Tobacco cigarette smoking is associated with disrupted brain network dynamics in resting brain networks including the Salience (SN) and Fronto parietal (FPN). Unified multimodal methods [Resting state connectivity analysis, Diffusion Tensor Imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and cortical thickness analysis] were employed to test the hypothesis that the impact of cigarette smoking on the balance among these networks is due to alterations in white matter connectivity, microstructural architecture, functional connectivity and cortical thickness (CT) and that these metrics define fundamental differences between people who smoke and nonsmokers. Multimodal analyses of previously collected 7 Tesla MRI data via the Human Connectome Project were performed on 22 people who smoke (average number of daily cigarettes was 10 ± 5) and 22 age- and sex-matched nonsmoking controls. First, functional connectivity analysis was used to examine SN-FPN-DMN interactions between people who smoke and nonsmokers. The anatomy of these networks was then assessed using DTI and CT analyses while microstructural architecture of WM was analyzed using the NODDI toolbox. Seed-based connectivity analysis revealed significantly enhanced within network [p = 0.001 FDR corrected] and between network functional coupling of the salience and R-frontoparietal networks in people who smoke [p = 0.004 FDR corrected]. The network connectivity was lateralized to the right hemisphere. Whole brain diffusion analysis revealed no significant differences between people who smoke and nonsmokers in Fractional Anisotropy, Mean diffusivity and in neurite orienting and density. There were also no significant differences in CT in the hubs of these networks. Our results demonstrate that tobacco cigarette smoking is associated with enhanced functional connectivity, but anatomy is largely intact in young adults. Whether this enhanced connectivity is pre-existing, transient or permanent is not known. The observed enhanced connectivity in resting state networks may contribute to the maintenance of smoking frequency.
Introduction: Proof-of-principle human studies suggest that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve depression severity. This open-label multicenter study tested remotely supervised multichannel tDCS delivered at home in patients (N=35) with major depressive disorder (MDD). The primary aim was to assess the feasibility and safety of our protocol. As an exploratory aim, we evaluated therapeutic efficacy: the primary efficacy measure was the median percent change from baseline to the end of the 4-week post-treatment follow-up period in the observer-rated Montgomery-Asberg Depression Mood Rating Scale (MADRS). Methods: Participants received 37 at-home stimulation sessions (30 minutes each) of specifically designed multichannel tDCS targeting the left DLPFC administered over eight weeks (4 weeks of daily treatments plus 4 weeks of taper), with a follow-up period of 4 weeks following the final stimulation session. The stimulation montage (electrode positions and currents) was optimized by employing computational models of the electric field generated by multichannel tDCS using available structural data from a similar population (group optimization). Conducted entirely remotely, the study employed the MADRS for assessment at baseline, at weeks 4 and 8 during treatment, and at 4-week follow-up visits. Results: 34 patients (85.3% women) with a mean age of 59 years, a diagnosis of MDD according to DSM-5 criteria, and a MADRS score ≥20 at the time of study enrolment completed all study visits. At baseline, the mean time since MDD diagnosis was 24.0 (SD 19.1) months. Concerning compliance, 85% of the participants (n=29) completed the complete course of 37 stimulation sessions at home, while 97% completed at least 36 sessions. No detrimental effects were observed, including suicidal ideation and/or behavior. The study observed a median MADRS score reduction of 64.5% (48.6, 72.4) 4 weeks post-treatment (Hedge's g = -3.1). We observed a response rate (≥ 50% improvement in MADRS scores) of 72.7% (n=24) from baseline to the last visit 4 weeks post-treatment. Secondary measures reflected similar improvements. Conclusions: These results suggest that remotely supervised and supported multichannel home-based tDCS is safe and feasible, and antidepressant efficacy motivates further appropriately controlled clinical studies.
