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2.
JAMA Neurol ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226425

RESUMO

Importance: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor nervous system. Clinical studies have demonstrated cortical and spinal motor neuron hyperexcitability using transcranial magnetic stimulation and threshold tracking nerve conduction studies, respectively, although metrics of excitability have not been used as pharmacodynamic biomarkers in multi-site clinical trials. Objective: To ascertain whether ezogabine decreases cortical and spinal motor neuron excitability in ALS. Design, Setting, and Participants: This double-blind, placebo-controlled phase 2 randomized clinical trial sought consent from eligible participants from November 3, 2015, to November 9, 2017, and was conducted at 12 US sites within the Northeast ALS Consortium. Participants were randomized in equal numbers to a higher or lower dose of ezogabine or to an identical matched placebo, and they completed in-person visits at screening, baseline, week 6, and week 8 for clinical assessment and neurophysiological measurements. Interventions: Participants were randomized to receive 600 mg/d or 900 mg/d of ezogabine or a matched placebo for 10 weeks. Main Outcomes and Measures: The primary outcome was change in short-interval intracortical inhibition (SICI; SICI-1 was used in analysis to reflect stronger inhibition from an increase in amplitude) from pretreatment mean at screening and baseline to the full-dose treatment mean at weeks 6 and 8. The secondary outcomes included levels of cortical motor neuron excitability (including resting motor threshold) measured by transcranial magnetic stimulation and spinal motor neuron excitability (including strength-duration time constant) measured by threshold tracking nerve conduction studies. Results: A total of 65 participants were randomized to placebo (23), 600 mg/d of ezogabine (23), and 900 mg/d of ezogabine (19 participants); 45 were men (69.2%) and the mean (SD) age was 58.3 (8.8) years. The SICI-1 increased by 53% (mean ratio, 1.53; 95% CI, 1.12-2.09; P = .009) in the 900-mg/d ezogabine group vs placebo group. The SICI-1 did not change in the 600-mg/d ezogabine group vs placebo group (mean ratio, 1.15; 95% CI, 0.87-1.52; P = .31). The resting motor threshold increased in the 600-mg/d ezogabine group vs placebo group (mean ratio, 4.61; 95% CI, 0.21-9.01; P = .04) but not in the 900-mg/d ezogabine group vs placebo group (mean ratio, 1.95; 95% CI, -2.64 to 6.54; P = .40). Ezogabine caused a dose-dependent decrease in excitability by several other metrics, including strength-duration time constant in the 900-mg/d ezogabine group vs placebo group (mean ratio, 0.73; 95% CI, 0.60 to 0.87; P < .001). Conclusions and Relevance: Ezogabine decreased cortical and spinal motor neuron excitability in participants with ALS, suggesting that such neurophysiological metrics may be used as pharmacodynamic biomarkers in multisite clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02450552.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33197507

RESUMO

BACKGROUND: Electroconvulsive therapy (ECT) is considered the most effective treatment for major depressive disorder (MDD). In recent years, the pursuit of the neurobiological mechanisms of ECT action has generated a significant amount of functional magnetic resonance imaging (fMRI) research. OBJECTIVE: In this systematic review, we integrated all fMRI research in patients with MDD receiving ECT and, importantly, evaluated the level of convergence and replicability across multiple fMRI metrics. RESULTS: While according to most studies changes in patients with MDD after ECT appear to be widely distributed across the brain, our multimetric review revealed specific changes involving functional connectivity increases in the superior and middle frontal gyri as the most replicated and across-modality convergent findings. Although this modulation of prefrontal connectivity was associated to ECT outcome, we also identified fMRI measurements of the subgenual anterior cingulate cortex as the fMRI signals most significantly linked to clinical response. CONCLUSION: We identified specific prefrontal and cingulate territories which activity and connectivity with other brain regions is modulated by ECT, critically accounting for its mechanism of action.

