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1.
J Neurophysiol ; 127(1): 279-289, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34936515

RESUMO

Aberrant brain oscillations are a hallmark of Parkinson's disease (PD) pathophysiology and may be related to both motor and nonmotor symptoms. Mild cognitive impairment (MCI) affects many people with PD even at the time of diagnosis and conversion risks to PD dementia (PDD) are very high. Unfortunately, pharmacotherapies are not addressing cognitive symptoms in PD. Profiling PD cognitive phenotypes (e.g., MCI, PDD, etc.) may therefore help inform future treatments. Neurophysiological methods, such as magnetoencephalography (MEG), offer the advantage of observing oscillatory patterns, whose regional and temporal profiles may elucidate how cognitive changes relate to neural mechanisms. We conducted a resting-state MEG cross-sectional study of 89 persons with PD stratified into three phenotypic groups: normal cognition, MCI, and PDD, to identify brain regions and frequencies most associated with each cognitive profile. In addition, a neuropsychological battery was administered to assess each domain of cognition. Our data showed higher power in lower frequency bands (delta and theta) observed along with more severe cognitive impairment and associated with memory, language, attention, and global cognition. Of the total 119 brain parcels assessed during source analysis, widespread group differences were found in the beta band, with significant changes mostly occurring between the normal cognition and MCI groups. Moreover, bilateral frontal and left-hemispheric regions were particularly affected in the other frequencies as cognitive decline becomes more pronounced. Our results suggest that MCI and PDD may be qualitatively distinct cognitive phenotypes, and most dramatic changes seem to have happened when the PD brain shows mild cognitive decline.NEW & NOTEWORTHY Can we better stage cognitive decline in patients with Parkinson's disease (PD)? Here, we provide evidence that mild cognitive impairment, rather than being simply a milder form of dementia, may be a qualitatively distinct phase in its development. We suggest that the most dramatic neurophysiological changes may occur during the time the PD brain transitions from normal cognition to MCI, then compensatory changes further occur as the brain "switches" to a dementia state.


Assuntos
Ondas Encefálicas/fisiologia , Disfunção Cognitiva/fisiopatologia , Conectoma , Progressão da Doença , Magnetoencefalografia , Doença de Parkinson/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/etiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações
2.
Sci Rep ; 11(1): 19704, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611218

RESUMO

Graph theory-based approaches are efficient tools for detecting clustering and group-wise differences in high-dimensional data across a wide range of fields, such as gene expression analysis and neural connectivity. Here, we examine data from a cross-sectional, resting-state magnetoencephalography study of 89 Parkinson's disease patients, and use minimum-spanning tree (MST) methods to relate severity of Parkinsonian cognitive impairment to neural connectivity changes. In particular, we implement the two-sample multivariate-runs test of Friedman and Rafsky (Ann Stat 7(4):697-717, 1979) and find it to be a powerful paradigm for distinguishing highly significant deviations from the null distribution in high-dimensional data. We also generalize this test for use with greater than two classes, and show its ability to localize significance to particular sub-classes. We observe multiple indications of altered connectivity in Parkinsonian dementia that may be of future use in diagnosis and prediction.


Assuntos
Mapeamento Encefálico , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Magnetoencefalografia , Modelos Biológicos , Transtornos Parkinsonianos/complicações , Idoso , Algoritmos , Mapeamento Encefálico/métodos , Biologia Computacional/métodos , Análise de Dados , Feminino , Humanos , Magnetoencefalografia/métodos , Masculino
3.
Int J Psychophysiol ; 165: 84-91, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33892017