Telehealth and telemedicine have encountered explosive growth since the beginning of the COVID-19 pandemic, resulting in increased access to care for patients located far from medical centers and clinics. Subspecialty clinicians in behavioral neurology & neuropsychiatry (BNNP) have implemented the use of telemedicine platforms to perform cognitive examinations that were previously office based. In this perspective article, BNNP clinicians at Massachusetts General Hospital (MGH) describe their experience performing cognitive examinations via telemedicine. The article reviews the goals, prerequisites, advantages, and potential limitations of performing a video- or telephone-based telemedicine cognitive examination. The article shares the approaches used by MGH BNNP clinicians to examine cognitive and behavioral areas, such as orientation, attention and executive functions, language, verbal learning and memory, visual learning and memory, visuospatial function, praxis, and abstract abilities, as well as to survey for neuropsychiatric symptoms and assess activities of daily living. Limitations of telemedicine-based cognitive examinations include limited access to and familiarity with telecommunication technologies on the patient side, limitations of the technology itself on the clinician side, and the limited psychometric validation of virtual assessments. Therefore, an in-person examination with a BNNP clinician or a formal in-person neuropsychological examination with a neuropsychologist may be recommended. Overall, this article emphasizes the use of standardized cognitive and behavioral assessment instruments that are either in the public domain or, if copyrighted, are nonproprietary and do not require a fee to be used by the practicing BNNP clinician.
COVID-19 , Neurology , Neuropsychiatry , Telemedicine , Humans , Hospitals, General , Pandemics , Activities of Daily Living , Massachusetts , Cognition
Background: The cerebellum contributes to the precise timing of non-motor and motor functions, and cerebellum abnormalities have been implicated in psychosis pathophysiology. In this study, we explored the effects of cerebellar theta burst stimulation (TBS), an efficient transcranial magnetic stimulation protocol, on temporal discrimination and self-reported mood and psychotic symptoms. Methods: We conducted a case-crossover study in which patients with psychosis (schizophrenias, schizoaffective disorders, or bipolar disorders with psychotic features) were assigned to three sessions of TBS to the cerebellar vermis: one session each of intermittent (iTBS), continuous (cTBS), and sham TBS. Of 28 enrolled patients, 26 underwent at least one TBS session, and 20 completed all three. Before and immediately following TBS, participants rated their mood and psychotic symptoms and performed a time interval discrimination task (IDT). We hypothesized that cerebellar iTBS and cTBS would modulate these measures in opposing directions, with iTBS being adaptive and cTBS maladaptive. Results: Reaction time (RT) in the IDT decreased significantly after iTBS vs. Sham (LS-mean difference = -73.3, p = 0.0001, Cohen's d = 1.62), after iTBS vs. cTBS (LS-mean difference = -137.6, p < 0.0001, d = 2.03), and after Sham vs. cTBS (LS-mean difference = -64.4, p < 0.0001, d = 1.33). We found no effect on IDT accuracy. We did not observe any effects on symptom severity after correcting for multiple comparisons. Conclusion: We observed a frequency-dependent dissociation between the effects of iTBS vs. cTBS to the cerebellar midline on the reaction time of interval discrimination in patients with psychosis. iTBS showed improved (adaptive) while cTBS led to worsening (maladaptive) speed of response. These results demonstrate behavioral target engagement in a cognitive dimension of relevance to patients with psychosis and generate testable hypotheses about the potential therapeutic role of cerebellar iTBS in this clinical population. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02642029.
Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this causal depression network (CDN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis Principal Component Analysis (PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CDN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CDN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes (t = -2.35, p = 0.019). This evidence further supports that treatment interventions converge on a CDN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.