4.
Cogn Behav Neurol ; 33(3): 226-229, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889955

RESUMO

Coronavirus 2019 (COVID-19) has profoundly impacted the well-being of society and the practice of medicine across health care systems worldwide. As with many other subspecialties, the clinical paradigm in behavioral neurology and neuropsychiatry (BN-NP) was transformed abruptly, transitioning to real-time telemedicine for the assessment and management of the vast majorities of patient populations served by our subspecialty. In this commentary, we outline themes from the BN-NP perspective that reflect the emerging lessons we learned using telemedicine during the COVID-19 pandemic. Positive developments include the ability to extend consultations and management to patients in our high-demand field, maintenance of continuity of care, enhanced ecological validity, greater access to a variety of well-reimbursed telemedicine options (telephone and video) that help bridge the digital divide, and educational and research opportunities. Challenges include the need to adapt the mental state examination to the telemedicine environment, the ability to perform detailed motor neurologic examinations in patients where motor features are important diagnostic considerations, appreciating nonverbal cues, managing acute safety and behavioral concerns in less controlled environments, and navigating intervention-based (neuromodulation) clinics requiring in-person contact. We hope that our reflections help to catalyze discussions that should take place within the Society for Behavioral and Cognitive Neurology, the American Neuropsychiatric Association, and allied organizations regarding how to optimize real-time telemedicine practices for our subspecialty now and into the future.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Doenças do Sistema Nervoso/diagnóstico , Exame Neurológico , Pandemias , Pneumonia Viral , Telemedicina/organização & administração , Humanos , Massachusetts , Neurologia , Neuropsiquiatria
5.
Clin Ther ; 42(7): 1169-1190.e1, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32674957

RESUMO

PURPOSE: The cerebellum is an intricate neural structure that orchestrates various cognitive and behavioral functions. In recent years, there has been an increasing interest in neuromodulation of the cerebellum with transcranial magnetic stimulation (TMS) for therapeutic and basic science applications. Theta burst stimulation (TBS) is an efficient and powerful TMS protocol that is able to induce longer-lasting effects with shorter stimulation times compared with traditional TMS. Parameters for cerebellar TBS are traditionally framed in the bounds of TBS to the cerebral cortex, even when the 2 have distinct histologic, anatomical, and functional characteristics. Tolerability limits have not been systematically explored in the literature for this specific application. Therefore, we aimed to determine the stimulation parameters that have been used for cerebellar. TBS to date and evaluate adverse events and adverse effects related to stimulation parameters. METHODS: We used PubMed to perform a critical review of the literature based on a systematic review of original research studies published between September 2008 and November 2019 that reported on cerebellar TBS. We recovered information from these publications and communication with authors about the stimulation parameters used and the occurrence of adverse events. FINDINGS: We identified 61 research articles on interventions of TBS to the cerebellum. These articles described 3176 active sessions of cerebellar TBS in 1203 individuals, including healthy participants and patients with various neurologic conditions, including brain injuries. Some studies used substantial doses (eg, pulse intensity and number of pulses) in short periods. No serious adverse events were reported. The specific number of patients who experienced adverse events was established for 48 studies. The risk of an adverse event in this population (n = 885) was 4.1%. Adverse events consisted mostly of discomfort attributable to involuntary muscle contractions. Authors used a variety of methods for calculating stimulation dosages, ranging from the long-established reference of electromyography of a hand muscle to techniques that atone for some of the differences between cerebrum and cerebellum. IMPLICATIONS: No serious adverse events have been reported for cerebellar TBS. There is no substantial evidence of a tolerable maximal-efficacy stimulation dose in humans. There is no assurance of equivalence in the translation of cortical excitability and stimulation intensities from the cerebral cortex to cerebellar regions. Further research for the stimulation dose in cerebellar TBS is warranted, along with consistent report of adverse events. © 2020 Elsevier HS Journals, Inc.

