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Biomedical subjects

Hugh Garavan

Publications and source records attributed to Hugh Garavan.

34 records · Page 2Linked to original sources

Neurocognitive insights into substance abuse.

Cognitive studies are revealing key aspects of how drug abusers monitor and respond to negative feedback differently from non-abusers, and in doing so are adding an important piece to the conceptual puzzle that must be solved to understand, treat, and prevent drug abuse. In this review, we bring together two quite different lines of research, one addressing the selection of gambles in a risky decision task, and the other focused on imaging neural systems related to the detection and processing of errors. We suggest that diminished behavioural control, which is a cardinal feature of drug abuse, may be linked to alterations in the psychological and neural mechanisms that detect error signals and which, in turn, lead to optimization of behavioural responses.

Brain Mapping↗

Working memory and executive function: the influence of content and load on the control of attention.

In a series of three experiments, increasing working memory (WM) load was demonstrated to reduce the executive control of attention, measured via task-switching and inhibitory control paradigms. Uniquely, our paradigms allowed comparison of the ability to exert executive control when the stimulus was either part of the currently rehearsed memory set or an unrelated distractor item. The results demonstrated a content-specific effect-insofar as switching attention away from, or exerting inhibitory control over, items currently held in WM was especially difficult-compounded by increasing WM load. This finding supports the attentional control theory that active maintenance of competing task goals is critical to executive function and WM capacity; however, it also suggests that the increased salience provided to the contents of WM through active rehearsal exerts a content-specific influence on attentional control. These findings are discussed in relation to cue-induced ruminations, where active rehearsal of evocative information (e.g., negative thoughts in depression or drug-related thoughts in addiction) in WM typically results from environmental cuing. The present study has demonstrated that when information currently maintained in WM is reencountered, it is harder to exert executive control over it. The difficulty with suppressing the processing of these stimuli presumably reinforces the maintenance of these items in WM, due to the greater level of attention they are afforded, and may help to explain how the cue-induced craving/rumination cycle is perpetuated.

Attention↗

Human functional neuroimaging of brain changes associated with practice.

The discovery that experience-driven changes in the human brain can occur from a neural to a cortical level throughout the lifespan has stimulated a proliferation of research into how neural function changes in response to experience, enabled by neuroimaging methods such as positron emission tomography and functional magnetic resonance imaging. Studies attempt to characterize these changes by examining how practice on a task affects the functional anatomy underlying performance. Results are incongruous, including patterns of increases, decreases and functional reorganization of regional activations. Following an extensive review of the practice-effects literature, we distinguish a number of factors affecting the pattern of practice effects observed, including the effects of task domain, changes at the level of behavioural and cognitive processes, the time-window of imaging and practice, and of a number of other influences and miscellaneous confounding factors. We make a novel distinction between patterns of reorganization and redistribution as effects of task practice on brain activation, and emphasize the need for careful attention to practice-related changes occurring on the behavioural, cognitive and neural levels of analysis. Finally, we suggest that functional and effective connectivity analyses may make important contributions to our understanding of changes in functional anatomy occurring as a result of practice on tasks.

Animals↗

Executive dysfunction in cocaine addiction: evidence for discordant frontal, cingulate, and cerebellar activity.

Using a GO-NOGO response inhibition task in which working memory (WM) demands can be varied, we demonstrate that the compromised abilities of cocaine users to exert control over strong prepotent urges are associated with reduced activity in anterior cingulate and right prefrontal cortices, two regions thought to be critical for implementing cognitive control. Furthermore, unlike drug-naive controls, and opposite to the anterior cingulate pattern, cocaine users showed an over-reliance on the left cerebellum, a compensatory pattern previously seen in alcohol addiction. The results indicate that cocaine users find it difficult to inhibit their own actions, particularly when WM demands, which have been shown previously to increase during cue-induced craving for the drug, are increased. The results reveal a neuroanatomical basis for this dysexecutive component to addiction, supporting the suggested importance cognitive functions may play in prolonging abuse or predisposing users toward relapse.

