Circuit and Computational Principles of Plasticity Following Damage

University Of Rochester, Rochester NY

Investigators

Abstract

Project Summary/Abstract A defining feature of the primate brain is its highly specialized organization: distinct brain areas support different functions. As a result, when an area is damaged, the brain may lose the functions for which the area was responsible. In some cases, these deficits can be compensated for through plasticity, but we know little about the principles, mechanisms, and consequences of functional reorganization in damaged brains. Here, we seek to address this gap by studying lesion-induced system reorganization in humans, marmosets, and macaques. We focus on damage to the primary visual cortex (V1), as a model system for studying cortical processing. V1 constructs a general-purpose visual representation by measuring the local distribution of orientation energy in the retinal input, informing the content of our perceptual interpretations of the environment as well as the confidence we have in these interpretations. V1 damage typically results in severely diminished orientation sensitivity and ability to evaluate its reliability. However, the lost perceptual capacity can be partially recovered, suggesting that V1 damage may be followed by a functional reorganization of the visual system. We will leverage the power of normative theory to establish the principles underlying system reorganization in idealized artificial visual systems trained to efficiently represent natural visual input. Guided by preliminary findings, we hypothesize that following V1 damage, extrastriate area MT becomes a primary node of visual connectivity and function and a primary cortical generator of orientation selectivity. Two subcortical routes of information transfer between the retina and MT make this possible: one via the lateral geniculate nucleus and the other via the pulvinar. We will use complementary methods in two species to establish the circuit mechanisms underlying system reorganization and the relative contribution of these two pathways. We will measure large-scale neural responses in MT in V1-damaged marmosets with genetically-encoded calcium indicators while selectively inactivating each subcortical pathway. We will also use state-of-the-art, 7T layer-fMRI to measure the laminar distribution and retinotopic specificity of orientation selectivity in area MT of humans with stroke-induced V1 lesions. To study higher-level, cognitive consequences of cortical damage, we will assess metacognitive judgments of confidence in perceptual decisions in the absence V1. A rich body of theoretical and empirical work suggests that perceptual confidence is directly informed by neural activity in sensory cortex. Damage to a sensory area may thus reduce metacognitive ability to evaluate the reliability of perceptual events. We will study the behavioral effects of V1 damage on metacognitive ability as well as its neural basis in human subjects using high-resolution 7T fMRI. Finally, we propose to develop an animal model of the reduction and recovery of metacognitive ability following the disruption of normal V1 function with macaque monkeys performing a recently developed perceptual confidence task. Together, this work will establish a foundation for studying the principles, mechanisms, and cognitive consequences of functional reorganization following brain damage.