scholarly journals Prefrontal cortical connectivity mediates locus coeruleus noradrenergic regulation of inhibitory control in older adults

2021 ◽  
Author(s):  
Alessandro Tomassini ◽  
Frank Hubert Hezemans ◽  
Rong Ye ◽  
Kamen Tsvetanov ◽  
Noham Wolpe ◽  
...  
Keyword(s):  
Older Adults ◽  
Locus Coeruleus ◽  
Inhibitory Control ◽  
Response Inhibition ◽  
Magnetization Transfer ◽  
Inferior Frontal Gyrus ◽  
Healthy Adults ◽  
Stop Signal Task ◽  
Adaptive Behaviour ◽  
Noradrenergic System

Response inhibition is a core executive function enabling adaptive behaviour in dynamic environments. Human and animal models indicate that inhibitory control and control networks are modulated by noradrenaline, arising from the locus coeruleus. The integrity (i.e., cellular density) of the locus coeruleus noradrenergic system can be estimated from magnetization transfer sensitive magnetic resonance imaging, in view of neuromelanin present in noradrenergic neurons of older adults. Noradrenergic psychopharmacological studies indicate noradrenergic modulation of prefrontal and frontostriatal stopping-circuits in association with behavioural change. Here we test the noradrenergic hypothesis of inhibitory control, in healthy adults. We predicted that locus coeruleus integrity is associated with age-adjusted variance in response inhibition, mediated by changes in connectivity between frontal inhibitory control regions. In a preregistered analysis, we used magnetization transfer MRI images from N=63 healthy adults aged above 50 years who performed a stop-signal task, with atlas-based measurement of locus coeruleus contrast. We confirm that better response inhibition is correlated with locus coeruleus integrity and stronger connectivity between pre-supplementary motor area and right inferior frontal gyrus, but not volumes of the cortical regions. We confirmed a significant role of prefrontal connectivity in mediating the effect of individual differences in the locus coeruleus on behaviour, whereby this effect was moderated by age, over and above adjustment for the mean effects of age. Our results support the hypothesis that in normal populations, as in clinical settings, the locus coeruleus noradrenergic system regulates inhibitory control.

scholarly journals Reduced locus coeruleus integrity linked to response inhibition deficits in parkinsonian disorders

2021 ◽  
Author(s):  
Rong Ye ◽  
Frank Hubert Hezemans ◽  
Claire O'Callaghan ◽  
Kamen A Tsvetanov ◽  
Catarina Rua ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Locus Coeruleus ◽  
Progressive Supranuclear Palsy ◽  
Inhibitory Control ◽  
Response Inhibition ◽  
Stop Signal Task ◽  
Model Parameters ◽  
Noradrenergic System ◽  
Parkinsonian Disorders

Parkinson's disease and progressive supranuclear palsy (PSP) both impair response inhibition, exacerbating impulsivity. Inhibitory control deficits vary across individuals, and have been linked with worse prognosis and lack of improvement on dopaminergic therapy. Motor and cognitive control are associated with noradrenergic innervation of the cortex, arising from the locus coeruleus noradrenergic system. Here we test the hypothesis that loss of structural integrity of the locus coeruleus explains response inhibition deficits in progressive supranuclear palsy and Parkinson's disease. This cross-sectional observational study recruited 24 people with idiopathic Parkinson's disease, 14 with PSP-Richardson's syndrome, and 24 age- and sex-matched controls. All participants undertook a stop-signal task and ultrahigh field 7T-magnetic transfer weighted imaging of the locus coeruleus. Hierarchical Bayesian estimation of the parameters of 'race models' of go- versus stop-decisions was used to quantify the cognitive processes of response inhibition. We tested the multivariate relationship between locus coeruleus integrity and model parameters using partial least squares. Both disorders impaired response inhibition at the group level. Progressive supranuclear palsy caused a distinct pattern of abnormalities in inhibitory control, relative to Parkinson's disease and healthy controls, with a paradoxically reduced threshold for go responses, but longer non-decision times, and more lapses of attention. The variation in response inhibition correlated with variation in the integrity of the locus coeruleus, across participants in both clinical groups. Structural imaging of the locus coeruleus, coupled with behavioural modelling in parkinsonian disorders, confirms that locus coeruleus integrity is associated with response inhibition and its degeneration contributes to neurobehavioural changes. The noradrenergic system is therefore a promising target to treat impulsivity in these conditions. The optimisation of noradrenergic treatment is likely to benefit from stratification according to locus coeruleus integrity.