Adult↗

EEG alpha power changes reflect response inhibition deficits after traumatic brain injury (TBI) in humans.

Brain damage due to traumatic brain injury (TBI) has been associated with deficits in executive functions and the dynamic control of behaviour. Event-related brain potentials and spectral power data were recorded from eight TBI participants and eight matched controls while they completed a Go/NoGo response inhibition task. The TBI group was found to be significantly impaired at the task compared to controls, and exhibited abnormal N2 and P3 waveform components in response to NoGo stimuli relative to controls. Significant correlations were also found between alpha power, Go-trial RT and errors. We conclude that abnormal activity in the structures damaged in this group may render such patients less capable of maintaining a state of alpha desynchronisation compared to controls, resulting in poorer performance on the task.

Adult↗

Individual differences in error processing: a review and reanalysis of three event-related fMRI studies using the GO/NOGO task.

Three previous studies using the GO/NOGO task were examined to characterize the pattern of functional activation seen during error-related processing. The large sample size (n = 44) also allowed investigation of the influence of individual differences in age, sex, self-reported absentmindedness and reaction speed on the level of activation. Errors were seen to activate a network of regions including the anterior cingulate cortex (ACC), pre-supplementary motor area (pre-SMA), bilateral insula, thalamus and right inferior parietal lobule. Split-half comparisons performed for each of the individual difference variables indicated greater ACC and pre-SMA activation for older subjects while slower responders showed greater activation in the parietal, lateral PFC, insula and ACC regions. Whereas males and females demonstrated equivalent levels of activation in both the ACC and insula, self-reported absentmindedness related to reduced activation in these regions. Our review of the current imaging literature on error-related activation indicates that, despite the use of a variety of other cognitive paradigms, the network of regions identified here is consistent with these previous studies, suggesting that these regions are critical to a 'general' error-related response. Furthermore, this response is, in part, influenced by individual differences in both demographic characteristics and behavioural performance.

Adolescent↗

Comparability of functional MRI response in young and old during inhibition.

When using fMRI to study age-related cognitive changes, it is important to establish the integrity of the hemodynamic response because, potentially, it can be affected by age and disease. However, there have been few attempts to document such integrity and no attempts using higher cognitive rather than perceptual or motor tasks. We used fMRI with 28 healthy young and older adults on an inhibitory control task. Although older and young adults differed in task performance and activation patterns, they had comparable hemodynamic responses. We conclude that activation during cognitive inhibition, which was predominantly increased in elders, was not due to vascular confounds or specific changes in hemodynamic coupling.

Adult↗

A functional MRI study of the influence of practice on component processes of working memory.

Previous neuroimaging studies have shown that neural activity changes with task practice. The types of changes reported have been inconsistent, however, and the neural mechanisms involved remain unclear. In this study, we investigated the influence of practice on different component processes of working memory (WM) using a face WM task. Event-related functional magnetic resonance imaging (fMRI) methodology allowed us to examine signal changes from early to late in the scanning session within different task stages (i.e., encoding, delay, retrieval), as well as to determine the influence of different levels of WM load on neural activity. We found practice-related decreases in fMRI signal and effects of memory load occurring primarily during encoding. This suggests that practice improves encoding efficiency, especially at higher memory loads. The decreases in fMRI signal we observed were not accompanied by improved behavioral performance; in fact, error rate increased for high WM load trials, indicating that practice-related changes in activation may occur during a scanning session without behavioral evidence of learning. Our results suggest that practice influences particular component processes of WM differently, and that the efficiency of these processes may not be captured by performance measures alone.

Adult↗

An empirical investigation into the number of subjects required for an event-related fMRI study.