RESUMO

Attending toward fearful faces and other threatening stimuli increase the chance of survival. The dot-probe task is a commonly used measure of spatial attention. Event-related potentials (ERPs) have been found to be a reliable measure of attentional bias. The dot-probe literature suggests that posterior contralateral N170 amplitudes are more enhanced by fearful faces compared to ipsilateral amplitudes. However, ERP methods remove non-phase locked frequencies, which provides additional information about neural activity. Specifically, theta oscillations (5-7 Hz) have been linked to attentional processing. The purpose of this study was to examine the relationship between posterior contralateral theta oscillations and N170 amplitudes in the dot-probe task. A modified dot-probe task was used with fear and neutral facial expressions and EEG data was recorded from 33 electrodes. The ERP and time-frequency data were extracted from the P7 and P8 electrodes (left and right occipitotemporal regions). This study found enhanced N170 amplitude and theta oscillations in the electrodes posterior contralateral to the fearful face. Contralateral N170 amplitudes and theta oscillations were related such that greater N170 amplitudes were associated with greater theta oscillations. The results indicated that increased contralateral N170 and theta oscillations are related to each other and underlie attentional bias to fearful faces.


Assuntos
Viés de Atenção , Eletroencefalografia , Potenciais Evocados , Expressão Facial , Medo , Humanos , Couro Cabeludo
4.
Sci Rep ; 10(1): 14345, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873844

RESUMO

Emotion is communicated via the integration of concurrently presented information from multiple information channels, such as voice, face, gesture and touch. This study investigated the neural and perceptual correlates of emotion perception as influenced by facial and vocal information by measuring changes in oxygenated hemoglobin (HbO) using functional near-infrared spectroscopy (fNIRS) and acquiring psychometrics. HbO activity was recorded from 103 channels while participants ([Formula: see text], [Formula: see text]) were presented with vocalizations produced in either a happy, angry or neutral prosody. Voices were presented alone or paired with an emotional face and compared with a face-only condition. Behavioral results indicated that when voices were paired with faces, a bias in the direction of the emotion of the voice was present. Subjects' responses also showed greater variance and longer reaction times when responding to the bimodal conditions when compared to the face-only condition. While both the happy and angry prosody conditions exhibited right lateralized increases in HbO compared to the neutral condition, these activations were segregated into posterior-anterior subdivisions by emotion. Specific emotional prosodies may therefore differentially influence emotion perception, with happy voices exhibiting posterior activity in receptive emotion areas and angry voices displaying activity in anterior expressive emotion areas.


Assuntos
Estimulação Acústica/métodos , Mapeamento Encefálico/métodos , Emoções/fisiologia , Expressão Facial , Reconhecimento Facial/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Percepção da Fala/fisiologia , Adulto , Ira , Feminino , Felicidade , Humanos , Masculino , Oxiemoglobinas/análise , Tempo de Reação , Voz , Adulto Jovem
5.
J Neurophysiol ; 123(6): 2504-2514, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32459551

RESUMO

Auditory gamma-band (>30 Hz) activity is a biomarker of cortical excitation/inhibition (E/I) balance in autism, schizophrenia, and bipolar disorder. We provide a comprehensive account of the effects of transcranial alternating current stimulation (tACS) and transcranial direct current stimulation (tDCS) on gamma responses. Forty-five healthy young adults listened to 40-Hz auditory click trains while electroencephalography (EEG) data were collected to measure stimulus-related gamma activity immediately before and after 10 min of 1 mA tACS (40 Hz), tDCS, or sham stimulation to left auditory cortex. tACS, but not tDCS, increased gamma power and phase locking to the auditory stimulus. However, both tACS and tDCS strengthened the gamma phase connectome, and effects persisted beyond the stimulus. Finally, tDCS strengthened the coupling of gamma activity to alpha oscillations after termination of the stimulus. No effects were observed in prestimulus gamma power, the gamma amplitude connectome, or any band-limited alpha measure. Whereas both stimulation techniques synchronize gamma responses between regions, tACS also tunes the magnitude and timing of gamma responses to the stimulus. Results reveal dissociable neurophysiological changes following tACS and tDCS and demonstrate that clinical biomarkers can be altered with noninvasive neurostimulation, especially frequency-tuned tACS.NEW & NOTEWORTHY Gamma frequency-tuned transcranial alternating current stimulation (tACS) adjusts the magnitude and timing of auditory gamma responses, as compared with both sham stimulation and transcranial direct current stimulation (tDCS). However, both tACS and tDCS strengthen the gamma phase connectome, which is disrupted in numerous neurological and psychiatric disorders. These findings reveal dissociable neurophysiological changes following two noninvasive neurostimulation techniques commonly applied in clinical and research settings.


