Biomedical subjects

Hugh Garavan

Publications and source records attributed to Hugh Garavan.

At least 19 recordsLinked to original sources

PubMed2026

Big data and psychiatry: advances, constraints and future directions.

Early work in psychiatry research, often involving single sites, small samples, and limited variables, has shifted to contemporary research involving multiple sites, large samples, and many variables. Such research raises important questions, including concerns about data quality and methodological rigor, uncertainty about its key lessons, issues regarding clinical relevance, and questions about how to optimize future advances. Here we consider these questions and concerns against the context of big data work on community and register-based surveys, cohort and biobank studies, electronic health records, digital phenotyping, brain imaging, genomics and other -omics, and randomized controlled trials. The development of large datasets allowing well-powered analyses is a major milestone, but sample size alone does not guarantee more precise estimates, and ongoing attention to the quality and rigor of big data collation and analysis is needed. Big data research has fostered trans-disciplinarity and given insights into mechanisms underlying psychiatric disorders, but also emphasizes the intricacy, heterogeneity and variability of such mechanisms, and the importance of triangulating between large-scale and small-scale research. The complexity of psychiatric phenotypes and psychobiological mechanisms contributes to the difficulty in bridging from big data to clinical application; big data research reinforces the importance of holding our diagnoses of psychiatric disorders lightly and providing explanations of these conditions humbly; and future work needs to be more attentive to clinical issues. There is enormous scope for further building databases relevant to psychiatry, but advances in conceptual models and asking the right questions are equally valuable. The full impact of big data, including artificial intelligence analyses, remains to be seen, but overenthusiastic support should be tempered by a better understanding of its strengths and limitations. At its best, such work will contribute in an iterative and integrative way to advancing our knowledge of psychiatric disorders and mental health.

Big data↗

PubMed2006

Variance in neurocognitive performance is associated with dysbindin-1 in schizophrenia: a preliminary study.

Susceptibility genes for schizophrenia have been hypothesised to mediate liability for the disorder at least partly by influencing cognitive performance. We investigated the association between genotype and cognitive performance for a Dysbindin risk haplotype which is associated with schizophrenia in our sample. Fifty-two patients with schizophrenia or schizoaffective disorder (24 risk haplotypes carriers versus 28 non-risk haplotype carriers) were assessed in areas of cognition showing evidence of familial deficits in schizophrenia. Verbal and spatial memory, working memory, and attentional control was assessed using selected measures from the Weschler memory scale (WMS), Cambridge automated test battery (CANTAB), continuous performance test (CPT), and a simple go/no-go task. Pre-morbid IQ was also assessed using the Weschler Test of Adult Reading (WTAR). Patients carrying the Dysbindin risk haplotype showed significantly lower spatial working memory performance than patients who were non-risk carriers, with genotype explaining 12% of variance in performance. Our study suggests that the increased risk for schizophrenia associated with dysbindin may be partly mediated by its influence on pre-frontal function.

Adolescent↗

PubMed2006

The anterior cingulate and error avoidance.

The precise role of the anterior cingulate cortex in monitoring, evaluating, and correcting behavior remains unclear despite numerous theories and much empirical data implicating it in cognitive control. The present event-related functional magnetic resonance imaging study was able to separate monitoring from error-specific functions by allowing subjects to reject a trial so as to avoid errors. Cingulate and left dorsolateral prefrontal activity was greatest on rejection trials but comparable for correct and error trials, whereas an error-specific response was observed in bilateral insula. A dissociation was also observed between the cingulate and the nucleus accumbens with the latter more active for error than reject trials. These results reveal that the functional role of the cingulate is not particular to errors but instead is related to an evaluative function concerned with on-line behavioral adjustment in the service of avoiding losses.

Adult↗

PubMed2006

Individual differences in the functional neuroanatomy of inhibitory control.

