Hugh Garavan

Introduction Impaired spatial working memory is a core cognitive deficit observed in people with 22q11 Deletion syndrome (22q11DS) and has been suggested as a candidate endophenotype for schizophrenia. However, to date, the neuroanatomical mechanisms describing its structural and functional underpinnings in 22q11DS remain unclear. We quantitatively investigate the cognitive processes and associated neuroanatomy of spatial working memory in people with 22q11DS compared to matched controls. We examine whether there are significant between‐group differences in spatial working memory using task related fMRI, Voxel based morphometry and white matter fiber tractography. Materials and Methods Multimodal magnetic resonance imaging employing functional, diffusion and volumetric techniques were used to quantitatively assess the cognitive and neuroanatomical features of spatial working memory processes in 22q11DS. Twenty‐six participants with genetically confirmed 22q11DS aged between 9 and 52 years and 26 controls aged between 8 and 46 years, matched for age, gender, and handedness were recruited. Results People with 22q11DS have significant differences in spatial working memory functioning accompanied by a gray matter volume reduction in the right precuneus. Gray matter volume was significantly correlated with task performance scores in these areas. Tractography revealed extensive differences along fibers between task‐related cortical activations with pronounced differences localized to interhemispheric commissural fibers within the parietal section of the corpus callosum. Conclusions Abnormal spatial working memory in 22q11DS is associated with aberrant functional activity in conjunction with gray and white matter structural abnormalities. These anomalies in discrete brain regions may increase susceptibility to the development of psychiatric disorders such as schizophrenia. Hum Brain Mapp 37:4689–4705, 2016.

This paper reviews the role of the insula in drug craving. Evidence is presented that drug craving may be a particular instance of the anterior insula’s broader role in interoception and subjective feeling states similar, for example, to thirst and hunger. An important role for the insula in craving is supported by evidence of insular activity changing with satiety and with the top–down cognitive modulation of cravings. Cognitive processes involving the insula’s role in awareness of one’s own behaviour may also contribute to craving insofar as the avoidance of craving might require subjective awareness of the endogenous and exogenous cues that initiate it. Finally, some consideration is given to sex differences and developmental processes in craving.

Top‐down control processes are thought to interact with bottom‐up stimulus‐driven task demands to facilitate the smooth execution of behaviour. Frontal and midline brain areas in humans are believed to subserve these control processes but their distinct roles and the interactions between them remain to be fully elucidated. In this functional magnetic resonance imaging (fMRI) study, we utilized a GO/NO‐GO task with cued and uncued inhibitory events to investigate the effect of cue‐induced levels of top‐down control on NO‐GO trial response conflict. We found that, on a within‐subjects, trial‐for‐trial basis, high levels of top‐down control, as indexed by left dorsolateral prefrontal activation prior to the NO‐GO, resulted in lower levels of activation on the NO‐GO trial in the pre‐supplementary motor area. These results suggest that prefrontal and midline regions work together to implement cognitive control and reveal that intra‐subject variability is reflected in these lateral and midline interactions.

Compromised ability to exert control over drug urges and drug-seeking behaviour is a characteristic of addiction. One specific cognitive control function, impulse control, has been shown to be a risk factor for the development of substance problems and has been linked in animal models to increased drug administration and relapse. We present evidence of a direct effect of cocaine on the neurobiology underlying impulse control. In a laboratory test of motor response inhibition, an intravenous cocaine administration improved task performance in 13 cocaine users. This improvement was accompanied by increased activation in right dorsolateral and inferior frontal cortex, regions considered critical for this cognitive function. Similarly, for both inhibitory control and action monitoring processes, cocaine normalized activation levels in lateral and medial prefrontal regions previously reported to be hypoactive in users relative to drug-naive controls. The acute amelioration of neurocognitive dysfunction may reflect a chronic dysregulation of those brain regions and the cognitive processes they subserve. Furthermore, the effects of cocaine on midline function suggest a dopaminergically mediated intersection between cocaine's acute reinforcing effects and its effects on cognitive control.

While hedonic and reward-related processes are central to drug use and dependence, this article focuses on the contribution that cognitive processes may make to addiction. In particular, attention is drawn to those processes involved in exercising control over behavior as drug dependence is characterized by risky, impulsive behavior. Functional neuroimaging implicates prefrontal deficits in cocaine dependence with an emerging picture of cocaine users having attentional biases towards drug-related stimuli, poor performance in laboratory tests of inhibitory control, and compromised monitoring and evaluation of their behavior. Combined, these deficits may contribute to the continuation of use in dependent individuals and may qualify as important targets for therapeutic interventions.

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. Hum Brain Mapp, 2006.