Densely sampled stimulus-response map of human cortex with single pulse TMS-EEG and its relation to whole brain neuroimaging measures.

Large-scale networks underpin brain functions. How such networks respond to focal stimulation can help decipher complex brain processes and optimize brain stimulation treatments. To map such stimulation-response patterns across the brain non-invasively, we recorded concurrent EEG responses from single-pulse transcranial magnetic stimulation (i.e., TMS-EEG) from over 100 cortical regions with two orthogonal coil orientations from one densely-sampled individual. We also acquired Human Connectome Project (HCP)-styled diffusion imaging scans (six), resting-state functional Magnetic Resonance Imaging (fMRI) scans (120 mins), resting-state EEG scans (108 mins), and structural MR scans (T1- and T2-weighted). Using the TMS-EEG data, we applied network science-based community detection to reveal insights about the brain's causal-functional organization from both a stimulation and recording perspective. We also computed structural and functional maps and the electric field of each TMS stimulation condition. Altogether, we hope the release of this densely sampled (n=1) dataset will be a uniquely valuable resource for both basic and clinical neuroscience research.

Cross-attractor modeling of resting-state functional connectivity in psychiatric disorders.

Resting-state functional connectivity (RSFC) is altered across various psychiatric disorders. Brain network modeling (BNM) has the potential to reveal the neurobiological underpinnings of such abnormalities by dynamically modeling the structure-function relationship and examining biologically relevant parameters after fitting the models with real data. Although innovative BNM approaches have been developed, two main issues need to be further addressed. First, previous BNM approaches are primarily limited to simulating noise-driven dynamics near a chosen attractor (or a stable brain state). An alternative approach is to examine multi(or cross)-attractor dynamics, which can be used to better capture non-stationarity and switching between states in the resting brain. Second, previous BNM work is limited to characterizing one disorder at a time. Given the large degree of co-morbidity across psychiatric disorders, comparing BNMs across disorders might provide a novel avenue to generate insights regarding the dynamical features that are common across (vs. specific to) disorders. Here, we address these issues by (1) examining the layout of the attractor repertoire over the entire multi-attractor landscape using a recently developed cross-attractor BNM approach; and (2) characterizing and comparing multiple disorders (schizophrenia, bipolar, and ADHD) with healthy controls using an openly available and moderately large multimodal dataset from the UCLA Consortium for Neuropsychiatric Phenomics. Both global and local differences were observed across disorders. Specifically, the global coupling between regions was significantly decreased in schizophrenia patients relative to healthy controls. At the same time, the ratio between local excitation and inhibition was significantly higher in the schizophrenia group than the ADHD group. In line with these results, the schizophrenia group had the lowest switching costs (energy gaps) across groups for several networks including the default mode network. Paired comparison also showed that schizophrenia patients had significantly lower energy gaps than healthy controls for the somatomotor and visual networks. Overall, this study provides preliminary evidence supporting transdiagnostic multi-attractor BNM approaches to better understand psychiatric disorders' pathophysiology.

Triad1 Promotes the Inflammatory Response and Neuronal Apoptosis to Aggravate Acute Spinal Cord Injury in Rats.

Objective: Spinal cord injury (SCI) is one of the most devastating central injuries, resulting in serious locomotor deficits. Triad1 is known to play an important role in SCI, but its effects on the inflammatory response and physiological behavior have not been thoroughly studied. This study is aimed at examining the effects of Triad1 on the inflammatory response and neuronal injury in acute SCI in rats. Methods: Twenty-four male Sprague-Dawley (SD) rats were randomly divided into a control group, SCI group, sh-NC group, and Triad1 knockout group (sh-Triad1). The Basso Beattie Bresnahan locomotor rating scale was utilized for the assessment of the motor ability of rats. Hematoxylin and eosin (H&E), Luxol fast blue (LFB), and TUNEL staining were used to assess the pathological injury, demyelination, and neuronal apoptosis, respectively. ELISA was used to detect the levels of IL-1ß, IL-10, and TNF-α, and qRT-PCR was used to examine the expression level of Triad1. Furthermore, the protein levels of Triad1, Bax, Bcl-2, and cleaved caspase-3 were determined using western blotting. Results: The Triad1 expression level was upregulated in damaged spinal cord tissue. Knockdown of Triad1 improved motor function and reduced SCI as well as apoptosis of spinal cord neurons. In addition, the knockdown of Triad1 inhibited the inflammatory response caused by SCI. Conclusion: Knockdown of Triad1 can reduce SCI in rats with acute SCI by inhibiting the inflammatory response and apoptosis.

