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The effects of methylphenidate on whole brain intrinsic functional connectivity.

ABSTRACT: Methylphenidate (MPH) is an indirect dopaminergic and noradrenergic agonist that is used to treat attention deficit hyperactivity disorder and that has shown therapeutic potential in neuropsychiatric diseases such as depression, dementia, and Parkinson's disease. While effects of MPH on task-induced brain activation have been investigated, little is known about how MPH influences the resting brain. To investigate the effects of 40 mg of oral MPH on intrinsic functional connectivity, we used resting state fMRI in 54 healthy male subjects in a double-blind, randomized, placebo-controlled study. Functional connectivity analysis employing ICA revealed seven resting state networks (RSN) of interest. Connectivity strength between the dorsal attention network and the thalamus was increased after MPH intake. Other RSN located in association cortex areas, such as the left and right frontoparietal networks and the executive control network, showed MPH-induced connectivity increase to sensory-motor and visual cortex regions and connectivity decrease to cortical and subcortical components of cortico-striato-thalamo-cortical circuits (CST). RSN located in sensory-motor cortex areas showed the opposite pattern with MPH-induced connectivity increase to CST components and connectivity decrease to sensory-motor and visual cortex regions. Our results provide evidence that MPH does not only alter intrinsic connectivity between brain areas involved in sustained attention, but that it also induces significant changes in the cortico-cortical and cortico-subcortical connectivity of many other cognitive and sensory-motor RSN.

SUBMITTER: Mueller S

PROVIDER: S-EPMC6869774 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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The effects of methylphenidate on whole brain intrinsic functional connectivity.

Mueller Sophia S Costa Anna A Keeser Daniel D Pogarell Oliver O Berman Albert A Coates Ute U Reiser Maximilian F MF Riedel Michael M Möller Hans-Jürgen HJ Ettinger Ulrich U Meindl Thomas T

Human brain mapping 20140523 11

Methylphenidate (MPH) is an indirect dopaminergic and noradrenergic agonist that is used to treat attention deficit hyperactivity disorder and that has shown therapeutic potential in neuropsychiatric diseases such as depression, dementia, and Parkinson's disease. While effects of MPH on task-induced brain activation have been investigated, little is known about how MPH influences the resting brain. To investigate the effects of 40 mg of oral MPH on intrinsic functional connectivity, we used rest ...[more]

PMID: 24862742

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Project description:UNLABELLED:Recent work has demonstrated that human whole-brain functional connectivity patterns measured with fMRI contain information about cognitive abilities, including sustained attention. To derive behavioral predictions from connectivity patterns, our group developed a connectome-based predictive modeling (CPM) approach (Finn et al., 2015; Rosenberg et al., 2016). Previously using CPM, we defined a high-attention network, comprising connections positively correlated with performance on a sustained attention task, and a low-attention network, comprising connections negatively correlated with performance. Validating the networks as generalizable biomarkers of attention, models based on network strength at rest predicted attention-deficit/hyperactivity disorder (ADHD) symptoms in an independent group of individuals (Rosenberg et al., 2016). To investigate whether these networks play a causal role in attention, here we examined their strength in healthy adults given methylphenidate (Ritalin), a common ADHD treatment, compared with unmedicated controls. As predicted, individuals given methylphenidate showed patterns of connectivity associated with better sustained attention: higher high-attention and lower low-attention network strength than controls. There was significant overlap between the high-attention network and a network with greater strength in the methylphenidate group, and between the low-attention network and a network with greater strength in the control group. Network strength also predicted behavior on a stop-signal task, such that participants with higher go response rates showed higher high-attention and lower low-attention network strength. These results suggest that methylphenidate acts by modulating functional brain networks related to sustained attention, and that changing whole-brain connectivity patterns may help improve attention. SIGNIFICANCE STATEMENT:Recent work identified a promising neuromarker of sustained attention based on whole-brain functional connectivity networks. To investigate the causal role of these networks in attention, we examined their response to a dose of methylphenidate, a common and effective treatment for attention-deficit/hyperactivity disorder, in healthy adults. As predicted, individuals on methylphenidate showed connectivity signatures of better sustained attention: higher high-attention and lower low-attention network strength than controls. These results suggest that methylphenidate acts by modulating strength in functional brain networks related to attention, and that changing whole-brain connectivity patterns may improve attention.

Dataset Information

The effects of methylphenidate on whole brain intrinsic functional connectivity.

Publications

The effects of methylphenidate on whole brain intrinsic functional connectivity.

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