Search

Background: Abnormalities of GABAergic (gamma-aminobutyric acidergic) systems may play a role in schizophrenia and mood disorders. Magnetic resonance spectroscopy allows for noninvasive in vivo quantification of GABA; however, studies of GABA in schizophrenia have yielded inconsistent findings. This may stem from grouping together disparate voxels from functionally heterogeneous regions., Methods: We searched PubMed for magnetic resonance spectroscopy studies of GABA in the medial frontal cortex (MFC) in patients with schizophrenia, bipolar disorder, and depression and in individuals meeting criteria for ultra-high risk for psychosis. Voxel placements were classified as rostral-, rostral-mid-, mid-, or posterior MFC, and meta-analyses were conducted for each group for each subregion., Results: Of 341 screened articles, 23 studies of schizophrenia, 6 studies of bipolar disorder, 20 studies of depression, and 7 studies of ultra-high risk met the inclusion criteria. Meta-analysis revealed lower mid- (standardized mean difference [SMD] = -0.28, 95% CI, -0.48 to -0.07, p < .01) and posterior (SMD = -0.29, 95% CI, -0.49 to -0.09, p < .01) MFC GABA in schizophrenia and increased rostral MFC GABA in bipolar disorder (SMD = 0.76, 95% CI, 0.25 to -1.25, p < .01). In depression, reduced rostral MFC GABA (SMD = -0.36, 95% CI, -0.64 to -0.08, p = .01) did not survive correction for multiple comparisons. We found no evidence for GABA differences in individuals at ultra-high risk for psychosis., Conclusions: While limited by small numbers of published studies, these results substantiate the relevance of GABA in the pathophysiology of psychosis spectrum and mood disorders and underline the importance of voxel placement., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Recent research has demonstrated that psychopathic offenders exhibit dynamic cognitive and behavioral deficits on a variety of lab tasks that differentially activate left hemisphere resources. The Left Hemisphere Activation (LHA) hypothesis is a cognitive perspective that aims to address these deficits by conceptualizing psychopathy as a disorder in which behavior and cognitive processing change dynamically as a function of the differential taxation of left hemisphere resources. This study aimed to investigate whether psychopathic traits are associated with electrophysiological anomalies under conditions that place differential demands on left hemisphere language processing systems. We examined in a sample of 43 incarcerated indivdiuals the evocation of the N320, an event-related potential (ERP) elicited by nontarget stimuli during a phonological/phonetic decision task that has been shown to elicit greater activation and cognitive processing within the left hemisphere than the right hemisphere. Findings for a subsample of 18 offenders low in psychopathic traits were generally consistent with previous findings in healthy individuals, suggesting similar electrophysiological activity during phonological processing. However, psychopathic traits impacted the amplitude of the N320. Higher levels of psychopathic traits were associated with reduced left-lateralization in phonological processing as well as enhanced ERP differentiation between pronounceable and nonpronounceable stimuli. These findings provide physiological evidence of a relationship between psychopathic traits and anomalous language processing at the phonological level of word processing., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Age-related neural dedifferentiation-a decline in the distinctiveness of neural representations in the aging brain-has been associated with age-related declines in cognitive abilities. But why does neural distinctiveness decline with age? Based on prior work in nonhuman primates and more recent work in humans, we hypothesized that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) declines with age and is associated with neural dedifferentiation in older adults. To test this hypothesis, we used magnetic resonance spectroscopy (MRS) to measure GABA and functional MRI (fMRI) to measure neural distinctiveness in the ventral visual cortex in a set of older and younger participants. Relative to younger adults, older adults exhibited lower GABA levels and less distinct activation patterns for faces and houses in the ventral visual cortex. Furthermore, individual differences in GABA within older adults positively predicted individual differences in neural distinctiveness. These results provide novel support for the view that age-related reductions of GABA contribute to age-related reductions in neural distinctiveness (i.e., neural dedifferentiation) in the human ventral visual cortex., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Triple network dysfunction theory of schizophrenia postulates that the interaction between the default-mode and the fronto-parietal executive network is disrupted by aberrant salience signals from the right anterior insula (rAI). To date, it is not clear how the proposed resting-state disruption translates to task-processing inefficiency in subjects with schizophrenia. Using a contiguous resting and 2-back task performance fMRI paradigm, we quantified the change in effective connectivity that accompanies rest-to-task state transition in 29 clinically stable patients with schizophrenia and 31 matched healthy controls. We found an aberrant task-evoked increase in the influence of the rAI to both executive (Cohen's d = 1.35, p = 2.8 × 10 -6 ) and default-mode (Cohen's d = 1.22, p = 1.5 × 10 -5 ) network regions occur in patients when compared to controls. In addition, the effective connectivity from middle occipital gyrus (dorsal visual cortex) to insula is also increased in patients as compared with healthy controls. Aberrant insula to executive network influence is pronounced in patients with more severe negative symptom burden. These findings suggest that control signals from rAI are abnormally elevated and directed towards both task-positive and task-negative brain regions, when task-related demands arise in schizophrenia. This aberrant, undiscriminating surge in salience signalling may disrupt contextually appropriate allocation of resources in the neuronal workspace in patients with schizophrenia., (Copyright © 2020. Published by Elsevier Inc.)