Cross-attractor repertoire provides new perspective on structure-function relationship in the brain.

The brain exhibits complex intrinsic dynamics, i.e., spontaneously arising activity patterns without any external inputs or tasks. Such intrinsic dynamics and their alteration are thought to play crucial roles in typical as well as atypical cognitive functioning. Linking the ever-changing intrinsic dynamics to the rather static anatomy is a challenging endeavor. Dynamical systems models are important tools for understanding how structure and function are linked in the brain. Here, we provide a novel modeling framework to examine how functional connectivity depends on structural connectivity in the brain. Existing modeling frameworks typically focus on noise-driven (or stochastic) dynamics near a single attractor. Complementing existing approaches, we examine deterministic features of the distribution of attractors, in particular, how regional states are correlated across all attractors - cross-attractor coordination. We found that cross-attractor coordination between brain regions better predicts human functional connectivity than noise-driven single-attractor dynamics. Importantly, cross-attractor coordination better accounts for the nonlinear dependency of functional connectivity on structural connectivity. Our findings suggest that functional connectivity patterns in the brain may reflect transitions between attractors, which impose an energy cost. The framework may be used to predict transitions and energy costs associated with experimental or clinical interventions.

Deep Learning-Based Cervical Spine Posterior Percutaneous Endoscopic Disc Nucleus Resection for the Treatment of Cervical Spondylotic Radiculopathy.

In the past 10 years, the technology of percutaneous spine endoscopy has been continuously developed. The indications have expanded from simple lumbar disc herniation to various degenerative diseases of the cervical, thoracic, and lumbar spine. Traditional surgery for the treatment of cervical radiculopathy includes anterior cervical decompression surgery, anterior cervical decompression plus fusion surgery, and posterior limited fenestration surgery. This article mainly studies the treatment of cervical spondylosis caused by radiculopathy caused by the nucleus resection of the posterior cervical spine percutaneous spinal endoscopy based on deep learning. In the PPECD group, the height of the intervertebral cavity was measured before the operation and during the final follow-up, and the height change of the intervertebral cavity was evaluated. The relative angle and relative displacement of the sagittal plane of the operation segment in the PPECD group were measured, and the stability was evaluated. Using the cervical spine X-ray Kelvin degeneration evaluation criteria, before and during the final follow-up operation, the degeneration of the adjacent segments of the two groups was evaluated. A retrospective analysis of 26 cases of cervical radiculopathy that met the criteria for diagnosis, inclusion, and exclusion was reviewed. Among them, 11 cases were treated with PPECD surgery; 15 cases were treated with ACDF surgery. According to the evaluation method of Odom, the excellent rate and the good rate of the two groups were compared. According to the location of the lesion, the nerve detection or dull tip device is exposed under the armpit or shoulder of the nerve root, and the protruding nucleus pulposus tissue is explored and removed, and annulus fibrosus is performed as needed. After hemostasis was detected, the surgical instruments were removed and the surgical incision was completely sutured. Before the operation and 3 months after the operation, the final follow-up made no significant difference in the overall average height of the intervertebral cavity (F = 2.586, P > 0.05). The results show that posterior foramen expansion is an effective surgical method for the treatment of cervical spondylotic radiculopathy, but surgical adaptation requires strict management. In order to achieve satisfactory results, appropriate cases must be selected.

Subgenual cingulate connectivity and hippocampal activation are related to MST therapeutic and adverse effects.