6.
Brain Behav ; 10(6): e01615, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32356600

RESUMO

BACKGROUND: Patterns of altered cerebral perfusion and cognitive dysfunction have been described in Bipolar Disorder (BD) acute episodes and euthymia. Knowledge of the relationship between cognitive function and perfusion in a manic state and status when followed up is still limited. OBJECTIVE: To describe brain perfusion alterations and its relationship with cognitive impairment in patients with BD during manic episodes and after 6 months. METHODS: Observational-prospective study in 10 type I BD adults during moderate-severe manic episodes. We assessed sociodemographic data and clinical variables as well as cognitive function through Screening for Cognitive Impairment in Psychiatry (SCIP-S). Finally, we performed a Brain Perfusion SPECT using a Tc99m-ethyl cysteine dimer. RESULTS: During manic episodes, patients showed cognitive impairment with a mean SCIP-S score of 63.8 ± 17.16. This was positively correlated with perfusion measured as relative reuptake index (RRI) at the right temporal pole (ρ = 0.65 p = .0435) and negatively correlated with right the orbitofrontal cortex (ρ = -0.70 p = .0077) and the right subgenual cingulate cortex (ρ = -0.70 p = .0256). Episode severity measured by the Young Mania Rating Scale (YMRS) positively correlated with RRI at the right temporal pole (ρ = 0.75, p = .01). At follow-up, six patients were taking treatment and were euthymic, we found a negative correlation with the YMRS and RRI at the bilateral orbitofrontal cortex (ρ = -0.8827, p = .019). They did not show significant improvement in cognitive performance at SCIP-S, and there was negative correlation with the following of the SCIP-S subscales; processing speed with the bilateral dorsolateral prefrontal, the bilateral medial prefrontal, the left temporal pole cortex RRI, and verbal fluency with the bilateral anterior cingulate cortex RRI. CONCLUSION: Cognitive impairment was correlated with brain perfusion patterns at baseline and follow-up. Large sample size studies with longer follow-up are needed to describe the changes in perfusion and cognitive functions in BD.

7.
Brain Stimul ; 13(4): 1124-1149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413554

RESUMO

BACKGROUND: The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19. OBJECTIVE: To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). METHODS: The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain-relevant expertise spanning NIBS technology, clinical services, and basic and clinical research - with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics. RESULTS: A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described. CONCLUSION: There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.


Assuntos
Pesquisa Biomédica/métodos , Assistência à Saúde/métodos , Doenças do Sistema Nervoso/terapia , Telemedicina/métodos , Estimulação Transcraniana por Corrente Contínua/métodos , Estimulação Magnética Transcraniana/métodos , Idoso , Comportamento Aditivo/terapia , Betacoronavirus , Encéfalo/fisiologia , Criança , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Guias de Prática Clínica como Assunto , Acidente Vascular Cerebral/terapia , Transtornos Relacionados ao Uso de Substâncias/terapia
8.
Front Neurosci ; 14: 251, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32327965

RESUMO

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder that affects 5% of the pediatric and adult population worldwide. The diagnosis remains essentially clinical, based on history and exam, with no available biomarkers. In this paper, we describe a convolutional neural network (CNN) with a four-layer architecture combining filtering and pooling, which we train using stacked multi-channel EEG time-frequency decompositions (spectrograms) of electroencephalography data (EEG), particularly of event-related potentials (ERP) from ADHD patients (n = 20) and healthy controls (n = 20) collected during the Flanker Task, with 2800 samples for each group. We treat the data as in audio or image classification approaches, where deep networks have proven successful by exploiting invariances and compositional features in the data. The model reaches a classification accuracy of 88% ± 1.12%, outperforming the Recurrent Neural Network and the Shallow Neural Network used for comparison, and with the key advantage, compared with other machine learning approaches, of avoiding the need for manual selection of EEG spectral or channel features. The event-related spectrograms also provide greater accuracy compared to resting state EEG spectrograms. Finally, through the use of feature visualization techniques such as DeepDream, we show that the main features exciting the CNN nodes are a decreased power in the alpha band and an increased power in the delta-theta band around 100 ms for ADHD patients compared to healthy controls, suggestive of attentional and inhibition deficits, which have been previously suggested as pathophyisiological signatures of ADHD. While confirmation with larger clinical samples is necessary, these results suggest that deep networks may provide a useful tool for the analysis of EEG dynamics even from relatively small datasets, highlighting the potential of this methodology to develop biomarkers of practical clinical utility.