We combined the data of five event-related fMRI studies of response inhibition. The re-analysis (n = 71) revealed response inhibition to be accomplished by a largely right hemisphere network of prefrontal, parietal, subcortical and midline regions, with converging evidence pointing to the particular importance of the right frontal operculum. Functional differences were observed between the sexes with greater activity in females in many of these cortical regions. Despite the relatively narrow age range (18-46), cortical activity, on the whole, tended to increase with age, echoing a pattern of functional recruitment often observed in the elderly. More absent minded subjects showed greater activity in fronto-parietal areas, while speed of Go trial responses produced a varied pattern of activation differences in more posterior and subcortical areas. Although response inhibition produces robust activation in a discrete network of brain regions, these results reveal that individual differences impact on the relative contribution made by the nodes of this network.

Adolescent↗

PubMed2006

Flexible cognitive control: effects of individual differences and brief practice on a complex cognitive task.

Brain activations underlying cognitive processes are subject to modulation as a result of increasing cognitive demands, individual differences, and practice. The present study investigated these modulatory effects in a cognitive control task which required inhibition of prepotent responses based on the contents of working memory (WM) and which enabled a novel dissociation of item-specific and task-skill effects resulting from brief practice. Distinct responses in areas underlying WM and inhibitory control in the absence of behavioral changes reflected different effects of item repetition and general task practice on tonic working memory and phasic inhibitory processes. Item repetition was associated with decreases in both unique and common areas subserving WM and inhibitory control. In contrast, general task practice was reflected in decreases in the level of tonic WM activity required to maintain a consistently high level of task performance but increased activity in a number of core inhibitory regions including dorsolateral and inferior PFC and inferior parietal cortex. Furthermore, both practice and individual differences in task performance were associated with the ability to modulate and maintain activity in frontostriatal areas mediating attentional control, suggesting that the areas that differ between individuals can be modulated by practice within an individual. These results raise the possibility that a fundamental human ability, reflexive cognitive control, is amenable to practice.

Adolescent↗

PubMed2006

Mapping the functional anatomy of task preparation: priming task-appropriate brain networks.

The present study used functional magnetic resonance imaging (fMRI) and a cued version of a flanker paradigm to elucidate the effects of task preparation on subsequent brain activation patterns. A mixed block and event-related design was employed to examine activations associated with the cue periods themselves and the cued and un-cued correct responses to incongruent flankers. A number of areas were active during the cues, most notably left dorsolateral prefrontal cortex (DLPFC), which was interpreted as subserving a role in task-set maintenance. Widespread activity was noted for correct responses to incongruent flankers, including bilateral parietal and frontal regions, consistent with previous studies. Activation was increased in these regions for correct responses after cue periods. An overlapping network of regions was also noted for cues and correct responses, suggesting preparation of task-appropriate anatomical regions during the cue period. These results suggest that cue periods allow participants to prime task-relevant areas within the brain and highlight the importance of left DLPFC in top-down control.

Adolescent↗

PubMed2006

Executive "brake failure" following deactivation of human frontal lobe.

In the course of daily living, humans frequently encounter situations in which a motor activity, once initiated, becomes unnecessary or inappropriate. Under such circumstances, the ability to inhibit motor responses can be of vital importance. Although the nature of response inhibition has been studied in psychology for several decades, its neural basis remains unclear. Using transcranial magnetic stimulation, we found that temporary deactivation of the pars opercularis in the right inferior frontal gyrus selectively impairs the ability to stop an initiated action. Critically, deactivation of the same region did not affect the ability to execute responses, nor did it influence physiological arousal. These findings confirm and extend recent reports that the inferior frontal gyrus is vital for mediating response inhibition.

Adolescent↗

PubMed2006

Automaticity and reestablishment of executive control-an fMRI study.

