Matthew Chafee, PhD
Professor, Department of Neuroscience
Professor, Department of Neuroscience
Intelligent behavior in higher primates and humans is often characterized by the ability to act on the basis of abstract information that is generated internally rather than strictly reflecting the sensory input. Examples include actions that are directed toward goals, based on rules, or informed by generalized principles. By changing goals, rules, or principles, the brain can flexibly process the same sensory input to produce different, context-appropriate actions, a capability referred to as executive control. In order to better understand executive control as a biological process, we record the electrical activity of individual neurons (typically 20-30 neurons at a time) in different cortical areas as the brain applies different rules to compute context-dependent information, relating the information coded by neural activity to the computational flexibility required. Two independent projects sharing this general approach are ongoing in our laboratory.
The first project investigates the network basis of executive control over spatial cognitive processing in a task that requires that the brain place the same visual stimulus into different spatial categories on the basis of a changing rule. We have compared the spatial information coded by neural activity recorded concurrently in the prefrontal and posterior parietal cortex; two cortical areas connected by direct axonal projections that are jointly recruited during spatial cognitive processing. Our findings thus far indicate that executive control is a distributed process, in the sense that activity patterns coding the spatial category of a stimulus, as a function of the rule applied, can be found to exist within both parietal and prefrontal cortex. However, we are finding that the rule exerts an earlier and stronger influence on neural signals coding categories in prefrontal cortex, suggesting this area may play a particularly large or early role in the computational flexibility that underlies executive control.
The second project seeks to better understand how neuronal information processing related to executive control is disrupted in schizophrenia. Converging lines of pharmacological, anatomical, and genetic evidence suggest that schizophrenia is the product of a disease process that disrupts neurotransmission at the NMDA glutamate receptor. We are currently developing experiments to investigate how blocking this receptor degrades the ability of prefrontal neurons to generate rule-dependent patterns of activity, leading to behavioral errors in executive control tasks that are characteristic of the disease. Our hope is that this work will extend our understanding of how schizophrenia disrupts information processing at the level of single prefrontal neurons to produce cognitive deficits.
Heilbronner, SR & Chafee, MV 2019, 'Learning How Neurons Fail Inside of Networks: Nonhuman Primates Provide Critical Data for Psychiatry' Neuron, vol. 102, no. 1, pp. 21-26. https://doi.org/10.1016/j.neuron.2019.02.030
Zick, JL, Blackman, RK, Crowe, DA, Amirikian, B, DeNicola, AL, Netoff, TI & Chafee, MV 2018, 'Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: Implications for Activity-Dependent Disconnection in Schizophrenia' Neuron, vol. 98, no. 6, pp. 1243-1255.e5. https://doi.org/10.1016/j.neuron.2018.05.010
Kang, SS, MacDonald, AW, Chafee, MV, Im, CH, Bernat, EM, Davenport, ND & Sponheim, SR 2018, 'Abnormal cortical neural synchrony during working memory in schizophrenia' Clinical Neurophysiology, vol. 129, no. 1, pp. 210-221. https://doi.org/10.1016/j.clinph.2017.10.024
Chafee, MV & Crowe, DA 2017, 'Implicit and Explicit Learning Mechanisms Meet in Monkey Prefrontal Cortex' Neuron, vol. 96, no. 2, pp. 256-258. https://doi.org/10.1016/j.neuron.2017.09.049
Averbeck, BB & Chafee, MV 2016, 'Using model systems to understand errant plasticity mechanisms in psychiatric disorders' Nature Neuroscience, vol. 19, no. 11, pp. 1418-1425. https://doi.org/10.1038/nn.4413
Blackman, RK, Crowe, DA, DeNicola, AL, Sakellaridi, S, MacDonald, A & Chafee, MV 2016, 'Monkey prefrontal neurons reflect logical operations for cognitive control in a variant of the AX continuous performance Task (AX-CPT)' Journal of Neuroscience, vol. 36, no. 14, pp. 4067-4079. https://doi.org/10.1523/JNEUROSCI.3578-15.2016
MacDonald, A, Zick, JL, Chafee, MV & Netoff, TI 2016, 'Integrating insults: Using fault tree analysis to guide schizophrenia research across levels of analysis' Frontiers in Human Neuroscience, vol. 9, no. JAN2016, 698. https://doi.org/10.3389/fnhum.2015.00698
Elshaikh, AA, Sponheim, SR, Chafee, MV & MacDonald, AW 2015, 'Spatial attentional control is not impaired in schizophrenia: Dissociating specific deficits from generalized impairments' Journal of abnormal psychology, vol. 124, no. 2, pp. 302-308. https://doi.org/10.1037/a0038537
Blackman, RK, MacDonald, A & Chafee, MV 2013, 'Effects of ketamine on context-processing performance in monkeys: A new animal model of cognitive deficits in schizophrenia' Neuropsychopharmacology, vol. 38, no. 11, pp. 2090-2100. https://doi.org/10.1038/npp.2013.118
Crowe, DA, Goodwin, SJ, Blackman, RK, Sakellaridi, S, Sponheim, SR, MacDonald, AW & Chafee, MV 2013, 'Prefrontal neurons transmit signals to parietal neurons that reflect executive control of cognition' Nature Neuroscience, vol. 16, no. 10, pp. 1484-1491. https://doi.org/10.1038/nn.3509
NSC 6112: Medical Neuroscience