Sharna Jamadar

Deficits in behavioural inhibition in substance abuse and addiction: A meta-analysis

AIMS Deficits in behavioural inhibitory control are attracting increasing attention as a factor behind the development and maintenance of substance dependence. However, evidence for such a deficit is varied in the literature. Here, we synthesised published results to determine whether inhibitory ability is reliably impaired in substance users compared to controls. METHODS The meta-analysis used fixed-effects models to integrate results from 97 studies that compared groups with heavy substance use or addiction-like behaviours with healthy control participants on two experimental paradigms commonly used to assess response inhibition: the Go/NoGo task, and the Stop-Signal Task (SST). The primary measures of interest were commission errors to NoGo stimuli and stop-signal reaction time in the SST. Additionally, we examined omission errors to Go stimuli, and reaction time in both tasks. Because inhibition is more difficult when inhibition is required infrequently, we considered papers with rare and equiprobable NoGo stimuli separately. RESULTS Inhibitory deficits were apparent for heavy use/dependence on cocaine, MDMA, methamphetamine, tobacco, and alcohol (and, to a lesser extent, non-dependent heavy drinkers), and in pathological gamblers. On the other hand, no evidence for an inhibitory deficit was observed for opioids or cannabis, and contradictory evidence was observed for internet addiction. CONCLUSIONS The results are generally consistent with the view that substance use disorders and addiction-like behavioural disorders are associated with impairments in inhibitory control. Implications for treatment of substance use are discussed, along with suggestions for future research arising from the limitations of the extant literature.

Advance preparation in task-switching: converging evidence from behavioral, brain activation, and model-based approaches.

Recent research has taken advantage of the temporal and spatial resolution of event-related brain potentials (ERPs) and functional magnetic resonance imaging (fMRI) to identify the time course and neural circuitry of preparatory processes required to switch between different tasks. Here we overview some key findings contributing to understanding strategic processes in advance preparation. Findings from these methodologies are compatible with advance preparation conceptualized as a set of processes activated for both switch and repeat trials, but with substantial variability as a function of individual differences and task requirements. We then highlight new approaches that attempt to capitalize on this variability to link behavior and brain activation patterns. One approach examines correlations among behavioral, ERP and fMRI measures. A second “model-based” approach accounts for differences in preparatory processes by estimating quantitative model parameters that reflect latent psychological processes. We argue that integration of behavioral and neuroscientific methodologies is key to understanding the complex nature of advance preparation in task-switching.

The spatial and temporal dynamics of anticipatory preparation and response inhibition in task-switching

We investigated ERP and fMRI correlates of anticipatory preparation and response inhibition in a cued task-switching paradigm with informatively cued, non-informatively cued and no-go trials. Cue-locked ERPs showed evidence for a multicomponent preparation process. An early cue-locked differential positivity was larger for informative vs. non-informative cues and its amplitude correlated with differential activity for informatively vs. non-informatively cued trials in the dorsolateral prefrontal cortex (DLPFC), consistent with a goal activation process. A later differential positivity was larger for informatively cued switch vs. repeat trials and its amplitude correlated with informatively cued switch vs. repeat activity in the posterior parietal cortex (PPC), compatible with a category-response (C-R) rule activation process. No-go trials elicited a frontal P3, whose amplitude was negatively correlated with activity in the ventrolateral prefrontal cortex (VLPFC) and basal ganglia motor network, suggesting that a network responsible for response execution was inhibited in the course of a no-go trial. These findings indicate that anticipatory preparation in task-switching is comprised of at least two processes: goal activation and C-R rule activation. They also support a functional dissociation between DLPFC and VLPFC, with the former involved in top-down biasing and the latter involved in response inhibition.

The many faces of preparatory control in task switching: reviewing a decade of fMRI research.