Aberrant connectivity between the dorsolateral prefrontal cortex (DLPFC) and the subgenual cingulate cortex (SGC) has been linked to the pathophysiology of depression. Indirect evidence also links hippocampal activation to the cognitive side effects of seizure treatments. Magnetic seizure therapy (MST) is a novel treatment for patients with treatment resistant depression (TRD). Here we combine transcranial magnetic stimulation with electroencephalography (TMS-EEG) to evaluate the effects of MST on connectivity and activation between the DLPFC, the SGC and hippocampus (Hipp) in patients with TRD. The TMS-EEG was collected from 31 TRD patients prior to and after an MST treatment trial. Through TMS-EEG methodology we evaluated significant current scattering (SCS) as an index of effective connectivity between the SGC and left DLPFC. Significant current density (SCD) was used to assess activity at the level of the Hipp. The SCS between the SGC and DLPFC was reduced after the course of MST (p < 0.036). The DLPFC-SGC effective connectivity reduction correlated with the changes in Hamilton depression score pre-to-post treatment (R = 0.46; p < 0.031). The SCD localized to the Hipp was reduced after the course of MST (p < 0.015), and the SCD change was correlated with montreal cognitive assessment (MOCA) scores pre-post the course of MST (R = -0.59; p < 0.026). Our findings suggest that MST treatment is associated with SGC-DLPFC connectivity reduction and that changes to cognition are associated with Hipp activation reduction. These findings demonstrate two distinct processes which drive efficacy and side effects separately, and might eventually aid in delineating physiological TRD targets in clinical settings.

Comparison Between Percutaneous Transforaminal Endoscopic Discectomy and Fenestration in the Treatment of Degenerative Lumbar Spinal Stenosis.

BACKGROUND This study aimed to investigate the therapeutic and prognostic effects of percutaneous transforaminal endoscopic decompression (PTED) for degenerative lumbar spinal stenosis (DLSS). MATERIAL AND METHODS One hundred eighty-eight patients with DLSS were randomly divided into the fenestration and the PTED group for decompression treatment. Operative time, incision length, amount of blood loss, length of hospitalization, and rates of complications in the 2 groups were compared. All patients underwent computed tomography (CT) scanning and magnetic resonance imaging (MRI) on the first postoperative day. All patients were assessed preoperatively and the treatment effects at 3, 6, and 12 months postoperatively were evaluated using visual analog scale (VAS), Japanese Orthopedic Association Score (JOA) and Oswestry Disability Index (ODI). The modified MacNab criteria were used to assess patient satisfaction 1 year after surgery at the last follow-up. RESULTS Patients who underwent PTED had shorter incisions, less blood loss, and shorter hospital stays than those in the fenestration group, but operative times and complication rates were similar in the 2 groups. Moreover, CT scanning and MRI revealed similar treatment effects in the 2 groups. Compared with preoperative status, improvements in VAS, ODI, and JOA scores occurred at different times after surgery in the 2 groups. In particular, all 3 scores in the PTED group were higher than those in the fenestration group at 3 and 6 months postoperatively. There were no significant differences in MacNab scores between the 2 groups. CONCLUSIONS PTED is safer and more effective than traditional fenestration for management of DLSS.

Magnetic seizure therapy (MST) for major depressive disorder.

Electroconvulsive therapy (ECT) is effective for major depressive disorder (MDD) but its effects on memory limit its widespread use. Magnetic seizure therapy (MST) is a potential alternative to ECT that may not adversely affect memory. In the current trial, consecutive patients with MDD consented to receive MST applied over the prefrontal cortex according to an open-label protocol. Depressive symptoms and cognition were assessed prior to, during and at the end of treatment. Patients were treated two to three times per week with high-frequency MST (i.e., 100 Hz) (N = 24), medium frequency MST (i.e., 60 or 50 Hz) (N = 26), or low-frequency MST (i.e., 25 Hz MST) (N = 36) using 100% stimulator output. One hundred and forty patients were screened; 86 patients with MDD received a minimum of eight treatments and were deemed to have an adequate course of MST; and 47 completed the trial per protocol, either achieving remission (i.e., 24-item Hamilton Rating Scale for Depression score <10 and a relative reduction of >60% at two consecutive assessments; n = 17) or received a maximum of 24 sessions (n = 30). High-frequency (100 Hz) MST produced the highest remission rate (33.3%). Performance on most cognitive measures remained stable, with the exception of significantly worsened recall consistency of autobiographical information and significantly improved brief visuospatial memory task performance. Under open conditions, MST led to clinically meaningful reduction in depressive symptoms in patients with MDD and produced minimal cognitive impairment. Future studies should compare MST and ECT under double-blind randomized condition.

