Alexander Korb | University of California, Los Angeles (original) (raw)

Papers by Alexander Korb

Dialogues in Clinical Neuroscience, Dec 12, 2009

Current treatment of Major Depressive Disorder utilizes a trial-and-error sequential treatment st... more Current treatment of Major Depressive Disorder utilizes a trial-and-error sequential treatment strategy that results in delays in achieving response and remission for a majority of patients. Protracted ineffective treatment prolongs patient suffering and increases health care costs. In addition, long and unsuccessful antidepressant trials may diminish patient expectations, reinforce negative cognitions, and condition patients not to respond during subsequent antidepressant trials, thus contributing to further treatment resistance. For these reasons, it is critical to identify reliable predictors of antidepressant treatment response that can be used to shorten or eliminate lengthy and ineffective trials. Research on possible endophenotypic as well as genomic predictors has not yet yielded reliable predictors. The most reliable predictors identified thus far are symptomatic and physiologic characteristics of patients that emerge early in the course of treatment. We propose here the term "response endophenotypes" (REs) to describe this class of predictors, defined as latent measurable symptomatic or neurobiologic responses of individual patients that emerge early in the course of treatment, and which carry strong predictive power for individual patient outcomes. Use of REs constitutes a new paradigm in which medication treatment trials that are likely to be ineffective could be stopped within 1 to 2 weeks and other medication more likely to be effective could be started. Data presented here suggest that early changes in symptoms, quantitative electroencephalography, and gene expression could be used to construct effective REs. We posit that this new paradigm could lead to earlier recovery from depressive illness and ultimately produce profound health and economic benefits.

The Journal of Neuropsychiatry and Clinical Neurosciences, Oct 15, 2014

UMI. ProQuest® Dissertations & Theses The world's most comprehensive collection of disse... more UMI. ProQuest® Dissertations & Theses The world's most comprehensive collection of dissertations and theses. Learn more... ProQuest. Investigating Rostral Anterior Cingulate Cortex in Major Depression: An EEG Source Localization Approach. ...

Current Behavioral Neuroscience Reports, 2015

The field of therapeutic focused ultrasound neuromodulation has made great advances in the last f... more The field of therapeutic focused ultrasound neuromodulation has made great advances in the last few years. While no clinical trials of focused ultrasound neuromodulation are yet underway, several human experiments have recently been conducted. There are many potential uses of this new technology, including treatment of numerous psychiatric and neurologic disorders, as well as a brainmapping tool for discoveries in basic science. In this review, we examine recent research data on the use of focused ultrasound in neuronal tissue, animal models, and humans. We also investigate ideal parameters for neuromodulation as well as potential mechanisms.

NeuroImage: Clinical, 2015

Schizophrenia patients have abnormal neural responses to salient, infrequent events. We integrate... more Schizophrenia patients have abnormal neural responses to salient, infrequent events. We integrated event-related potentials (ERP) and fMRI to examine the contributions of the ventral (salience) and dorsal (sustained) attention networks to this dysfunctional neural activation. Twenty-one schizophrenia patients and 22 healthy controls were assessed in separate sessions with ERP and fMRI during a visual oddball task. Visual P100, N100, and P300 ERP waveforms and fMRI activation were assessed. A joint independent components analysis (jICA) on the ERP and fMRI data were conducted. Patients exhibited reduced P300, but not P100 or N100, amplitudes to targets and reduced fMRI neural activation in both dorsal and ventral attentional networks compared with controls. However, the jICA revealed that the P300 was linked specifically to activation in the ventral (salience) network, including anterior cingulate, anterior insula, and temporal parietal junction, with patients exhibiting significantly lower activation. The P100 and N100 were linked to activation in the dorsal (sustained) network, with no group differences in level of activation. This joint analysis approach revealed the nature of target detection deficits that were not discernable by either imaging methodology alone, highlighting the utility of a multimodal fMRI and ERP approach to understand attentional network deficits in schizophrenia.