9.
Neuroreport ; 31(4): 346-351, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32058431

RESUMO

Research on the feasibility of using transcranial direct current stimulation to modulate the function of the anterior cingulate cortex is limited in part due to its anatomical depth. However, high-definition transcranial direct current stimulation may be better able to reach the anterior cingulate cortex and modulate its function and behavioral outputs. The purpose of this study was to assess the feasibility of using high-definition transcranial direct current stimulation, as compared to traditional bipolar transcranial direct current stimulation, to modulate behavioral measures of anterior cingulate cortex function. In a mixed design, 36 participants received either high-definition transcranial direct current stimulation or bipolar transcranial direct current stimulation, and experienced anodal, cathodal, and sham stimulation over the course of three visits. Two behavioral tasks were used to assess anterior cingulate cortex function before and after stimulation: the multi-source interference task and an emotional facial expression interference task. High-definition transcranial direct current stimulation and bipolar transcranial direct current stimulation groups did not differ in their performance (as measured via response times and error rates) on either task. High-definition transcranial direct current stimulation and bipolar transcranial direct current stimulation were similarly ineffective in modulating behavior related to the anterior cingulate cortex. Future research should explore other transcranial direct current stimulation montages including extracephalic montages (e.g. shoulder, neck) for targeted stimulation of the anterior cingulate cortex.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33549516

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with significant morbidity and mortality that may affect over 5% of children and approximately 2.8% of adults worldwide. Pharmacological and behavioral therapies for ADHD exist, but critical symptoms such as dysexecutive deficits remain unaffected. In a randomized, sham-controlled, double-blind, crossover mechanistic study, we assessed the cognitive and physiological effects of transcranial direct current stimulation (tDCS) in 40 adult patients with ADHD in order to identify diagnostic (cross-sectional) and treatment biomarkers (targets). METHODS: Patients performed three experimental sessions in which they received 30 minutes of 2 mA anodal tDCS targeting the left dorsolateral prefrontal cortex, 30 minutes of 2 mA anodal tDCS targeting the right dorsolateral prefrontal cortex, and 30 minutes of sham. Before and after each session, half the patients completed the Eriksen flanker task and the other half completed the stop signal task while we assessed behavior (reaction time, accuracy) and neurophysiology (event-related potentials). RESULTS: Anodal tDCS to the left dorsolateral prefrontal cortex modulated cognitive (reaction time) and physiological (P300 amplitude) measures in the Eriksen flanker task in a state-dependent manner, but no effects were found in the stop signal reaction time of the stop signal task. CONCLUSIONS: These findings show procognitive effects in ADHD associated with the modulation of event-related potential signatures of cognitive control, linking target engagement with cognitive benefit, proving the value of event-related potentials as cross-sectional biomarkers of executive performance, and mechanistically supporting the state-dependent nature of tDCS. We interpret these results as an improvement in cognitive control but not action cancellation, supporting the existence of different impulsivity constructs with overlapping but distinct anatomical substrates, and highlighting the implications for the development of individualized therapeutics.

11.
Brain Stimul ; 12(6): 1456-1463, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31221553

RESUMO

BACKGROUND: The use of transcranial Direct Current Stimulation (tDCS) to study anatomical and physiological dynamics and circuits supporting cognition and executive functions in particular has dramatically increased in recent years. However, its mechanisms of action remain only partially understood. OBJECTIVE: In this study we assess the cognitive and physiological effects of anodal tDCS to the DLPFC on executive function in order to understand (1) the role of DLPFC laterality, (2) the physiological dynamics sustaining the modulation of executive function by tDCS, and (3) the impact of state-dependent dynamics. METHODS: In a randomized, placebo-controlled, cross-over study, we applied anodal tDCS targeting the left vs. right DLPFC vs. sham in 20 healthy individuals (10 males, 10 females). Immediately before and after tDCS, subjects performed the Flanker Task while we measured behavioral (reaction time and accuracy) and neurophysiological (ERP) responses. Specifically, the amplitude of N200, P300, ERN and Pe is compared before and after stimulation. RESULTS: Anodal tDCS to the left DLPFC lead to a significant improvement in reaction time, an increase in P300 amplitude and a decrease in N200 amplitude in a state-dependent manner: baseline ERP amplitudes conditioned the effects of tDCS. CONCLUSION: Given the role of these ERPs in conflict-related tasks, we speculate that tDCS is modulating the subconstructs of selective attention, conflict monitoring and response inhibition. These findings contribute to a further understanding of the role of left DLPFC in the modulation of executive function, and shed light into the mechanisms of action and the state dependent nature of tDCS.


Assuntos
Cognição/fisiologia , Função Executiva/fisiologia , Lateralidade Funcional/fisiologia , Córtex Pré-Frontal/fisiologia , Estimulação Transcraniana por Corrente Contínua/métodos , Adolescente , Adulto , Atenção/fisiologia , Estudos Cross-Over , Método Duplo-Cego , Eletroencefalografia/métodos , Eletroencefalografia/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Reação/fisiologia , Estimulação Transcraniana por Corrente Contínua/tendências , Adulto Jovem
12.
J Neuropsychiatry Clin Neurosci ; 31(2): 152-158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30458664

RESUMO

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.