A large body of behavioural research has used the cued task‐switching paradigm to characterize the nature of trial‐by‐trial preparatory adjustments that enable fluent task implementation when demands on cognitive flexibility are high. This work reviews the growing number of fMRI studies on the same topic, mostly focusing on the central hypothesis that preparatory adjustments should be indicated by enhanced prefrontal and parietal BOLD activation in task switch when compared with task repeat trials under conditions that enable advance task preparation. The evaluation of this straight‐forward hypothesis reveals surprisingly heterogeneous results regarding both the precise localization and the very existence of switch‐related preparatory activation. Explanations for these inconsistencies are considered on two levels. First, we discuss methodological issues regarding (i) the possible impact of different fMRI‐specific experimental design modifications and (ii) statistical uncertainty in the context of massively multivariate imaging data. Second, we discuss explanations related to the multidimensional nature of task preparation itself. Specifically, the precise localization and the size of switch‐related preparatory activation might depend on the differential interplay of hierarchical control via abstract task goals and attentional versus action‐directed preparatory processes. We argue that different preparatory modes can be adopted relying either on advance goal activation alone or on the advance resolution of competition within action sets or attentional sets. Importantly, while either mode can result in a reduction of behavioral switch cost, only the latter two are supposed to be associated with enhanced switch versus repeat BOLD activation in prepared trial conditions. Hum Brain Mapp, 2013.

Adjustments of response threshold during task switching: a model-based functional magnetic resonance imaging study

Adjustment of response threshold for speed compared with accuracy instructions in two-choice decision-making tasks is associated with activation in the fronto-striatal network, including the pre-supplementary motor area (pre-SMA) and striatum (Forstmann et al., 2008). In contrast, increased response conservativeness is associated with activation of the subthalamic nucleus (STN) (Frank et al., 2007). We investigated the involvement of these regions in trial-by-trial adjustments of response threshold in humans, using a cued-trials task-switching paradigm. Fully and partially informative switch cues produced more conservative thresholds than repeat cues. Repeat cues were associated with higher activation in pre-SMA and striatum than switch cues. For all cue types, individual variability in response threshold was associated with activation level in pre-SMA, with higher activation linked to lower threshold setting. In the striatum, this relationship was found for repeat cues only. These findings support the notion that pre-SMA biases the striatum to lower response threshold under more liberal response regimens. In contrast, a high threshold for switch cues was associated with greater activation in right STN, consistent with increasing response caution under conservative response regimens. We conclude that neural models of response threshold adjustment can help explain executive control processes in task switching.

Quantitative meta-analysis of fMRI and PET studies reveals consistent activation in fronto-striatal-parietal regions and cerebellum during antisaccades and prosaccades.

The antisaccade task is a classic task of oculomotor control that requires participants to inhibit a saccade to a target and instead make a voluntary saccade to the mirror opposite location. By comparison, the prosaccade task requires participants to make a visually-guided saccade to the target. These tasks have been studied extensively using behavioral oculomotor, electrophysiological, and neuroimaging in both non-human primates and humans. In humans, the antisaccade task is under active investigation as a potential endophenotype or biomarker for multiple psychiatric and neurological disorders. A large and growing body of literature has used functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) to study the neural correlates of the antisaccade and prosaccade tasks. We present a quantitative meta-analysis of all published voxel-wise fMRI and PET studies (18) of the antisaccade task and show that consistent activation for antisaccades and prosaccades is obtained in a fronto-subcortical-parietal network encompassing frontal and supplementary eye fields (SEFs), thalamus, striatum, and intraparietal cortex. This network is strongly linked to oculomotor control and was activated to a greater extent for antisaccade than prosaccade trials. Antisaccade but not prosaccade trials additionally activated dorsolateral and ventrolateral prefrontal cortices. We also found that a number of additional regions not classically linked to oculomotor control were activated to a greater extent for antisaccade vs. prosaccade trials; these regions are often reported in antisaccade studies but rarely commented upon. While the number of studies eligible to be included in this meta-analysis was small, the results of this systematic review reveal that antisaccade and prosaccade trials consistently activate a distributed network of regions both within and outside the classic definition of the oculomotor network.

