Adam X Gorka1, Tiffany R Lago2, Nicholas Balderston2,3, Salvatore Torrisi2, Bari Fuchs4, Christian Grillon2, Monique Ernst2. 1. Section on the Neurobiology of Fear & Anxiety, National Institute of Mental Health, 15K North Drive Rm 300-F, Bethesda, MD, 20892, USA. adam.gorka@nih.gov. 2. Section on the Neurobiology of Fear & Anxiety, National Institute of Mental Health, 15K North Drive Rm 300-F, Bethesda, MD, 20892, USA. 3. Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA. 4. Department of Nutritional Sciences, Penn State University, State College, PA, 16801, USA.
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.
RCT Entities:
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.