Association of Repetitive Transcranial Magnetic Stimulation Treatment With Subgenual Cingulate Hyperactivity in Patients With Major Depressive Disorder: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Hyperactivity in the subgenual cingulate cortex (SGC) is associated with major depressive disorder (MDD) and anticorrelated with activity in the dorsolateral prefrontal cortex (DLPFC). This association was found to be predictive of responsiveness to repetitive transcranial magnetic stimulation (rTMS) treatment. Such findings suggest that DLPFC-SGC connectivity is important for understanding both the therapeutic mechanism of rTMS in patients with MDD and the underlying pathophysiology of MDD. Objective: To evaluate SGC hyperactivity in patients with MDD before and after rTMS treatment. Design, Setting, and Participants: In this diagnostic study, among participants recruited from the adult and geriatric mood and anxiety services at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada, who had participated in a randomized clinical trial, baseline SGC activity of patients with MDD was compared with healthy controls. In patients with MDD, SGC activity was compared before and after active or sham high-frequency rTMS treatment. Data collection started in July 2008 and concluded in March 2012. Neurophysiological data analysis started in January 2017 and ended in May 2018. Main Outcomes and Measures: Hyperactivity in the SGC before and after rTMS treatment was measured. Subgenual cingulate cortex hyperactivity activity was quantified using significant current density (SCD), and effective connectivity between the left DLPFC and SGC was computed using significant current scattering (SCS). Both measures were computed around TMS evoked potentials standard peak latencies prior to rTMS and after rTMS treatment, comparing patients with MMD treated with active and sham rTMS. Patients with MDD were assessed with the 17-item Hamilton Rating Scale for Depression. Results: Of 121 patients with MDD in the initial trial, 30 (15 [50.0%] women) were compared with 30 healthy controls (15 [50.0%] women) at rTMS treatment baseline. The mean (SD) age of the cohort with MDD was 39.1 (10.9) years, and the mean (SD) age of healthy controls was 37.0 (11.0) years. Following rTMS treatment, 26 patients with MDD who had active rTMS treatment (21.5%) were compared with 17 patients with MDD who had sham treatment (14.0%). At baseline, the SGC mean (SD) SCD and mean (SD) SCS at 200 milliseconds after TMS pulse were higher in participants with MDD compared with healthy controls (SCD: 1.04 × 10-6 [1.41 × 10-6] µA/mm2 vs 3.8 × 10-7 [7.8 × 10-7] µA/mm2; z = -2.95; P = .004; SCS: 0.87 [0.86] mm vs 0.54 [0.87] mm; z = -2.27; P = .02). Baseline source current density was able to classify MDD with 77% accuracy. Scores on the 17-item Hamilton Rating Scale for Depression were correlated with current density at the SGC (ρ = 0.41; P = .03). After rTMS treatment, SGC mean (SD) SCD and mean (SD) SCS at 200 milliseconds after rTMS pulse were attenuated to approximately the standard TMS-evoked potential latencies in the active rTMS group compared with the sham rTMS group (SCD: 1.57 × 10-7 [3.67 × 10-7] µA/mm2 vs 7.00 × 10-7 [7.51 × 10-7] µA/mm2; z = -2.91; P = .004; SCS: 0.20 [0.44] mm vs 0.74 [0.73] mm; z = -2.78; P = .006). Additionally, the SGC SCS change was correlated with symptom improvement on the 17-item Hamilton Rating Scale for Depression in the active rTMS group (ρ = 0.58; P = .047). Conclusions and Relevance: The findings of this study further implicate left DLPFC-SGC effective connectivity and SGC excitability in the pathophysiology of MDD and treatment with rTMS. These findings suggest that DLPFC-SGC connectivity may be a marker of rTMS treatment responsiveness. Trial Registration: ClinicalTrials.gov identifier: NCT01515215.

