Our over-arching goal is to understand the neural bases of cognitive and behavioral sequences through research that integrates human and animal experimental models. These complementary levels of analysis allow us to construct an understanding of sequential control spanning cells, networks, and behavior.

Recent work in humans using fMRI and TMS has shown that the rostrolateral prefrontal cortex (RLPFC) shows distinct activity across a task sequence, and is necessary for performance of repeated sequences of simple feature judgment tasks (e.g. Color, Shape, Shape, Color). We found that RLPFC activity increases (“ramps”) from the first position in the sequence to the last, then resets (Desrochers et al., 2015b, Neuron). Neural activity with similar dynamics has been recorded electrophysiologically from rodents and monkeys. There is active debate both as to the neural activity underlying this imaging signal (e.g., single cells vs. population), and process (e.g., evidence accumulation vs. progress towards a goal). We have hypothesized that ramping activation in RLPFC aids in tracking and resolving positional uncertainty in the sequence, but the neural basis of this novel sequential control dynamic determined with fMRI remains unknown.

Research Questions:
  1. Which brain areas support sequential task performance in animals, and how?  Using awake-behaving neuroimaging, we will determine the relative contributions of frontal cortical areas to tracking sequential information.
  2. Which brain areas support sequential task performance in humans, and how do they relate to those in animals? Using the same kind of neuroimaging in the same task, we will directly determine the functional homology across species.
  3. What are the specific neural mechanisms underlying sequential control in frontal cortex?  We will use electrophysiology in animals guided by neuroimaging to determine the cellular makup of sequential control signals.
  4. Does the novel representation of cost we observed in the striatum (Desrochers et al., 2015a, Neuron) during habitual motor sequences generalize to more abstract sequential control, i.e. task sequences? Our working hypothesis is yes, and that these more abstract representations will be more anterior in striatum, paralleling caudal-to-rostral gradients in frontal cortex and its connections with striatum (Desrochers & Badre, 2012, TICS). This work will employ more abstract tasks in animals where invasive neural recordings and manipulation are possible, and the study of parallel tasks in humans.
  5. Despite the commonality of OCD, which affects ~2.3% (3.3 million) of the US population, we know relatively little about the specific brain circuits responsible. A specific outstanding question is: Do patients with OCD have deficits in sequential control? This intuitive prediction has, surprisingly, not received detailed investigation.  Do patients perform sequences of tasks, in a controlled lab setting, the same way as healthy controls? What brain areas are recruited? Is there a deficit in striatal end signaling or the cost/reward signals we previously delineated? We will apply our sequential control tasks in OCD populations to investigate these questions. Such studies could have clinical importance and lead to novel understandings of this disorder.