scholarly journals GABA and glutamate deficits from frontotemporal lobar degeneration are associated with disinhibition

Brain ◽  
2020 ◽  
Vol 143 (11) ◽  
pp. 3449-3462
Author(s):  
Alexander G Murley ◽  
Matthew A Rouse ◽  
P Simon Jones ◽  
Rong Ye ◽  
Frank H Hezemans ◽  
...  
Keyword(s):  
Reaction Time ◽  
Progressive Supranuclear Palsy ◽  
Frontotemporal Dementia ◽  
Response Inhibition ◽  
Frontotemporal Lobar Degeneration ◽  
Inferior Frontal Gyrus ◽  
Stop Signal ◽  
Resonance Spectroscopy ◽  
Stop Signal Reaction Time ◽  
The Right

Abstract Behavioural disinhibition is a common feature of the syndromes associated with frontotemporal lobar degeneration (FTLD). It is associated with high morbidity and lacks proven symptomatic treatments. A potential therapeutic strategy is to correct the neurotransmitter deficits associated with FTLD, thereby improving behaviour. Reductions in the neurotransmitters glutamate and GABA correlate with impulsive behaviour in several neuropsychiatric diseases and there is post-mortem evidence of their deficit in FTLD. Here, we tested the hypothesis that prefrontal glutamate and GABA levels are reduced by FTLD in vivo, and that their deficit is associated with impaired response inhibition. Thirty-three participants with a syndrome associated with FTLD (15 patients with behavioural variant frontotemporal dementia and 18 with progressive supranuclear palsy, including both Richardson’s syndrome and progressive supranuclear palsy-frontal subtypes) and 20 healthy control subjects were included. Participants undertook ultra-high field (7 T) magnetic resonance spectroscopy and a stop-signal task of response inhibition. We measured glutamate and GABA levels using semi-LASER magnetic resonance spectroscopy in the right inferior frontal gyrus, because of its strong association with response inhibition, and in the primary visual cortex, as a control region. The stop-signal reaction time was calculated using an ex-Gaussian Bayesian model. Participants with frontotemporal dementia and progressive supranuclear palsy had impaired response inhibition, with longer stop-signal reaction times compared with controls. GABA concentration was reduced in patients versus controls in the right inferior frontal gyrus, but not the occipital lobe. There was no group-wise difference in partial volume corrected glutamate concentration between patients and controls. Both GABA and glutamate concentrations in the inferior frontal gyrus correlated inversely with stop-signal reaction time, indicating greater impulsivity in proportion to the loss of each neurotransmitter. We conclude that the glutamatergic and GABAergic deficits in the frontal lobe are potential targets for symptomatic drug treatment of frontotemporal dementia and progressive supranuclear palsy.

scholarly journals Lateralized deficit of response inhibition in early-onset schizophrenia

2005 ◽  
Vol 36 (4) ◽  
pp. 495-505 ◽  
Author(s):  
MARK A. BELLGROVE ◽  
CHRISTOPHER D. CHAMBERS ◽  
ALASDAIR VANCE ◽  
NICOLE HALL ◽  
MARY KARAMITSIOS ◽  
...  
Keyword(s):  
Reaction Time ◽  
Response Inhibition ◽  
Early Onset ◽  
Poor Response ◽  
Stop Signal ◽  
Stop Signal Task ◽  
Early Onset Schizophrenia ◽  
Left Hand ◽  
Stop Signal Reaction Time ◽  
The Right

Background. The ability to inhibit inappropriate or unwanted actions is a key element of executive control. The existence of executive function deficits in schizophrenia is consistent with frontal lobe theories of the disorder. Relatively few studies have examined response inhibition in schizophrenia, and none in adolescent patients with early-onset schizophrenia (EOS).Methods. Twenty-one adolescents with the onset of clinically impairing psychosis before 19 years of age and 16 matched controls performed a stop-signal task to assess response inhibition. The patients with EOS were categorized as paranoid (n=10) and undifferentiated subtypes (n=11). The undifferentiated group had higher levels of negative symptomatology. Stop-signal reaction time (SSRT) and go-signal reaction time (Go-RT) were analysed with respect to hand of response.Results. The undifferentiated early-onset patients had significantly longer SSRTs, indicative of poor response inhibition, for the left hand compared to the paranoid early-onset patients and control participants. No differences existed for inhibitory control with the right hand. The three groups did not differ in Go-RT.Conclusions. Our results indicate a specific lateralized impairment of response inhibition in patients with undifferentiated, but not paranoid, EOS. These findings are consistent with reports of immature frontostriatal networks in EOS and implicate areas such as the pre-motor cortex and supplementary motor area (SMA) that are thought to play a role in both voluntary initiation and inhibition of movement.