LEARNING OBJECTIVES: ⢠Outline and discuss the fundamental physiologic, cellular, and molecular mechanisms of ECT to devise strategies to optimize therapeutic outcomes⢠Summarize the overview of ECT, its efficacy in treating depression, the known effects on cognition, evidence of mechanisms, and future directions. ABSTRACT: Electroconvulsive therapy (ECT) is the most effective treatment for a variety of psychiatric illnesses, including treatment-resistant depression, bipolar depression, mania, catatonia, and clozapine-resistant schizophrenia. ECT is a medical and psychiatric procedure whereby electrical current is delivered to the brain under general anesthesia to induce a generalized seizure. ECT has evolved a great deal since the 1930s. Though it has been optimized for safety and to reduce adverse effects on cognition, issues persist. There is a need to understand fundamental physiologic, cellular, and molecular mechanisms of ECT to devise strategies to optimize therapeutic outcomes. Clinical trials that set out to adjust parameters, electrode placement, adjunctive medications, and patient selection are critical steps towards the goal of improving outcomes with ECT. This narrative review provides an overview of ECT, its efficacy in treating depression, its known effects on cognition, evidence of its mechanisms, and future directions.
Bipolar Disorder , Catatonia , Electroconvulsive Therapy , Schizophrenia , Humans , Bipolar Disorder/drug therapy , Schizophrenia/drug therapy , Catatonia/therapy , Treatment Outcome
ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative for the treatment of major depressive disorder (MDD), although its clinical effectiveness varies substantially. The effects of sex hormone fluctuations on cortical excitability have been identified as potential factors that can explain this variability. However, data on how sex hormone changes affect clinical response to rTMS is limited. To address this gap, we reviewed the literature examining the effects of sex hormones and hormonal treatments on transcranial magnetic stimulation (TMS) measures of cortical excitability. Results show that variations of endogenous estrogen, testosterone, and progesterone have modulatory effects on TMS-derived measures of cortical excitability. Specifically, higher levels of estrogen and testosterone were associated with greater cortical excitability, while higher progesterone was associated with lower cortical excitability. This highlights the importance of additional investigation into the effects of hormonal changes on rTMS outcomes and circuit-specific physiological variables. These results call for TMS clinicians to consider performing more frequent motor threshold (MT) assessments in patients receiving high doses of estrogen, testosterone, and progesterone in cases such as in vitro fertilization, hormone replacement therapy, and gender-affirming hormonal treatments. It may also be important to consider physiological hormonal fluctuations and their impact on depressive symptoms and the MT when treating female patients with rTMS.
Cortical Excitability , Depressive Disorder, Major , Humans , Female , Transcranial Magnetic Stimulation/methods , Depressive Disorder, Major/therapy , Progesterone , Evoked Potentials, Motor/physiology , Estrogens , Testosterone
BACKGROUND: Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) are effective neuromodulation therapies for treatment-resistant depression (TRD). While ECT is generally considered the most effective antidepressant, rTMS is less invasive, better tolerated and leads to more durable therapeutic benefits. Both interventions are established device antidepressants, but it remains unknown if they share a common mechanism of action. Here we aimed to compare the brain volumetric changes in patients with TRD after right unilateral (RUL) ECT versus left dorsolateral prefrontal cortex (lDLPFC) rTMS. METHODS: We assessed 32 patients with TRD before the first treatment session and after treatment completion using structural magnetic resonance imaging. Fifteen patients were treated with RUL ECT and seventeen patients received lDLPFC rTMS. RESULTS: Patients receiving RUL ECT, in comparison with patients treated with lDLPFC rTMS, showed a greater volumetric increase in the right striatum, pallidum, medial temporal lobe, anterior insular cortex, anterior midbrain, and subgenual anterior cingulate cortex. However, ECT- or rTMS-induced brain volumetric changes were not associated with the clinical improvement. LIMITATIONS: We evaluated a modest sample size with concurrent pharmacological treatment and without neuromodulation therapies randomization. CONCLUSIONS: Our findings suggest that despite comparable clinical outcomes, only RUL ECT is associated with structural change, while rTMS is not. We hypothesize that structural neuroplasticity and/or neuroinflammation may explain the larger structural changes observed after ECT, whereas neurophysiological plasticity may underlie the rTMS effects. More broadly, our results support the notion that there are multiple therapeutic strategies to move patients from depression to euthymia.
