Alex Carter, M.D., Ph.D.
stroke, resting state connectivity, brain
Network plasticity as it pertains to neurorehabilitation, particularly in recovery from stroke
Our interests lie within the area of network plasticity as it pertains to neurorehabilitation, particularly in recovery from stroke. We are trying to apply a two-pronged approach to this difficult problem. First we are using the novel technique of resting-state functional connectivity MRI (fcMRI) to better characterize distributed brain networks in healthy individuals and those with stroke. In particular we seek to better understand the behavioral relevance as well as the determinants of resting state connectivity. One approach, with the help and guidance of the Corbetta lab, has been to investigate the effects of stroke on resting state connectivity in distributed brain networks. Interesting findings have included that connectivity is decreased between brain regions that are not structurally damaged but that are connected to regions of structural damage, demonstrating that focal lesions can have remote physiological effects on network functioning. Also, we have shown that behavioral impairment is significantly correlated with the decrease in interhemispheric connectivity which has reignited our interest in understanding interhemispheric interactions.
In addition to this preliminary work in stroke patients, we are also investigating the determinants of resting state connectivity in the healthy brain in multiple ways. In one approach, we are studying the effect of extensive training on connectivity in the somatomotor network by comparing connectivity in advanced musicians to connectivity in age and education matched non-musician control subjects. We hypothesize that if resting state connectivity reflects the history of coactivation between brain regions that the manual dexterity of musicians will manifest as an increase in resting connectivity that is specific to the somatomotor network. Effects on other networks are also being investigated. Conversely, we predict that prolonged arm immobilization would be associated with decreased connectivity. This is also being tested experimentally.
A second approach to investigating resting state connectivity takes advantage of the presence of somatotopy in the motor cortex and the fact that we have different degrees of dexterity and left-right lateralizability across the human body plan. We hypothesize that increased dexterity or lateralizability requires more interhemispheric communication to select and implement specific motor programs while inhibiting undesired ones. Therefore we are investigating differences in interhemispheric connectivity between regions corresponding to various body parts (hand, foot, face, tongue, brow) using their somatotopic cortical representation.
The second prong to our overarching goal is to use the tools of non-invasive brain stimulation to attempt to directly modulate brain network connectivity. With transcranial magnetic stimulation we have begun to manipulate brain networks to observe the effect on behavior and on resting connectivity. We now have the technical capability of imaging a network, modulating it through behavioral training or non-invasive brain stimulation, and then imaging the network again to see how it has changed – all while being able to collect behavioral data at different time points in the experimental process. This approach can be used in healthy individuals to increase our understanding of brain network function, but may ultimately allow us to optimize recovery of brain function after stroke. Two stroke syndromes where we hope to apply this methodology include the recovery from hemiparesis and the recovery from hemi-spatial neglect. Increasing evidence suggests that, paradoxically, suppression of the unaffected hemisphere, in the regions opposite to those damaged by stroke, may lead to better recovery. Whether altered resting state connectivity plays a role is not known. With the tools at our disposal, we can now determine the conditions under which this general concept may hold true as well as probe the underlying mechanisms.
Carter AR, Astafiev SV, Lang CE, Connor LT, Rengachary J, Strube MJ, Pope DL, Shulman GL and Corbetta M. Resting inter-hemispheric fMRI connectivity predicts performance after stroke. Ann Neurol. 2010 Mar;67(3):365-75.
Carter AR, Connor LT, Dromerick AW. Rehabilitation After Stroke: Current State of the Science. Curr Neurol Neurosci Rep. 2010 May;10(3):158-66.
Carter AR, Shulman GL, and Corbetta M. Brain mapping of the attentional system after stroke (chapter submitted for upcoming book “Brain Repair after Stroke”, S. Cramer, R. Nudo, editors, October 2010, Cambridge University Press).
Crowner BE, Torres-Russotto D, Carter AR, Racette BA. Systemic weakness after therapeutic injections of botulinum toxin a: a case series and review of the literature. Clin Neuropharmacol. 2010 Sep-Oct;33(5):243-7.