Assuntos
Córtex Cerebral/patologia , Transtorno Depressivo Resistente a Tratamento/terapia , Eletroconvulsoterapia/métodos , Sistema Límbico/patologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Sistema Límbico/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
13.
Brain Stimul ; 12(1): 129-138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30344110

RESUMO

BACKGROUND: Transcranial magnetic stimulation (TMS) is a noninvasive neuromodulation technique with therapeutic applications for the treatment of major depressive disorder (MDD). The standard protocol uses high frequency stimulation over the left dorsolateral prefrontal cortex (DLPFC) identified in a heuristic manner leading to moderate clinical efficacy. A proposed strategy to increase the anatomical precision in targeting, based on resting-state functional MRI (rsfMRI), identifies the subregion within the DLPFC having the strongest anticorrelated functional connectivity with the subgenual cortex (SGC) for each individual subject. OBJECTIVE: In this work, we comprehensively test the reliability and reproducibility of this targeting method for different scan lengths on 100 subjects from the Human Connectome Project (HCP) where each subject had a four 15-min rsfMRI scan on 2 different days. METHODS: We quantified the inter-scan and inter-day distance between the rsfMRI-guided DLPFC targets for each subject controlling for a number of expected sources of noise using volumetric as well as surface analyses. RESULTS: Our results show that the average inter-day distance (with fMRI scans lasting 30 min on each day) is 25% less variable than the inter-scan distance, which uses 50% less data. Specifically, the inter-scan distance was more than 37 mm, while for the longer-scan, the inter-day distance had lower variability at 25 mm. Finally, we tested the same rsfMRI strategy using the nucleus accumbens (NAc) as a control region relevant to MDD but less susceptible to artifacts, using both volume and surface rsfMRI data. The results showed similar variability to the SGC-DLPFC functional connectivity. Moreover, our results suggest that a smoothing kernel with 12 mm full-width half maximum (FWHM) lead to more stable and reliable target estimates. CONCLUSION: Our work provides a quantitative assessment of the topographic precision of this targeting method, describing an anatomical variability that may surpass the spatial resolution of some forms of focal TMS as it is commonly applied, and provides recommendations for improved accuracy.


Assuntos
Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Imagem por Ressonância Magnética/normas , Córtex Pré-Frontal/fisiologia , Estimulação Magnética Transcraniana/normas , Adulto , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Reprodutibilidade dos Testes , Estimulação Magnética Transcraniana/métodos , Resultado do Tratamento , Adulto Jovem
14.
Clin Neurophysiol ; 129(9): 1873-1883, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30005214

RESUMO

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.


Assuntos
Encéfalo/fisiologia , Cabeça/anatomia & histologia , Estimulação Magnética Transcraniana/métodos , Simulação por Computador , Cabeça/fisiologia , Humanos , Individualidade , Reprodutibilidade dos Testes
15.
Neuroimage Clin ; 19: 98-105, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30035007

RESUMO

Background: The mesocorticolimbic system is particularly susceptible to the effects of chronic alcoholism. Disruption of this system has been linked to drug seeking and the development of Reward Deficiency Syndrome, a neurobiological framework for describing the development and relapsing patterns of addictions. In this study, we evaluated the association of alcoholism and sex with major connections of the medial forebrain bundle (MFB), a prominent mesocorticolimbic fiber pathway connecting the ventral tegmental area with the basal forebrain. Given sex differences in clinical consequences of alcohol consumption, we hypothesized that alcoholic men and women would differ in structural abnormalities of the MFB. Methods: Diffusion magnetic resonance imaging (dMRI) data were acquired from 30 abstinent long-term alcoholic individuals (ALC; 9 men) and 25 non-alcoholic controls (NC; 8 men). Major connections of the MFB were extracted using multi-tensor tractography. We compared groups on MFB volume, fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD), with hemisphere and sex as independent variables. We also evaluated associations between abnormal structural measures and drinking measures. Results: Analyses revealed significant group-by-sex interactions for FA and RD: while ALC men had lower FA and higher RD compared to NC men, ALC women had higher FA and lower RD compared to NC women. We also detected a significant negative association between FA and number of daily drinks in ALC women. Conclusion: Alcoholism is associated with sexually dimorphic structural abnormalities in the MFB. The results expand upon other findings of differences in brain reward circuitry of alcoholic men and women.