Journal of Therapeutic Ultrasound, 2015

NeuroImage: Clinical, 2014

Introduction: Although social cognitive impairments are key determinants of functional outcome in... more Introduction: Although social cognitive impairments are key determinants of functional outcome in schizophrenia their neural bases are poorly understood. This study investigated neural activity during imitation and observation of finger movements and facial expressions in schizophrenia, and their correlates with self-reported empathy. Methods: 23 schizophrenia outpatients and 23 healthy controls were studied with functional magnetic resonance imaging (fMRI) while they imitated, executed, or simply observed finger movements and facial emotional expressions. Between-group activation differences, as well as relationships between activation and self-reported empathy, were evaluated. Results: Both patients and controls similarly activated neural systems previously associated with these tasks. We found no significant between-group differences in task-related activations. There were, however, between-group differences in the correlation between self-reported empathy and right inferior frontal (pars opercularis) activity during observation of facial emotional expressions. As in previous studies, controls demonstrated a positive association between brain activity and empathy scores. In contrast, the pattern in the patient group reflected a negative association between brain activity and empathy. Conclusions: Although patients with schizophrenia demonstrated largely normal patterns of neural activation across the finger movement and facial expression tasks, they reported decreased self perceived empathy and failed to show the typical relationship between neural activity and self-reported empathy seen in controls. These findings suggest that patients show a disjunction between automatic neural responses to low level social cues and higher level, integrative social cognitive processes involved in self-perceived empathy.

Journal of Neuropsychiatry, 2013

Clinical Eeg and Neuroscience, 2010

Neuroimaging experiments of amygdala activity during rest have shown abnormal amygdalar lateraliz... more Neuroimaging experiments of amygdala activity during rest have shown abnormal amygdalar lateralization in Major Depressive Disorder (MDD). The current study is an exploratory investigation of the use of the neuroimaging technique Low Resolution Electromagnetic Tomography (LORETA) to measure current source density (CSD) in the amygdala. We examined seven adults with MDD and nine healthy control subjects at rest, and while

Journal of psychiatric research, 2014

Brain oscillatory activity from the midline prefrontal region has been shown to reflect brain dys... more Brain oscillatory activity from the midline prefrontal region has been shown to reflect brain dysfunction in subjects with Major Depressive Disorder (MDD). It is not known, however, whether electrodes from this area provide unique information about brain function in MDD. We examined a set of midline sites and two other prefrontal locations for detecting cerebral activity differences between subjects with MDD and healthy controls. Resting awake quantitative EEG (qEEG) data were recorded from 168 subjects: 47 never-depressed adults and 121 with a current major depressive episode. Individual midline electrodes (Fpz, Fz, Cz, Pz, and Oz) and prefrontal electrodes outside the hairline (Fp1, Fp2) were examined with absolute and relative power and cordance in the theta band. We found that MDD subjects exhibited higher values of cordance (p = 0.0066) at Fpz than controls; no significant differences were found at other locations, and power measures showed trend-level differences. Depressed ad...

Journal of psychiatric research, 2014

Atomoxetine is a non-stimulant medication with sustained benefit throughout the day, and is a use... more Atomoxetine is a non-stimulant medication with sustained benefit throughout the day, and is a useful pharmacologic treatment option for young adults with Attention-Deficit/Hyperactivity Disorder (ADHD). It is difficult to determine, however, those patients for whom atomoxetine will be both effective and advantageous. Patients may need to take the medication for several weeks before therapeutic benefit is apparent, so a biomarker that could predict atomoxetine effectiveness early in the course of treatment could be clinically useful. There has been increased interest in the study of thalamocortical oscillatory activity using quantitative electroencephalography (qEEG) as a biomarker in ADHD. In this study, we investigated qEEG absolute power, relative power, and cordance, which have been shown to predict response to reuptake inhibitor antidepressants in Major Depressive Disorder (MDD), as potential predictors of response to atomoxetine. Forty-four young adults with ADHD (ages 18-30) e...