Assuntos
Percepção Auditiva/fisiologia , Conectoma , Eletroencefalografia , Potenciais Evocados Auditivos/fisiologia , Ritmo Gama/fisiologia , Lobo Temporal/fisiologia , Adulto , Ritmo alfa/fisiologia , Feminino , Humanos , Masculino , Estimulação Transcraniana por Corrente Contínua , Adulto Jovem
6.
Neurosci Lett ; 708: 134331, 2019 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-31226362

RESUMO

Medical therapies applied to Parkinson's disease (PD) have advanced tremendously since the 1960's based on advances in our understanding of the underlying neurophysiology. Behavioral therapies, such as rhythmic auditory stimulation (RAS), have been developed more recently and demonstrated efficacy. However, the neural mechanisms of RAS are only vaguely understood. In this study, we examined the neurophysiology of RAS using magnetoencephalography (MEG) in a sample of older adults with (21 people) and without PD (23 participants). All participants underwent high-density MEG during a beat-based cued tapping task with rhythmic and non-rhythmic patterns, and the resulting data were analyzed using a Bayesian image reconstruction method. Complex wavelet based time-frequency decomposition was used to compute inter-trial phase locking factor (PLF) to auditory stimuli for left and right signal space projection vectors. Tapping with a rhythm compared to a non-rhythmic sequence resulted in differential brain activity in each group: (i) a greater activation of temporal, motor and parietal areas was found in healthy adults; (ii) a greater reliance on parietal and frontal gyri was found in PD participants. During rhythmic tapping, older adults without PD had significantly stronger neural activity in bilateral frontal, supplementary and primary motor areas compared to those with PD. Conversely, older adults with PD exhibited significantly stronger activity in the bilateral parietal regions, as well as the rolandic operculum and bilateral supramarginal gyri, relative to their healthy peers. These data suggest that RAS mobilizes diverse oscillatory networks; Healthy controls may shift to frontal areas mobilization whereas PD patients rely on parietal areas to a greater extent, which may reflect frontal network dysfunction with compensation in PD, and could serve as specific regions of interest for further RAS studies.


Assuntos
Doença de Parkinson/fisiopatologia , Desempenho Psicomotor , Estimulação Acústica , Adulto , Gânglios da Base/fisiopatologia , Mapeamento Encefálico , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Magnetoencefalografia , Masculino , Doença de Parkinson/psicologia , Periodicidade
7.
Front Psychol ; 10: 69, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30774608

RESUMO

Cannabis use has been associated with anxiogenic effects when used in low frequency for a short duration, but cannabis can also have anxiogenic effects when used heavily for a long duration. Animal studies have indicated the neurobiological mechanisms related to cannabis and anxiety; however, research has been limited on the related neurocognitive mechanisms. Previous research has indicated that cannabis use is associated with alterations in event-related potentials (ERPs). The purpose of the current study was to examine anxiety related attentional processing of emotional expressions using ERP methods. We used a backward masking paradigm to restrict awareness of facial expressions (i.e., fearful, happy, and neutral). The results indicated that cannabis use was associated with differences in emotional processing. Specifically, the results suggested cannabis users had increased P1 amplitudes toward happy facial expressions compared to fearful and neutral. Additionally, cannabis users seemed to have reduced N170 hemisphere lateralization.

