Exposure to methylphenidate during peri-adolescence decouples the prefrontal cortex: a multimodal MRI study
Jack L Demaree1, Richard J Ortiz2, Xuezhu Cai1
1Center for Translational NeuroImaging, Northeastern University Boston, MA, USA.
Abstract:
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.
Insights
Chronic psychostimulant exposure in young rats minimally impacted brain structure but significantly disrupted functional connectivity in key brain circuits, affecting prefrontal cortex, basal ganglia, and sensory motor areas.
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.
