Abstract
Behavioral consequences of a brain insult represent an interaction between the injury and the capacity of the rest of the brain to adapt to it. We provide experimental support for the notion that genetic factors play a critical role in such adaptation. We induced a controlled brain disruption using repetitive transcranial magnetic stimulation (rTMS) and show that APOE status determines its impact on distributed brain networks as assessed by functional MRI (fMRI).Twenty non-demented elders exhibiting mild memory dysfunction underwent two fMRI studies during face-name encoding tasks (before and after rTMS). Baseline task performance was associated with activation of a network of brain regions in prefrontal, parietal, medial temporal and visual associative areas. APOE ε4 bearers exhibited this pattern in two separate independent components, whereas ε4-non carriers presented a single partially overlapping network. Following rTMS all subjects showed slight ameliorations in memory performance, regardless of APOE status. However, after rTMS APOE ε4-carriers showed significant changes in brain network activation, expressing strikingly similar spatial configuration as the one observed in the non-carrier group prior to stimulation. Similarly, activity in areas of the default-mode network (DMN) was found in a single component among the ε4-non bearers, whereas among carriers it appeared disaggregated in three distinct spatiotemporal components that changed to an integrated single component after rTMS.Our findings demonstrate that genetic background play a fundamental role in the brain responses to focal insults, conditioning expression of distinct brain networks to sustain similar cognitive performance.
Highlights
A growing body of evidence from neuropsychological, neurophysiological, and neuroimaging studies in animals and humans suggests that interactions between brain regions engaged in functional networks underlie cognitive processing and determine behavior [1,2]
Group comparisons and behavioral effects of repetitive transcranial magnetic stimulation (rTMS) apolipoprotein E (APOE) e4-carriers and noncarrier groups were comparable in terms of age, gender distribution, years of formal education and cognitive status, including verbal and visual memory assessments
Consistent with our previous report [31], we observed an improvement of recognition memory scores during the second functional magnetic resonance imaging (fMRI), following rTMS for the whole sample
Summary
A growing body of evidence from neuropsychological, neurophysiological, and neuroimaging studies in animals and humans suggests that interactions between brain regions engaged in functional networks underlie cognitive processing and determine behavior [1,2]. Following a focal brain insult (e.g. following a stroke), or as a consequence of the alteration of function in a specific brain region (for example due to a sustained change in afferent input or efferent demand), the affected neural network adapts fluidly. This dynamic, neural plasticity can confer no perceptible change in the behavioral output of the brain, lead to changes demonstrated only under special testing conditions, or cause behavioral changes that may constitute symptoms of disease or represent paradoxical functional facilitations [7,8]. TMS can be applied in trains of variable frequency and intensity to modulate the activity of a given cortical area, increase or decrease it transiently, while the subject performs a given behavior, and the brain activity associated with such behavioral activation can be measured using techniques such as functional magnetic resonance imaging (fMRI; [12])
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