8.
PeerJ ; 6: e5707, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30310749

RESUMO

BACKGROUND: For students entering a science PhD program, a tenure-track faculty research position is often perceived as the ideal long-term goal. A relatively small percentage of individuals ultimately achieve this goal, however, with the vast majority of PhD recipients ultimately finding employment in industry or government positions. Given the disparity between academic career ambitions and outcomes, it is useful to understand factors that may predict those outcomes. Toward this goal, the current study examined employment status of PhD graduates from biomedical sciences programs at the University of Colorado Anschutz Medical Campus (CU AMC) and related this to metrics of predoctoral publication records, as well as to other potentially important factors, such as sex and time-since-degree, to determine if these measures could predict career outcomes. METHODS: Demographic information (name, PhD program, graduation date, sex) of CU AMC biomedical sciences PhD graduates between 2000 and 2015 was obtained from University records. Career outcomes (academic faculty vs. non-faculty) and predoctoral publication records (number and impact factors of first-author and non-first-author publications) were obtained via publicly available information. Relationships between predoctoral publication record and career outcomes were investigated by (a) comparing faculty vs. non-faculty publication metrics, using t-tests, and (b) investigating the ability of predoctoral publication record, sex, and time-since-degree to predict career outcomes, using logistic regression. RESULTS: Significant faculty vs. non-faculty differences were observed in months since graduation (p < 0.001), first-author publication number (p = 0.001), average first-author impact factor (p = 0.006), and highest first-author impact factor (p = 0.004). With sex and months since graduation as predictors of career outcome, the logistic regression model was significant (p < 0.001), with both being male and having more months since graduation predicting career status. First-author related publication metrics (number of publications, average impact factor, highest impact factor) all significantly improved model fit (χ2 < 0.05 for all) and were all significant predictors of faculty status (p < 0.05 for all). Non-first-author publication metrics did not significantly improve model fit or predict faculty status. DISCUSSION: Results suggest that while sex and months since graduation also predict career outcomes, a strong predoctoral first-author publication record may increase likelihood of obtaining an academic faculty research position. Compared to non-faculty, individuals employed in faculty positions produced more predoctoral first-author publications, with these being in journals with higher impact factors. Furthermore, first-author publication record, sex, and months since graduation were significant predictors of faculty status.

9.
Front Neurol ; 8: 615, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29230189

RESUMO

Sensory dysfunction is a core symptom of autism spectrum disorder (ASD), and abnormalities with sensory responsivity and processing can be extremely debilitating to ASD patients and their families. However, relatively little is known about the underlying neuroanatomical and neurophysiological factors that lead to sensory abnormalities in ASD. Investigation into these aspects of ASD could lead to significant advancements in our general knowledge about ASD, as well as provide targets for treatment and inform diagnostic procedures. Thus, the current study aimed to measure the covariation of volumes of brain structures (i.e., structural magnetic resonance imaging) that may be involved in abnormal sensory processing, in order to infer connectivity of these brain regions. Specifically, we quantified the structural covariation of sensory-related cerebral cortical structures, in addition to the cerebellum and amygdala by computing partial correlations between the structural volumes of these structures. These analyses were performed in participants with ASD (n = 36), as well as typically developing peers (n = 32). Results showed decreased structural covariation between sensory-related cortical structures, especially between the left and right cerebral hemispheres, in participants with ASD. In contrast, these same participants presented with increased structural covariation of structures in the right cerebral hemisphere. Additionally, sensory-related cerebral structures exhibited decreased structural covariation with functionally identified cerebellar networks. Also, the left amygdala showed significantly increased structural covariation with cerebral structures related to visual processing. Taken together, these results may suggest several patterns of altered connectivity both within and between cerebral cortices and other brain structures that may be related to sensory processing.