Electroconvulsive Therapy , Humans , Electroconvulsive Therapy/methods , Transcranial Magnetic Stimulation/methods , Depression/therapy , Gyrus Cinguli , Temporal Lobe , Treatment Outcome
For individuals with increased levels of neuroticism, experiencing criticism or receiving negative feedback has been associated with worse psychological and cognitive outcomes. Transcranial direct current stimulation (tDCS) can change cognitive processes in clinical populations. We bilaterally stimulated the posterior inferior parietal lobule (pIPL), a critical superficial node of the default model network. We investigated how baseline neuroticism modulates the impact of bilateral tDCS to pIPL on qualitative measures of memory after hearing criticism, hypothesizing that cathodal stimulation of the IPL would offer qualitative memory improvements for individuals with higher levels of neuroticism. Ninety individuals from the community were randomly assigned to receive anodal, cathodal, or sham stimulation while they were exposed to critical comments before and after stimulation. Participants then recalled the critical comments, and their linguistic responses were analyzed using Pennebaker's Linguistic Inquiry and Word Count software, a quantitative analysis software for linguistic data. Results showed that for individuals receiving cathodal tDCS, higher neuroticism scores corresponded with greater proportions of non-personal language (i.e., words such as "us," "they," or "other" instead of "I" or "me") when recalling negative feedback. For individuals with higher neuroticism, cathodal tDCS stimulation, rather than anodal or sham, of the pIPL prompted increased emotional distancing and perspective taking strategies when recalling criticism. These results further highlight the state-dependent nature of tDCS effects and the role of the IPL in interpersonal processing - a clinically meaningful outcome that current tDCS studies solely examining quantitative measures of memory (e.g., task-based accuracy or speed) do not reveal.
Transcranial Direct Current Stimulation , Humans , Emotions , Neuroticism , Parietal Lobe , Thinking , Transcranial Direct Current Stimulation/methods
This article discusses 2 possible mechanisms of action of electroconvulsive therapy.
Electroconvulsive Therapy , Humans , Neuronal Plasticity
Decision-making (DM) impairments are important predictors of cannabis initiation and continued use. In cannabis users, how decision-making abnormalities related to structural and functional connectivity in the brain are not fully understood. We employed a three-method multimodal image analysis and multivariate pattern analysis (MVPA) on high dimensional 7 tesla MRI images examining functional connectivity, white matter microstructure and gray matter volume in a group of cannabis users and non-users. Neuroimaging and cognitive analyses were performed on 92 CU and 92 age- matched NU from a total of 187 7T scans. CU were selected on the basis of their scores on the Semi-Structured Assessment for the Genetics of Alcoholism. The groups were first compared on a decision-making test and then on ICA based functional connectivity between corticocerebellar networks. An MVPA was done as a confirmatory analysis. The anatomy of these networks was then assessed using Diffusion Tensor imaging (DTI) and cortical volume analyses. Cannabis Users had significantly higher scores on the Iowa Gambling task (IGT) [Gambling task Percentage larger] and significantly lower scores on the [Gambling task reward Percentage smaller]. Left accumbens (L NAc) volume was significantly larger in cannabis users. DTI analysis between the groups yielded no significant (FWE corrected) differences. Resting state FC analysis of the left Cerebellum region 9 showed enhanced functional connectivity with the right nucleus accumbens and left pallidum and left putamen in CU. In addition, posterior cerebellum showed enhanced functional connectivity (FWE corrected) with 2 nodes of the DMN and left and right paracingulate (sub genual ACC) and the sub callosal cortex in CU. IGT percentage larger scores correlated with posterior cerebellar functional connectivity in non-user women. A multivariate pattern analysis confirmed this cerebellar hyperconnectivity in both groups. Our results demonstrate for the first time that deficits in DM observed in cannabis users are mirrored in hyper connectivity in corticocerebellar networks. Cortical volumes of some of the nodes of these networks showed increases in users. However, the underlying white matter was largely intact in CU. The observed DM deficits and hyper connectivity in resting networks may contribute to difficulties in quitting and/or facilitating relapse.