Psychiatry Research: Neuroimaging, 2011

In treatment trials for Major Depressive Disorder (MDD), early symptom improvement is predictive ... more In treatment trials for Major Depressive Disorder (MDD), early symptom improvement is predictive of eventual clinical response. Clinical response may also be predicted by elevated pretreatment theta (4-7 Hz) current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC). We investigated the relationship between pretreatment EEG and early improvement in predicting clinical outcome in 72 MDD subjects across three placebocontrolled treatment trials. Subjects were randomized to receive fluoxetine, venlafaxine, or placebo. Theta current density in the rACC and mOFC was computed with Low-Resolution Brain Electromagnetic Tomography (LORETA). An ANCOVA, examining week 8 Hamilton Depression Rating Scale (HamD) percent change, showed a significant effect of week-2-HamDpercent-change, and a significant three-way interaction of week-2-HamD-percent-change × Treatment × rACC. Medication subjects with robust early improvement showed almost no relationship between rACC theta current density and final clinical outcome. However, in subjects with little early improvement, rACC activity showed a strong relationship with clinical outcome. The model examining mOFC showed a trend in the three-way interaction. A combination of pretreatment rACC activity and early symptom improvement may be useful for predicting treatment response.

Psychiatry Research: Neuroimaging, 2008

Schizophrenia patients exhibit deficits in various stages of visual information processing. Despi... more Schizophrenia patients exhibit deficits in various stages of visual information processing. Despite recent informative efforts to examine visual processing in schizophrenia with functional magnetic resonance imaging (fMRI), much remains unknown about the basic function, structure, and organization of key early visual processing areas in schizophrenia. This study examined magnitude and topography of regional brain activity in three early visual processing areas: early retinotopically organized areas (V1-V4), motion-sensitive areas (human area MT, hMT+), and object-recognition areas (lateral occipital complex, LO). Using visual stimuli that are known to preferentially activate each respective region, we compared responses in these areas in 22 schizophrenia patients and 19 normal controls. Activity in all three regions was of similar amplitude in schizophrenia patients and normal controls. Activity in retinotopically organized areas and hMT+ showed good spatial overlap between groups. However, activation of LO was more widely distributed in patients compared with normal controls. The findings of abnormal spatial organization of LO in schizophrenia patients may converge with behavioral evidence of deficits in schizophrenia patients for object-recognition tasks that are believed to be mediated by LO activity.

Neuromodulation: Technology at the Neural Interface, 2014

Objective: The objective of this study was to determine magnetic resonance imaging (MRI)-related ... more Objective: The objective of this study was to determine magnetic resonance imaging (MRI)-related heating for a low-intensity focused ultrasound pulsation (LIFUP) device used during MRI performed at 3 T/128 MHz.

Clinical Neurophysiology, 2009

Objective-To assess whether pretreatment theta current density in the rostral anterior cingulate ... more Objective-To assess whether pretreatment theta current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC) differentiates responders from non-responders to antidepressant medication or placebo in a double-blinded study.

Clinical EEG and Neuroscience, 2009

Brain Topography, 2008

Many brain regions show metabolic and perfusion abnormalities in major depressive disorder (MDD),... more Many brain regions show metabolic and perfusion abnormalities in major depressive disorder (MDD), including anterior cingulate and prefrontal cortices. Some of these same areas also show abnormal function with low resolution electromagnetic tomography (LORETA). However, LORETA results are not always consistent across studies, nor with findings from other imaging modalities. These discrepancies may be due, among other factors, to the sensitivity of EEG source localization to different electrode montages. Thirty-six channel EEG was collected from healthy controls and age-and gender-matched unmedicated subjects with MDD (n = 74). EEGs were analyzed with LORETA to assess resting state current density at each of 2,394 cortical voxels. For comparison to previous studies, LORETA was performed using all electrodes or with specific prefrontal electrodes removed. Voxel-by-voxel differences between the depressed and healthy groups were calculated using non-parametric statistics. MDD subjects showed significantly elevated current density in delta, theta, alpha, beta1, and beta2 frequency bands relative to controls in anterior cingulate and prefrontal cortices. Removal of certain prefrontal electrodes from input to LORETA decreased or eliminated significant differences between groups. LORETA detects differences in brain activity between MDD subjects and healthy controls that are consistent with previous findings using other imaging modalities. Inconsistent findings among LORETA studies, and between LORETA studies and those using other functional imaging techniques, may result from differences in electrode montages.

