Noninvasive Brain Stimulation to Improve Memory and Cognition After Stroke

Approximately 44% of stroke survivors demonstrate lasting cognitive impairment. This corresponds to about 1.3% of the US adult population affected yearly, or about 2.4 million Americans. These cognitive impairments are devastating for long--‐term outcome, and there are no current effective treatments. Cognitive impairments that follow stroke have been linked to disrupted functional integrity of the hippocampal brain system, which is a collection of distributed structures that together mediate memory and many forms of memory--‐based self--‐regulation (e.g., decision making). Disruption of the hippocampal brain system is a serious challenge for clinical intervention. This is because it includes a heterogeneous mixture of limbic and cortical brain regions, and therefore there are no clear neuropharmacological targets. Further, the hippocampus is a central aspect of this system, and it lies deep within the brain and therefore cannot be easily manipulated via either surgical or noninvasive methods. To this end, my laboratory has recently developed the first noninvasive treatment that can be used to improve the function of the hippocampal brain system. We use noninvasive electromagnetic pulses to induce electrical activity in cortical areas of the hippocampal brain system, which we have shown increases the functional interconnectivity of the system as a whole. This change in interconnectivity is associated with an increase in long--‐term memory performance. Notably, we have found that these beneficial changes to the function of the hippocampal brain system outlast the treatment (by a period of at least 24 hours in our control studies). This new treatment thus provides the first opportunity to improve the hippocampal brain system and the memory and cognitive functions that it supports. With support from a Brinson Foundation Junior Investigator Translational Research Grant, we would determine the extent to which it can be used to treat disruptions of the hippocampal brain system from stroke. With support from the Brinson Foundation, we will use a staged research approach that will allow us to explore the ability for noninvasive stimulation of the hippocampal brain system to improve memory and cognition in stroke survivors. For the first step, we will run a small, randomized trial to measure effects of our noninvasive brain stimulation procedures on memory performance in stroke survivors (N=10). This first step will allow us to assess the suitability of these methods for stroke survivors, including tolerability, and will generate data that will allow us to estimate effect sizes that will facilitate plan subsequent experiments. Given success of the first stage of the project, we anticipate that a second stage will include testing in a larger sample using MRI--‐based assessment of the effects of stimulation on the hippocampal brain system. A staged approach is ideal in that it allows for preliminary exploration of feasibility followed by more intensive assessment motivated by initial findings.