Cannabis , Diffusion Tensor Imaging , Humans , Female , Young Adult , Brain/diagnostic imaging , Decision Making
BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) shows efficacy in the treatment of major depressive disorder using a standard course of 20-36 treatment sessions. However, research efforts are being made to improve overall response and remission rates. Evidence from open-label extension studies of randomized control trials suggests that extending the rTMS treatment course beyond 36 treatments may improve outcomes, however, little has been published on the benefit of extended TMS treatment courses in clinical practice. OBJECTIVE: In this retrospective naturalistic observational study, we studied response rates on continuation of rTMS following failure of the first round of 36 treatments. METHODS: From 142 patients who received conventional rTMS and 29 who underwent theta-burst stimulation (TBS) at Massachusetts General Hospital TMS clinical service, 28 non-responders (23 to rTMS and 5 to TBS) opted to continue their treatment beyond session 36. The treatment protocol allowed personalization in target, TMS protocol, as well as number of pulses and sessions as clinically indicated. Sustained response and remission using Hamilton Rating Scale for Depression, 17-items (HAMD-17) was the primary outcome. RESULTS: The average number of overall treatment sessions was 70.54 ± 16.73 for the sample. Overall, there was a 53.57% response rate and a 32.14% remission rate. Response and remission rates rose as the number of sessions increased and there did not appear to be a plateau in response over time. CONCLUSION: Our results support the idea that subpopulation of TMS patients are late responders. Continuation of TMS up to 72 treatments among those patients who do not meet response criteria by session 36 may improve overall response rates. While the number of subjects and study design limit generalization, given the fact that these patients were medication refractory and had failed initial course of TMS, the result of this study is encouraging.
Depressive Disorder, Major , Transcranial Magnetic Stimulation , Humans , Transcranial Magnetic Stimulation/methods , Depressive Disorder, Major/therapy , Depressive Disorder, Major/etiology , Depression , Retrospective Studies , Research Design , Treatment Outcome , Prefrontal Cortex/physiology
Cognitive impairment, and working memory deficits in particular, are debilitating, treatment-resistant aspects of schizophrenia. Dysfunction of brain network hubs, putatively related to altered neurodevelopment, is thought to underlie the cognitive symptoms associated with this illness. Here, we used weighted degree, a robust graph theory metric representing the number of weighted connections to a node, to quantify centrality in cortical hubs in 29 patients with schizophrenia and 29 age- and gender-matched healthy controls and identify the critical nodes that underlie working memory performance. In both patients and controls, elevated weighted degree in the default mode network (DMN) was generally associated with poorer performance (accuracy and reaction time). Higher degree in the ventral attention network (VAN) nodes in the right superior temporal cortex was associated with better performance (accuracy) in patients. Degree in several prefrontal and parietal areas was associated with cognitive performance only in patients. In regions that are critical for sustained attention, these correlations were primarily driven by between-network connectivity in patients. Moreover, a cross-validated prediction analysis showed that a linear model using a summary degree score can be used to predict an individual's working memory accuracy (r = 0.35). Our results suggest that schizophrenia is associated with dysfunctional hubs in the cortical systems supporting internal and external cognition and highlight the importance of topological network analysis in the search of biomarkers for cognitive deficits in schizophrenia.
Persistent symptoms following COVID-19 infection have been termed postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection. Many of these symptoms are neuropsychiatric, such as inattention, impaired memory, and executive dysfunction; these are often colloquially termed "brain fog". These symptoms are common and often persist long after the acute phase. The pattern of these deficits combined with laboratory, neuroimaging, electroencephalographic, and neuropsychological data suggest that these symptoms may be driven by direct and indirect damage to the frontal-subcortical neural networks. Here, we review this evidence, share our clinical experience at an academic medical center, and discuss potential treatment implications. While the exact etiology remains unknown, a neurocircuit-informed understanding of postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection can help guide pharmacology, neuromodulation, and physical and psychological therapeutic approaches.