Optimising the number of subjects required for an event-related functional imaging study is critical for ensuring sufficient statistical power. We report an empirical investigation of this issue by employing a resampling approach to the data of 58 subjects drawn from four previous GO/NOGO studies. Using voxelwise measures and setting the activation map from the complete sample to be a "gold standard", analyses revealed the statistical power to be surprisingly low at typical sample sizes (n = 20). However, voxels that were significantly active from smaller samples tended to be true positives, that is, they were typically active in the gold standard map and correlated well with the gold standard activation measure. The numerous false negatives that resulted from the lower SNR of the smaller samples drove the poor statistical power of those samples. Splitting the sample into two groups provided a test of the reproducibility of activation maps that was assessed using an alternative measure that quantified the distances between centres-of-mass of activated areas. These analyses revealed that although the voxelwise overlap may be poor, the locations of activated areas provide some optimism for studies with typical sample sizes. With n = 20 in each of two groups, it was found that the centres-of-mass for 80% of activated areas fell within 25 mm of each other. The reported analyses, by quantifying the spatial reproducibility for various sample sizes performing a typical event-related cognitive task, thus provide an empirical measure of the disparity to be expected in comparing activation maps.

Adult↗

Beyond common resources: the cortical basis for resolving task interference.

Recent studies have suggested that declining inhibitory control observed during simultaneous increases in working memory (WM) demands may be due to sharing common neural resources, although it is relatively unclear how these processes are successfully combined at a neural level. Event-related functional MRI was used to examine task performance that required inhibition of varying numbers of items held in WM. Common activation regions for WM and inhibition were observed and this functional overlap may constitute the cortical basis for task interference. However, maintaining successful inhibitory control under increasing WM demands tended not to increase activation in these overlapping regions as might be expected if these common areas reflect common resources essential for task performance. Instead, increased activation was observed predominantly in unique, inhibition-specific regions including dorsolateral prefrontal cortex. The finding that successfully maintaining weaker stimulus--response relationships in the face of competition from stronger, prepotent responses requires greater activity in these regions reveals the means by which the brain resolves task interference and supports theories of how top-down attentional control is implemented.

Adult↗

The functional neuroanatomical correlates of response variability: evidence from a response inhibition task.

Intra-individual performance variability may be an important index of the efficiency with which executive control processes are implemented, Lesion studies suggest that damage to the frontal lobes is accompanied by an increase in such variability. Here we sought for the first time to investigate how the functional neuroanatomy of executive control is modulated by performance variability in healthy subjects by using an event-related functional magnetic resonance imaging (ER-fMRI) design and a Go/No-go response inhibition paradigm. Behavioural results revealed that individual differences in Go response time variability were a strong predictor of inhibitory success and that differences in mean Go response time could not account for this effect. Task-related brain activation was positively correlated with intra-individual variability within a distributed inhibitory network consisting of bilateral middle frontal areas and right inferior parietal and thalamic regions. Both the behavioural and fMRI data are consistent with the interpretation that those subjects with relatively higher intra-individual variability activate inhibitory regions to a greater extent, perhaps reflecting a greater requirement for top-down executive control in this group, a finding that may be relevant to disorders of executive/attentional control.

Adolescent↗

Prefrontal-subcortical dissociations underlying inhibitory control revealed by event-related fMRI.

Using event-related fMRI, this study investigated the neural dynamics of response inhibition under fluctuating task demands. Fourteen participants performed a GO/NOGO task requiring inhibition of a prepotent motor response to NOGO events that occurred as part of either a Fast or Slow presentation stream of GO stimuli. We compared functional activations associated with correct withholds (Stops) required during the Fast presentation stream of stimuli to Stops required during the Slow presentation stream. A predominantly right hemispheric network was activated across conditions, consistent with previous studies. Furthermore, a functional dissociation of activations between conditions was observed. Slow Stops elicited additional activation in anterior dorsal and polar prefrontal cortex and left inferior parietal cortex. Fast Stops showed additional activation in a network that included right dorsolateral prefrontal cortex, insula and dorsal striatum. These results are discussed in terms of our understanding of the impact of preparation on the distributed network underlying response inhibition and the contribution of subcortical areas, such as the basal ganglia, to executive control processes.