scholarly journals Response inhibition is driven by top-down network mechanisms and enhanced with focused ultrasound

2019 ◽  
Author(s):  
Justin M. Fine ◽  
Maria E. Fini ◽  
Archana S. Mysore ◽  
William J. Tyler ◽  
Marco Santello
Keyword(s):  
Cognitive Control ◽  
Inhibitory Control ◽  
Response Inhibition ◽  
Focused Ultrasound ◽  
Control Function ◽  
Inferior Frontal Gyrus ◽  
Causal Modeling ◽  
Stop Signal Task ◽  
Top Down ◽  
Inhibitory Mechanisms

AbstractResponse inhibition is necessary for humans to safeguard against undesirable action consequences. Inhibitory control consistently recruits the prefrontal right inferior frontal gyrus (rIFG) and pre-supplementary motor area. Yet, whether inhibitory control is a defining function of rIFG, distinct from attentional orienting, remains widely debated. The issue emerges from previous studies reporting inhibitory and attentional demands both elicit rIFG activation. Here, we address this issue based on the proposition that inhibitory and attentional control are predicated on different network mechanisms. We derived and causally tested network mechanisms using EEG, dynamic causal modeling (DCM) and focused ultrasound stimulation in humans performing a Stop-Signal task. rIFG stimulation increased inhibitory performance and speed. DCM of evoked responses linked behavioral inhibition to rIFG top-down gain modulation of pre-SMA inhibitory populations. These results reconcile competing accounts of prefrontal cognitive control function, by identifying rIFG-based inhibitory mechanisms as distinct from other top-down cognitive control processes.

scholarly journals Inhibitory control and problematic Internet-pornography use – The important balancing role of the insula

2020 ◽  
Vol 9 (1) ◽  
pp. 58-70
Author(s):  
Stephanie Antons ◽  
Brand Matthias
Keyword(s):  
Image Processing ◽  
Inhibitory Control ◽  
Symptom Severity ◽  
Inferior Frontal Gyrus ◽  
Dual Process ◽  
Stop Signal Task ◽  
Addictive Behaviors ◽  
Control Performance ◽  
Internet Pornography

Abstract Background and aims Diminished control over a specific behavior is a core characteristic in addictive behaviors such as problematic Internet-pornography (IP) use. First studies suggest that a hyperactivity of the impulsive system is one reason for impulsive behaviors in the context of problematic IP use. The tripartite-process theory of addiction explains neurocognitive mechanisms beyond common dual-process theories in addictive behaviors. However, the role of the reflective and interoceptive system is still unresolved. Methods The study comprised a stop-signal task (SST) including neutral and pornographic images during fMRI and questionnaires to investigate associations between symptoms of problematic IP use, craving, and neural activity of the impulsive, reflective, and interoceptive system. We examined 28 heterosexual males with varying symptom severity of problematic IP use. Results Data indicates that individuals with more symptoms of problematic IP use showed better performance in the SST which was linked to decreased insula and inferior frontal gyrus activity during pornographic image processing. An increase in craving was associated with lower activity of the ventral striatum during pornographic image processing. The interoceptive system showed varying effects. Increased insula activity during inhibitory control and decreased activity during pornographic image processing were associated with higher inhibitory control performance. Discussion and Conclusion Effects of tolerance and motivational aspects may explain the better inhibitory control performance in individuals with higher symptom severity which was associated with differential activity of the interoceptive and reflective system. Diminished control over IP use presumably results from the interaction between the impulsive, reflective, and interoceptive systems.

scholarly journals Neurometabolic Correlates of Reactive and Proactive Motor Inhibition in Young and Older Adults: Evidence from Multiple Regional 1H-MR Spectroscopy