Classification of TMS evoked potentials using ERP time signatures and SVM versus deep learning.

Modeling transcranial magnetic stimulation (TMS) evoked potentials (TEP) begins with classification of stereotypical single-pulse TMS responses in order to select validation targets for generative dynamical models. Several dimensionality reduction techniques are commonly in use to extract statistically independent features from experimental data for regression against model parameters. Here, we first designed a 3-dimensional feature space based on commonly described event-related potentials (ERP) from the literature. We then compared classification schemes which take as inputs either the 3D projection space or the original full rank input space. Their ability to discriminate TEP recorded from different brain regions given a stimulus site were evaluated. We show that a deep learning architecture, employing Convolutional Neural Network (CNN) and Multi-Layer Perceptron (MLP), yields better accuracy than the 3D projection and raw TEP input combined with Support Vector Machines. Such supervised feature extraction models may therefore be useful for scoring neural circuit simulations based on their ability to reproduce the underlying dynamical processes responsible for differential TEP responses.

Magnetic seizure therapy reduces suicidal ideation and produces neuroplasticity in treatment-resistant depression.

Therapeutic seizures may work for treatment-resistant depression (TRD) by producing neuroplasticity. We evaluated whether magnetic seizure therapy (MST) produces changes in suicidal ideation and neuroplasticity as indexed through transcranial magnetic stimulation and electroencephalography (TMS-EEG) of the dorsolateral prefrontal cortex (DLPFC). Twenty-three patients with TRD were treated with MST. Changes in suicidal ideation was assessed through the Scale for Suicidal Ideation (SSI). Before and after the treatment course, neuroplasticity in excitatory and inhibitory circuits was assessed with TMS-EEG measures of cortical-evoked activity (CEA) and long-interval cortical inhibition (LICI) from the left DLPFC, and the left motor cortex as a control condition. As in our previous report, the relationship between TMS-EEG measures and suicidal ideation was examined with the SSI. Results show that 44.4% of patients experienced resolution of suicidal ideation. Based on DLPFC assessment, MST produced significant CEA increase over the frontal central electrodes (cluster p < 0.05), but did not change LICI on a group level. MST also reduced the SSI scores (p < 0.005) and the amount of reduction correlated with the decrease in LICI over the right frontal central electrodes (cluster p < 0.05; rho = 0.73 for Cz). LICI change identified patients who were resolved of suicidal ideation with 90% sensitivity and 88% specificity (AUC = 0.9, p = 0.004). There was no significant finding with motor cortex assessment. Overall, MST produced significant rates of resolution of suicidal ideation. MST also produced neuroplasticity in the frontal cortex, likely through long-term potentiation (LTP)-like mechanisms. The largest reduction in suicidal ideation was demonstrated in patients showing concomitant decreases in cortical inhibition-a mechanism linked to enhanced LTP-like plasticity. These findings provide insights into the mechanisms through which patients experience resolution of suicidal ideation following seizure treatments in depression.

Paired-Associative Stimulation-Induced Long-term Potentiation-Like Motor Cortex Plasticity in Healthy Adolescents.