COVID-19 , Cognitive Dysfunction , Humans , SARS-CoV-2 , Disease Progression , Memory Disorders
Importance: Transcranial direct current stimulation (tDCS) may improve symptoms of inattention in adults with attention-deficit/hyperactivity disorder (ADHD). However, previous trials are characterized by small sample sizes, heterogeneous methodologies, and short treatment periods using clinic-based tDCS. Objective: To determine the efficacy and safety of home-based tDCS in treating inattention symptoms in adult patients with ADHD. Design, Setting, and Participants: Randomized, double-blind, parallel, sham-controlled clinical trial (tDCS for the Treatment of Inattention Symptoms in Adult Patients With ADHD [TUNED]), conducted from July 2019 through July 2021 in a single-center outpatient academic setting. Of 277 potential participants screened by phone, 150 were assessed for eligibility on site, and 64 were included. Participants were adults with ADHD, inattentive or combined subtype. Exclusion criteria included current stimulant drug treatment, current moderate to severe symptoms of depression or anxiety, diagnosis of bipolar disorder with a manic or depressive episode in the last year, diagnosis of schizophrenia or another psychotic disorder, and diagnosis of autism spectrum disorder; 55 of participants completed follow-up after 4 weeks. Interventions: Thirty-minute daily sessions of home-based tDCS for 4 weeks, 2 mA anodal-right and cathodal-left prefrontal stimulation with 35-cm2 carbon electrodes. Main Outcomes and Measures: Inattentive scores in the clinician-administered version of the Adult ADHD Self-report Scale version 1.1 (CASRS-I). Results: Included in this trial were 64 participants with ADHD (31 [48%] inattentive presentation and 33 [52%] combined presentation), with a mean (SD) age of 38.3 (9.6) years. Thirty participants (47%) were women and 34 (53%) were men. Fifty-five finished the trial. At week 4, the mean (SD) inattention score, as measured with CASRS-I, was 18.88 (5.79) in the active tDCS group and 23.63 (3.97) in the sham tDCS group. Linear mixed-effects models revealed a statistically significant treatment by time interaction for CASRS-I (ßinteraction = -3.18; 95% CI, -4.60 to -1.75; P < .001), showing decreased symptoms of inattention in the active tDCS group over the 3 assessments compared to the sham tDCS group. Mild adverse events were more frequent in the active tDCS group, particularly skin redness, headache, and scalp burn. Conclusions and Relevance: In this randomized clinical trial, daily treatment with a home-based tDCS device over 4 weeks improved attention in adult patients with ADHD who were not taking stimulant medication. Home-based tDCS could be a nonpharmacological alternative for patients with ADHD. Trial Registration: ClinicalTrials.gov Identifier: NCT04003740.
Attention Deficit Disorder with Hyperactivity , Autism Spectrum Disorder , Bipolar Disorder , Transcranial Direct Current Stimulation , Adult , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/therapy , Autism Spectrum Disorder/therapy , Bipolar Disorder/therapy , Double-Blind Method , Female , Humans , Male , Transcranial Direct Current Stimulation/methods , Treatment Outcome
BACKGROUND: Anhedonia is a core symptom of major depressive disorder (MDD) resulting from maladaptive reward processing. Electroconvulsive therapy (ECT) is an effective treatment for patients with MDD. No previous neuroimaging studies have taken a dimensional approach to assess whether ECT-induced volume changes are specifically related to improvements in anhedonia and positive valence emotional constructs. We aimed to assess the relationship between ECT-induced brain volumetric changes and improvement in anhedonia and reward processing in patients with MDD. METHODS: We evaluated 15 patients with MDD before and after ECT. We used magnetic resonance imaging, clinical scales (i.e., Quick Inventory of Depressive Symptomatology for syndromal depression severity and Snaith-Hamilton Pleasure Scale for anhedonia) and the Temporal Experience of Pleasure Scale for anticipatory and consummatory experiences of pleasure. We identified 5 regions of interest within the reward circuit and a 6th control region relevant for MDD but not core to the reward system (Brodmann Area 25). RESULTS: Anhedonia, anticipatory and consummatory reward processing improved after ECT. Volume increases within the right reward system separated anhedonia responders and non-responders. Improvement in anticipatory (but not consummatory) reward correlated with increases in volume in hippocampus, amygdala, ventral tegmental area and nucleus accumbens. LIMITATIONS: We evaluated a modest sample size of patients with concurrent pharmacological treatment using a subjective psychometric assessment. CONCLUSIONS: We highlight the importance of a dimensional and circuit-based approach to understanding target engagement and the mechanism of action of ECT, with the goal to define symptom- and circuit-specific response biomarkers for device neuromodulation therapies.