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Akila Weerasekera ◽  
Oron Levin ◽  
Amanda Clauwaert ◽  
Kirstin-Friederike Heise ◽  
Lize Hermans ◽  
...  
Keyword(s):  
Older Adults ◽  
Inhibitory Control ◽  
Inferior Frontal Gyrus ◽  
Proactive Inhibition ◽  
Older Age ◽  
Resonance Spectroscopy ◽  
Reactive Inhibition ◽  
Age Related ◽  
The Right ◽  
Age Range

Abstract Suboptimal inhibitory control is a major factor contributing to motor/cognitive deficits in older age and pathology. Here, we provide novel insights into the neurochemical biomarkers of inhibitory control in healthy young and older adults and highlight putative neurometabolic correlates of deficient inhibitory functions in normal aging. Age-related alterations in levels of glutamate–glutamine complex (Glx), N-acetylaspartate (NAA), choline (Cho), and myo-inositol (mIns) were assessed in the right inferior frontal gyrus (RIFG), pre-supplementary motor area (preSMA), bilateral sensorimotor cortex (SM1), bilateral striatum (STR), and occipital cortex (OCC) with proton magnetic resonance spectroscopy (1H-MRS). Data were collected from 30 young (age range 18–34 years) and 29 older (age range 60–74 years) adults. Associations between age-related changes in the levels of these metabolites and performance measures or reactive/proactive inhibition were examined for each age group. Glx levels in the right striatum and preSMA were associated with more efficient proactive inhibition in young adults but were not predictive for reactive inhibition performance. Higher NAA/mIns ratios in the preSMA and RIFG and lower mIns levels in the OCC were associated with better deployment of proactive and reactive inhibition in older adults. Overall, these findings suggest that altered regional concentrations of NAA and mIns constitute potential biomarkers of suboptimal inhibitory control in aging.

scholarly journals Locus coeruleus integrity and the effect of atomoxetine on response inhibition in Parkinson's disease

2020 ◽  
Author(s):  
Claire O'Callaghan ◽  
Frank Hubert Hezemans ◽  
Rong Ye ◽  
Catarina Rua ◽  
P Simon Jones ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Locus Coeruleus ◽  
Response Inhibition ◽  
Therapeutic Potential ◽  
Reaction Times ◽  
Stop Signal ◽  
Stop Signal Task ◽  
Double Blind ◽  
Caudal Portion

Cognitive decline is a common feature of Parkinson's disease, and many of these cognitive deficits fail to respond to dopaminergic therapy. Therefore, targeting other neuromodulatory systems represents an important therapeutic strategy. Among these, the locus coeruleus-noradrenaline system has been extensively implicated in response inhibition deficits. Restoring noradrenaline levels using the noradrenergic reuptake inhibitor atomoxetine can improve response inhibition in some patients with Parkinson's disease, but there is considerable heterogeneity in treatment response. Accurately predicting the patients who would benefit from therapies targeting this neurotransmitter system remains a critical goal, in order to design the necessary clinical trials with stratified patient selection to establish the therapeutic potential of atomoxetine. Here, we test the hypothesis that integrity of the noradrenergic locus coeruleus explains the variation in improvement of response inhibition following atomoxetine. In a double-blind placebo-controlled randomised crossover design, 19 people with Parkinson's disease completed an acute psychopharmacological challenge with 40 mg of oral atomoxetine or placebo. A stop-signal task was used to measure response inhibition, with stop-signal reaction times obtained through hierarchical Bayesian estimation of an ex-Gaussian race model. Twenty-six control subjects completed the same task without undergoing the drug manipulation. In a separate session, patients and controls underwent ultra-high field 7T imaging of the locus coeruleus using a neuromelanin-sensitive magnetisation transfer sequence. The principal result was that atomoxetine improved stop-signal reaction times in those patients with lower locus coeruleus integrity. This was in the context of a general impairment in response inhibition, as patients on placebo had longer stop-signal reaction times compared to controls. We also found that the caudal portion of the locus coeruleus showed the largest neuromelanin signal decrease in the patients compared to controls. Our results highlight a link between the integrity of the noradrenergic locus coeruleus and response inhibition in Parkinson's disease patients. Furthermore, they demonstrate the importance of baseline noradrenergic state in determining the response to atomoxetine. We suggest that locus coeruleus neuromelanin imaging offers a marker of noradrenergic capacity that could be used to stratify patients in trials of noradrenergic therapy and to ultimately inform personalised treatment approaches.

