Center Investigators

Jason Weick, PhD

Neurosciences

Functional Recovery from Acute Brain Injury via Human Neural Stem Cell Transplantation

Specific Aim 1: What is the time course and magnitude of functional recovery following intracortical transplantation of hPSNs in a mouse model of focal cerebral ischemia? We will establish the rate and time course of behavioral recovery following hPSNS transplantations in a focal photothrombotic model of ischemic injury. hPSNs will be transplanted one week after ischemic injury and behavioral and anatomic recovery will be assessed using multiple motor, sensory, and immunochemical tests.

Specific Aim 2: Is behavioral recovery enhanced by increased activation of transplanted hPSNs? Ontogenetic stimulation of hPSNs via hannelrhodopsin-2 will be used to test whether the rate or magnitude of behavioral recovery is enhanced by chronic intermittent depolarization of transplanted cells.

Specific Aim 3: Do transplanted hPSNs receive physiologically relevant afferent innervation from host? Using in-vivo multi-electrode recording of transplanted neurons during peripheral sensory stimulation we will determine whether hPSNs display altered spiking behavior during simulation that would normally activate endogenous cortical circuits.


Denis Bragin, PhD

Neurosurgery

Brain Stimulation in Animal Models of Recovery of Acute Brain Injury

Specific Aim 1: To evaluate the time and polarity-dependent effectiveness of tDCS in improving neurologic recovery after traumatic brain injury. These experiments will test the hypothesis that stimulation beginning at one and three weeks following TBI improves motor and cognitive function. Using an established mouse TBI model (controlled cortical impact), we will assess effects of repetitive tDCS stimulation of different polarity, applied beginning at either one week or three weeks after TBI on behavioral outcomes at two and three months post-injury.

Specific Aim 2: To determine whether tDCS enhances migration and differentiation of endogenous neural stem cells after traumatic brain injury. These experiments will test the hypothesis that repetitive tDCS modulates recruitment of endogenous NSC to areas of focal injury. Mice will be sacrificed at multiple time points post stimulation, and numbers and phenotypes of neural stem-derived cells will be identified by stereological analysis in brain sections.

Specific Aim 3: To determine whether tDCS induces long-lasting modulation of regional and microvascular flow during recovery from traumatic brain injury. These experiments will test the hypothesis that repetitive tDCS can modulate neurovascular coupling in peri-infarct area. Laser speckle contrast imaging and two-photon imaging will be used to identify regional and microvascular flow changes, respectively, to assess the effect of stimulation during the recovery period.


James Cavanagh, PhD

Psychology

Predicting Recovery of Cognitive Control Deficits in Traumatic Brain Injury

Specific Aim 1: To investigate whether functional EEG abnormalities (theta band phase synchrony) underlie common disturbances of cognitive control during the semi-acute injury stage.
Hypothesis 1: Theta band phase synchrony during cognitive control will be diminished during the semi-acute stage of mmTBI, and will be correlated with dysfunctional performance across multiple measures of cognitive control (e.g. accuracy and response times)
Hypothesis 2: Functional EEG Abnormalities will be related to the degree of white matter lesions as assessed by DTI, linking white matter abnormalities with functional consequences.

Specific Aim 2: To investigate whether functional EEG activities predict recovery post-injury.
Hypothesis 1: A restoration in theta band phase synchrony during cognitive control will be predictive of better cognitive control recovery at 4 months post-injury, providing a biomarker of recovery.
Hypothesis 2: The functional measure of theta band phase synchrony will predict the extent of recovery in cognitive control over and above the predictive power of more traditional measures of structural pathology.
Hypothesis 3: Novel pattern classification techniques bases on these predictive measures will exhibit high sensitivity for classifying patients relative to controls and for defining the independent contribution of separate prognostic measures (structural, functional, behavioral) for predicting recovery.


Davin Quinn, MD

Pyschiatry

Transcranial Direct Current Stimulation for Treatment of Deficits after Traumatic Brain Injury

Specific Aim 1: tDCS for executive dysfunction in mmTBI. Experiments in this aim will test the hypothesis that in patients with mmTBI, left prefrontal anodal tDCS concurrent with cognitive training for ten consecutive weekdays will result in significantly more improvement in executive function compared to sham stimulation. Patients with cognitive complaints 3 months to 2 years after mmTBI will be recruited from local emergency departments and brain injury clinics.
Aim 1.1: tDCS will be paired with computer-based cognitive training tasks of response inhibition, set shifting and working memory. Executive function will be measured with the NIH Examiner batter before, immediately after, and one month after stimulations.
Aim 1.2: Persistence of post-traumatic symptom reduction and quality of life improvement will be assessed with Common Data Elements instruments via telephone interview at six months and one year.
Aim 1.3: Clinical predictor of tDCS response including injury severity, premorbid intelligence and post-traumatic symptom burden will be determined with linear mixed-models analysis.

Specific Aim 2: tDCS for depressive symptoms in mmTBI. Experiments in this aim will test hypothesis that left prefrontal anodal tDCS in patients with mmTBI will significantly reduce depressive symptoms compared to sham stimulation.
Aim 2.1: Patients will be assessed for symptoms of depression via self-report instruments and clinician-administered scales from NIH common Data Elements before, immediately after, and one month after the stimulation protocol.
Aim 2.2: Persistence of antidepressant benefit will be assessed via telephone interview at 6 months and one year.
Aim 2.3: Clinical predictor of tDCS response such as injury severity, premorbid intelligence, and symptom burden will be determined. Accomplishment of these Aims will have a tremendous clinical impact on the treatment of chronic and debilitating TBI-related symptoms, and will establish tDCS as an effective and safe tool to be used for the important clinical problem. Future studies would be able to refine and expand this technique to different TBI populations, as well as other similar neuropsychiatric disorders. 


Jessica Richardson, PhD

Speech & Hearing Sciences

Targeted tDCS to Enhance Treatment Outcomes in Persons with Aphasia

Specific Aim 1: Measure treatment-induced improvements in language abilities.
We postulate that participants will demonstrate improved naming and language use (i.e., narrative abilities, confidence), with greater and longer lasting gains following adjuvant brain stimulation.

Specific Aim 2: Measure connectivity and balance pre- and post- aphasia treatment.
Our working hypothesis is that increased intra- and inter-hemispheric connectivity (measured with resting-state fMRI) and more normalized interhemispheric balance (measured with quantitative EEG) will be observed following aphasia treatment, with greater and longer-lasting changes following adjuvant brain stimulation.

Specific Aim 3: Examine relationship between language outcomes and changes in brain dynamics (e.g., connectivity and balance).
We hypothesize that greater gains in language abilities will be related to greater adaptive changes in brain dynamics.