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

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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.

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Acknowledgments

This work utilized the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov).

Funding

This work was supported by the Intramural Research Program of the National Institutes of Mental Health, project no. ZIAMH002798 (clinical protocol 02-M-0321, NCT00047853) to CG.

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Authors and Affiliations

  1. Section on the Neurobiology of Fear & Anxiety, National Institute of Mental Health, 15K North Drive Rm 300-F, Bethesda, MD, 20892, USA

    Adam X. Gorka, Tiffany R. Lago, Nicholas Balderston, Salvatore Torrisi, Christian Grillon & Monique Ernst

  2. Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA

    Nicholas Balderston

  3. Department of Nutritional Sciences, Penn State University, State College, PA, 16801, USA

    Bari Fuchs

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  1. Adam X. Gorka
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Correspondence to Adam X. Gorka.

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Gorka, A.X., Lago, T.R., Balderston, N. et al. Intrinsic connections between thalamic sub-regions and the lateral prefrontal cortex are differentially impacted by acute methylphenidate. Psychopharmacology 237, 1873–1883 (2020). https://doi.org/10.1007/s00213-020-05505-z

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