Working memory is the ability to hold items ‘in mind’. It is at the core of cognition, providing the workspace for
complex behaviors. However, despite its critical nature, working memory is surprisingly limited, holding 3-4
items at a time. To compensate for this limited capacity, working memory is dynamically controlled: access to
working memory is tightly regulated and representations in working memory are selectively manipulated.
Disrupting one’s ability to control working memory can be pathological. Such disruptions are believed to be a
core cognitive deficit in schizophrenia1 and may underlie intrusive thoughts in anxiety2 and depression3. To
develop novel, mechanistically-informed, treatments for these diseases, we must first develop a detailed
understanding of the neural mechanisms that control working memory. We propose to investigate three ways
in which working memory is controlled:
First, one must be able to control access to working memory. A ‘gating’ signal is thought to provide this
control: to-be-remembered stimuli are gated into memory; to-be-ignored stimuli are not. Our first aim will
distinguish hypotheses on the source of this gating signal. We will leverage our novel many-electrode
recording techniques in non-human primates to test how interactions between prefrontal cortex and basal
ganglia gate representations into memory. In addition, we will test the prediction that gating changes the
temporal dynamics of sensory representations to maintain them in memory.
Second, once a set of items are in working memory, one must be able to select a specific item to use it to
guide behavior. This process is akin to attention, which selects specific external stimuli. Our second aim will
use our many-electrode recording techniques to a) discover the neural mechanisms that control selection from
working memory and b) test hypotheses that relate these mechanisms to those that control attention.
Third, when remembering multiple stimuli, one must judiciously allocate the limited resource of working
memory amongst them: stimuli with greater behavioral relevance should be more accurately remembered. Our
third aim will determine how neurons in prefrontal and parietal cortex control the prioritization of items in
working memory and how this prioritization impacts working memory representations throughout prefrontal,
parietal, and sensory cortices.
While our proposed research is basic in nature, we believe it is an important first step in a mechanistic
understanding of the core cognitive deficits of several mental illnesses, including schizophrenia and anxiety.
Our hope is that this understanding will improve mental health by leading to new diagnostics and treatments for
cognitive disorders. In particular, we hope to use our results to develop physiological markers that will improve
detection, allow for earlier intervention, and guide targeted treatments.