10.
Int J Psychophysiol ; 114: 16-23, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28161286

RESUMO

The auditory steady-state response (ASSR) is increasingly being used as a biomarker in neuropsychiatric disorders, but research investigating the test-retest reliability of this measure is needed. We previously reported ASSR reliability, measured by electroencephalography (EEG), to 40Hz amplitude-modulated white noise and click train stimuli. The purpose of the current study was to (a) assess the reliability of the MEG-measured ASSR to 40Hz amplitude-modulated white noise and click train stimuli, and (b) compare test-retest reliability between MEG and EEG measures of ASSR, which has not previously been investigated. Additionally, impact of stimulus parameter choice on reliability was assessed, by comparing responses to white noise and click train stimuli. Test-retest reliability, across sessions approximately one week apart, was assessed in 17 healthy adults. On each study day, participants completed two passive listening tasks (white noise and click train stimuli) during separate MEG and EEG recordings. Between-session correlations for evoked power and inter-trial phase coherence (ITPC) were assessed following source-space projection. Overall, the MEG-measured ASSR was significantly correlated between sessions (p<0.05, FDR corrected), suggesting acceptable test-retest reliability. Results suggest greater response reproducibility for ITPC compared to evoked responses and for click train compared to white noise stimuli, although further study is warranted. No significant differences in reliability were observed between MEG and EEG measures, suggesting they are similarly reliable. This work supports use of the ASSR as a biomarker in clinical interventions with repeated measures.


Assuntos
Percepção Auditiva/fisiologia , Eletroencefalografia/normas , Potenciais Evocados Auditivos/fisiologia , Magnetoencefalografia/normas , Adulto , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Adulto Jovem
11.
Hum Brain Mapp ; 37(1): 410-21, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26518728

RESUMO

Although nicotine has been shown to improve attention deficits in schizophrenia, the neurobiological mechanisms underlying this effect are poorly understood. We hypothesized that nicotine would modulate attention-associated neuronal response in schizophrenia patients in the ventral parietal cortex (VPC), hippocampus, and anterior cingulate based on previous findings in control subjects. To test this hypothesis, the present study examined response in these regions in a cohort of nonsmoking patients and healthy control subjects using an auditory selective attention task with environmental noise distractors during placebo and nicotine administration. In agreement with our hypothesis, significant diagnosis (Control vs. Patient) X drug (Placebo vs. Nicotine) interactions were observed in the VPC and hippocampus. The interaction was driven by task-associated hyperactivity in patients (relative to healthy controls) during placebo administration, and decreased hyperactivity in patients after nicotine administration (relative to placebo). No significant interaction was observed in the anterior cingulate. Task-associated hyperactivity of the VPC predicted poor task performance in patients during placebo. Poor task performance also predicted symptoms in patients as measured by the Brief Psychiatric Rating Scale. These results are the first to suggest that nicotine may modulate brain activity in a selective attention-dependent manner in schizophrenia.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Encéfalo , Nicotina/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Esquizofrenia/complicações , Estimulação Acústica , Adulto , Análise de Variância , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Mapeamento Encefálico , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Reação/efeitos dos fármacos , Psicologia do Esquizofrênico , Método Simples-Cego , Resultado do Tratamento
12.
Am J Clin Nutr ; 102(2): 249-55, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26109580

RESUMO

BACKGROUND: In our increasingly obesogenic environment, in which high-calorie convenience foods are readily available, food choices can drastically affect weight and overall health. Learned food preferences, which are developed through repeated pairings with positively and negatively valenced stimuli, can contribute to obesity susceptibility if positive attitudes toward high-calorie foods are developed. Thus, the modification of automatic associations with food may be a viable strategy to promote healthier eating behaviors. OBJECTIVE: In this study, we investigated the ability of an implicit priming (IP) intervention to alter responses to visual food cues by using an evaluative conditioning approach. The main objective was to implicitly (i.e., below conscious perception) associate disgust with high-calorie foods with the aim of reducing liking of these foods. DESIGN: Participants were randomly assigned to active or control IP. In active IP (n = 22), high-calorie food images were implicitly primed with negatively valenced images, and low-calorie food images were implicitly primed with positively valenced images. In control IP (n = 20), all food images were primed with neutral images of fixation crosses. Food images were rated on the desire to eat immediately before and after IP. RESULTS: A significant main effect of calorie (high compared with low; P < 0.001) and a significant calorie-by-group (active compared with control) interaction (P = 0.025) were observed. Post hoc tests identified a significantly greater high-calorie rating decline after active IP than after control IP (P = 0.036). Furthermore, there was significantly greater change in high-calorie ratings than in low-calorie ratings in the active group (P = 0.001). Active IP effects extended to high-calorie foods not specifically included in the intervention, which suggested an effect generalization. Moreover, a greater change in high-calorie ratings than in low-calorie ratings persisted 3-5 d after active IP (P < 0.007), which suggested lasting effects. CONCLUSION: This study provides initial evidence that IP can be used to alter high-calorie food preferences, which could promote healthier eating habits.