Background: Transcranial magnetic stimulation (TMS) is a non-invasive method to stimulate localized brain regions. Despite widespread use in motor cortex, TMS is seldom performed in sensory areas due to variable, qualitative metrics., Objective: Assess the reliability and validity of tracing phosphenes, and to investigate the stimulation parameters necessary to elicit decreased visual cortex excitability with paired-pulse TMS at short inter-stimulus intervals., Methods: Across two sessions, single and paired-pulse recruitment curves were derived by having participants outline elicited phosphenes and calculating resulting average phosphene sizes., Results: Phosphene size scaled with stimulus intensity, similar to motor cortex. Paired-pulse recruitment curves demonstrated inhibition at lower conditioning stimulus intensities than observed in motor cortex. Reliability was high across sessions., Conclusions: TMS-induced phosphenes are a valid and reliable tool for measuring cortical excitability and inhibition in early visual areas. Our results also provide appropriate stimulation parameters for measuring short-latency intracortical inhibition in visual cortex., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Individuals with depression are excessively sensitive to negative feedback and therefore overly cautious. To explore the neural mechanisms of response monitoring which contributed to their impaired behavioral adjustment, we recruited 22 individuals with depressive disorder and 24 healthy controls. Component analysis of the error-related negativity (ERN) and correct-related negativity (CRN), and sLORETA analysis of the ERN and CRN were combined. The comparable error rate and longer reaction time (RT) in individuals with depression as compared to healthy controls suggested a trade-off between accuracy and speed. The amplitude of the ERN and CRN was significantly enhanced in depression. Further sLORETA localizations of the ERN and CRN showed a significantly stronger current density with an extensive distribution in the anterior cingulate cortex (ACC), medial frontal cortex (MFC), inferior parietal lobule (IPL) and superior temporal gyrus (STG) in individuals with depression than in healthy controls. Increased activities in the ACC and MFC indexed increased response monitoring during automatic error detection, while hyperactivity over IPL and STG might indicate high uncertainness after error responses in depression. The hyperactivity within an extensive cortical distribution might be the neural basis of the excessive sensitivity to errors and the conservative accuracy/speed strategy in depression., (© 2013.)

A reduction in the error-related negativity (ERN), a response-locked event-related potential (ERP) observed when participants commit errors during processing of stimuli, is a well-replicated cerebral abnormality in schizophrenia. However, the extent to which this abnormality reflects susceptibility to schizophrenia rather than overt change in behavioural state is unclear. As the unaffected siblings of individuals with schizophrenia are at an increased genetic risk, this study examines whether they display abnormality of the ERN similar to that observed in individuals with schizophrenia. ERPs were recorded from 29 individuals with schizophrenia, 36 unaffected siblings and 35 healthy control participants while they performed a simple Go/No-Go task. Group differences in the ERN and also in the error positivity (Pe), a response-locked positive component that follows the ERN, were investigated. Reductions of ERN amplitudes were found in both individuals with schizophrenia and siblings. No significant abnormalities were observed in Pe. The finding of reduced ERN amplitudes in siblings without prodromal symptoms supports the hypothesis that the abnormality is not a consequence of behavioural disturbance, and that it is a trait marker for susceptibility to schizophrenia, rather than being a result of illness or medication., (Copyright © 2012 Elsevier B.V. All rights reserved.)