Dataset Information

Connectivity of the Frontal Cortical Oscillatory Dynamics Underlying Inhibitory Control During a Go/No-Go Task as a Predictive Biomarker in Major Depression.

ABSTRACT: Background:Major depressive disorder (MDD) is characterized by core functional deficits in cognitive inhibition, which is crucial for emotion regulation. To assess the response to ruminative and negative mood states, it was hypothesized that MDD patients have prolonged disparities in the oscillatory dynamics of the frontal cortical regions across the life course of the disease. Method:A "go/no-go" response inhibition paradigm was tested in 31 MDD patients and 19 age-matched healthy controls after magnetoencephalography (MEG) scanning. The use of minimum norm estimates (MNE) examined the changes of inhibitory control network which included the right inferior frontal gyrus (rIFG), pre-supplementary motor area (preSMA), and left primary motor cortex (lM1). The power spectrum (PS) within each node and the functional connectivity (FC) between nodes were compared between two groups. Furthermore, Pearson correlation was calculated to estimate the relationship between altered FC and clinical features. Result:PS was significantly reduced in left motor and preSMA of MDD patients in both beta (13-30 Hz) and low gamma (30-50 Hz) bands. Compared to the HC group, the MDD group demonstrated higher connectivity between lM1 and preSMA in the beta band (t = 3.214, p = 0.002, FDR corrected) and showed reduced connectivity between preSMA and rIFG in the low gamma band (t = -2.612, p = 0.012, FDR corrected). The FC between lM1 and preSMA in the beta band was positively correlated with illness duration (r = 0.475, p = 0.005, FDR corrected), while the FC between preSMA and rIFG in the low gamma band was negatively correlated with illness duration (r = -0.509, p = 0.002, FDR corrected) and retardation factor scores (r = -0.288, p = 0.022, uncorrected). Conclusion:In this study, a clinical neurophysiological signature of cognitive inhibition leading to sustained negative affect as well as functional non-recovery in MDD patients is highlighted. Duration of illness (DI) plays a key role in negative emotional processing, heighten rumination, impulsivity, and disinhibition.

SUBMITTER: Han YL

PROVIDER: S-EPMC7416643 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Connectivity of the Frontal Cortical Oscillatory Dynamics Underlying Inhibitory Control During a Go/No-Go Task as a Predictive Biomarker in Major Depression.

Han Ying-Lin YL Dai Zhong-Peng ZP Ridwan Mohammad Chattun MC Lin Pin-Hua PH Zhou Hong-Liang HL Wang Hao-Fei HF Yao Zhi-Jian ZJ Lu Qing Q

Frontiers in psychiatry 20200803

<h4>Background</h4>Major depressive disorder (MDD) is characterized by core functional deficits in cognitive inhibition, which is crucial for emotion regulation. To assess the response to ruminative and negative mood states, it was hypothesized that MDD patients have prolonged disparities in the oscillatory dynamics of the frontal cortical regions across the life course of the disease.<h4>Method</h4>A "go/no-go" response inhibition paradigm was tested in 31 MDD patients and 19 age-matched health ...[more]

PMID: 32848905

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Project description:The distribution of pathology in frontotemporal dementia is anatomically selective, to distinct cortical regions and with differential neurodegeneration across the cortical layers. The cytoarchitecture and connectivity of cortical laminae preferentially supports frequency-specific oscillations and hierarchical information transfer between brain regions. We therefore predicted that in frontotemporal dementia, core functional deficits such as disinhibition would be associated with differences in the frequency spectrum and altered cross-frequency coupling between frontal cortical regions. We examined this hypothesis using a 'Go-NoGo' response inhibition paradigm with 18 patients with behavioural variant frontotemporal dementia and 20 healthy aged-matched controls during magnetoencephalography. During Go and NoGo trials, beta desynchronization was severely attenuated in patients. Beta power was associated with increased impulsivity, as measured by the Cambridge Behavioural Inventory, a carer-based questionnaire of changes in everyday behaviour. To quantify the changes in cross-frequency coupling in the frontal lobe, we used dynamic causal modelling to test a family of hierarchical casual models, which included the inferior frontal gyrus, pre-supplementary motor area (preSMA) and primary motor cortex. This analysis revealed evidence for cross-frequency coupling in a fully connected network in both groups. However, in the patient group, we identified a significant loss of reciprocal connectivity of the inferior frontal gyrus, particularly for interactions in the gamma band and for theta to alpha coupling. Importantly, although prefrontal coupling was diminished, gamma connectivity between preSMA and motor cortex was enhanced in patients. We propose that the disruption of behavioural control arises from reduced frequency-specific connectivity of the prefrontal cortex, together with a hyper-synchronous reorganization of connectivity among preSMA and motor regions. These results are supported by preclinical evidence of the selectivity of frontotemporal lobar degeneration on oscillatory dynamics, and provide a clinically relevant yet precise neurophysiological signature of behavioural control as a potential pharmacological target for early phase experimental medicines studies.