Assuntos
Terapia Comportamental , Ingestão de Energia , Preferências Alimentares , Política Nutricional , Sobrepeso/prevenção & controle , Cooperação do Paciente , Priming de Repetição , Adulto , Terapia Aversiva , Colorado , Gráficos por Computador , Condicionamento Psicológico , Sinais (Psicologia) , Feminino , Humanos , Perda de Seguimento , Masculino , Sobrepeso/psicologia , Cooperação do Paciente/psicologia , Método Simples-Cego , Fatores de Tempo
13.
J Autism Dev Disord ; 45(2): 425-43, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23975145

RESUMO

The EEG reflects the activation of large populations of neurons that act in synchrony and propagate to the scalp surface. This activity reflects both the brain's background electrical activity and when the brain is being challenged by a task. Despite strong theoretical and methodological arguments for the use of EEG in understanding the neural correlates of autism, the practice of collecting, processing and evaluating EEG data is complex. Scientists should take into consideration both the nature of development in autism given the life-long, pervasive course of the disorder and the disability of altered or atypical social, communicative, and motor behaviors, all of which require accommodations to traditional EEG environments and paradigms. This paper presents guidelines for the recording, analyzing, and interpreting of EEG data with participants with autism. The goal is to articulate a set of scientific standards as well as methodological considerations that will increase the general field's understanding of EEG methods, provide support for collaborative projects, and contribute to the evaluation of results and conclusions.


Assuntos
Transtorno Autístico/fisiopatologia , Encéfalo/fisiopatologia , Coleta de Dados/normas , Eletroencefalografia , Eletrofisiologia , Humanos
14.
Neuropsychiatr Dis Treat ; 10: 1349-59, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25092980

RESUMO

PURPOSE: Infant resting-state networks do not exhibit the same connectivity patterns as those of young children and adults. Current theories of brain development emphasize developmental progression in regional and network specialization. We compared infant and adult functional connectivity, predicting that infants would exhibit less regional specificity and greater internetwork communication compared with adults. PATIENTS AND METHODS: Functional magnetic resonance imaging at rest was acquired in 12 healthy, term infants and 17 adults. Resting-state networks were extracted, using independent components analysis, and the resulting components were then compared between the adult and infant groups. RESULTS: Adults exhibited stronger connectivity in the posterior cingulate cortex node of the default mode network, but infants had higher connectivity in medial prefrontal cortex/anterior cingulate cortex than adults. Adult connectivity was typically higher than infant connectivity within structures previously associated with the various networks, whereas infant connectivity was frequently higher outside of these structures. Internetwork communication was significantly higher in infants than in adults. CONCLUSION: We interpret these findings as consistent with evidence suggesting that resting-state network development is associated with increasing spatial specificity, possibly reflecting the corresponding functional specialization of regions and their interconnections through experience.

15.
Biomark Med ; 8(3): 353-68, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24712425

RESUMO

Autism is a behaviorally diagnosed neurodevelopmental disorder with no current biomarkers with high specificity and sensitivity. γ-band abnormalities have been reported in many studies of autism spectrum disorders. γ-band activity is associated with perceptual and cognitive functions that are compromised in autism. Some γ-band deficits have also been seen in unaffected first-degree relatives, suggesting heritability of these findings. This review covers the published literature on γ abnormalities in autism, the proposed mechanisms underlying the deficits and the potential for translation into new treatments. Although the utility of γ-band metrics as diagnostic biomarkers is currently limited, such changes in autism are also useful as endophenotypes, for evaluating potential neural mechanisms, and for use as surrogate markers of treatment response to interventions.


