Impact of non-brain anatomy and coil orientation on inter- and intra-subject variability in TMS at midline

Objective: To investigate inter-subject variability with respect to cerebrospinal fluid thickness and brain-scalp distance, and to investigate intra-subject variability with different coil orientations. Methods: Simulations of the induced electric field (E-Field) using a figure-8 coil over the vertex were conducted on 50 unique head models, and varying orientations on 25 models. Metrics exploring stimulation intensity, spread, and localization were used to describe inter-subject variability and effects of non-brain anatomy. Results: Both brain-scalp distance and CSF thickness were correlated with weaker stimulation intensity, and greater spread. Coil rotations show that for the dorsal portion of the stimulated brain, E-Field intensities are highest when the anterior-posterior axis of the coil is perpendicular to the longitudinal fissure, but highest for the medial portion of the stimulated brain when the coil is oriented parallel to the longitudinal fissure. Conclusions: Normal anatomical variation in healthy individuals leads to significant differences in the site of TMS, the intensity and the spread. These variables are generally neglected but could explain significant variability in basic and clinical studies. Significance: This is the first work to show how brain-scalp distance and cerebrospinal fluid thickness influence focality, and to show the disassociation between dorsal and medial TMS

Predictive processing in depression: Increased prediction error following negative valence contexts and influence of recent mood-congruent yet irrelevant experiences

Depressió psíquica; Emocions; Expressió facialDepression; Emotions; Facial ExpressionDepresión; Emociones; Expresión facialBackground: 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

Cerebellar transcranial magnetic stimulation in psychotic disorders: intermittent, continuous, and sham theta-burst stimulation on time perception and symptom severity

BackgroundThe 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.MethodsWe 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.ResultsReaction 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.ConclusionWe 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 Registrationclinicaltrials.gov, identifier NCT02642029

Predictive processing in depression : Increased prediction error following negative valence contexts and influence of recent mood-congruent yet irrelevant experiences

Acord transformatiu CRUE-CSICBackground: 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

Brain Volumetric Correlates of Right Unilateral Versus Bitemporal Electroconvulsive Therapy for Treatment-Resistant Depression.

Objective: The selection of a bitemporal (BT) or right unilateral (RUL) electrode placement affects the efficacy and side effects of ECT. Previous studies have not entirely described the neurobiological underpinnings of such differential effects. Recent neuroimaging research on gray matter volumes is contributing to our understanding of the mechanism of action of ECT and could clarify the differential mechanisms of BT and RUL ECT. Methods: To assess the whole-brain gray matter volumetric changes observed after treating patients with treatment-resistant depression with BT or RUL ECT, the authors used MRI to assess 24 study subjects with treatment-resistant depression (bifrontotemporal ECT, N=12; RUL ECT, N=12) at two time points (before the first ECT session and after ECT completion). Results: Study subjects receiving BT ECT showed gray matter volume increases in the bilateral limbic system, but subjects treated with RUL ECT showed gray matter volume increases limited to the right hemisphere. The authors observed significant differences between the two groups in midtemporal and subcortical limbic structures in the left hemisphere. Conclusions: These findings highlight that ECT-induced gray matter volume increases may be specifically observed in the stimulated hemispheres. The authors suggest that electrode placement may relevantly contribute to the development of personalized ECT protocols

Development and validation of a multimodal neuroimaging biomarker for electroconvulsive therapy outcome in depression: A multicenter machine learning analysis

Background Electroconvulsive therapy (ECT) is the most effective intervention for patients with treatment resistant depression. A clinical decision support tool could guide patient selection to improve the overall response rate and avoid ineffective treatments with adverse effects. Initial small-scale, monocenter studies indicate that both structural magnetic resonance imaging (sMRI) and functional MRI (fMRI) biomarkers may predict ECT outcome, but it is not known whether those results can generalize to data from other centers. The objective of this study was to develop and validate neuroimaging biomarkers for ECT outcome in a multicenter setting. Methods Multimodal data (i.e. clinical, sMRI and resting-state fMRI) were collected from seven centers of the Global ECT-MRI Research Collaboration (GEMRIC). We used data from 189 depressed patients to evaluate which data modalities or combinations thereof could provide the best predictions for treatment remission (HAM-D score ⩽7) using a support vector machine classifier. Results Remission classification using a combination of gray matter volume and functional connectivity led to good performing models with average 0.82–0.83 area under the curve (AUC) when trained and tested on samples coming from the three largest centers (N = 109), and remained acceptable when validated using leave-one-site-out cross-validation (0.70–0.73 AUC). Conclusions These results show that multimodal neuroimaging data can be used to predict remission with ECT for individual patients across different treatment centers, despite significant variability in clinical characteristics across centers. Future development of a clinical decision support tool applying these biomarkers may be feasible.publishedVersio

Applications of Non-invasive Neuromodulation for the Management of Disorders Related to COVID-19