Adult↗

Predicting success: patterns of cortical activation and deactivation prior to response inhibition.

The present study investigated the relationships between attention and other preparatory processes prior to a response inhibition task and the processes involved in the inhibition itself. To achieve this, a mixed fMRI design was employed to identify the functional areas activated during both inhibition decision events and the block of trials following a visual cue introduced 2 to 7 sec prior (cue period). Preparing for successful performance produced increases in activation for both the cue period and the inhibition itself in the frontoparietal cortical network. Furthermore, preparation produced activation decreases in midline areas (insula and medial prefrontal) argued to be responsible for monitoring internal emotional states, and these cue period deactivations alone predicted subsequent success or failure. The results suggest that when cues are provided to signify the imminent requirement for behavioral control, successful performance results from a coordinated pattern of preparatory activation in task-relevant areas and deactivation of task-irrelevant ones.

Adult↗

Multiple neuronal networks mediate sustained attention.

Sustained attention deficits occur in several neuropsychiatric disorders. However, the underlying neurobiological mechanisms are still incompletely understood. To that end, functional MRI was used to investigate the neural substrates of sustained attention (vigilance) using the rapid visual information processing (RVIP) task in 25 healthy volunteers. In order to better understand the neural networks underlying attentional abilities, brain regions where task-induced activation correlated with task performance were identified. Performance of the RVIP task activated a network of frontal, parietal, occipital, thalamic, and cerebellar regions. Deactivation during task performance was seen in the anterior and posterior cingulate, insula, and the left temporal and parahippocampal gyrus. Good task performance, as defined by better detection of target stimuli, was correlated with enhanced activation in predominantly right fronto-parietal regions and with decreased activation in predominantly left temporo-limbic and cingulate areas. Factor analysis revealed that these performance-correlated regions were grouped into two separate networks comprised of positively activated and negatively activated intercorrelated regions. Poor performers failed to significantly activate or deactivate these networks, whereas good performers either activated the positive or deactivated the negative network, or did both. The fact that both increased activation of task-specific areas and increased deactivation of task-irrelevant areas mediate cognitive functions underlying good RVIP task performance suggests two independent circuits, presumably reflecting different cognitive strategies, can be recruited to perform this vigilance task.

Adolescent↗

Cingulate hypoactivity in cocaine users during a GO-NOGO task as revealed by event-related functional magnetic resonance imaging.

Although extensive evidence exists for the reinforcing properties of drugs of abuse such as cocaine, relatively less research has addressed the functional neuroanatomical correlates of the cognitive sequelae of these drugs. We present a functional magnetic resonance imaging study of a GO-NOGO task in which successful performance required prepotent behaviors to be inhibited. Significant cingulate, pre-supplementary motor and insula hypoactivity was observed for both successful NOGOs and errors of commission in chronic cocaine users relative to cocaine-naive controls. This attenuated response, in the presence of comparable activation levels in other task-related cortical areas, suggests cortical and psychological specificity in the locus of drug abuse-related cognitive dysfunction. The results suggest that addiction may be accompanied by a disruption of brain structures critical for the higher-order, cognitive control of behavior.

Adult↗

Differences in the functional neuroanatomy of inhibitory control across the adult life span.

Inhibitory control, the ability to suppress irrelevant or interfering stimuli, is a fundamental cognitive function that deteriorates during aging, but little is understood about the bases of decline. Thus, we used event-related functional magnetic resonance imaging (fMRI) to study inhibitory control in healthy adults aged 18 to 78. Activation during "successful inhibition" occurred predominantly in right prefrontal and parietal regions and was more extensive, bilaterally and prefrontally, in the older groups. Presupplementary motor area was also more active in poorer inhibitory performers. Therefore, older adults activate areas that are comparable to those activated by young adults during inhibition, as well as additional regions. The results are consistent with a compensatory interpretation and extend the aging neuroimaging literature into the cognitive domain of inhibition.

Adolescent↗