Cortical and Sensory Systems
Charles J. Hodge, MD, Professor
Cortical Plasticity Laboratory
Cortical Reorganization Following Alterations in Peripheral Input Patterns
Cortical organization is established and maintained by the patterns of peripheral inputs comprising the somatosensory system. We use the rodent whisker barrel system to examine pattern-dependent changes in cortical functional organization following alterations in patterns of whisker follicle inputs.
Using intrinsic optical imaging, we examined the cortical response to single whisker stimulation in normal adult rat and compared these to adults with various patterns of whisker follicle ablations 7-days after birth. Results showed a distortion of the functional response in follicle-ablated animals that expanded toward adjacent, hypo-active cortical regions, presumably as a result of disinhibition. Questions remain concerning temporal aspects of the cortical plasticity, affects of age on the ability of cortex to reorganize, as well as ability of pharmacological treatments to affect the plastic response.
—Charles J. Hodge, Jr., Rick Stevens
Pharmacological Treatments Effecting Cortical Reorganization Following Central Lesions
In our laboratory we are evaluating mechanisms of cortical plasticity following excitotoxic injury and testing the efficacy of pharmacological interventions in modulating this plasticity. Recent work has shown that post-injury treatment with d-amphetamine (d-amp) greatly enhances behavioral recovery in both experimental animals and humans. By contrast, Phenytoin, a commonly used anti-seizure medication, impairs long-term recovery. Using the rodent whisker-barrel system as our model, we induce focal lesions in the somatosensory cortex using microinjections of the excitotoxin kainic acid. Previous work in our laboratory has shown that these lesions produce a relocation of the functional response of effected whisker barrel into adjacent, non-lesioned cortex. An incomplete recovery occurs over time (Nguyen et al., 2000). In more recent studies we have shown that the rate and extent of post-injury recovery can be manipulated with pharmacological treatment. Specifically, the catecholamine agonist, d-amphetamine can facilitate post-injury plasticity while the calcium blocker Phenytoin has an opposite effect.
Following these studies, many questions remain including how behavioral manifestations of these drugs in the animals may contribute to the observed functional recovery. Additionally, it is important to know how this recovery observed at the cortical level translates to improved somatosensory function for the animal. Charles J. Hodge, Jr., Aneela Darbar, Rick Stevens
Amphetamine Therapy to Enhance Post-Stroke Recovery
Animal studies have demonstrated dramatic improvement in the speed and extent of behavioral recovery after brain injury with the use of the neurostimulant d-amphetamine (d-amp) when combined with physical training. Although preliminary evidence in humans suggests similar beneficial effects of d-amp, their precise influence on mechanisms of plasticity remains largely unknown. Our studies will utilize the standard of care protocols of occupational and physical therapy in patients soon after acute ischemic strokes and evaluate the effects of d-amp using motor, psychometric, functional MRI, electrophysiologic and transcranial magnetic stimulation paradigms. These studies will allow elaboration of underlying mechanisms in a longitudinal fashion using behavioral, structural and electrophysiological correlates. The insight gained from these studies will help determine the most effective management of patients to maximize recovery after stroke.
—Charles J. Hodge, Jr., Aneela Darbar, Brian Rieger, Blair Calancie
Cortical Electrical Stimulation Combined with Physical Therapy to Enhance Motor Recovery Following Stroke
Given the strong clinical evidence that epidural cortical stimulation (CS) combined with physical therapy enhances motor recovery in stroke patients, we have studied this process in the rodent whisker-barrel model in order to better understand the mechanisms involved. Using intrinsic optical imaging, normal cortical responses to single whisker stimulation will be compared with responses following periods of CS coincident with whisker stimulation. It is anticipated that cortical response to whisker stimulation will be enhanced following a period of CS-whisker co-stimulation.
Subsequently, similar CS-whisker treatments will be performed in kainic acid-lesioned cortex to determine if functional recovery which we have observed in our previous studies to occur over time, can be enhanced. These findings can have important implications in the care and management of post-stroke patients.
—Charles J. Hodge, Jr., Rick Stevens
