Dataset Information

The effects of methylphenidate on resting-state striatal, thalamic and global functional connectivity in healthy adults.

ABSTRACT: By blocking dopamine and norepinephrine transporters, methylphenidate affects cognitive performance and regional brain activation in healthy individuals as well as those with neuropsychiatric disorders. Resting-state connectivity evaluates the functional integrity of a network of brain regions. Here, we examined how methylphenidate effects resting-state functional connectivity of the dorsal striatum and thalamus, areas each with dense dopaminergic and noradrenergic innervations, as well as global cerebral connectivity. We administered a single, oral dose (45 mg) to 24 healthy adults and compared resting-state connectivity to 24 demographically matched adults who did not receive any medication. The results showed that methylphenidate alters seed-based and global connectivity between the thalamus/dorsal striatum with primary motor cortex, amygdala/hippocampus and frontal executive areas (p < 0.05, corrected). Specifically, while methylphenidate at this dosage enhances connectivity to the motor cortex and memory circuits, it dampens prefrontal cortical connectivity perhaps by increasing catecholaminergic signalling past the 'optimal' level. These findings advance our understanding of a critical aspect of the multifaceted effects of methylphenidate on brain functions. The results may also facilitate future studies of the aetiology and treatment of neurological and psychiatric disorders that implicate catecholaminergic dysfunction.

SUBMITTER: Farr OM

PROVIDER: S-EPMC4506752 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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The effects of methylphenidate on resting-state striatal, thalamic and global functional connectivity in healthy adults.

Farr Olivia M OM Zhang Sheng S Hu Sien S Matuskey David D Abdelghany Osama O Malison Robert T RT Li Chiang-Shan R CS

The international journal of neuropsychopharmacology 20140513 8

By blocking dopamine and norepinephrine transporters, methylphenidate affects cognitive performance and regional brain activation in healthy individuals as well as those with neuropsychiatric disorders. Resting-state connectivity evaluates the functional integrity of a network of brain regions. Here, we examined how methylphenidate effects resting-state functional connectivity of the dorsal striatum and thalamus, areas each with dense dopaminergic and noradrenergic innervations, as well as globa ...[more]

PMID: 24825078

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Project description:Alcohol misuse is associated with thalamic dysfunction. The thalamus comprises subnuclei that relay and integrate information between cortical and subcortical structures. However, it is unclear how the subnuclei contribute to thalamic dysfunctions in problem drinking. We investigated resting-state functional connectivity (rsFC) of thalamic subregions in 107 nondependent drinkers (57 women), using masks delineated by white matter tractography. Thalamus was parceled into motor, somatosensory, visual, premotor, frontal association, parietal association, and temporal association subregions. Whole-brain linear regression, each against Alcohol Use Disorders Identification Test (AUDIT) and positive alcohol expectancy (AE) score with age as a covariate, was performed for each seed, for men and women combined, and separately. Overall, problem drinking was associated with increased thalamic connectivities, whereas AE was associated with a mixed pattern of increased and decreased connectivities. Motor, premotor, somatosensory, and frontal association thalamic connectivity with bilateral caudate head was positively correlated with AUDIT score in men and women combined. Connectivity of the right caudate head with frontal association and premotor thalamus was also positively correlated with AE score in men and women combined. In contrast, motor and premotor thalamic connectivity with a number of cortical and subcortical structures showed sex differences in the correlation each with AUDIT and AE score. In mediation analyses, AE score completely mediated the correlation between thalamic caudate connectivity and AUDIT score, whereas the model where AE contributed to problem drinking and, in turn, altered thalamic caudate connectivity was not supported. To conclude, thalamic subregional rsFCs showed both shared and distinct changes and sex differences in association with problem drinking and AE. Increased thalamic caudate connectivity may contribute to problem drinking via enhanced AE. The findings suggest the importance of examining thalamic subdivisions and sex in investigating the functional roles of thalamus in problem drinking.

Project description:The 22q11.2 deletion syndrome (22q11DS) is a recurrent copy number variant with high penetrance for developmental neuropsychiatric disorders. Study of individuals with 22q11DS therefore may offer key insights into neural mechanisms underlying such complex illnesses. Resting-state functional connectivity MRI studies in idiopathic schizophrenia have consistently revealed disruption of thalamic and hippocampal circuitry. Here, we sought to test whether this circuitry is similarly disrupted in the context of this genetic high-risk condition. To this end, resting-state functional connectivity patterns were assessed in a sample of human youth with 22q11DS (n = 42; 59.5% female) and demographically matched healthy controls (n = 39; 53.8% female). Neuroimaging data were acquired via single-band protocols and analyzed in line with methods provided by the Human Connectome Project. We computed functional relationships between individual-specific anatomically defined thalamic and hippocampal seeds and all gray matter voxels in the brain. Whole-brain Type I error protection was achieved through nonparametric permutation-based methods. The 22q11DS patients displayed dissociable disruptions in thalamic and hippocampal functional connectivity relative to control subjects. Thalamocortical coupling was increased in somatomotor regions and reduced across associative networks. The opposite effect was observed for the hippocampus in regards to somatomotor and associative network connectivity. The thalamic and hippocampal dysconnectivity observed in 22q11DS suggests that high genetic risk for psychiatric illness is linked with disruptions in large-scale corticosubcortical networks underlying higher-order cognitive functions. These effects highlight the translational importance of large-effect copy number variants for informing mechanisms underlying neural disruptions observed in idiopathic developmental neuropsychiatric disorders.SIGNIFICANCE STATEMENT Investigation of neuroimaging biomarkers in highly penetrant genetic syndromes represents a more biologically tractable approach to identify neural circuit disruptions underlying developmental neuropsychiatric conditions. The 22q11.2 deletion syndrome confers particularly high risk for psychotic disorders and is thus an important translational model in which to investigate systems-level mechanisms implicated in idiopathic illness. Here, we show resting-state fMRI evidence of large-scale sensory and executive network disruptions in youth with 22q11DS. In particular, this study provides the first evidence that these networks are disrupted in a dissociable fashion with regard to the functional connectivity of the thalamus and hippocampus, suggesting circuit-level dysfunction.

Dataset Information

The effects of methylphenidate on resting-state striatal, thalamic and global functional connectivity in healthy adults.

Publications

The effects of methylphenidate on resting-state striatal, thalamic and global functional connectivity in healthy adults.

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