The ability to exert control over automatic behavior is of particular importance as it allows us to interrupt our behavior when the automatic response is no longer adequate or even dangerous. However, despite the literature that exists on the effects of practice on brain activation, little is known about the neuroanatomy involved in reestablishing executive control over previously automatized behavior. We present a visual search task that enabled participants to automatize according to defined criteria within about 3 hr of practice and then required them to reassert control without changing the stimulus set. We found widespread cortical activation early in practice. Activation in all frontal areas and in the inferior parietal lobule decreased significantly with practice. Only selected prefrontal (Brodmann's areas [BAs] 9/46/8) and parietal areas (BAs 39/40) were specifically reactivated when executive control was required, underlining the crucial role of the dorsolateral prefrontal cortex in executive control to guide our behavior.

Adolescent↗

PubMed2006

A validation of event-related FMRI comparisons between users of cocaine, nicotine, or cannabis and control subjects.

OBJECTIVE: Noninvasive brain imaging techniques are a powerful tool for researching the effects of drug abuse on brain activation measures. However, because many drugs have direct vascular effects, the validity of techniques that depend on blood flow measures as a reflection of neuronal activity may be called into question. This may be of particular concern in event-related functional magnetic resonance imaging (fMRI), where current analytic techniques search for a specific shape in the hemodynamic response to neuronal activity. METHOD: To investigate possible alterations in task-related activation as a result of drug abuse, fMRI scans were conducted on subjects in four groups as they performed a simple event-related finger-tapping task: users of cocaine, nicotine, or cannabis and control subjects. RESULTS: Activation measures, as determined by two different analytic methods, did not differ between the groups. A comparison between an intravenous saline and an intravenous cocaine condition in cocaine users found a similar null result. Further in-depth analyses of the shape of the hemodynamic responses in each group also showed no differences. CONCLUSIONS: This study demonstrates that drug groups may be compared with control subjects using event-related fMRI without the need for any post hoc procedures to correct for possible drug-induced cardiovascular alterations. Thus, fMRI activation differences reported between these drug groups can be more confidently interpreted as reflecting neuronal differences.

Adult↗

PubMed2005

Deriving the optimal number of events for an event-related fMRI study based on the spatial extent of activation.

Event-related fMRI is a powerful tool for localising psychological functions to specific brain areas. However, the number of events required to produce stable activation maps is a poorly investigated and understood problem. Huettel and McCarthy [Huettel, S.A., McCarthy, G., 2001. The effects of single-trial averaging upon the spatial extent of fMRI activation. NeuroReport 12, 2411-2416] have shown that the spatial extent of activation increases monotonically with the number of events in an analysis. In the present paper, this result is replicated and shown to be a consequence of the cross-correlation technique used to determine active voxels and does not hold, for example, for a GLM analysis. Another analysis technique, that does not depend on goodness-of-fit to the data, is also proposed. This technique calculates an impulse response function (IRF) for each voxel, finds the best fitting haemodynamic shape to the IRF and returns an area-under-the-curve (%AUC) activation measure. Using spatial extent as a measure, asymptotic behaviour is evident after as few as 25 events for the %AUC analysis technique in a finger-tapping task with non-overlapping haemodynamic responses and for both the GLM and %AUC techniques in a similar task that allows responses to overlap. The experimental validity of the %AUC technique to identify active brain regions while minimising false positive levels is demonstrated in a group study with 25 participants.

Adult↗

PubMed2005

A consistent attentional bias for drug-related material in active cocaine users across word and picture versions of the emotional Stroop task.

Evidence from a number of drug-abuse populations suggests that an attentional bias for drug-related stimuli can be identified in chronic users. Such an effect has yet to be reliably demonstrated in cocaine users, despite mounting evidence of the salience and reinforcing properties of cocaine-related cues. The aim of the current study was to administer word (modeled on the versions shown to successfully identify attentional biases in alcohol abusers) and picture versions of the emotional Stroop tasks to gauge the reliability of cocaine-specific attentional biases across stimuli domains. A comparison of active cocaine users (n = 23), and their age and education matched controls revealed a significant bias for cocaine-related pictures and words in users. This attentional bias could not be attributed to confounding factors such as slowed response speed of cocaine users, cocaine-related material sharing category ownership, or that the cocaine-related material used in the current study was generally arousing for all participants. A comparison of the different classes of stimuli indicated that cocaine users had a very similar level of difficulty controlling their attention towards both cocaine-related material and incongruent-colour word stimuli, the latter being the traditional measure of attentional control from the Stroop task. These results provide corroborating evidence for cognitive biases being a hallmark of substance dependence.

Adult↗

PubMed2005

Neural correlates of high and craving during cocaine self-administration using BOLD fMRI.

Modern theories of drug dependence hold the hedonic effects of drug-taking central to understanding the motivation for compulsive drug use. Previous neuroimaging studies have begun to identify brain regions associated with acute drug effects after passive delivery. In this study, a more naturalistic model of cocaine self-administration (SA) was employed in order to identify those sites associated with drug-induced high and craving as measures of reward and motivation. Non-treatment seeking cocaine-dependent subjects chose both when and how often i.v. cocaine administration occurred within a medically supervised SA procedure. Both functional magnetic resonance imaging (fMRI) data and real-time behavioral ratings were acquired during the 1-h SA period. Drug-induced HIGH was found to correlate negatively with activity in limbic, paralimbic, and mesocortical regions including the nucleus accumbens (NAc), inferior frontal/orbitofrontal gyrus (OFC), and anterior cingulate (AC), while CRAVING correlated positively with activity in these regions. This study provides the first evidence in humans that changes in subjective state surrounding cocaine self-administration reflect neural activity of the endogenous reward system.

Adult↗

PubMed2005

Individual differences discriminate event-related potentials but not performance during response inhibition.

Event-related brain potentials (ERPs) were recorded from 20 normal participants while they completed a Go/NoGo response inhibition task. Previous ERP studies have implicated the N2 and P3 waveforms as the main indices of processing in this task, and functional brain imaging has shown parietal, prefrontal and anterior cingulate cortices to be involved in response inhibition. 32-channel ERP analysis revealed amplitude differences in the N2/P3 components when stimuli that required a button-press (Go stimuli) were compared with stimuli for which the response had to be withheld (No-Go stimuli), and in N2 and P3 latencies when successful withholds to No-Go stimuli were compared with unsuccessful attempts to inhibit. Further differences in the N2/P3 complex emerged when participants were grouped in terms of a measure of absentmindedness (the Cognitive Failures Questionnaire, CFQ); larger and earlier components were found for high CFQ respondents. We conclude that the latencies of the N2 and P3 may be the critical indicators of active inhibitory processes for this task, suggesting that a pattern of sequential activation rather than altered activity level in key structures may mediate success on the task. In addition, highly absentminded participants exhibited larger components for errors than did less absentminded participants when performing at the same level, which implies that the absentminded may require greater activity in the neural substrates of response inhibition in order to accomplish this task at a comparable level of performance to less absentminded participants.

Adolescent↗

PubMed2005

Neural mechanisms involved in error processing: a comparison of errors made with and without awareness.

The ability to detect an error in one's own performance and then to improve ongoing performance based on this error processing is critical for effective behaviour. In our event-related fMRI experiment, we show that explicit awareness of a response inhibition commission error and subsequent post-error behaviour were associated with bilateral prefrontal and parietal brain activation. Activity in the anterior cingulate region, typically associated with error detection, was equivalent for both errors subjects were aware of and those they were not aware of making. While anterior cingulate activation has repeatedly been associated with error-related processing, these results suggest that, in isolation, it is not sufficient for conscious awareness of errors or post-error adaptation of response strategies. Instead, it appears, irrespective of awareness, to detect information about stimuli/responses that requires interpretation in other brain regions for strategic implementation of post-error adjustments of behaviour.

Adult↗

PubMed2005

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↗

PubMed2005

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↗

PubMed2004

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↗

PubMed2004

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↗