scholarly journals Taking control! Structural and behavioural plasticity in response to game-based inhibition training in older adults

2018 ◽  
Author(s):  
Simone Kühn ◽  
Maxi Becker
Keyword(s):  
Older Adults ◽  
Response Inhibition ◽  
Passive Control ◽  
Response Times ◽  
Inferior Frontal Gyrus ◽  
Self Control ◽  
Control Group ◽  
Behavioural Plasticity ◽  
Treatment Research ◽  
Inhibition Training

While previous attempts to train self-control in humans have frequently failed, we set out to train response inhibition using computer-game elements. We trained older adults with newly developed game-based inhibition training on a tablet for two months and compared them to an active and passive control group. Behavioural effects reflected in shorter stop signal response times were observed only in the inhibition-training group. This was accompanied by structural growth in cortical thickness of right inferior frontal gyrus (rIFG) triangularis, a brain region that has been associated with response inhibition. The structural plasticity effect was positively associated with time spent on the training-task and predicted the final percentage of successful inhibition trials in the stop task. The data provide evidence for successful trainability of inhibition when game-based training is employed. The results extend our knowledge on game-based cognitive training effects in older age and may foster treatment research in psychiatric diseases related to impulse control.

scholarly journals Right inferior frontal gyrus implements motor inhibitory control via beta-band oscillations in humans

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Michael Schaum ◽  
Edoardo Pinzuti ◽  
Alexandra Sebastian ◽  
Klaus Lieb ◽  
Pascal Fries ◽  
...  
Keyword(s):  
Inhibitory Control ◽  
Response Inhibition ◽  
Supplementary Motor Area ◽  
Inferior Frontal Gyrus ◽  
Neural Mechanisms ◽  
Beta Band ◽  
Changing Environments ◽  
Band Power ◽  
The Right ◽  
Band Activity

Motor inhibitory control implemented as response inhibition is an essential cognitive function required to dynamically adapt to rapidly changing environments. Despite over a decade of research on the neural mechanisms of response inhibition, it remains unclear, how exactly response inhibition is initiated and implemented. Using a multimodal MEG/fMRI approach in 59 subjects, our results reliably reveal that response inhibition is initiated by the right inferior frontal gyrus (rIFG) as a form of attention-independent top-down control that involves the modulation of beta-band activity. Furthermore, stopping performance was predicted by beta-band power, and beta-band connectivity was directed from rIFG to pre-supplementary motor area (pre-SMA), indicating rIFG’s dominance over pre-SMA. Thus, these results strongly support the hypothesis that rIFG initiates stopping, implemented by beta-band oscillations with potential to open up new ways of spatially localized oscillation-based interventions.

scholarly journals Negative Emotional Response Inhibition: Support for a cognitive mechanism underlying negative urgency in nonsuicidal self-injury

2018 ◽  
Author(s):  
Kenneth Javad Dale Allen ◽  
D.Phil. Jill Miranda Hooley
Keyword(s):  
Inhibitory Control ◽  
Response Inhibition ◽  
Emotional Response ◽  
Stop Signal ◽  
Stop Signal Task ◽  
Control Group ◽  
Late Response ◽  
Negative Urgency ◽  
Self Injury ◽  
Nonsuicidal Self Injury

Negative urgency, the self-reported tendency to act impulsively when distressed, increases risk for nonsuicidal self-injury (NSSI). Prior research also suggests that NSSI is associated with impaired negative emotional response inhibition (NERI), a cognitive process theoretically related to negative urgency. Specifically, individuals with a history of NSSI had difficulty inhibiting behavioral responses to negative affective images in an Emotional Stop-Signal Task, but not to those depicting positive or neutral content. The present study sought to replicate this finding, determine whether this deficit extends to an earlier stage of NERI, and explore whether impairment in these two stages of emotional inhibitory control helps explain the relationship between negative urgency and NSSI. To address these aims, 88 adults with NSSI histories (n = 45) and healthy control participants (n = 43) without NSSI history or psychopathology completed a clinical interview, symptom inventories, an impulsivity questionnaire, and behavioral impulsivity tasks measuring early and late emotional response inhibition. The NSSI group had worse late NERI than the control group on the Emotional Stop-Signal Task, but no group differences were observed in early NERI on an Emotional Go/no-go task. However, both early and late stages of NERI accounted for independent variance in negative urgency. We additionally found that late NERI explained variance in the association between negative urgency and NSSI. These results suggest that impulsive behavior in NSSI may involve specifically impaired inhibitory control over negative emotional impulses during late response inhibition, and that this cognitive deficit might reflect one mechanism or pathway to elevated negative urgency among people who self-injure.

scholarly journals Exploration of Brain Connectivity during Human Inhibitory Control Using Inter-Trial Coherence

Sensors ◽  
2020 ◽  
Vol 20 (6) ◽  
pp. 1722 ◽  
Author(s):  
Rupesh Kumar Chikara ◽  
Wei-Cheng Lo ◽  
Li-Wei Ko
Keyword(s):  
Neural Network ◽  
Frontal Lobe ◽  
Inhibitory Control ◽  
Response Inhibition ◽  
Visual Stimulation ◽  
Brain Connectivity ◽  
Stop Signal Task ◽  
Phase Lag ◽  
Human Response ◽  
Traffic Light

Inhibitory control is a cognitive process that inhibits a response. It is used in everyday activities, such as driving a motorcycle, driving a car and playing a game. The effect of this process can be compared to the red traffic light in the real world. In this study, we investigated brain connectivity under human inhibitory control using the phase lag index and inter-trial coherence (ITC). The human brain connectivity gives a more accurate representation of the functional neural network. Results of electroencephalography (EEG), the data sets were generated from twelve healthy subjects during left and right hand inhibitions using the auditory stop-signal task, showed that the inter-trial coherence in delta (1–4 Hz) and theta (4–7 Hz) band powers increased over the frontal and temporal lobe of the brain. These EEG delta and theta band activities neural markers have been related to human inhibition in the frontal lobe. In addition, inter-trial coherence in the delta-theta and alpha (8–12 Hz) band powers increased at the occipital lobe through visual stimulation. Moreover, the highest brain connectivity was observed under inhibitory control in the frontal lobe between F3-F4 channels compared to temporal and occipital lobes. The greater EEG coherence and phase lag index in the frontal lobe is associated with the human response inhibition. These findings revealed new insights to understand the neural network of brain connectivity and underlying mechanisms during human response inhibition.

Emotional Stop Cues Facilitate Inhibitory Control in Schizophrenia

2019 ◽  
Vol 26 (3) ◽  
pp. 286-293
Author(s):  
Qi Zheng ◽  
Tian-Xiao Yang ◽  
Zheng Ye
Keyword(s):  
Reaction Time ◽  
Inhibitory Control ◽  
Significant Influence ◽  
Response Inhibition ◽  
Stop Signal Task ◽  
Enhancement Effect ◽  
Healthy Controls ◽  
Inhibitory Process ◽  
After Effects ◽  
Effective Interventions

AbstractObjective:Inhibitory control is a key deficit in patients with schizophrenia. This study aims to test whether emotions can facilitate inhibition in patients with schizophrenia when they increase attention to inhibitory process.Method:A total of 36 patients with schizophrenia and 36 healthy controls completed an emotional stop-signal task. The task involved selective responses to “Go” stimuli and stopped response when emotional or neutral stop cues occurred.Results:In all conditions, patients with schizophrenia took longer time to inhibit response compared with healthy controls, indicating an overall impairment in response inhibition. Importantly, patients with schizophrenia and controls acquired similar size of benefit from the negative stop cues, showing as reduced reaction time to negative than neutral stop cues. However, the negative stop cues impaired subsequent Go performance only in patients with schizophrenia, indicating additional cost of the negative stop cues for patients with schizophrenia. In both groups, the positive stop cues did not have any significant influence on response inhibition.Conclusions:These findings provide novel evidence for the benefit of emotional stop cues on inhibitory control in patients with schizophrenia and reveal different after-effects of emotional enhancement effect in patients and healthy populations. The findings may help develop effective interventions for improving inhibitory control in patients with schizophrenia and other clinical populations.

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