Assuntos
Consumo de Bebidas Alcoólicas/patologia , Alcoolismo/patologia , Feixe Prosencefálico Mediano/patologia , Caracteres Sexuais , Adulto , Idoso , Idoso de 80 Anos ou mais , Anisotropia , Prosencéfalo Basal/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Substância Branca/patologia
16.
J Affect Disord ; 238: 383-391, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29909301

RESUMO

BACKGROUND: Anxiety in bipolar disorder (BD) exacerbates emotion dysregulation and reduces treatment response. We recently conducted a pilot trial of transdiagnostic CBT to target anxiety and emotion dysregulation in BD adjunctive to pharmacotherapy. Reductions in depression and anxiety symptoms were significantly predicted by baseline levels of neuroticism and perceived affective control, as well as changes over time in emotion regulation skills. The present study investigates mechanism of treatment response by examining the relationship between baseline emotion regulation-related neural circuitry and trial outcomes. METHODS: Nineteen patients completed baseline resting state fMRI scans prior to treatment randomization. Functional connectivity between the anterior insula (AI) and regions in the salience network (SN), default mode network (DMN), and executive control network (ECN) were examined as predictors of baseline and treatment-related changes in emotion regulation. RESULTS: Greater improvements in emotion regulation were predicted by weaker right dorsal AI - right ventrolateral prefrontal cortex (VLPFC; SN) and stronger bilateral dorsal AI - bilateral amygdala functional connectivity. Baseline neuroticism was negatively correlated with right dorsal AI- inferior parietal lobule (ECN) functional connectivity, and baseline deficits in perceived affective control were positively associated with ventral AI - bilateral dACC (SN) connectivity. LIMITATIONS: Small sample limits interpretability of treatment-specific effects. CONCLUSION: Baseline functional connectivity of emotion-regulation related neural circuitry significantly predicted change in emotion regulation-related dimensions associated with anxiety and depression symptom reduction. Future studies are needed to determine if employing methods such as neuromodulation to rehabilitate relevant neural circuitry may improve ultimate treatment outcomes of transdiagnostic CBT for BD and anxiety.


Assuntos
Ansiedade/complicações , Transtorno Bipolar/psicologia , Terapia Cognitivo-Comportamental , Adulto , Tonsila do Cerebelo/fisiopatologia , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/terapia , Córtex Cerebral/fisiopatologia , Emoções , Função Executiva/fisiologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Projetos Piloto , Psicotrópicos/uso terapêutico , Descanso/fisiologia , Resultado do Tratamento
17.
Artigo em Inglês | MEDLINE | ID: mdl-29580768

RESUMO

BACKGROUND: Patients with bipolar depression are characterized by dysregulation across the full spectrum of mood, differentiating them from patients with unipolar depression. The ability to switch neural resources among the default mode network, salience network, and executive control network (ECN) has been proposed as a key mechanism for adaptive mood regulation. The anterior insula is implicated in the modulation of functional network switching. Differential connectivity between anterior insula and functional networks may provide insights into pathophysiological differences between bipolar and unipolar mood disorders, with implications for diagnosis and treatment. METHODS: Resting-state functional magnetic resonance imaging data were collected from 98 subjects (35 unipolar, 24 bipolar, and 39 healthy control subjects). Pearson correlations were computed between bilateral insula seed regions and a priori defined target regions from the default mode network, salience network, and ECN. After r-to-z transformation, a one-way multivariate analysis of covariance was conducted to identify significant differences in connectivity between groups. Post hoc pairwise comparisons were conducted and Bonferroni corrections were applied. Receiver-operating characteristics were computed to assess diagnostic sensitivity. RESULTS: Patients with bipolar depression evidenced significantly altered right anterior insula functional connectivity with the inferior parietal lobule of the ECN relative to patients with unipolar depression and control subjects. Right anterior insula-inferior parietal lobule connectivity significantly discriminated patients with bipolar depression. CONCLUSIONS: Impaired functional connectivity between the anterior insula and the inferior parietal lobule of the ECN distinguishes patients with bipolar depression from those with unipolar depression and healthy control subjects. This finding highlights a pathophysiological mechanism with potential as a therapeutic target and a clinical biomarker for bipolar disorder, exhibiting reasonable sensitivity and specificity.