scholarly journals Shifting and stopping: fronto-striatal substrates, neurochemical modulation and clinical implications

2007 ◽  
Vol 362 (1481) ◽  
pp. 917-932 ◽  
Author(s):  
T.W Robbins
Keyword(s):  
Functional Neuroimaging ◽  
Inferior Frontal Gyrus ◽  
Stop Signal ◽  
Task Set ◽  
Prefrontal Cortical ◽  
Set Switching ◽  
State Dependent ◽  
Stop Signal Reaction Time ◽  
Neuropsychological Investigation ◽  
The Right

The neuropsychological basis of attentional set-shifting, task-set switching and stop-signal inhibition is reviewed through comparative studies of humans and experimental animals. Using human functional neuroimaging, plus neuropsychological investigation of patients with frontal damage quantified by structural magnetic resonance imaging, and through parallels with effects of specific lesions of the prefrontal cortex (PFC) and striatum in rats and marmosets, it is possible to define both distinct and overlapping loci for tasks such as extra-dimensional shifting and reversal learning, stop-signal reaction time and task-set switching. Notably, most of the paradigms implicate a locus in the right PFC, specifically the right inferior frontal gyrus, possibly associated with processes of response inhibition. The neurochemical modulation of fronto-striatal circuitry in parallel with effects on task performance has been investigated using specific neuropharmacological agents in animals and by human psychopharmacological investigations, sometimes in conjunction with functional imaging. Evidence is provided for double dissociations of effects of manipulations of prefrontal cortical catecholamine and indoleamine (5-HT) systems that have considerable implications in the treatment of disorders such as Parkinson's disease, attention deficit/hyperactivity disorder and depression, as well as in theoretical notions of how ‘fronto-executive’ functions are subject to state-dependent influences, probably related to stress, arousal and motivation.

Proactive and Reactive Motor Inhibition in Top Athletes Versus Nonathletes

2018 ◽  
Vol 125 (2) ◽  
pp. 289-312 ◽  
Author(s):  
Damien Brevers ◽  
Etienne Dubuisson ◽  
Fabien Dejonghe ◽  
Julien Dutrieux ◽  
Mathieu Petieau ◽  
...  
Keyword(s):  
Reaction Time ◽  
Response Inhibition ◽  
Motor Response ◽  
Proactive Inhibition ◽  
Stop Signal ◽  
Stop Signal Task ◽  
Reactive Inhibition ◽  
Stop Signal Reaction Time ◽  
Motor Response Inhibition ◽  
Inhibition Performance

We examined proactive (early restraint in preparation for stopping) and reactive (late correction to stop ongoing action) motor response inhibition in two groups of participants: professional athletes ( n = 28) and nonathletes ( n = 25). We recruited the elite athletes from Belgian national taekwondo and fencing teams. We estimated proactive and reactive inhibition with a modified version of the stop-signal task (SST) in which participants inhibited categorizing left/right arrows. The probability of the stop signal was manipulated across blocks of trials by providing probability cues from the background computer screen color (green = 0%, yellow =17%, orange = 25%, red = 33%). Participants performed two sessions of the SST, where proactive inhibition was operationalized with increased go-signal reaction time as a function of increased stop-signal probability and reactive inhibition was indicated by stop-signal reaction time latency. Athletes exhibited higher reactive inhibition performance than nonathletes. In addition, athletes exhibited higher proactive inhibition than nonathletes in Session 1 (but not Session 2) of the SST. As top-level athletes exhibited heightened reactive inhibition and were faster to reach and maintain consistent proactive motor response inhibition, these results confirm an evaluative process that can discriminate elite athleticism through a fine-grained analysis of inhibitory control.

Dissociable Mechanisms of Cognitive Control in Prefrontal and Premotor Cortex

2007 ◽  
Vol 98 (6) ◽  
pp. 3638-3647 ◽  
Author(s):  
Christopher D. Chambers ◽  
Mark A. Bellgrove ◽  
Ian C. Gould ◽  
Therese English ◽  
Hugh Garavan ◽  
...  
Keyword(s):  
Response Inhibition ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Flanker Task ◽  
Inferior Frontal Gyrus ◽  
Premotor Cortex ◽  
Response Competition ◽  
Stop Signal ◽  
Stop Signal Task ◽  
The Right ◽  
Stimulation Of

Intelligent behavior depends on the ability to suppress inappropriate actions and resolve interference between competing responses. Recent clinical and neuroimaging evidence has demonstrated the involvement of prefrontal, parietal, and premotor areas during behaviors that emphasize conflict and inhibition. It remains unclear, however, whether discrete subregions within this network are crucial for overseeing more specific inhibitory demands. Here we probed the functional specialization of human prefrontal cortex by combining repetitive transcranial magnetic stimulation (rTMS) with integrated behavioral measures of response inhibition (stop-signal task) and response competition (flanker task). Participants undertook a combined stop-signal/flanker task after rTMS of the inferior frontal gyrus (IFG) or dorsal premotor cortex (dPM) in each hemisphere. Stimulation of the right IFG impaired stop-signal inhibition under conditions of heightened response competition but did not influence the ability to suppress a competing response. In contrast, stimulation of the right dPM facilitated execution but had no effect on inhibition. Neither of these results was observed during rTMS of corresponding left-hemisphere regions. Overall, our findings are consistent with existing evidence that the right IFG is crucial for inhibitory control. The observed double dissociation of neurodisruptive effects between the right IFG and right dPM further implies that response inhibition and execution rely on distinct neural processes despite activating a common cortical network.

scholarly journals Obsessive Compulsive Disorder and Response Inhibition: Meta-analysis of the Stop-Signal Task

2021 ◽  
Author(s):  
Kendall Mar ◽  
Parker Townes ◽  
Petros Pechlivanoglou ◽  
Paul Arnold ◽  
Russell James Schachar
Keyword(s):  
Reaction Time ◽  
Obsessive Compulsive Disorder ◽  
Response Inhibition ◽  
Meta Analysis ◽  
Stop Signal ◽  
Mean Difference ◽  
Stop Signal Task ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Stop Signal Reaction Time

This systematic review and meta-analysis updates evidence pertaining to deficient response inhibition in obsessive-compulsive disorder (OCD) as measured by the stop-signal task (SST). We conducted a meta-analysis of the literature to compare response inhibition in patients with OCD and healthy controls, meta-regressions to determine relative influences of age and sex on response inhibition impairment, and a risk of bias assessment for included studies using the Newcastle-Ottawa Scale (NOS). Stop-signal reaction time (SSRT), which estimates the latency of the stopping process deficit, was significantly longer in OCD samples than in controls, reflecting inferior inhibitory control (Raw mean difference = 23.43ms; p = <0.001; 95% CI = [17.42, 29.45]). We did not observe differences in mean reaction time (MRT) in OCD compared to controls (Raw mean difference = 2.51ms; p = 0.755; 95% CI = [-13.27, 18.30]). Age impacted effect size of SSRT, indicating a greater deficit in older patients than younger ones. We did not observe a significant effect of sex on SSRT or MRT scores.

scholarly journals An ERP study on proactive and reactive response inhibition in individuals with schizotypy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lu-xia Jia ◽  
Xiao-jing Qin ◽  
Ji-fang Cui ◽  
Qi Zheng ◽  
Tian-xiao Yang ◽  
...  
Keyword(s):  
Reaction Time ◽  
Response Inhibition ◽  
Proactive Inhibition ◽  
Stop Signal ◽  
Stop Signal Task ◽  
Signal Probability ◽  
Reactive Inhibition ◽  
Eeg Data ◽  
Stop Signal Reaction Time ◽  
Stop Condition

AbstractSchizotypy, a subclinical group at risk for schizophrenia, has been found to show impairments in response inhibition. However, it remains unclear whether this impairment is accompanied by outright stopping (reactive inhibition) or preparation for stopping (proactive inhibition). We recruited 20 schizotypy and 24 non-schizotypy individuals to perform a modified stop-signal task with electroencephalographic (EEG) data recorded. This task consists of three conditions based on the probability of stop signal: 0% (no stop trials, only go trials), 17% (17% stop trials), and 33% (33% stop trials), the conditions were indicated by the colour of go stimuli. For proactive inhibition (go trials), individuals with schizotypy exhibited significantly lesser increase in go response time (RT) as the stop signal probability increasing compared to non-schizotypy individuals. Individuals with schizotypy also exhibited significantly increased N1 amplitude on all levels of stop signal probability and increased P3 amplitude in the 17% stop condition compared with non-schizotypy individuals. For reactive inhibition (stop trials), individuals with schizotypy exhibited significantly longer stop signal reaction time (SSRT) in both 17% and 33% stop conditions and smaller N2 amplitude on stop trials in the 17% stop condition than non-schizotypy individuals. These findings suggest that individuals with schizotypy were impaired in both proactive and reactive response inhibition at behavioural and neural levels.

