Brain activation and functional connectivity in premanifest Huntington's disease during states of intrinsic and phasic alertness

Abstract

Previous functional neuroimaging studies have shown brain activation abnormalities in clinically presymptomatic carriers of the Huntington's disease (preHD) gene mutation when performing complex cognitive tasks. However, little is known about the neural correlates of attentional processes in preHD. In this study, we used functional magnetic resonance imaging to investigate basic aspects of attentional processing in preHD individuals (n = 18) compared to healthy participants (n = 18) during an alertness task. Uni- and multivariate statistical techniques were used to assess task-related regional brain activation and functional network connectivity. Compared to healthy controls, preHD individuals near to the estimated onset of clinical signs showed lower activation of right frontostriatal regions during phasic alertness (P < 0.001, uncorrected). Decreased striatal activation in this preHD subgroup was also evident when compared with those preHD individuals far from the estimated onset of HD signs. Lower putaminal activity was associated with longer reaction times and with proximity to onset. In addition, preHD participants near to onset had lower functional connectivity of motor regions when compared with controls and preHD individuals far from onset. Our data suggest that while alertness-related performance remains normal, the underlying frontostriatal activity and motor cortex connectivity decline only when approaching the onset of unequivocal signs of HD. However, these attentional network changes might not be the sole explanation for the differences in cognitive task performance previously observed in preHD.

Disruption of response inhibition circuits in prodromal Huntington disease

“…For example, prHD individuals close to a diagnosis showed reduced right DLPFC and putamen activation during a phasic alerting task (Wolf et al, 2012) and reduced left DLPFC, but increased left inferior parietal activation during verbal working memory (Wolf et al, 2007). In contrast, basal ganglia activation declined with proximity to diagnosis during time discrimination (Paulsen et al, 2004), but was hyperactive during a set shifting task, irrespective of genetic exposure (Gray et al, 2013).…”

“…Yet the brain mechanisms that govern different facets of cognitive decline in prHD are not well understood. Emerging functional imaging studies report different disease-related patterns of activation during working memory (Wolf et al, 2008; Wolf, Vasic, Schonfeldt-Lecuona, Landwehrmeyer, & Ecker, 2007), attention (Wolf et al, 2012), interference (Reading et al, 2004), temporal processing (Paulsen et al, 2004; Zimbelman et al, 2007), set shifting (Gray et al, 2013), and implicit emotion processing (Novak et al, 2012), typically without deficits in task performance. Some studies report changes in brain functioning in individuals far from a diagnosis (Paulsen et al, 2004; Wolf et al, 2007; Zimbelman et al, 2007), despite the absence of cognitive decline and/or striatal atrophy.…”

Abnormal synchrony of resting state networks in premanifest and symptomatic Huntington disease: the IMAGE-HD study

“…In patients with Huntington disease, there is some evidence for altered connectivity between brain regions both during cognitive task performance [18][19][20][21] and at rest. 10,14 Wolf and colleagues 21 found significant reduction in left frontoparietal and putamen connectivity during working memory.…”

Task-specific brain reorganization in motor recovery induced by a hybrid-rehabilitation combining training with brain stimulation after stroke

“…While the threshold of uncorrected p values combined with minimum voxel clustering value of 10 voxels has been practically used in various neuroimaging analyses (Absher et al, 2000;Ahmed et al, 2012;Bartos et al, 2009;Busatto et al, 2000;Gizewski et al, 2006;Havel et al, 2006;Matsumoto et al, 2010;Pinto et al, 2011;Schacter et al, 1996;Scheuerecker et al, 2009;Wolf et al, 2012;Yoo et al, 2005), it is still controversial due to less rigorous control of false positive errors (Bennett et al, 2009). To confirm our findings, a further investigation would be necessary in future.…”