Project description:Functional connectivity, both in resting state and task performance, has steadily increased its share of neuroimaging research effort in the last 1.5 decades. In the current study, we investigated the predictive utility regarding behavioral performance and task information for 240 participants, aged 20-77, for both voxel activation and functional connectivity in 12 cognitive tasks, belonging to 4 cognitive reference domains (Episodic Memory, Fluid Reasoning, Perceptual Speed, and Vocabulary). We also added a model only comprising brain-structure information not specifically acquired during performance of a cognitive task. We used a simple brain-behavioral prediction technique based on Principal Component Analysis (PCA) and regression and studied the utility of both modalities in quasi out-of-sample predictions, using split-sample simulations (= 5-fold Monte Carlo cross validation) with 1,000 iterations for which a regression model predicting a cognitive outcome was estimated in a training sample, with a subsequent assessment of prediction success in a non-overlapping test sample. The sample assignments were identical for functional connectivity, voxel activation, and brain structure, enabling apples-to-apples comparisons of predictive utility. All 3 models that were investigated included the demographic covariates age, gender, and years of education. A minimal reference model using simple linear regression with just these 3 covariates was included for comparison as well and was evaluated with the same resampling scheme as described above. Results of the comparison between voxel activation and functional connectivity were mixed and showed some dependency on cognitive outcome; however, mean differences in predictive utility between voxel activation and functional connectivity were rather small in terms of within-modality variability or predictive success. More notably, only in the case of Fluid Reasoning did concurrent functional neuroimaging provided compelling about cognitive performance beyond structural brain imaging or the minimal reference model.

Project description:ObjectiveTrauma, particularly when experienced early in life, can alter neurophysiologic and behavioral development, thereby increasing risk for substance use disorders and related psychopathology. However, few studies have empirically examined trauma using well-characterized developmental samples that are followed longitudinally.MethodThe association of assaultive, non-assaultive, and sexual assaultive experiences before 10 years of age with developmental trajectories of brain function during response inhibition was examined by measuring electrophysiologic theta and delta oscillations during no-go and go conditions in an equal probability go/no-go task. Data were drawn from the Collaborative Study of the Genetics of Alcoholism (COGA) prospective cohort, composed of offspring who were aged 12 through 22 years at enrollment from high-risk and comparison families, with follow-ups at 2-year intervals since 2004. In addition, other important predictors of neurophysiologic functioning (eg, substance use, impulsivity, and parental alcohol use disorders) were investigated. Moreover, associations of neurophysiologic functioning with alcohol and cannabis use disorder symptom counts and externalizing and internalizing psychopathology were examined.ResultsIndividuals exposed to sexual assaultive trauma before 10 years of age had slower rates of change in developmental trajectories of no-go frontal theta during response inhibition. Importantly, effects remained significant after accounting for exposure to other traumatic exposures, such as parental history of alcohol use disorder and participants' substance use, but not measures of impulsivity. Further, slower rates of change in no-go frontal theta adolescent and young adult development were associated with increased risk for alcohol use disorder symptoms and internalizing psychopathology, but not for cannabis use disorder symptoms or externalizing psychopathology.ConclusionChildhood sexual assault is associated with atypical frontal neurophysiologic development during response inhibition. This could reflect alterations in frontal lobe development, synaptic pruning, and/or cortical maturation involving neural circuits for inhibitory control. These same areas could be associated with increased risk for young adult alcohol use disorder symptoms and internalizing psychopathology. These findings support the hypothesis that changes in neurocognitive development related to early sexual trauma exposure could increase the risk for mental health and substance use problems in young adulthood.

Dataset Information

Connectivity of the Frontal Cortical Oscillatory Dynamics Underlying Inhibitory Control During a Go/No-Go Task as a Predictive Biomarker in Major Depression.

Publications

Connectivity of the Frontal Cortical Oscillatory Dynamics Underlying Inhibitory Control During a Go/No-Go Task as a Predictive Biomarker in Major Depression.

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