Ventral midbrain stimulation induces perceptual learning and cortical plasticity in primates

Abstract

Practice improves perception and enhances neural representations of trained visual stimuli, a phenomenon known as visual perceptual learning (VPL). While attention to task-relevant stimuli plays an important role in such learning, Pavlovian stimulus-reinforcer associations are sufficient to drive VPL, even subconsciously. It has been proposed that reinforcement facilitates perceptual learning through the activation of neuromodulatory centers, but this has not been directly confirmed in primates. Here, we paired task-irrelevant visual stimuli with microstimulation of a dopaminergic center, the ventral tegmental area (VTA), in macaques. Pairing VTA microstimulation with a task-irrelevant visual stimulus increased fMRI activity and improved classification of fMRI activity patterns selectively for the microstimulation-paired stimulus. Moreover, pairing VTA microstimulation with a task-irrelevant visual stimulus improved the subject’s capacity to discriminate that stimulus. This is the first causal demonstration of the role of neuromodulatory centers in VPL in primates.

Selective Mesoaccumbal Pathway Inactivation Affects Motivation but Not Reinforcement-Based Learning in Macaques

“…Although our results are in line with literature asserting that reinforcement learning does not critically depend on DA (Shiner et al, 2012;Yin et al, 2008), alternative interpretations may exist. First, the most refined causal evidence supporting a positive relationship between DA and reinforcement learning derives from rodent studies, which is somewhat corroborated by far coarser causal primate data (Arsenault et al, 2014;Arsenault and Vanduffel, 2019;Frank et al, 2004Frank et al, , 2007Pessiglione et al, 2006;Stauffer et al, 2016). In addition, it should be noted that important species differences between rodents and primates have been documented regarding dopamine receptor distributions and connection patterns (Berger et al, 1991).…”

Frequency- and State-Dependent Network Effects of Electrical Stimulation Targeting the Ventral Tegmental Area in Macaques

“…Both monkeys underwent initial surgery to implant an MR-compatible headset attached to the skull with ceramic screws that is subsequently covered with dental cement, as previously described in detail ( Vanduffel et al 2001 ). The 2 monkeys participated in other experiments in which we combined VTA-EM with behavioral paradigms, and awake contrast-agent-enhanced fMRI ( Arsenault and Vanduffel 2019 ). Animal care and all surgical and experimental procedures have been approved by the ethical committee of the medical school at KU Leuven and conform to national and European guidelines (Directive 2010/63/EU).…”

“…Biphasic pulses were triggered consisting of an anodal (positive) leading pulse of 0.2 ms followed by a cathodal (negative) 0.2 ms pulse (0.4 ms pulse width). We chose anodal leading pulses based on previous studies in which we successfully employed EM in the macaque ( Ekstrom et al 2008 ; Arsenault and Vanduffel 2019 ). The effect of the AC frequency of the stimulation pulses within a train was the main thrust of our current investigation, which we will address in further detail below.…”

Subcortical Atlas of the Rhesus Macaque (SARM) for Magnetic Resonance Imaging

“…Technological improvements in data collection methods have also resulted in greater potential for employing fMRI concurrently with subcortical electrical microstimulation (Logothetis et al, 2010;Arsenault & Vanduffel, 2019;Murris, Arsenault & Vanduffel, 2020), optogenetics (Nassi et al, 2015;Klein et al, 2016;Stauffer et al, 2016), or electrophysiological recordings (Logothetis et al, 2012), all the while capturing the mesoscopic and systems-level effects (see also, Klink et al, this issue). Such studies require fine-grain delineations of the subcortex to aid both in planning stereotaxic implantations and interpreting local signal modulation.…”