Prefrontal hypoactivity associated with impaired inhibition in stimulant-dependent individuals but evidence for hyperactivation in their unaffected siblings - PubMed (original) (raw)

Prefrontal hypoactivity associated with impaired inhibition in stimulant-dependent individuals but evidence for hyperactivation in their unaffected siblings

Sharon Morein-Zamir et al. Neuropsychopharmacology. 2013 Sep.

Abstract

A neurocognitive endophenotype has been proposed for stimulant dependence, based on behavioral measures of inhibitory response control associated with white matter changes in the frontal cortex. This study investigated the functional neuroimaging correlates of inhibitory response control, as functional activity serves as a more dynamic measure than brain structure, allowing refinement of the suggested endophenotype. Stimulant-dependent individuals (SDIs), their unaffected siblings (SIBs), and healthy controls (CTs) performed the stop-signal task, including stop-signal reaction time (SSRT) as a measure of response inhibition, while undergoing functional magnetic resonance imaging. SDIs had impaired response inhibition accompanied by hypoactivation in the ventrolateral prefrontal cortex (PFC). In addition, they demonstrated hypoactivation in the anterior cingulate when failing to stop. In contrast, no hypoactivations were noted in their unaffected SIBs. Rather, they exhibited increased activation in the dorsomedial PFC relative to controls, together with inhibitory performance that was intermediate between that of the stimulant group and the healthy CT group. Such hyperactivations within the neurocircuitry underlying response inhibition and control are suggestive of compensatory mechanisms that could be protective in nature or could reflect coping with a pre-existing vulnerability, thus expressing potential aspects of resilience. The functional activation associated with response inhibition and error monitoring showed differential patterns of results between SDIs and their unaffected first-degree relatives, suggesting that the proposed endophenotype does not generalize to functional brain activity.

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Figures

Figure 1

Figure 1

Significant brain activation maps associated with stopping in each group (P<0.05, Family-wise error). Note. Brain activation maps per group: row (a) stimulant-dependent individuals; row (b) unaffected siblings of stimulant-dependent individuals; row (c) healthy controls. Axial brain slices demonstrate main activation clusters per group at family-wise error P<0.05. The _z_-coordinate slices are: −4, 8, 24 and 48. Right side of each slice corresponds to the right side of the brain.

Figure 2

Figure 2

Group mean percent signal change of 8-mm spheres associated with stopping (a and b) and error monitoring (c). (a) Anterio-insula/frontal operculum, centred around coordinates: _x_=34, _y_=20, _z_=−10; (b) pre-SMA, centred around coordinates: _x_=−12, _y_=8, _z_=46; (c) anterior cingulate, centred around coordinates: _x_=16, _y_=32, _z_=18. Error bars index standard error of the mean. CT, controls; SDI, stimulant dependent individuals; SIB, unaffected siblings.

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