Brain Stimulation, 2011

With the recent approval by the Food and Drug Administration (FDA) of Deep Brain Stimulation (DBS... more With the recent approval by the Food and Drug Administration (FDA) of Deep Brain Stimulation (DBS) for Parkinson's Disease, dystonia and obsessive compulsive disorder (OCD), vagus nerve stimulation (VNS) for epilepsy and depression, and repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression, neuromodulation has become increasingly relevant to clinical research. However, these techniques have significant drawbacks (eg, lack of special specificity and depth for the rTMS, and invasiveness and cumbersome maintenance for DBS). This article reviews the background, rationale, and pilot studies to date, using a new brain stimulation methoddlow-intensity focused ultrasound pulsation (LIFUP). The ability of ultrasound to be focused noninvasively through the skull anywhere within the brain, together with concurrent imaging (ie, functional magnetic resonance imaging [fMRI]) techniques, may create a role for research and clinical use of LIFUP. This technique is still in preclinical testing and needs to be assessed thoroughly before being advanced to clinical trials. In this study, we review over 50 years of research data on the use of focused ultrasound (FUS) in neuronal tissue and live brain, and propose novel applications of this noninvasive neuromodulation method.

Archives of General Psychiatry, 2009

Context: Visual masking procedures assess the earliest stages of visual processing. Patients with... more Context: Visual masking procedures assess the earliest stages of visual processing. Patients with schizophrenia reliably show deficits on visual masking, and these procedures have been used to explore vulnerability to schizophrenia, probe underlying neural circuits, and help explain functional outcome.

Biological Psychiatry, 2007

In cigarette smokers, the most commonly reported areas of brain activation during visual cigarett... more In cigarette smokers, the most commonly reported areas of brain activation during visual cigarette cue exposure are the prefrontal, anterior cingulate, and visual cortices. We sought to determine changes in brain activity in response to cigarette cues when smokers actively resist craving.

Dialogues in Clinical Neuroscience, Dec 12, 2009

Current treatment of Major Depressive Disorder utilizes a trial-and-error sequential treatment st... more Current treatment of Major Depressive Disorder utilizes a trial-and-error sequential treatment strategy that results in delays in achieving response and remission for a majority of patients. Protracted ineffective treatment prolongs patient suffering and increases health care costs. In addition, long and unsuccessful antidepressant trials may diminish patient expectations, reinforce negative cognitions, and condition patients not to respond during subsequent antidepressant trials, thus contributing to further treatment resistance. For these reasons, it is critical to identify reliable predictors of antidepressant treatment response that can be used to shorten or eliminate lengthy and ineffective trials. Research on possible endophenotypic as well as genomic predictors has not yet yielded reliable predictors. The most reliable predictors identified thus far are symptomatic and physiologic characteristics of patients that emerge early in the course of treatment. We propose here the term "response endophenotypes" (REs) to describe this class of predictors, defined as latent measurable symptomatic or neurobiologic responses of individual patients that emerge early in the course of treatment, and which carry strong predictive power for individual patient outcomes. Use of REs constitutes a new paradigm in which medication treatment trials that are likely to be ineffective could be stopped within 1 to 2 weeks and other medication more likely to be effective could be started. Data presented here suggest that early changes in symptoms, quantitative electroencephalography, and gene expression could be used to construct effective REs. We posit that this new paradigm could lead to earlier recovery from depressive illness and ultimately produce profound health and economic benefits.

The Journal of Neuropsychiatry and Clinical Neurosciences, Oct 15, 2014

UMI. ProQuest® Dissertations & Theses The world's most comprehensive collection of disse... more UMI. ProQuest® Dissertations & Theses The world's most comprehensive collection of dissertations and theses. Learn more... ProQuest. Investigating Rostral Anterior Cingulate Cortex in Major Depression: An EEG Source Localization Approach. ...

