System-based therapies for neuropsychiatric disorders

Can we harness the brain’s plasticity to improve mental health?

Currently, neuropsychiatric treatment is dominated by pharmacology, which has many limitations. Our goal is to develop neuroprosthetics that induce neuroplasticity to rewire the brain after an insult, bypass a traumatic lesion, and unlearn maladaptive conditions. Such devices could revolutionize the domains of neurology and neuropsychiatry in the same way the pacemaker revolutionized cardiology decades ago.

Characterization and manipulation of emotional state and decision making variables in mesolimbic and mesocortico networks

We have recently shown that deep brain stimulation can bias decision-making. Electrical microstimulation is known to induce neural plasticity. When presented with one of two choices, coincident electrical microstimulation of the caudate nucleus increased the value of that choice and the likelihood that it would be selected. The caudate nucleus is part of the striatum and has connections with the cortex and thalamus that are known to be important for goal-directed action and mood. These results support potential future applications of microstimulation to correct maladaptive plasticity underlying dysfunctional decision-making related to neuropsychiatric conditions.

From “Caudate microstimulation increases value of specific choices.” Click to view in Current Biology.

Selected Publication

Caudate microstimulation increases value of specific choices (2017)

Santacruz S.R., Rich E.L., Wallis J.D., and Carmena J.M. (2017) Caudate microstimulation increases value of specific choices. Current Biology Online Now DOI: http://dx.doi.org/10.1016/j.cub.2017.09.051.

Abstract

Value-based decision-making involves an assessment of the value of items available and the actions required to obtain them. The basal ganglia are highly implicated in action selection and goal-directed behavior [, , , ], and the striatum in particular plays a critical role in arbitrating between competing choices [, , , , ]. Previous work has demonstrated that neural activity in the caudate nucleus is modulated by task-relevant action values [, ]. Nonetheless, how value is represented and maintained in the striatum remains unclear since decision-making in these tasks relied on spatially lateralized responses, confounding the ability to generalize to a more abstract choice task [, , ]. Here, we investigate striatal value representations by applying caudate electrical stimulation in macaque monkeys (n = 3) to bias decision-making in a task that divorces the value of a stimulus from motor action. Electrical microstimulation is known to induce neural plasticity [, ], and caudate microstimulation in primates has been shown to accelerate associative learning [, ]. Our results indicate that stimulation paired with a particular stimulus increases selection of that stimulus, and this effect was stimulus dependent and action independent. The modulation of choice behavior using microstimulation was best modeled as resulting from changes in stimulus value. Caudate neural recordings (n = 1) show that changes in value-coding neuron activity are stimulus value dependent. We argue that caudate microstimulation can differentially increase stimulus values independent of action, and unilateral manipulations of value are sufficient to mediate choice behavior. These results support potential future applications of microstimulation to correct maladaptive plasticity underlying dysfunctional decision-making related to neuropsychiatric conditions.
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