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1.
Psychol Addict Behav ; 38(1): 153-159, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37326533

RESUMO

OBJECTIVE: The purpose of our study was to provide a more rigorous test of the causal hypothesis that chronic alcohol use impairs working memory performance. METHOD: We measured linear associations between a latent factor representing alcohol consumption and accuracy across four working memory tasks before and after accounting for familial confounding using a cotwin control design. Specifically, this study examined accuracy through a latent working memory score, the National Institutes of Health (NIH) Toolbox List Sorting, NIH Toolbox Picture Sequence, Penn Word Memory, and 2-back tasks. The study included data from 158 dizygotic and 278 monozygotic twins (Mage = 29 ± 3 years). RESULTS: In our initial sample-wide analysis, we did not detect any statistically significant associations between alcohol use and working memory accuracy. However, our cotwin control analyses showed that twins with greater levels of alcohol use exhibited worse scores on the latent working memory composite measure (B = -.25, CI [-.43, -.08], p < .01), Picture Sequence (B = -.31, CI [-.55, -.08], p < .01), and List Sorting (B = -.28, CI [-.51, -.06 ], p = .01) tasks than did their cotwins. CONCLUSIONS: These results are consistent with a potentially causal relationship between alcohol use and working memory performance that can be detected only after accounting for confounding familial factors. This highlights the importance of understanding the mechanisms that may underlie negative associations between alcohol use and cognitive performance, as well as the potential factors that influence both alcohol behaviors and cognition. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Cognição , Memória de Curto Prazo , Adulto , Humanos , Consumo de Bebidas Alcoólicas/efeitos adversos , Etanol , Gêmeos
2.
Schizophr Bull ; 49(3): 669-678, 2023 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-36772948

RESUMO

BACKGROUND AND HYPOTHESIS: We used the uniquely high combined spatial and temporal resolution of magnetoencephalography to characterize working memory (WM)-related modulation of beta band activity in neuroleptic-free patients with schizophrenia in comparison to a large sample of performance-matched healthy controls. We also tested for effects of antipsychotic medication on identified differences in these same patients. STUDY DESIGN: Inpatients with schizophrenia (n = 21) or psychotic disorder not otherwise specified (n = 4) completed N-back and control tasks during magnetoencephalography while on placebo and during antipsychotic medication treatment, in a blinded, randomized, counterbalanced manner. Healthy, performance-matched controls (N = 100) completed the same tasks. WM-related neural activation was estimated as beta band (14-30 Hz) desynchronization throughout the brain in successive 400 ms time windows. Voxel-wise statistical comparisons were performed between controls and patients while off-medication at each time window. Significant clusters resulting from this between-groups analysis were then used as regions-of-interest, the activations of which were compared between on- and off-medication conditions in patients. STUDY RESULTS: Controls showed beta-band desynchronization (activation) of a fronto-parietal network immediately preceding correct button press responses-the time associated with WM updating and task execution. Altered activation in medication-free patients occurred largely during this time, in prefrontal, parietal, and visual cortices. Medication altered patients' neural responses such that the activation time courses in these regions-of-interest more closely resembled those of controls. CONCLUSIONS: These findings demonstrate that WM-related beta band alterations in schizophrenia are time-specific and associated with neural systems targeted by antipsychotic medications. Future studies may investigate this association by examining its potential neurochemical basis.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/complicações , Magnetoencefalografia , Memória de Curto Prazo/fisiologia , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Mapeamento Encefálico
3.
J Affect Disord ; 279: 239-249, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33074143

RESUMO

BACKGROUND: The glutamatergic modulator ketamine rapidly reduces depressive symptoms in individuals with treatment-resistant major depressive disorder (MDD). However, ketamine's effects on emotional processing biases remain largely unknown, and understanding these processes may help elucidate ketamine's mechanism of action. METHODS: Magnetoencephalography (MEG) was used to investigate ketamine's effects on early visual responses to affective stimuli in individuals with MDD (n=31) and healthy volunteers (HVs; n=24). Participants were enrolled in a double-blind, placebo-controlled, crossover clinical trial and were assessed at baseline and after subanesthetic-dose ketamine and placebo-saline infusions. During MEG recording, participants completed an emotional evaluation task in which they indicated the sex or emotional valence (happy-neutral or sad-angry) of facial stimuli. Source-localized event-related field (ERF) M100 and M170 amplitudes and latencies were extracted from regions of interest. Linear fixed effects models examined interactions between diagnosis, stimulus valence, and drug session for behavioral and MEG data. RESULTS: In baseline behavioral analyses, MDD participants exhibited higher accuracy for sad-angry than happy-neutral faces, and HVs responded faster to happy-neutral than sad-angry faces. In the MEG post-infusion analyses, calcarine M100 amplitudes were larger in MDD than HV participants post-placebo but became more similar post-ketamine. Finally, fusiform M170 amplitudes were associated with antidepressant response in MDD participants. LIMITATIONS: The modest sample size and the need to collapse across responses to happy and neutral faces to increase statistical power limit the generalizability of the findings. CONCLUSIONS: Ketamine rapidly altered emotional stimulus processing in MDD, laying the groundwork for future investigations of biomarkers of antidepressant treatment response. CLINICAL TRIAL: Clinicaltrials.gov, NCT#00088699.


Assuntos
Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Ketamina , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Emoções , Expressão Facial , Humanos , Ketamina/farmacologia , Ketamina/uso terapêutico
4.
Hum Brain Mapp ; 40(6): 1774-1785, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30556224

RESUMO

In human electrophysiology research, the high gamma part of the power spectrum (~>60 Hz) is a relatively new area of investigation. Despite a low signal-to-noise ratio, evidence exists that it contains significant information about activity in local cortical networks. Here, using magnetoencephalography (MEG), we found high gamma activity when comparing data from an n-back working memory task to resting data in a large sample of normal volunteers. Initial analysis of power spectra from 0-back, 2-back, and rest trials showed three frequency bands exhibiting task-related differences: alpha, beta, and high gamma. Unlike alpha and beta, the high gamma spectrum was broad, without a peak at a single frequency. In addition, power in high gamma was highest for the 2-back and lowest during rest, while the opposite pattern occurred in the other bands. Beamformer source localization of each of the three frequency bands revealed a distinct set of sources for high gamma. These included several regions of prefrontal cortex that exhibited greater power when both n-back conditions were compared to rest. A subset of these regions had more power when the 2-back was compared to 0-back, which indicates a role in working memory performance. Our results show that high gamma will be important for understanding cortical processing during cognitive and other tasks. Furthermore, data from human intracortical recordings suggest that high gamma is the aggregate of spiking in local cortical networks, which implies that MEG could serve to bridge experimental modalities by noninvasively observing task-related modulation of spiking rates.


Assuntos
Ritmo Gama/fisiologia , Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/fisiologia , Adulto , Feminino , Humanos , Magnetoencefalografia , Masculino , Testes Neuropsicológicos , Adulto Jovem
5.
Elife ; 62017 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-28555565

RESUMO

Anxiety disorders affect approximately 1 in 5 (18%) Americans within a given 1 year period, placing a substantial burden on the national health care system. Therefore, there is a critical need to understand the neural mechanisms mediating anxiety symptoms. We used unbiased, multimodal, data-driven, whole-brain measures of neural activity (magnetoencephalography) and connectivity (fMRI) to identify the regions of the brain that contribute most prominently to sustained anxiety. We report that a single brain region, the intraparietal sulcus (IPS), shows both elevated neural activity and global brain connectivity during threat. The IPS plays a key role in attention orienting and may contribute to the hypervigilance that is a common symptom of pathological anxiety. Hyperactivation of this region during elevated state anxiety may account for the paradoxical facilitation of performance on tasks that require an external focus of attention, and impairment of performance on tasks that require an internal focus of attention.


Assuntos
Transtornos de Ansiedade/fisiopatologia , Excitabilidade Cortical , Lobo Parietal/fisiologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Magnetoencefalografia , Masculino , Adulto Jovem
6.
Hum Brain Mapp ; 38(2): 779-791, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27770478

RESUMO

Recently, independent components analysis (ICA) of resting state magnetoencephalography (MEG) recordings has revealed resting state networks (RSNs) that exhibit fluctuations of band-limited power envelopes. Most of the work in this area has concentrated on networks derived from the power envelope of beta bandpass-filtered data. Although research has demonstrated that most networks show maximal correlation in the beta band, little is known about how spatial patterns of correlations may differ across frequencies. This study analyzed MEG data from 18 healthy subjects to determine if the spatial patterns of RSNs differed between delta, theta, alpha, beta, gamma, and high gamma frequency bands. To validate our method, we focused on the sensorimotor network, which is well-characterized and robust in both MEG and functional magnetic resonance imaging (fMRI) resting state data. Synthetic aperture magnetometry (SAM) was used to project signals into anatomical source space separately in each band before a group temporal ICA was performed over all subjects and bands. This method preserved the inherent correlation structure of the data and reflected connectivity derived from single-band ICA, but also allowed identification of spatial spectral modes that are consistent across subjects. The implications of these results on our understanding of sensorimotor function are discussed, as are the potential applications of this technique. Hum Brain Mapp 38:779-791, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Mapeamento Encefálico , Ondas Encefálicas/fisiologia , Encéfalo/fisiologia , Magnetoencefalografia , Rede Nervosa/fisiologia , Descanso , Adulto , Encéfalo/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Oxigênio/sangue , Análise de Componente Principal
7.
Neurosci Lett ; 610: 86-91, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26536074

RESUMO

This study investigated whether catechol-O-methyltransferase (COMT) Val/Met polymorphism was associated with variation in event-related desynchronization/synchronization (ERD/ERS) of responses during working memory (WM). 11 Val/Val and 11 Met/Met homozygous participants underwent magnetoencephalography (MEG) while performing a WM task. In contrast to small effects behaviourally, during the delay period Val/Val individuals showed lower ERS in the gamma band (Hz 30-50) in frontal regions, increased ERS in the alpha band (Hz 8-12) in the right frontal and parietal regions and increased ERD in the beta band (Hz 14-30) in the left fronto-temporal regions as compared with Met/Met homozygous individuals. During the response period Val/Val participants showed greater beta ERD in the prefrontal and parietotemporal regions. These results demonstrate that COMT genotype has a strong impact on brain responses (oscillatory activity) during WM performance likely a consequence of compensatory activity during the delay and response periods.


Assuntos
Encéfalo/fisiologia , Catecol O-Metiltransferase/genética , Memória de Curto Prazo , Adulto , Encéfalo/enzimologia , Feminino , Humanos , Magnetoencefalografia , Masculino , Lobo Parietal/fisiologia , Polimorfismo Genético , Córtex Pré-Frontal/fisiologia , Lobo Temporal/fisiologia
8.
Brain Connect ; 5(6): 336-48, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25599264

RESUMO

In typical magnetoencephalography and/or electroencephalography functional connectivity analysis, researchers select one of several methods that measure a relationship between regions to determine connectivity, such as coherence, power correlations, and others. However, it is largely unknown if some are more suited than others for various types of investigations. In this study, the authors investigate seven connectivity metrics to evaluate which, if any, are sensitive to audiovisual integration by contrasting connectivity when tracking an audiovisual object versus connectivity when tracking a visual object uncorrelated with the auditory stimulus. The authors are able to assess the metrics' performances at detecting audiovisual integration by investigating connectivity between auditory and visual areas. Critically, the authors perform their investigation on a whole-cortex all-to-all mapping, avoiding confounds introduced in seed selection. The authors find that amplitude-based connectivity measures in the beta band detect strong connections between visual and auditory areas during audiovisual integration, specifically between V4/V5 and auditory cortices in the right hemisphere. Conversely, phase-based connectivity measures in the beta band as well as phase and power measures in alpha, gamma, and theta do not show connectivity between audiovisual areas. The authors postulate that while beta power correlations detect audiovisual integration in the current experimental context, it may not always be the best measure to detect connectivity. Instead, it is likely that the brain utilizes a variety of mechanisms in neuronal communication that may produce differential types of temporal relationships.


Assuntos
Percepção Auditiva/fisiologia , Encéfalo/fisiologia , Percepção Visual/fisiologia , Estimulação Acústica/métodos , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Magnetoencefalografia , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiologia , Estimulação Luminosa/métodos , Adulto Jovem
9.
Cereb Cortex ; 25(7): 1878-88, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24464944

RESUMO

The processing of social information in the human brain is widely distributed neuroanatomically and finely orchestrated over time. However, a detailed account of the spatiotemporal organization of these key neural underpinnings of human social cognition remains to be elucidated. Here, we applied functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in the same participants to investigate spatial and temporal neural patterns evoked by viewing videos of facial muscle configurations. We show that observing the emergence of expressions elicits sustained blood oxygenation level-dependent responses in the superior temporal sulcus (STS), a region implicated in processing meaningful biological motion. We also found corresponding event-related changes in sustained MEG beta-band (14-30 Hz) oscillatory activity in the STS, consistent with the possible role of beta-band activity in visual perception. Dynamically evolving fearful and happy expressions elicited early (0-400 ms) transient beta-band activity in sensorimotor cortex that persisted beyond 400 ms, at which time it became accompanied by a frontolimbic spread (400-1000 ms). In addition, individual differences in sustained STS beta-band activity correlated with speed of emotion recognition, substantiating the behavioral relevance of these signals. This STS beta-band activity showed valence-specific coupling with the time courses of facial movements as they emerged into full-blown fearful and happy expressions (negative and positive coupling, respectively). These data offer new insights into the perceptual relevance and orchestrated function of the STS and interconnected pathways in social-emotion cognition.


Assuntos
Cognição/fisiologia , Emoções/fisiologia , Reconhecimento Facial/fisiologia , Lobo Frontal/fisiologia , Sistema Límbico/fisiologia , Lobo Temporal/fisiologia , Adulto , Ritmo beta/fisiologia , Mapeamento Encefálico , Circulação Cerebrovascular/fisiologia , Potenciais Evocados , Feminino , Humanos , Imageamento por Ressonância Magnética , Magnetoencefalografia , Masculino , Vias Neurais/fisiologia , Testes Neuropsicológicos , Oxigênio/sangue , Estimulação Luminosa , Tempo de Reação/fisiologia
10.
Neurosci Lett ; 558: 73-7, 2014 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-24080375

RESUMO

The prediction of future events is fundamental in a large number of critical neurobehavioral contexts including implicit motor learning. This learning process relies on the probabilities with which events occur, and is a dynamic phenomenon. The aim of present study was to investigate the development of anticipatory processes during implicit learning. A decision making task was employed in which the frequency of trial types was manipulated such that one trial type was disproportionately prevalent as compared to the remaining three trial types. A 275 channel whole-head magnetoencephalography (MEG) system was used to investigate the spatiotemporal distribution of event-related desynchronization (ERD) and synchronization (ERS). The results revealed that oscillations within the alpha (10-12 Hz) and beta (14-30 Hz) frequencies were associated with anticipatory processes in distinct networks in the course of learning. During early phases of learning the contralateral motor cortex, the anterior cingulate, the caudate and the inferior frontal gyrus showed ERDs within beta and alpha frequencies, putatively reflecting preparation of next motor response. As the task progressed, alpha ERSs in occipitotemporal regions and putamen likely reflect perceptual anticipation of the forthcoming stimuli.


