title: Methylphenidate Enhances Early-Stage Sensory Processing and Rodent Performance of a Visual Signal Detection Task.
abstract: Methylphenidate (MPH) is used clinically to treat attention-deficit/hyperactivity disorder (ADHD) and off-label as a performance-enhancing agent in healthy individuals. MPH enhances catecholamine transmission via blockade of norepinephrine (NE) and dopamine (DA) reuptake transporters. However, it is not clear how this action affects neural circuits performing cognitive and sensorimotor functions driving performance enhancement. The dorsal lateral geniculate nucleus (dLGN) is the primary thalamic relay for visual information from the retina to the cortex and is densely innervated by NE-containing fibers from the locus coeruleus (LC), a pathway known to modulate state-dependent sensory processing. Here, MPH was evaluated for its potential to alter stimulus-driven sensory responses and behavioral outcomes during performance of a visual signal detection task. MPH enhanced activity within individual neurons, ensembles of neurons, and visually-evoked potentials (VEPs) in response to task light cues, while increasing coherence within theta and beta oscillatory frequency bands. MPH also improved reaction times to make correct responses, indicating more efficient behavioral performance. Improvements in reaction speed were highly correlated with faster VEP latencies. Finally, immunostaining revealed that catecholamine innervation of the dLGN is solely noradrenergic. This work suggests that MPH, acting via noradrenergic mechanisms, can substantially affect early-stage sensory signal processing and subsequent behavioral outcomes.
authors.affiliation: Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Rachel L
authors.identifier: http://orcid.org/0000-0002-4893-5468
authors.initials: RL
authors.lastname: Navarra
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Clark
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Gargiulo
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Barry D
authors.initials: BD
authors.lastname: Waterhouse
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D058256:Brain Waves / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D005074:Evoked Potentials, Visual / Q000502:physiology*; D005829:Geniculate Bodies / Q000187:drug effects*; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D017603:Signal Detection, Psychological / Q000187:drug effects*; D014796:Visual Perception / Q000502:physiology*
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate