Exposure to methylphenidate during peri-adolescence decouples the prefrontal cortex: a multimodal MRI study

Area of Science:

• Neuroscience
• Developmental Neuroscience
• Neuroimaging

Background:

• Psychostimulant medications are widely prescribed for attention-deficit/hyperactivity disorder.
• Understanding their long-term effects on the developing brain is crucial.
• Juvenile and peri-adolescent periods are critical for brain maturation.

Purpose of the Study:

• To investigate the impact of chronic psychostimulant exposure on brain morphology and functional connectivity.
• To determine if methylphenidate enhances prefrontal cortex connectivity as hypothesized.
• To assess behavioral outcomes following long-term psychostimulant treatment.

Main Methods:

• Male rats received daily methylphenidate, dextroamphetamine, or saline from postnatal day 21 to 42.
• Multimodal magnetic resonance imaging (MRI) including Voxel-Based Morphometry and Diffusion Weighted Imaging was employed.
• Resting-state functional connectivity (rsFC) was analyzed using a 3D rat brain atlas covering 171 areas.

Main Results:

• Chronic psychostimulant treatment showed minimal effects on brain volume and anisotropy.
• rsFC revealed significantly decreased coupling between the prefrontal cortex, basal ganglia, and sensory motor cortices.
• No significant cognitive differences were observed between groups in novel object preference tests.

Conclusions:

• Long-term psychostimulant exposure during development has limited effects on brain structure.
• Significant uncoupling of cerebral/basal ganglia circuitry connectivity was observed.
• Further research is needed to understand the long-term implications of these connectivity changes.