Current Behavioral Neuroscience Reports, 2015

The field of therapeutic focused ultrasound neuromodulation has made great advances in the last f... more The field of therapeutic focused ultrasound neuromodulation has made great advances in the last few years. While no clinical trials of focused ultrasound neuromodulation are yet underway, several human experiments have recently been conducted. There are many potential uses of this new technology, including treatment of numerous psychiatric and neurologic disorders, as well as a brainmapping tool for discoveries in basic science. In this review, we examine recent research data on the use of focused ultrasound in neuronal tissue, animal models, and humans. We also investigate ideal parameters for neuromodulation as well as potential mechanisms.

NeuroImage: Clinical, 2015

Schizophrenia patients have abnormal neural responses to salient, infrequent events. We integrate... more Schizophrenia patients have abnormal neural responses to salient, infrequent events. We integrated event-related potentials (ERP) and fMRI to examine the contributions of the ventral (salience) and dorsal (sustained) attention networks to this dysfunctional neural activation. Twenty-one schizophrenia patients and 22 healthy controls were assessed in separate sessions with ERP and fMRI during a visual oddball task. Visual P100, N100, and P300 ERP waveforms and fMRI activation were assessed. A joint independent components analysis (jICA) on the ERP and fMRI data were conducted. Patients exhibited reduced P300, but not P100 or N100, amplitudes to targets and reduced fMRI neural activation in both dorsal and ventral attentional networks compared with controls. However, the jICA revealed that the P300 was linked specifically to activation in the ventral (salience) network, including anterior cingulate, anterior insula, and temporal parietal junction, with patients exhibiting significantly lower activation. The P100 and N100 were linked to activation in the dorsal (sustained) network, with no group differences in level of activation. This joint analysis approach revealed the nature of target detection deficits that were not discernable by either imaging methodology alone, highlighting the utility of a multimodal fMRI and ERP approach to understand attentional network deficits in schizophrenia.

Journal of Therapeutic Ultrasound, 2015

NeuroImage: Clinical, 2014

Introduction: Although social cognitive impairments are key determinants of functional outcome in... more Introduction: Although social cognitive impairments are key determinants of functional outcome in schizophrenia their neural bases are poorly understood. This study investigated neural activity during imitation and observation of finger movements and facial expressions in schizophrenia, and their correlates with self-reported empathy. Methods: 23 schizophrenia outpatients and 23 healthy controls were studied with functional magnetic resonance imaging (fMRI) while they imitated, executed, or simply observed finger movements and facial emotional expressions. Between-group activation differences, as well as relationships between activation and self-reported empathy, were evaluated. Results: Both patients and controls similarly activated neural systems previously associated with these tasks. We found no significant between-group differences in task-related activations. There were, however, between-group differences in the correlation between self-reported empathy and right inferior frontal (pars opercularis) activity during observation of facial emotional expressions. As in previous studies, controls demonstrated a positive association between brain activity and empathy scores. In contrast, the pattern in the patient group reflected a negative association between brain activity and empathy. Conclusions: Although patients with schizophrenia demonstrated largely normal patterns of neural activation across the finger movement and facial expression tasks, they reported decreased self perceived empathy and failed to show the typical relationship between neural activity and self-reported empathy seen in controls. These findings suggest that patients show a disjunction between automatic neural responses to low level social cues and higher level, integrative social cognitive processes involved in self-perceived empathy.

Journal of Neuropsychiatry, 2013

Clinical Eeg and Neuroscience, 2010

Neuroimaging experiments of amygdala activity during rest have shown abnormal amygdalar lateraliz... more Neuroimaging experiments of amygdala activity during rest have shown abnormal amygdalar lateralization in Major Depressive Disorder (MDD). The current study is an exploratory investigation of the use of the neuroimaging technique Low Resolution Electromagnetic Tomography (LORETA) to measure current source density (CSD) in the amygdala. We examined seven adults with MDD and nine healthy control subjects at rest, and while

Journal of psychiatric research, 2014

Brain oscillatory activity from the midline prefrontal region has been shown to reflect brain dys... more Brain oscillatory activity from the midline prefrontal region has been shown to reflect brain dysfunction in subjects with Major Depressive Disorder (MDD). It is not known, however, whether electrodes from this area provide unique information about brain function in MDD. We examined a set of midline sites and two other prefrontal locations for detecting cerebral activity differences between subjects with MDD and healthy controls. Resting awake quantitative EEG (qEEG) data were recorded from 168 subjects: 47 never-depressed adults and 121 with a current major depressive episode. Individual midline electrodes (Fpz, Fz, Cz, Pz, and Oz) and prefrontal electrodes outside the hairline (Fp1, Fp2) were examined with absolute and relative power and cordance in the theta band. We found that MDD subjects exhibited higher values of cordance (p = 0.0066) at Fpz than controls; no significant differences were found at other locations, and power measures showed trend-level differences. Depressed ad...

Journal of psychiatric research, 2014

Atomoxetine is a non-stimulant medication with sustained benefit throughout the day, and is a use... more Atomoxetine is a non-stimulant medication with sustained benefit throughout the day, and is a useful pharmacologic treatment option for young adults with Attention-Deficit/Hyperactivity Disorder (ADHD). It is difficult to determine, however, those patients for whom atomoxetine will be both effective and advantageous. Patients may need to take the medication for several weeks before therapeutic benefit is apparent, so a biomarker that could predict atomoxetine effectiveness early in the course of treatment could be clinically useful. There has been increased interest in the study of thalamocortical oscillatory activity using quantitative electroencephalography (qEEG) as a biomarker in ADHD. In this study, we investigated qEEG absolute power, relative power, and cordance, which have been shown to predict response to reuptake inhibitor antidepressants in Major Depressive Disorder (MDD), as potential predictors of response to atomoxetine. Forty-four young adults with ADHD (ages 18-30) e...

Psychiatry Research: Neuroimaging, 2011

In treatment trials for Major Depressive Disorder (MDD), early symptom improvement is predictive ... more In treatment trials for Major Depressive Disorder (MDD), early symptom improvement is predictive of eventual clinical response. Clinical response may also be predicted by elevated pretreatment theta (4-7 Hz) current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC). We investigated the relationship between pretreatment EEG and early improvement in predicting clinical outcome in 72 MDD subjects across three placebocontrolled treatment trials. Subjects were randomized to receive fluoxetine, venlafaxine, or placebo. Theta current density in the rACC and mOFC was computed with Low-Resolution Brain Electromagnetic Tomography (LORETA). An ANCOVA, examining week 8 Hamilton Depression Rating Scale (HamD) percent change, showed a significant effect of week-2-HamDpercent-change, and a significant three-way interaction of week-2-HamD-percent-change × Treatment × rACC. Medication subjects with robust early improvement showed almost no relationship between rACC theta current density and final clinical outcome. However, in subjects with little early improvement, rACC activity showed a strong relationship with clinical outcome. The model examining mOFC showed a trend in the three-way interaction. A combination of pretreatment rACC activity and early symptom improvement may be useful for predicting treatment response.

Psychiatry Research: Neuroimaging, 2008

Schizophrenia patients exhibit deficits in various stages of visual information processing. Despi... more Schizophrenia patients exhibit deficits in various stages of visual information processing. Despite recent informative efforts to examine visual processing in schizophrenia with functional magnetic resonance imaging (fMRI), much remains unknown about the basic function, structure, and organization of key early visual processing areas in schizophrenia. This study examined magnitude and topography of regional brain activity in three early visual processing areas: early retinotopically organized areas (V1-V4), motion-sensitive areas (human area MT, hMT+), and object-recognition areas (lateral occipital complex, LO). Using visual stimuli that are known to preferentially activate each respective region, we compared responses in these areas in 22 schizophrenia patients and 19 normal controls. Activity in all three regions was of similar amplitude in schizophrenia patients and normal controls. Activity in retinotopically organized areas and hMT+ showed good spatial overlap between groups. However, activation of LO was more widely distributed in patients compared with normal controls. The findings of abnormal spatial organization of LO in schizophrenia patients may converge with behavioral evidence of deficits in schizophrenia patients for object-recognition tasks that are believed to be mediated by LO activity.