Assuntos
Biomarcadores/metabolismo , Transtornos Globais do Desenvolvimento Infantil/metabolismo , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Eletroencefalografia , Humanos , Magnetoencefalografia
16.
J Neural Transm (Vienna) ; 121(8): 891-905, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24752754

RESUMO

Glutamate is the major excitatory neurotransmitter in the brain and may be a key neurotransmitter involved in autism. Literature pertaining to glutamate and autism or related disorders (e.g., Fragile X syndrome) is reviewed in this article. Interest in glutamatergic dysfunction in autism is high due to increasing convergent evidence implicating the system in the disorder from peripheral biomarkers, neuroimaging, protein expression, genetics and animal models. Currently, there are no pharmaceutical interventions approved for autism that address glutamate deficits in the disorder. New treatments related to glutamatergic neurotransmission, however, are emerging. In addition, older glutamate-modulating medications with approved indications for use in other disorders are being investigated for re-tasking as treatments for autism. This review presents evidence in support of glutamate abnormalities in autism and the potential for translation into new treatments for the disorder.


Assuntos
Transtorno Autístico/tratamento farmacológico , Transtorno Autístico/metabolismo , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Ácido Glutâmico/metabolismo , Psicotrópicos/uso terapêutico , Receptores de Glutamato/metabolismo , Animais , Transtorno Autístico/genética , Humanos , Transmissão Sináptica
17.
PLoS One ; 9(1): e85748, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24465679

RESUMO

Auditory evoked steady-state responses are increasingly being used as a marker of brain function and dysfunction in various neuropsychiatric disorders, but research investigating the test-retest reliability of this response is lacking. The purpose of this study was to assess the consistency of the auditory steady-state response (ASSR) across sessions. Furthermore, the current study aimed to investigate how the reliability of the ASSR is impacted by stimulus parameters and analysis method employed. The consistency of this response across two sessions spaced approximately 1 week apart was measured in nineteen healthy adults using electroencephalography (EEG). The ASSR was entrained by both 40 Hz amplitude-modulated white noise and click train stimuli. Correlations between sessions were assessed with two separate analytical techniques: a) channel-level analysis across the whole-head array and b) signal-space projection from auditory dipoles. Overall, the ASSR was significantly correlated between sessions 1 and 2 (p<0.05, multiple comparison corrected), suggesting adequate test-retest reliability of this response. The current study also suggests that measures of inter-trial phase coherence may be more reliable between sessions than measures of evoked power. Results were similar between the two analysis methods, but reliability varied depending on the presented stimulus, with click train stimuli producing more consistent responses than white noise stimuli.


Assuntos
Córtex Auditivo/fisiologia , Percepção Auditiva/fisiologia , Eletroencefalografia/métodos , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Potenciais Evocados Auditivos/fisiologia , Estimulação Acústica/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
18.
Neuroimage ; 86: 28-34, 2014 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23370056

