Dataset Information

Intrinsic connections between thalamic sub-regions and the lateral prefrontal cortex are differentially impacted by acute methylphenidate.

ABSTRACT: BACKGROUND:The thalamus is a major target of dopaminergic projections and is densely connected with the prefrontal cortex. A better understanding of how dopamine changes thalamo-cortical communication may shed light on how dopamine supports cognitive function. Methylphenidate has been shown to facilitate cognitive processing and reduce connectivity between the thalamus and lateral prefrontal cortex. AIMS:The thalamus is a heterogeneous structure, and the present study sought to clarify how the intrinsic connections of thalamic sub-regions are differentially impacted by acute dopamine transporter blockade. METHODS:Sixty healthy volunteers were orally administered either 20 mg of methylphenidate (N?=?29) or placebo (N?=?31) in a double-blind, randomized, between-subject design. Multi-echo fMRI was used to assess intrinsic functional connectivity of sub-regions of the thalamus during a resting state scan. An N-back working-memory paradigm provided a measure of cognitive performance. RESULTS:Acute methylphenidate significantly reduced connectivity of the lateral prefrontal cortex with the motor and somatosensory sub-regions of the thalamus and reduced connectivity with the parietal and visual sub-regions at a trend level. Connectivity with the premotor, prefrontal, and temporal sub-regions was not impacted. The intrinsic connectivity between the thalamus and the lateral prefrontal cortex was not associated with working-memory performance. CONCLUSIONS:Methylphenidate decreases functional connections between the lateral prefrontal cortex and thalamus broadly, while sparing intrinsic connectivity with thalamic sub-regions involved with working-memory and language related processes. Collectively, our results suggest that the dopamine transporter regulates functional connections between the prefrontal cortex and non-cognitive areas of the thalamus.

SUBMITTER: Gorka AX

PROVIDER: S-EPMC7437544 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Intrinsic connections between thalamic sub-regions and the lateral prefrontal cortex are differentially impacted by acute methylphenidate.

Gorka Adam X AX Lago Tiffany R TR Balderston Nicholas N Torrisi Salvatore S Fuchs Bari B Grillon Christian C Ernst Monique M

Psychopharmacology 20200419 6

<h4>Background</h4>The thalamus is a major target of dopaminergic projections and is densely connected with the prefrontal cortex. A better understanding of how dopamine changes thalamo-cortical communication may shed light on how dopamine supports cognitive function. Methylphenidate has been shown to facilitate cognitive processing and reduce connectivity between the thalamus and lateral prefrontal cortex.<h4>Aims</h4>The thalamus is a heterogeneous structure, and the present study sought to cl ...[more]

PMID: 32307560

Similar Datasets

Project description:BackgroundEarly drug intervention in childhood disorders aims to maximize individual potential in the short- and long-term. Consistently, juvenile exposure to psychostimulants, such as methylphenidate (MPH), reduces risk for substance use in animals and sub-populations of individuals with attention deficit hyperactivity disorder (ADHD). We investigated the effects of MPH on brain plasticity via dopamine receptor D3 (D3R) and brain-derived neurotrophic factor (BDNF) expression in developing rats.MethodsBetween postnatal days 20-35, rat pups were administered saline vehicle (Veh) or MPH (2 mg/kg), the D3R-preferring agonist ±7-OHDPAT, or the antagonist nafadotride (0.05 mg/kg) alone, or in combination with MPH twice a day. In adulthood, subjects were challenged to Veh or cocaine (10 mg/kg for two days). The prefrontal cortex was analyzed for protein and mRNA levels of total BDNF, its splice variants I, IIc, III/IV, and IV/VI, and D3 receptors. A separate group of subjects was assessed for splice variants at 20, 35, 40, and 60 days of age.ResultsAcross age strong correlations were evident between Drd3 and Bdnf mRNA levels (r = 0.65) and a negative relationship between Drd3 and exon IIc after MPH treatment (r = -0.73). BDNF protein levels did not differ between Veh- and MPH subjects at baseline, but were significantly lower in MPH-treated and cocaine challenged subjects (30.3 ± 9.7%). Bdnf mRNA was significantly higher in MPH-treated subjects, and reversed upon exposure to cocaine. This effect was blocked by nafadotride. Furthermore, Bdnf total and Bdnf splice variants I, IIc, III/IV, and IV/VI changed across the transitions between juvenility and late adolescence.ConclusionsThese data suggest a sensitive window of vulnerability to modulation of BDNF expression around adolescence, and that compared to normal animals, juvenile exposure to MPH permanently reduces prefrontal BDNF transcription and translation upon cocaine exposure in adulthood by a D3R-mediated mechanism.

Dataset Information

Intrinsic connections between thalamic sub-regions and the lateral prefrontal cortex are differentially impacted by acute methylphenidate.

Publications

Intrinsic connections between thalamic sub-regions and the lateral prefrontal cortex are differentially impacted by acute methylphenidate.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets