifying biosignatures to assess the probability of response to an antidepressant for patients with major depressive disorder (MDD) is critically needed. Functional connectivity MRI (fcMRI) offers the promise to provide such a measure. Previous work with fcMRI demonstrated that the correlation in signal from one region to another is a measure of functional connectivity. In this pilot work, a baseline non-task fcMRI was acquired in 14 adults with MDD who were free of all medications. Participants were then treated for 8 weeks with an antidepressant and then clinically re-evaluated. Probabilistic anatomic regions of interest (ROI) were defined for 16 brain regions (eight for each hemisphere) previously identified as being important in mood disorders. These ROIs were used to determine mean time courses for each individual's baseline non-task fcMRI. The correlations in time courses between 16 brain regions were calculated. These calculated correlations were considered to signify measures of functional connectivity. The degree of connectivity for each participant was correlated with treatment outcome. Among 13 participants with 8 weeks follow-up data, connectivity measures in several regions, especially the subcallosal cortex, were highly correlated with treatment outcome. These connectivity measures could provide a means to evaluate how likely a patient is to respond to an antidepressant treatment. Further work using larger samples is required to confirm these findings and to assess if measures of functional connectivity can be used to predict differential outcomes between antidepressant treatments.

Replication of Functional MRI Detection of Deception

by Andrew Kozel and Kimberly Mapes

The Open Forensic Science Journal, 2009

Background-Several studies support the use of fMRI for detecting deception. There have been, howe... more Background-Several studies support the use of fMRI for detecting deception. There have been, however, no reported replications on different scanners or at different locations. In a previous study, deception was accurately detected in at least 90% of the participants in two independent cohorts. This study attempted to replicate those findings using a different scanner and location.