OBJECTIVE: The objective of this study was to evaluate the feasibility of using paired-associative stimulation (PAS) to study excitatory and inhibitory plasticity in adolescents while examining variables that may moderate plasticity (such as sex and environment). METHODS: We recruited 34 healthy adolescents (aged 13-19, 13 males, 21 females). To evaluate excitatory plasticity, we compared mean motor-evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS) before and after PAS at 0, 15, and 30 min. To evaluate inhibitory plasticity, we evaluated the cortical silent period (CSP) elicited by single-pulse TMS in the contracted hand before and after PAS at 0, 15, and 30 min. RESULTS: All participants completed PAS procedures. No adverse events occurred. PAS was well tolerated. PAS-induced significant increases in the ratio of post-PAS MEP to pre-PAS MEP amplitudes (p < 0.01) at all post-PAS intervals. Neither socioeconomic status nor sex was associated with post-PAS MEP changes. PAS induced significant CSP lengthening in males but not females. CONCLUSION: PAS is a feasible, safe, and well-tolerated index of adolescent motor cortical plasticity. Gender may influence PAS-induced changes in cortical inhibition. PAS is safe and well tolerated by healthy adolescents and may be a novel tool with which to study adolescent neuroplasticity.

Neurophysiological Characterization of Attentional Performance Dysfunction in Schizophrenia Patients in a Reverse-Translated Task.

Attentional dysfunction in schizophrenia (SZ) contributes to the functional deficits ubiquitous to the disorder. Identifying the neural substrates of translational measures of attentional dysfunction would prove invaluable for developing therapeutics. Attentional performance is typically assessed via continuous performance tasks (CPTs), though many place additional cognitive demands with little cross-species test-relevance. Herein, event-related potentials (ERPs) were used to investigate the neurophysiological correlates of attention and response inhibition of SZ and healthy participants, whereas they performed the cross-species-translated five-choice CPT (5C-CPT). Chronically ill, medicated SZ patients and matched controls (n=25 SZ and 26 controls) were tested in the 5C-CPT, in conjunction with ERP and source localization assessments. The ERPs generated in response to correctly identified target and non-target trials revealed three peaks for analysis, corresponding to sensory registration (P1), response selection (N2), and response action (P3). Behavioral responses revealed that SZ patients exhibited impaired attention driven by impaired and slower target detection, and poorer cognitive control. ERPs revealed decreased N2 amplitudes reflecting poorer response selection for both target and non-target trials, plus reduced non-target P3s in SZ patients, the latter accounting for 37% of variance in negative symptoms. Source analyses revealed that the brain regions of significant differences localized to the left dorsolateral prefrontal cortex during response selection and the posterior cingulate cortex for cognitive processes. SZ patients exhibited impaired attention and cognitive control, characterized by less robust frontal and parietal ERP distributions across the response selection and cognitive response time windows, providing neurophysiological characterization of attentional dysfunction in SZ using the reverse-translated 5C-CPT.

The Relationship Between Cortical Inhibition and Electroconvulsive Therapy in the Treatment of Major Depressive Disorder.

Dysfunctional cortical inhibition (CI) is postulated as a key neurophysiological mechanism in major depressive disorder. Electroconvulsive therapy (ECT) is the treatment of choice for resistant depression and ECT has been associated with enhanced CI. The objective of this study was to evaluate the relationship between CI and ECT response in resistant depression. Twenty-five patients with treatment resistant depression underwent an acute course of ECT. CI was indexed by the cortical silent period (CSP) and short-interval cortical inhibition (SICI), through TMS-EMG. CI and clinical response was measured prior to beginning an acute ECT course and within 48 hours of the last ECT treatment in the course. Clinical response to ECT was assessed by HDRS-17 before and after an acute course of ECT. We found that there was a significant difference in CSP at baseline between responder and non-responder groups (p = 0.044). Baseline CSP predicted therapeutic response to ECT with sensitivity of 80% and specificity of 60%. There were no changes in CSP or SICI after administration of the ECT course. Our findings suggest that duration of pre-treatment CSP may be a useful predictor of therapeutic response to ECT in patients with TRD.

Unbiased cluster estimation of electrophysiological brain response.

