Nathan C. Rowland - US grants

DESCRIPTION (provided by applicant): In the basal ganglia-thalamocortical motor circuit, network activity is precisely timed to facilitate execution of voluntary movement. In Parkinson's Disease (PD), this functional network is impaired by excessive neuronal synchronization that disrupts local oscillations necessary for integrated motor performance. The role of the cortex within this distributed hypersynchronous state is not well understood. Functional imaging studies in PD patients suggest decreased resting state metabolic activity in movement preparatory areas such as the premotor cortex (PreMC), while other studies suggest increased resting state metabolic activity in primary motor cortex (M1). In a previous study (Crowell et al., 2012), our la demonstrated an increase in M1 gamma frequency power spectral density over a very broad band (30-250 Hz) in PD patients versus controls, indicative of increased resting state activity. However, it was not clear if this alteration is also associated with voluntary movement. This is a critical question because one potential explanation for diminished motor performance in PD is that pathological overactivity in M1 at rest reduces the dynamic range over which it can respond to other frontal areas involved in executive motor control. An alternative explanation is that, prir to motor tasks, premotor cortical areas are not appropriately recruited to prepare movement sequences, resulting in attenuated motor execution. A third explanation is that abnormal oscillatory activity in the basal ganglia prevents appropriate selection of motor plans required fo goal-directed movement. Here, we propose a novel approach to testing these hypotheses in patients with basal ganglia dysfunction: electrocorticographic (ECoG) recordings of PreMC and M1 in PD patients performing motor tasks during awake DBS surgery along with detailed structural mapping of cortico-basal ganglia pathways in these same patients using diffusion tensor imaging (DTI). The advantage of this approach is high spatial and temporal resolution of cortical activity matched with precise cortical gyral anatomy of activated and deactivated subcortical pathways. The novelty of this approach is further enhanced in that one motor task will consist of a Go-No Go exercise in which the patient must activate or suppress cued reaching movements to a touch-screen device. This will allow the critical evaluation of the basal ganglia's role in response inhibition at the level of the premotor and motor cortices. We hypothesize that increases in broadband gamma activity (BGA) will be suppressed in PreMC and M1 in PD patients before and during Go trials versus patients without a movement disorder. We also predict that the pattern of PreMC and M1 BGA will be unchanged between successful and unsuccessful No Go trials in patients with PD.

Neuromodulatory approaches for chronic stroke patients are limited. Transcranial direct current stimulation (tDCS) has shown the potential to improve motor deficits in this population; however, its effects have not been consistent in randomized studies to date, limiting widespread adoption. A critical gap in our knowledge is a detailed understanding of how tDCS affects motor cortical oscillations, which are important in guiding voluntary movement. Our long-term goal is to develop effective neuromodulation-based therapeutic systems in chronic stroke patients based on a better understanding of how neuromodulation of cortical signals can improve recovery of motor behavior in this population. In a previous study, we recorded subdural electrocorticography (sECoG) in akinetic-rigid Parkinson?s disease (PD) patients undergoing DBS surgery, and observed significant modulation of motor cortical oscillations in relation to an arm-reaching task. Thus, changes in cortical oscillations supported improved motor performance in this group. Based on these results, our central hypothesis is that modulation of motor cortical oscillations both prior to and during movement may be one mechanism by which tDCS promotes recovery after chronic motor stroke. To test this hypothesis, in PD patients undergoing DBS surgery, we will measure cortical beta (13-30 Hz) and broadband gamma (70-200 Hz) oscillations during a cued arm-reaching task (Aim 1) and a motor imagery task (Aim 2) before and after anodal tDCS activation of primary motor cortex. In these patients, simultaneous sECoG and EEG will be performed. In order to ensure that our findings in PD will be directly translatable to a stroke model, in Aim 3 we will collect pilot data using combined tDCS and EEG in a cohort of chronic stroke patients performing the same arm task as PD patients in Aim 1. Aims 1 and 2 will be performed in the operating room, while Aim 3 will take place in the NI Core EEG lab. We anticipate that tDCS will modulate motor cortical oscillations in a way that biases movement planning and initiation in both populations. This proposal to combine tDCS with sECoG and EEG during neurosurgery is novel. If our hypotheses are confirmed, the findings may have use in developing a closed-loop form of tDCS for stroke recovery, for which we will have pilot data (from Aim 3) to inform such an approach. Furthermore, the measurement of EEG in both PD and chronic stroke patients, using an identical experimental paradigm and recording modality, ensures that the results will be directly interpretable between both models. Finally, our sECoG recordings will provide detailed spatial and frequency domain (above 70 Hz) information not captured by EEG. In the future, these results may potentially set the stage for an invasive system in chronic stroke patients based on sensing and responding to pathological oscillations, as is already commercially available for epilepsy patients and currently in development for PD.