Background: Novel coronavirus disease (COVID-19) morbidity is not restricted to the respiratory system, but also affects the nervous system. Non-invasive neuromodulation may be useful in the treatment of the disorders associated with COVID-19. Objective: To describe the rationale and empirical basis of the use of non-invasive neuromodulation in the management of patients with COVID-10 and related disorders. Methods: We summarize COVID-19 pathophysiology with emphasis of direct neuroinvasiveness, neuroimmune response and inflammation, autonomic balance and neurological, musculoskeletal and neuropsychiatric sequela. This supports the development of a framework for advancing applications of non-invasive neuromodulation in the management COVID-19 and related disorders. Results: Non-invasive neuromodulationmaymanage disorders associated with COVID- 19 through four pathways: (1) Direct infection mitigation through the stimulation of regions involved in the regulation of systemic anti-inflammatory responses and/or autonomic responses and prevention of neuroinflammation and recovery of respiration; (2) Amelioration of COVID-19 symptoms of musculoskeletal pain and systemic fatigue; (3) Augmenting cognitive and physical rehabilitation following critical illness; and (4) Treating outbreak-relatedmental distress including neurological and psychiatric disorders exacerbated by surrounding psychosocial stressors related to COVID-19. The selection of the appropriate techniques will depend on the identified target treatment pathway. Conclusion: COVID-19 infection results in a myriad of acute and chronic symptoms, both directly associated with respiratory distress (e.g., rehabilitation) or of yet-tobe- determined etiology (e.g., fatigue). Non-invasive neuromodulation is a toolbox of techniques that based on targeted pathways and empirical evidence (largely in non- COVID-19 patients) can be investigated in the management of patients with COVID-19

Anàlisi de la mecànica d'un esquí: anàlisi a flexió d’un esquí d’esquí alpí mitjançant el mètode dels elements finits

In this project, the mechanics of a ski have been studied to see its mechanical strength and behaviour. First of all, a review of the history of skiing, where it comes from and its evolution. The process of making a current ski has also been explained. To make the ski, we looked for the materials that made it up, we took measurements of a sample ski to model it with the 3D design program SOLIDWORKS® Student Edition 2019-2020. From the modelling, it has been exported to the FEM ABAQUS® Student version 2019 calculation program to perform the simulation by the finite elements method and obtain the results of the mechanical strength of the ski according to the bending force apply. With these results, a conclusion has been drawn about whether the modelling is well done or not and whether the ski is safe enough or not. It has been concluded that the ski would not break as in the first simulation the stress states are not exaggerated and in the second one the ski would skid and never get to adopt the simulated geometry

Functional hyperconnectivity between corticocerebellar networks and altered decision making in young adult cannabis users: Evidence from 7T and multivariate pattern analysis

Highlights In a first of its kind, this study used advanced brain imaging analyses on high dimensional 7 Tesla images from 92 Cannabis Users and 92 age- matched Non Users from the Human connectome study. We examined the impact of cannabis smoking on the brain networks in grey matter and white matter and psychological function.• We found that cannabis users had altered corticocerebellar functional connectivity mirrored in aberrant decision making with intriguing correlations between these modalities. Abstract 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

Threat-Modulation of Executive Functions : A Novel Biomarker of Depression?

Background: Alterations in executive functions, emotion regulation, and their interaction are common concomitants of depression. Executive dysfunction frequently lingers after treatment, has adverse effects on daily life, and predisposes to recurrence of depression. Yet, sensitive measures of executive function for reliable assessment of cognitive outcomes are still lacking in clinical practice. To better understand the impact of depression and its most effective treatment, electroconvulsive therapy (ECT), on cognition, we assessed executive functions pre- and post-ECT and whether objective measures reflecting alterations in emotion–executive function interaction correlate with depression severity or with cognitive outcome. Methods: Executive functions were assessed in 21 patients with major depressive disorder (MDD) before and after ECT using subjective measures from the Behavior Rating Inventory of Executive Function—Adult version (BRIEF-A) and objective cognitive performance measures derived from computer-based test of executive function, Executive Reaction Time (RT) Test. In addition, we created novel indices reflecting emotional modulation of cognitive performance by subtracting different performance measures in the context of neutral distractors from those in the context of threat-related distractors. We correlated these indices with Beck Depression Inventory (BDI) and BRIEF-A scores. Results: Depression was significantly alleviated, and executive functions improved post-ECT, as seen in reduced BDI scores, BRIEF-A scores, and number of errors in Executive RT Test. Pre-ECT BDI scores correlated with threat modulation of RT (tmRT) and threat modulation of working memory (tmWM). Post-ECT tmRT correlated with several Behavioral Regulation scales and tmWM with several Metacognition scales of BRIEF-A. Conclusion: While caution is warranted, results from both subjective and objective measures suggest that ECT significantly improves executive functions and emotion regulation along with alleviation of depression. Novel indices derived from threat modulation of executive function and working memory show promise as objective biomarkers of depression severity pre-ECT and cognitive outcome post-ECT with potential for guiding depression treatments.publishedVersionPeer reviewe