BACKGROUND: Recent increase in the size and complexity of electrophysiological data from multidimensional electroencephalography (EEG) and magnetoencephalography (MEG) studies has prompted the development of sophisticated statistical frameworks for data analysis. One of the main challenges for such frameworks is the multiple comparisons problem, where the large number of statistical tests performed within a high-dimensional dataset lead to an increased risk of Type I errors (false positives). A solution to this problem, cluster analysis, applies the biologically-motivated knowledge of correlation between adjacent voxels in one or more dimensions of the dataset to correct for the multiple comparisons problem and detect true neurophysiological effects. Cluster-based methods provide increased sensitivity towards detecting neurophysiological events compared to conservative methods such as Bonferroni correction, but are limited by their dependency on an initial cluster-forming statistical threshold (e.g. t-score, alpha) obstructing precise comparisons of results across studies. NEW METHOD: Rather than selecting a single threshold value, unbiased cluster estimation (UCE) computes a significance distribution across all possible threshold values to provide an unbiased overall significance value. COMPARISON TO EXISTING METHODS: UCE functions as a novel extension to existing cluster analysis methods. RESULTS: Using data from EEG combined with brain stimulation study, we showed the impact of statistical threshold on outcome measures and introduction of bias. We showed the application of UCE for different study designs (e.g., within-group, between-group comparisons). CONCLUSION: We propose that researchers consider employing UCE for multidimensional EEG/MEG datasets toward an unbiased comparison of results between subjects, groups, and studies.

Indicators for Remission of Suicidal Ideation Following Magnetic Seizure Therapy in Patients With Treatment-Resistant Depression.

IMPORTANCE: Magnetic seizure therapy (MST) is a novel therapeutic option for treatment-resistant depression (TRD). Suicidal ideation is often associated with TRD and contributes to the increased mortality and morbidity of the disorder. OBJECTIVE: To identify a biomarker that may serve as an indicator of remission of suicidal ideation following a course of MST by using cortical inhibition measures from interleaved transcranial magnetic stimulation and electroencephalography (TMS-EEG). DESIGN, SETTING, AND PARTICIPANTS: Thirty-three patients with TRD were part of an open-label clinical trial of MST treatment. Data from 27 patients (82%) were available for analysis in this study. Baseline TMS-EEG measures were assessed within 1 week before the initiation of MST treatment using the TMS-EEG measures of cortical inhibition (ie, N100 and long-interval cortical inhibition [LICI]) from the left dorsolateral prefrontal cortex and the left motor cortex, with the latter acting as a control site. INTERVENTIONS: The MST treatments were administered under general anesthesia, and a stimulator coil consisting of 2 individual cone-shaped coils was used. MAIN OUTCOMES AND MEASURES: Suicidal ideation was evaluated before initiation and after completion of MST using the Scale for Suicide Ideation (SSI). Measures of cortical inhibition (ie, N100 and LICI) from the left dorsolateral prefrontal cortex were selected. N100 was quantified as the amplitude of the negative peak around 100 milliseconds in the TMS-evoked potential (TEP) after a single TMS pulse. LICI was quantified as the amount of suppression in the double-pulse TEP relative to the single-pulse TEP. RESULTS: Of the 27 patients included in the analyses, 15 (56%) were women; mean (SD) age of the sample was 46.0 (15.3) years. At baseline, patients had a mean SSI score of 9.0 (6.8), with 8 of 27 patients (30%) having a score of 0. After completion of MST, patients had a mean SSI score of 4.2 (6.3) (pre-post treatment mean difference, 4.8 [6.7]; paired t26 = 3.72; P = .001), and 18 of 27 individuals (67%) had a score of 0 for a remission rate of 53%. The N100 and LICI in the frontal cortex-but not in the motor cortex-were indicators of remission of suicidal ideation with 89% accuracy, 90% sensitivity, and 89% specificity (area under the curve, 0.90; P = .003). CONCLUSIONS AND RELEVANCE: These results suggest that cortical inhibition may be used to identify patients with TRD who are most likely to experience remission of suicidal ideation following a course of MST. Stronger inhibitory neurotransmission at baseline may reflect the integrity of transsynaptic networks that are targeted by MST for optimal therapeutic response.

Deep Brain Stimulation Modulates Gamma Oscillations and Theta-Gamma Coupling in Treatment Resistant Depression.

BACKGROUND: Deep brain stimulation (DBS) in the subcallosal cingulate gyrus (SCG) is becoming an effective therapeutic option for treatment resistant depression (TRD). OBJECTIVE/HYPOTHESIS: Identifying the neurophysiological mechanisms altered by DBS may lead to more tailored treatment parameters and enhanced efficacy. METHODS: Twenty TRD patients with implanted DBS in the SCG were recruited. Patients participated in three EEG recording sessions, one with DBS ON, one with DBS randomized to ON or OFF, and one with DBS OFF. During each session, subjects performed N-back working memory tasks, namely the 0-back and 3-back. Fourteen subjects with valid EEG were included in the analysis. Changes in frontal gamma oscillations (30-50 Hz) and coupling between theta (4-7 Hz) and gamma oscillations as a result of DBS stimulation were quantified and correlated with depressive symptoms. RESULTS: DBS stimulation resulted in suppression of frontal oscillations in the ON state relative to the OFF state during the N-back tasks. Greatest suppression was demonstrated in beta and gamma oscillations and most pronounced during the 3-back. Suppression of gamma oscillations in the 3-back correlated with a reduction in depressive symptoms. DBS ON relative to OFF in the 3-back also resulted in an increase in theta-gamma coupling that correlated with a reduction in depressive symptoms. CONCLUSION: Suppression of gamma oscillations and increased theta-gamma coupling through DBS is likely mediated by both SCG activation of inhibitory circuits and an enhancement of plasticity in the frontal cortex. Activation of both pathways may explain the therapeutic properties of DBS in TRD.

Imaging-based neurochemistry in schizophrenia: a systematic review and implications for dysfunctional long-term potentiation.

Cognitive deficits are commonly observed in patients with schizophrenia. Converging lines of evidence suggest that these deficits are associated with impaired long-term potentiation (LTP). In our systematic review, this hypothesis is evaluated using neuroimaging literature focused on proton magnetic resonance spectroscopy, positron emission tomography, and single-photon emission computed tomography. The review provides evidence for abnormal dopaminergic, GABAergic, and glutamatergic neurotransmission in antipsychotic-naive/free patients with schizophrenia compared with healthy controls. The review concludes with a model illustrating how these abnormalities could lead to impaired LTP in patients with schizophrenia and consequently cognitive deficits.

A novel method for removal of deep brain stimulation artifact from electroencephalography.

BACKGROUND: Deep brain stimulation (DBS) has treatment efficacy in neurological and psychiatric disorders such as Parkinson's disease and major depression. Electroencephalography (EEG) is a versatile neurophysiological tool that can be used to better understand DBS treatment mechanisms. DBS causes artifacts in EEG recordings that preclude meaningful neurophysiological activity from being quantified during stimulation. NEW METHOD: In this study, we modeled the DBS stimulation artifact and illustrated a technique for removing the artifact using matched filters. The approach was validated using a synthetically generated DBS artifact superimposed on EEG data. Mean squared error (MSE) between the recovered signal and the artifact-free signal was used to quantify the effectiveness of the approach. RESULTS: The DBS artifact was characterized by a series of narrow band components at the harmonic frequencies of DBS stimulation. The filtering approach successfully removed the DBS artifact with MSE value being less than 2% of base signal power for the typical stimulation and recording setups. General guidelines on how to setup DBS EEG studies and configure the subsequent artifact removal process are described. COMPARISON WITH PREVIOUS METHOD: To avoid stimulus artifacts, a number of EEG studies with DBS subjects have resorted to turning the stimulator off during recording, while other studies have used low pass filters to remove artifacts and look at frequencies well below 50 Hz. CONCLUSIONS: This study establishes a method through which DBS artifact in EEG recordings can be reliably eliminated, thereby preserving a meaningful neurophysiological signal through which to better understand DBS treatment mechanisms.