Assuntos
Antecipação Psicológica , Córtex Cerebral/fisiologia , Aprendizagem/fisiologia , Adulto , Mapeamento Encefálico , Tomada de Decisões , Feminino , Humanos , Magnetoencefalografia , Masculino , Estimulação Luminosa , Probabilidade
11.
Artigo em Inglês | MEDLINE | ID: mdl-23874288

RESUMO

Complex networks have been observed to comprise small-world properties, believed to represent an optimal organization of local specialization and global integration of information processing at reduced wiring cost. Here, we applied magnitude squared coherence to resting magnetoencephalographic time series in reconstructed source space, acquired from controls and patients with schizophrenia, and generated frequency-dependent adjacency matrices modeling functional connectivity between virtual channels. After configuring undirected binary and weighted graphs, we found that all human networks demonstrated highly localized clustering and short characteristic path lengths. The most conservatively thresholded networks showed efficient wiring, with topographical distance between connected vertices amounting to one-third as observed in surrogate randomized topologies. Nodal degrees of the human networks conformed to a heavy-tailed exponentially truncated power-law, compatible with the existence of hubs, which included theta and alpha bilateral cerebellar tonsil, beta and gamma bilateral posterior cingulate, and bilateral thalamus across all frequencies. We conclude that all networks showed small-worldness, minimal physical connection distance, and skewed degree distributions characteristic of physically-embedded networks, and that these calculations derived from graph theoretical mathematics did not quantifiably distinguish between subject populations, independent of bandwidth. However, post-hoc measurements of edge computations at the scale of the individual vertex revealed trends of reduced gamma connectivity across the posterior medial parietal cortex in patients, an observation consistent with our prior resting activation study that found significant reduction of synthetic aperture magnetometry gamma power across similar regions. The basis of these small differences remains unclear.

12.
J Neurosci ; 33(16): 7079-90, 2013 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-23595765

RESUMO

What constitutes normal cortical dynamics in healthy human subjects is a major question in systems neuroscience. Numerous in vitro and in vivo animal studies have shown that ongoing or resting cortical dynamics are characterized by cascades of activity across many spatial scales, termed neuronal avalanches. In experiment and theory, avalanche dynamics are identified by two measures: (1) a power law in the size distribution of activity cascades with an exponent of -3/2 and (2) a branching parameter of the critical value of 1, reflecting balanced propagation of activity at the border of premature termination and potential blowup. Here we analyzed resting-state brain activity recorded using noninvasive magnetoencephalography (MEG) from 124 healthy human subjects and two different MEG facilities using different sensor technologies. We identified large deflections at single MEG sensors and combined them into spatiotemporal cascades on the sensor array using multiple timescales. Cascade size distributions obeyed power laws. For the timescale at which the branching parameter was close to 1, the power law exponent was -3/2. This relationship was robust to scaling and coarse graining of the sensor array. It was absent in phase-shuffled controls with the same power spectrum or empty scanner data. Our results demonstrate that normal cortical activity in healthy human subjects at rest organizes as neuronal avalanches and is well described by a critical branching process. Theory and experiment have shown that such critical, scale-free dynamics optimize information processing. Therefore, our findings imply that the human brain attains an optimal dynamical regime for information processing.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Magnetoencefalografia , Modelos Neurológicos , Neurônios/fisiologia , Descanso/fisiologia , Adulto , Feminino , Humanos , Masculino , Dinâmica não Linear , Adulto Jovem
13.
Front Hum Neurosci ; 7: 940, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24550804

RESUMO

Neuronal oscillations in the theta and gamma bands have been shown to be important for cognition. Here we examined the temporal and spatial relationship between the two frequency bands in emotional processing using magnetoencephalography and an advanced dynamic beamformer source imaging method called synthetic aperture magnetometry. We found that areas including the amygdala, visual and frontal cortex showed significant event-related synchronization in both bands, suggesting a functional association of neuronal oscillations in the same areas in the two bands. However, while the temporal profile in both bands was similar in the amygdala, the peak in gamma band power was much earlier within both visual and frontal areas. Our results do not support a traditional view that the localizations of lower and higher frequencies are spatially distinct. Instead, they suggest that in emotional processing, neuronal oscillations in the gamma and theta bands may reflect, at least in visual and frontal cortex either different but related functional processes or, perhaps more probably, different computational components of the same functional process.