Depressive Disorder, Major , Electroconvulsive Therapy , Anhedonia/physiology , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/therapy , Humans , Magnetic Resonance Imaging , Neuroimaging , Reward
BACKGROUND: Novel theoretical models of depression have recently emerged based on an influential new perspective in neuroscience known as predictive processing. In these models, depression may be understood as an imbalance of predictive signals in the brain; more specifically, a dominance of predictions leading to a relative insensitivity to prediction error. Despite these important theoretical advances, empirical evidence remains limited, and how expectations are generated and used dynamically in individuals with depression remains largely unexplored. METHODS: In this study, we induced facial expression predictions using emotion contexts in 34 individuals with depression and 34 healthy controls. RESULTS: Compared to controls, individuals with depression perceived displayed facial expressions as less similar to their expectations (i.e., increased difference between expectations and actual sensory input) following contexts evoking negative valence emotions, indicating that depressed individuals have increased prediction error in such contexts. This effect was amplified by recent mood-congruent yet irrelevant experiences. LIMITATIONS: The clinical sample included participants with comorbid psychopathology and taking medication. Additionally, the two groups were not evaluated in the same setting, and only three emotion categories (fear, sadness, and happiness) were explored. CONCLUSIONS: Our results shed light on potential mechanisms underlying processing abnormalities regarding negative information, which has been consistently reported in depression, and may be a relevant point of departure for exploring transdiagnostic vulnerability to mental illness. Our data also has the potential to improve clinical practice through the implementation of novel diagnostic and therapeutic tools based on the assessment and modulation of predictive signals.
Depression , Facial Expression , Affect , Depression/psychology , Emotions , Happiness , Humans
Non-invasive brain stimulation has been increasingly recognized for its potential as an investigational, diagnostic and therapeutic tool across the clinical neurosciences. Transcranial magnetic stimulation (TMS) is a non-invasive method of focal neuromodulation. Diagnostically, TMS can be used to probe cortical excitability and plasticity, as well as for functional mapping. Therapeutically, depending on the pattern employed, TMS can either facilitate or inhibit stimulated cortex potentially modulating maladaptive physiology through its effects on neuroplasticity. Despite this potential, applications of TMS in neurology have only been approved for diagnostic clinical neurophysiology, pre-surgical mapping of motor and language cortex, and the treatment of migraines. In this article, we discuss the principles of TMS and its clinical applications in neurology, including experimental applications in stroke rehabilitation, seizures, autism spectrum disorder, neurodegenerative disorders, movement disorders, tinnitus, chronic pain and functional neurological disorder. To promote increased cross-talk across neurology and psychiatry, we also succinctly review the TMS literature for the treatment of major depression and obsessive compulsive disorder. Overall, we argue that larger clinical trials that are better informed by circuit-level biomarkers and pathophysiological models will lead to an expansion of the application of TMS for patients cared for by neurologists.
Autism Spectrum Disorder , Neurology , Autism Spectrum Disorder/therapy , Humans , Seizures , Transcranial Magnetic Stimulation