Neuromodulation: Technology at the Neural Interface, 2014

Objective: The objective of this study was to determine magnetic resonance imaging (MRI)-related ... more Objective: The objective of this study was to determine magnetic resonance imaging (MRI)-related heating for a low-intensity focused ultrasound pulsation (LIFUP) device used during MRI performed at 3 T/128 MHz.

Clinical Neurophysiology, 2009

Objective-To assess whether pretreatment theta current density in the rostral anterior cingulate ... more Objective-To assess whether pretreatment theta current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC) differentiates responders from non-responders to antidepressant medication or placebo in a double-blinded study.

Clinical EEG and Neuroscience, 2009

Brain Topography, 2008

Many brain regions show metabolic and perfusion abnormalities in major depressive disorder (MDD),... more Many brain regions show metabolic and perfusion abnormalities in major depressive disorder (MDD), including anterior cingulate and prefrontal cortices. Some of these same areas also show abnormal function with low resolution electromagnetic tomography (LORETA). However, LORETA results are not always consistent across studies, nor with findings from other imaging modalities. These discrepancies may be due, among other factors, to the sensitivity of EEG source localization to different electrode montages. Thirty-six channel EEG was collected from healthy controls and age-and gender-matched unmedicated subjects with MDD (n = 74). EEGs were analyzed with LORETA to assess resting state current density at each of 2,394 cortical voxels. For comparison to previous studies, LORETA was performed using all electrodes or with specific prefrontal electrodes removed. Voxel-by-voxel differences between the depressed and healthy groups were calculated using non-parametric statistics. MDD subjects showed significantly elevated current density in delta, theta, alpha, beta1, and beta2 frequency bands relative to controls in anterior cingulate and prefrontal cortices. Removal of certain prefrontal electrodes from input to LORETA decreased or eliminated significant differences between groups. LORETA detects differences in brain activity between MDD subjects and healthy controls that are consistent with previous findings using other imaging modalities. Inconsistent findings among LORETA studies, and between LORETA studies and those using other functional imaging techniques, may result from differences in electrode montages.

Brain Stimulation, 2011

With the recent approval by the Food and Drug Administration (FDA) of Deep Brain Stimulation (DBS... more With the recent approval by the Food and Drug Administration (FDA) of Deep Brain Stimulation (DBS) for Parkinson's Disease, dystonia and obsessive compulsive disorder (OCD), vagus nerve stimulation (VNS) for epilepsy and depression, and repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression, neuromodulation has become increasingly relevant to clinical research. However, these techniques have significant drawbacks (eg, lack of special specificity and depth for the rTMS, and invasiveness and cumbersome maintenance for DBS). This article reviews the background, rationale, and pilot studies to date, using a new brain stimulation methoddlow-intensity focused ultrasound pulsation (LIFUP). The ability of ultrasound to be focused noninvasively through the skull anywhere within the brain, together with concurrent imaging (ie, functional magnetic resonance imaging [fMRI]) techniques, may create a role for research and clinical use of LIFUP. This technique is still in preclinical testing and needs to be assessed thoroughly before being advanced to clinical trials. In this study, we review over 50 years of research data on the use of focused ultrasound (FUS) in neuronal tissue and live brain, and propose novel applications of this noninvasive neuromodulation method.

Archives of General Psychiatry, 2009

Context: Visual masking procedures assess the earliest stages of visual processing. Patients with... more Context: Visual masking procedures assess the earliest stages of visual processing. Patients with schizophrenia reliably show deficits on visual masking, and these procedures have been used to explore vulnerability to schizophrenia, probe underlying neural circuits, and help explain functional outcome.

Biological Psychiatry, 2007

In cigarette smokers, the most commonly reported areas of brain activation during visual cigarett... more In cigarette smokers, the most commonly reported areas of brain activation during visual cigarette cue exposure are the prefrontal, anterior cingulate, and visual cortices. We sought to determine changes in brain activity in response to cigarette cues when smokers actively resist craving.