14.
PLoS One ; 7(8): e42618, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22912714

RESUMO

Examining real-time cortical dynamics is crucial for understanding time perception. Using magnetoencephalography we studied auditory duration discrimination of short (<.5 s) versus long tones (>.5 s) versus a pitch control. Time-frequency analysis of event-related fields showed widespread beta-band (13-30 Hz) desynchronization during all tone presentations. Synthetic aperture magnetometry indicated automatic primarily sensorimotor responses in short and pitch conditions, with activation specific to timing in bilateral inferior frontal gyrus. In the long condition, a right lateralized network was active, including lateral prefrontal cortices, inferior frontal gyrus, supramarginal gyrus and secondary auditory areas. Activation in this network peaked just after attention to tone duration was no longer necessary, suggesting a role in sustaining representation of the interval. These data expand our understanding of time perception by revealing its complex cortical spatiotemporal signature.


Assuntos
Magnetoencefalografia , Percepção do Tempo/fisiologia , Adulto , Comportamento/fisiologia , Encéfalo/fisiologia , Análise por Conglomerados , Discriminação Psicológica/fisiologia , Feminino , Neuroimagem Funcional , Humanos , Masculino , Análise Espaço-Temporal
15.
Hippocampus ; 22(9): 1848-59, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22467298

RESUMO

Current views of the hippocampus assign this structure, and its prominent theta rhythms, a key role in both cognition and affect. We studied this duality of function in humans, where no direct evidence exists. Whole-head magnetoencephalographic (MEG) data were recorded to measure theta activity while healthy participants (N = 25) navigated two virtual Morris water mazes, one in which they risked receiving aversive shocks without warning to induce anxiety and one in which they were safe from shocks. Results showed that threat of shock elevated anxiety level and enhanced navigation performance as compared to the safe condition. MEG source analyses revealed that improved navigation performance during threat was preferentially associated with increased left septal (posterior) hippocampal theta (specifically 4-8 Hz activity), replicating previous research that emphasizes a predominant role of the septal third of the hippocampus in spatial cognition. Moreover, increased self-reported anxiety during threat was preferentially associated with increased left temporal (anterior) hippocampal theta (specifically 2-6 Hz activity), consistent with this region's involvement in mediating conditioned and innate fear. Supporting contemporary theory, these findings highlight simultaneous involvement of the human hippocampus in spatial cognition and anxiety, and clarify their distinct correlates.


Assuntos
Ansiedade/fisiopatologia , Cognição/fisiologia , Hipocampo/fisiologia , Ritmo Teta/fisiologia , Adulto , Afeto/fisiologia , Algoritmos , Feminino , Hipocampo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Magnetoencefalografia , Masculino , Aprendizagem em Labirinto/fisiologia , Modelos Neurológicos , Modelos Psicológicos , Análise de Regressão , Análise e Desempenho de Tarefas , Interface Usuário-Computador , Adulto Jovem
16.
J Child Psychol Psychiatry ; 53(6): 678-86, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22136196

RESUMO

BACKGROUND: Attention biases toward threat are often detected in individuals with anxiety disorders. Threat biases can be measured experimentally through dot-probe paradigms, in which individuals detect a probe following a stimulus pair including a threat. On these tasks, individuals with anxiety tend to detect probes that occur in a location previously occupied by a threat (i.e., congruent) faster than when opposite threats (i.e., incongruent). In pediatric anxiety disorders, dot-probe paradigms detect abnormal attention biases toward threat and abnormal ventrolateral prefrontal cortex (vlPFC) function. However, it remains unclear if this aberrant vlPFC activation occurs while subjects process threats (e.g., angry faces) or, alternatively, while they process and respond to probes. This magnetoencephalography (MEG) study was designed to answer this question. METHODS: Adolescents with either generalized anxiety disorder (GAD, n = 17) or no psychiatric diagnosis (n = 25) performed a dot-probe task involving angry and neutral faces while MEG data were collected. Synthetic Aperture Magnetometry (SAM) beamformer technique was used to determine whether there were group differences in power ratios while subjects processed threats (i.e., angry vs. neutral faces) or when subjects responded to incongruent versus. congruent probes. RESULTS: Group differences in vlPFC activation during the response period emerged with a 1-30 Hz frequency band. No group differences in vlPFC activation were detected in response to angry-face cues. CONCLUSIONS: In the dot-probe task, anxiety-related perturbations in vlPFC activation reflect abnormal attention control when responding to behaviorally relevant probes, but not to angry faces. Given that motor responses to these probes are used to calculate threat bias, this study provides insight into the pathophysiology reflected in this commonly used marker of anxiety. In addition, this finding may inform the development of novel anxiety-disorder treatments targeting the vlPFC to enhance attention control to task-relevant demands.


Assuntos
Ansiedade/patologia , Atenção , Córtex Pré-Frontal/patologia , Adolescente , Ira , Estudos de Casos e Controles , Criança , Reação de Fuga/fisiologia , Expressão Facial , Feminino , Humanos , Magnetoencefalografia , Masculino , Estados Unidos
17.
J Psychiatr Res ; 45(10): 1283-94, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21561628

RESUMO

Questions persist regarding the presentation of bipolar disorder (BD) in youth and the nosological significance of irritability. Of particular interest is whether severe mood dysregulation (SMD), characterized by severe non-episodic irritability, hyper-arousal, and hyper-reactivity to negative emotional stimuli, is a developmental presentation of pediatric BD and, therefore, whether the two conditions are pathophysiologically similar. We administered the affective Posner paradigm, an attentional task with a condition involving blocked goal attainment via rigged feedback. The sample included 60 youth (20 BD, 20 SMD, and 20 controls) ages 8-17. Magnetoencephalography (MEG) examined neuronal activity (4-50 Hz) following negative versus positive feedback. We also examined reaction time (RT), response accuracy, and self-reported affect. Both BD and SMD youth reported being less happy than controls during the rigged condition. Also, SMD youth reported greater arousal following negative feedback than both BD and controls, and they responded to negative feedback with significantly greater activation of the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG) than controls. Compared to SMD and controls, BD youth displayed greater superior frontal gyrus (SFG) activation and decreased insula activation following negative feedback. Data suggest a greater negative affective response to blocked goal attainment in SMD versus BD and control youth. This occurs in tandem with hyperactivation of medial frontal regions in SMD youth, while BD youth show dysfunction in the SFG and insula. Data add to a growing empirical base that differentiates pediatric BD and SMD and begin to elucidate potential neural mechanisms of irritability.


Assuntos
Afeto , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Retroalimentação Psicológica , Magnetoencefalografia , Vias Neurais/fisiopatologia , Adolescente , Mapeamento Encefálico/métodos , Criança , Feminino , Lobo Frontal/fisiopatologia , Giro do Cíngulo/fisiopatologia , Humanos , Masculino , Testes Neuropsicológicos , Tempo de Reação , Índice de Gravidade de Doença
18.
Artigo em Inglês | MEDLINE | ID: mdl-20689717

