American journal of translational researchAug 11, 2021

Methylphenidate use during early adolescence disrupts connections in thinking and decision-making brain areas

Psychedelic Science Weekly Brief ↗PubMed ↗

Updated Apr 2, 2026

Abstract

Long-lasting psychostimulant treatment was associated with minimal changes in brain volume and significant uncoupling of connectivity in the cerebral/basal ganglia circuitry.

Daily injections of methylphenidate or dextroamphetamine during juvenile and peri-adolescent stages were given to male rats.
Imaging techniques included voxel-based morphometry, diffusion weighted imaging, and resting state functional connectivity.
Only a few significant changes in brain volume and anisotropy measures were observed compared to the saline vehicle group.
Resting state functional connectivity imaging showed decreased coupling between the prefrontal cortex, basal ganglia, and sensory motor cortices.
No significant differences in cognitive behavior were found between the experimental groups.

Simplified

This study was designed to assess the effects of daily psychostimulant exposure during juvenility and peri-adolescence on brain morphology and functional connectivity using multimodal magnetic resonance imaging. We hypothesized that long-term exposure to methylphenidate would enhance connectivity with the prefrontal cortex. Male rats were given daily injections of either methylphenidate (n=10), dextroamphetamine (n=10) or saline vehicle (n=10) from postnatal day 21 to 42. They were imaged between postnatal day 43 and 48. Voxel-based morphometry, diffusion weighted imaging, and resting state functional connectivity were used to quantify brain structure and function. Images from each modality were registered and analyzed, using a 3D MRI rat atlas providing site-specific data over 171 different brain areas. Following imaging, rats were tested for cognitive function using novel object preference. Long-lasting psychostimulant treatment was associated with only a few significant changes in brain volume and measures of anisotropy compared to vehicle. Resting state functional connectivity imaging revealed decreased coupling between the prefrontal cortex, basal ganglia and sensory motor cortices. There were no significant differences between experimental groups for cognitive behavior. In this exploratory study, we showed that chronic psychostimulant treatment throughout juvenility and preadolescence has a minimal effect on brain volume and gray matter microarchitecture, but significantly uncouples the connectivity in the cerebral/basal ganglia circuitry.

Methylphenidate use during early adolescence disrupts connections in thinking and decision-making brain areas

Abstract

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