Motor and non-motor inhibition in the Go/NoGo task: an ERP and fMRI study

The contribution of movement-related activity to Go/NoGo ERP differences has been debated for 25 years. In this study, we examined ERP and fMRI measures of activity in twenty adults performing non-motor (count) and motor (right-handed button press) trials of the Go/NoGo task. Task performance was highly accurate and similar in the ERP and fMRI environments. No significant task-related effects were observed for the N2 component; however, we observed a substantial increase in positivity for Press NoGo compared to Count NoGo trials. The fMRI results also revealed significant deactivations for Press NoGo relative to Count NoGo trials in several left-lateralised motor-related areas, including the inferior frontal gyrus, precentral gyrus and supplementary motor area. Together, the results indicate that the P3 NoGo>Go effect in motor tasks is caused not by movement-related negativity on Go trials but by inhibition-related positivity on NoGo trials, and that this is associated with deactivation of motor areas involved in the Go response.

Genetic influences of cortical gray matter in language-related regions in healthy controls and schizophrenia

Individuals with schizophrenia show a broad range of language impairments, including reading difficulties. A recent structural MRI (sMRI) study linked these difficulties to structural abnormalities in language-related regions (Leonard et al., 2008). Similar regions have been implicated in primary reading disability (RD). Major hypotheses of RD implicate abnormal embryonic neuronal migration in the cortex, and genetic linkage and association studies have identified a number of candidate RD genes that are associated with neuronal migration (Paracchini et al., 2007). Interestingly, evidence suggests at least some individuals with schizophrenia also show impaired neuronal migration in the cortex (Akbarian et al., 1996). Thus the aim of this study was to examine the link between RD-related genes and gray matter volumes in healthy controls and schizophrenia. We used parallel independent component analysis (parallel-ICA) to examine the relationship between gray matter volumes extracted using voxel-based morphometry (VBM) and 16 single nucleotide polymorphisms (SNPs) spanning FOXP2 and four RD-related genes, DCDC2, DYX1C1, KIAA0319 and TTRAP. Parallel-ICA identified five sMRI-SNP relationships. Superior and inferior cerebellar networks were related to DYX1C1 and DCDC2/KIAA0319 respectively in both groups. The superior prefrontal, temporal and occipital networks were positively related to DCDC2 in the schizophrenia, but not the control group. The identified networks closely correspond to the known distribution of language processes in the cortex. Thus, reading and language difficulties in schizophrenia may be related to distributed cortical structural abnormalities associated with RD-related genes.

Sequence effects in cued task switching modulate response preparedness and repetition priming processes

In task-switching paradigms, reaction time (RT) switch cost is eliminated on trials after a no-go trial (no-go/go sequence effect). We examined the locus of no-go interference on task-switching performance by comparing the event-related potential (ERP) time course of go/go and no-go/go sequences from cue onset to response execution. We also examined whether noninformative trials (i.e., delayed reconfiguration, no response inhibition) produce similar sequence effects. Participants switched using informative and noninformative cues (Experiment 2) intermixed with no-go trials (Experiment 1). Repeat RT was slower for both no-go/informative (pNG/I) and noninformative/informative (pNI/I) than informative/informative sequences. ERPs linked to anticipatory preparation showed no effect of trial sequence. ERPs indicated that pNG/I sequences reduce response readiness whereas pNI/I sequences reduce repetition benefit for repeat trials. Implications for task-switching models are discussed.

Compensatory mechanisms underlie intact task-switching performance in schizophrenia

Individuals with schizophrenia tend to perform poorly on many measures of cognitive control. However, recent task-switching studies suggest that they show intact task-switching performance, despite the fact that the regions involved in task-switching are known to be structurally and functionally impaired in the disorder. Behavioral, event-related potential (ERP) and functional magnetic resonance imaging (fMRI) measures were used to compare the temporal and spatial dynamics of task-switching performance in individuals with schizophrenia and controls. Consistent with previous studies, reaction time (RT) switch cost and its reduction with anticipatory preparation did not differ between groups. There were also no group differences on cue-locked ERP components associated with anticipatory preparation processes. However, both stimulus- and response-locked ERPs were significantly disrupted in schizophrenia, suggesting difficulty with task-set implementation. fMRI analyses indicated that individuals with schizophrenia showed hyperactivity in the dorsolateral prefrontal cortex and posterior parietal cortex. RT-fMRI and ERP-fMRI associations suggested that individuals with schizophrenia employ compensatory mechanisms to overcome difficulties in task-set implementation and thereby achieve the same behavioral outcomes as controls.