RESUMO

During the anticipation of task demands frontal control is involved in the assembly of stimulus-response mappings based on current goals. It is not clear whether prefrontal modulations occur in higher-order cortical regions, likely reflecting cognitive anticipation processes. The goal of this paper was to investigate prefrontal modulation during anticipation of upcoming working memory demands as revealed by magnetoencephalography (MEG). Twenty healthy volunteers underwent MEG while they performed a variation of the Sternberg Working Memory (WM) task. Beta band (14-30 Hz) SAM (Synthetic Aperture Magnetometry) analysis was performed. During the preparatory periods there was an increase in beta power (event-related synchronization) in dorsolateral prefrontal cortex (DLPFC) bilaterally, left inferior prefrontal gyrus, left parietal, and temporal areas. Our results provide support for the hypothesis that, during preparatory states, the prefrontal cortex is important for biasing higher order brain regions that are going to be engaged in the upcoming task.

19.
Am J Psychiatry ; 167(7): 836-44, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20439387

RESUMO

OBJECTIVE: Dysfunction of the hippocampus has long been suspected to be a key component of the pathophysiology of major depressive disorder. Despite evidence of hippocampal structural abnormalities in depressed patients, abnormal hippocampal functioning has not been demonstrated. The authors aimed to link spatial navigation deficits previously documented in depressed patients to abnormal hippocampal functioning using a virtual reality navigation task. METHOD: Whole-head magnetoencephalography (MEG) recordings were collected while participants (19 patients diagnosed with major depressive disorder and 19 healthy subjects matched by gender and age) navigated a virtual Morris water maze to find a hidden platform; navigation to a visible platform served as a control condition. Behavioral measures were obtained to assess navigation performance. Theta oscillatory activity (4-8 Hz) was mapped across the brain on a voxel-wise basis using a spatial-filtering MEG source analysis technique. RESULTS: Depressed patients performed worse than healthy subjects in navigating to the hidden platform. Robust group differences in theta activity were observed in right medial temporal cortices during navigation, with patients exhibiting less engagement of the anterior hippocampus and parahippocampal cortices relative to comparison subjects. Left posterior hippocampal theta activity was positively correlated with individual performance within each group. CONCLUSIONS: Consistent with previous findings, depressed patients showed impaired spatial navigation. Dysfunction of right anterior hippocampus and parahippocampal cortices may underlie this deficit and stem from structural abnormalities commonly found in depressed patients.


Assuntos
Transtorno Depressivo Maior/fisiopatologia , Hipocampo/fisiopatologia , Magnetoencefalografia , Comportamento Espacial/fisiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Aprendizagem em Labirinto/fisiologia , Desempenho Psicomotor/fisiologia , Ritmo Teta
20.
Front Hum Neurosci ; 4: 30, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20463867

RESUMO

Experience with visual objects leads to later improvements in identification speed and accuracy ("repetition priming"), but generally leads to reductions in neural activity in single-cell recording studies in animals and fMRI studies in humans. Here we use event-related, source-localized MEG (ER-SAM) to evaluate the possibility that neural activity changes related to priming in occipital, temporal, and prefrontal cortex correspond to more temporally coordinated and synchronized activity, reflected in local increases in the amplitude of low-frequency activity fluctuations (i.e. evoked power) that are time-locked to stimulus onset. Subjects (N = 17) identified pictures of objects that were either novel or repeated during the session. Tests in two separate low-frequency bands (theta/alpha: 5-15 Hz; beta: 15-35 Hz) revealed increases in evoked power (5-15 Hz) for repeated stimuli in the right fusiform gyrus, with the earliest significant increases observed 100-200 ms after stimulus onset. Increases with stimulus repetition were also observed in striate/extrastriate cortex (15-35 Hz) by 200-300 ms post-stimulus, along with a trend for a similar pattern in right lateral prefrontal cortex (5-15 Hz). Our results suggest that experience-dependent reductions in neural activity may affect improved behavioral identification through more coordinated, synchronized activity at low frequencies, constituting a mechanism for more efficient neural processing with experience.

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