RESUMO

Imbalanced levels of excitation and inhibition (E/I) have been proposed to account for various behavioral and electrophysiological phenotypes in autism. Although proton magnetic resonance spectroscopy ((1)H-MRS) studies have been published on various metabolite levels in autism, including glutamate, the major excitatory neurotransmitter, few (1)H-MRS studies have yet been conducted the major inhibitory neurotransmitter GABA. Seventeen individuals with autism spectrum disorders (ASD) participated in a single-voxel, point resolved spectroscopy (PRESS) study conducted on a 3T magnet. Data were also acquired on 14 unaffected siblings of children with autism, and 17 age- and gender-matched healthy control subjects. GABA concentration was measured along with Creatine (Cr) in a single voxel aligned with the auditory cortex in the perisylvian region of the left hemisphere. The ratio of GABA to Cr was significantly lower in the ASD group than the control subjects. Siblings also exhibited lower GABA/Cr ratios compared to controls. Cr concentration did not differ between groups. The volumes of gray matter, white matter and CSF did not differ between groups in the whole brain or within the spectroscopy voxel. Reduced auditory GABA concentration in ASD is consistent with one previous MRS study of GABA concentration in the frontal lobe in autism, suggesting that multiple neocortical areas may be involved. Lower GABA levels are consistent with theories of ASD as a disorder involving impaired inhibitory neurotransmission and E/I imbalance. The reduction in unaffected siblings suggests that it may be a heritable biomarker, or endophenotype, of autism.


Assuntos
Córtex Auditivo/metabolismo , Transtornos Globais do Desenvolvimento Infantil/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Ácido gama-Aminobutírico/metabolismo , Criança , Feminino , Humanos , Masculino , Irmãos , Distribuição Tecidual
19.
Front Hum Neurosci ; 7: 742, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24265611

RESUMO

Similar behavioral deficits are shared between individuals with autism spectrum disorders (ASD) and their first-degree relatives, such as impaired face memory, object recognition, and some language aspects. Functional neuroimaging studies have reported abnormalities in ASD in at least one brain area implicated in those functions, the fusiform gyrus (FG). High frequency oscillations have also been described as abnormal in ASD in a separate line of research. The present study examined whether low- and high-frequency oscillatory power, localized in part to FG and other language-related regions, differs in ASD subjects and first-degree relatives. Twelve individuals with ASD, 16 parents of children with ASD, and 35 healthy controls participated in a picture-naming task using magnetoencephalography (MEG) to assess oscillatory power and connectivity. Relative to controls, we observed reduced evoked high-gamma activity in the right superior temporal gyrus (STG) and reduced high-beta/low-gamma evoked power in the left inferior frontal gyrus (IFG) in the ASD group. Finally, reductions in phase-locked beta-band were also seen in the ASD group relative to controls, especially in the occipital lobes (OCC). First degree relatives, in contrast, exhibited higher high-gamma band power in the left STG compared with controls, as well as increased high-beta/low-gamma evoked power in the left FG. In the left hemisphere, beta- and gamma-band functional connectivity between the IFG and FG and between STG and OCC were higher in the autism group than in controls. This suggests that, contrary to what has been previously described, reduced connectivity is not observed across all scales of observation in autism. The lack of behavioral correlation for the findings warrants some caution in interpreting the relevance of such changes for language function in ASD. Our findings in parents implicates the gamma- and beta-band ranges as potential compensatory phenomena in autism relatives.

20.
Psychiatry Res ; 213(2): 115-21, 2013 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-23768913

RESUMO

People with autism spectrum disorders (ASD) have atypical visual perception of global and local information. Previous neuroimaging studies have examined the functional anatomy of locally directed attention during visual processing in ASD, but few have examined differences in both globally and locally directed attention. We performed functional magnetic resonance imaging (fMRI) in 17 adults with ASD and 16 typically developing (TD) subjects to examine the neurobiology of both global- and local-level information processing in ASD using an abstract hierarchical design task. TD subjects showed no regions of increased brain activation relative to subjects with ASD as assessed using whole brain analysis. Subjects with ASD exhibited greater activation in right superior frontal gyrus during locally directed attention. During globally directed attention, the ASD group showed greater right lateral occipital activation. Additionally, subjects with ASD showed less deactivation in medial prefrontal cortex (part of the default mode network) in the globally directed attention condition. Our findings help elucidate networks of brain activation related to atyipcal global and local feature processing in ASD.


Assuntos
Atenção/fisiologia , Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Transtornos Globais do Desenvolvimento Infantil/psicologia , Lateralidade Funcional/fisiologia , Adolescente , Adulto , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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