scholarly journals Stop Signal Reaction Time Deficits in a Lifetime Obsessive-Compulsive Disorder Sample

2016 ◽  
Vol 22 (7) ◽  
pp. 785-789 ◽  
Author(s):  
Nicole C.R. McLaughlin ◽  
Jason Kirschner ◽  
Hallee Foster ◽  
Chloe O’Connell ◽  
Steven A. Rasmussen ◽  
...  
Keyword(s):  
Reaction Time ◽  
Obsessive Compulsive Disorder ◽  
Response Inhibition ◽  
Stop Signal ◽  
Stop Signal Task ◽  
Control Group ◽  
Healthy Controls ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Stop Signal Reaction Time

AbstractObjectives: Several studies have found impaired response inhibition, measured by a stop-signal task (SST), in individuals who are currently symptomatic for obsessive-compulsive disorder (OCD). The aim of this study was to assess stop-signal reaction time (SSRT) performance in individuals with a lifetime diagnosis of OCD, in comparison to a healthy control group. This is the first study that has examined OCD in participants along a continuum of OCD severity, including approximately half of whom had sub-syndromal symptoms at the time of assessment. Methods: OCD participants were recruited primarily from within the OCD clinic at a psychiatric hospital, as well as from the community. Healthy controls were recruited from the community. We used the stop signal task to examine the difference between 21 OCD participants (mean age, 42.95 years) and 40 healthy controls (mean age, 35.13 years). We also investigated the relationship between SST and measures of OCD, depression, and anxiety severity. Results: OCD participants were significantly slower than healthy controls with regard to mean SSRT. Contrary to our prediction, there was no correlation between SSRT and current levels of OCD, anxiety, and depression severity. Conclusions: Results support prior studies showing impaired response inhibition in OCD, and extend the findings to a sample of patients with lifetime OCD who were not all currently above threshold for diagnosis. These findings indicate that response inhibition deficits may be a biomarker of OCD, regardless of current severity levels. (JINS, 2016, 22, 785–789)

scholarly journals Proton magnetic resonance spectroscopy in frontotemporal lobar degeneration-related syndromes

2021 ◽  
Author(s):  
Alexander G Murley ◽  
Kamen A Tsvetanov ◽  
Matthew A Rouse ◽  
P Simon Jones ◽  
Katrine Sværke ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Correlation Analysis ◽  
Progressive Supranuclear Palsy ◽  
Canonical Correlation Analysis ◽  
Canonical Correlation ◽  
Frontotemporal Lobar Degeneration ◽  
Resonance Spectroscopy ◽  
Metabolite Concentrations ◽  
The Right

AbstractObjectiveTo measure cortical metabolite deficits in vivo in syndromes associated with frontotemporal lobar degeneration, in relation to cognitive and behavioral change.MethodsSixty patients were recruited with a clinical syndrome associated with frontotemporal lobar degeneration (behavioral variant frontotemporal dementia n=11, progressive supranuclear palsy n=26, corticobasal syndrome n=11, primary progressive aphasias n=12), and 38 age- and sex-matched healthy controls. We measured nine metabolites in the right inferior frontal gyrus, superior temporal gyrus and right primary visual cortex using 3T semi-laser magnetic resonance spectroscopy. Metabolite concentrations were corrected for age, sex, and partial volume. We related corrected metabolite concentrations to cognitive and behavioral measures using canonical correlation analysis.ResultsMetabolite concentrations varied significantly by brain region and diagnosis (region x metabolite x diagnosis interaction F(64)=1.73, p<0.001, corrected for age, sex, and atrophy within the voxel). N-acetyl aspartate and glutamate concentrations were reduced in the right prefrontal cortex in behavioral variant frontotemporal dementia and progressive supranuclear palsy, even after partial volume correction. The reduction of these metabolites was associated with executive dysfunction and behavioral impairment (canonical correlation analysis R=0.95, p<0.001).ConclusionMagnetic resonance spectroscopy confirms behaviourally relevant metabolite deficits including glutamate, in syndromes associated with frontotemporal lobar degeneration. Magnetic resonance spectroscopy may be a useful index of neurodegeneration, and highlight candidates for pharmacological treatment.

A Bayesian Parametric Approach for the Estimation of Stop-Signal Reaction Time Distributions

2011 ◽  
Author(s):  
Dora Matzke ◽  
Conor V. Dolan ◽  
Gordon D. Logan ◽  
Scott D. Brown ◽  
Eric-Jan Wagenmakers
Keyword(s):  
Reaction Time ◽  
Stop Signal ◽  
Parametric Approach ◽  
Stop Signal Reaction Time
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