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

• Published in: Psychopharmacology Vol. 237; no. 6; pp. 1873 - 1883
• Main Authors: Gorka, Adam X., Lago, Tiffany R., Balderston, Nicholas, Torrisi, Salvatore, Fuchs, Bari, Grillon, Christian, Ernst, Monique
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2020; Springer; Springer Nature B.V
• Subjects: Adult; Analysis; Animal cognition; Biomedical and Life Sciences; Biomedicine; Blindness; Cognition; Cognitive ability; Cortex (motor); Dopamine; Dopamine receptors; Dopamine transporter; Dopamine Uptake Inhibitors - administration & dosage; Dosage and administration; Double-Blind Method; Female; Functional magnetic resonance imaging; Healthy Volunteers; Humans; Information processing; Magnetic Resonance Imaging - methods; Male; Memory; Memory, Short-Term - drug effects; Memory, Short-Term - physiology; Methylphenidate; Methylphenidate - administration & dosage; Methylphenidate hydrochloride; Monkeys & apes; Nerve Net - diagnostic imaging; Nerve Net - drug effects; Nerve Net - physiology; Neurosciences; Oral administration; Original Investigation; Pharmacology/Toxicology; Physiological aspects; Prefrontal cortex; Prefrontal Cortex - diagnostic imaging; Prefrontal Cortex - drug effects; Prefrontal Cortex - physiology; Psychiatry; Psychological aspects; Short term memory; Somatosensory cortex; Stimulants; Temporal cortex; Thalamus; Thalamus - diagnostic imaging; Thalamus - drug effects; Thalamus - physiology; Young Adult; United States; Resting state fMRI; Thalamus; Intrinsic functional connectivity; Dopamine; Prefrontal cortex; Acute methylphenidate
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-020-05505-z

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.