Assuntos
Transtorno Bipolar/fisiopatologia , Córtex Cerebral/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Função Executiva/fisiologia , Voluntários Saudáveis , Adulto , Transtorno Bipolar/diagnóstico , Mapeamento Encefálico/métodos , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Lobo Parietal/fisiopatologia , Descanso/fisiologia
18.
Psychiatry Res Neuroimaging ; 265: 26-34, 2017 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-28500965

RESUMO

Sleep abnormalities are extremely common in anxiety disorders and may contribute to their development and persistence. Their shared pathophysiological mechanisms could thus serve as biomarkers or targets for novel therapeutics. Individuals with Primary Insomnia were age- and sex-matched to controls and to persons with Generalized Anxiety Disorder. All underwent fMRI resting-state scans at 3-T. In Primary Insomnia and controls, sleep was recorded for 2 weeks using diaries and actigraphy. All participants completed state-anxiety and neuroticism inventories. Whole-brain connectivity of 6 fear- and extinction-related seeds were compared between the 3 groups using ANOVA. The only significant between-group main effect was seen for connectivity between the left amygdala seed and a bilateral cluster in the rostral anterior cingulate cortex. The latter is believed to exert top-down control over amygdala activity and their interaction may thus constitute an emotion regulatory circuit. This connectivity was significantly greatest in controls while Primary Insomnia was intermediate between that of controls and Generalized Anxiety Disorder. Across Primary Insomnia and control subjects, mean connectivity decreased with poorer sleep. Across all 3 groups, connectivity decreased with greater neuroticism and pre-scan anxiety. Decreased top-down control of the amygdala may increase risk of developing an anxiety disorder with preexisting Primary Insomnia.


Assuntos
Transtornos de Ansiedade/fisiopatologia , Vias Neurais/fisiopatologia , Descanso/fisiologia , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Adulto , Tonsila do Cerebelo/fisiopatologia , Transtornos de Ansiedade/psicologia , Mapeamento Encefálico , Medo/fisiologia , Medo/psicologia , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Descanso/psicologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Adulto Jovem
19.
Neuropsychiatr Dis Treat ; 13: 347-355, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28203084

RESUMO

INTRODUCTION: Auditory hallucinations are defined as experiences of auditory perceptions in the absence of a provoking external stimulus. They are the most prevalent symptoms of schizophrenia with high capacity for chronicity and refractoriness during the course of disease. The transcranial direct current stimulation (tDCS) - a safe, portable, and inexpensive neuromodulation technique - has emerged as a promising treatment for the management of auditory hallucinations. OBJECTIVE: The aim of this study is to analyze the level of evidence in the literature available for the use of tDCS as a treatment for auditory hallucinations in schizophrenia. METHODS: A systematic review was performed, searching in the main electronic databases including the Cochrane Library and MEDLINE/PubMed. The searches were performed by combining descriptors, applying terms of the Medical Subject Headings (MeSH) of Descriptors of Health Sciences and descriptors contractions. PRISMA protocol was used as a guide and the terms used were the clinical outcomes ("Schizophrenia" OR "Auditory Hallucinations" OR "Auditory Verbal Hallucinations" OR "Psychosis") searched together ("AND") with interventions ("transcranial Direct Current Stimulation" OR "tDCS" OR "Brain Polarization"). RESULTS: Six randomized controlled trials that evaluated the effects of tDCS on the severity of auditory hallucinations in schizophrenic patients were selected. Analysis of the clinical results of these studies pointed toward incongruence in the information with regard to the therapeutic use of tDCS with a view to reducing the severity of auditory hallucinations in schizophrenia. Only three studies revealed a therapeutic benefit, manifested by reductions in severity and frequency of auditory verbal hallucinations in schizophrenic patients. CONCLUSION: Although tDCS has shown promising results in reducing the severity of auditory hallucinations in schizophrenic patients, this technique cannot yet be used as a therapeutic alternative due to lack of studies with large sample sizes that portray the positive effects that have been described.

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