Biology subjects

Bundy, D. T.

Publications and source records attributed to Bundy, D. T..

3 recordsLinked to original sources

bioRxiv2025

Absence of cortical reorganization following an internal capsule stroke in rodents

Stroke is a leading cause of disability, causing chronic motor impairments in many survivors. Although recovery is correlated with cortical reorganization, the impact of lesion location on post-stroke reorganization is uncertain. We compared movement-related neural activity following experimental infarcts to the motor cortex (M1) or internal capsule in rats. Neural activity was recorded from motor and somatosensory regions during a skilled pellet retrieval task longitudinally during the course of recovery. Cortical lesions resulted in early behavioral recovery accompanied by widespread reductions in neural activity across ipsilesional regions, indicative of large-scale reorganization. In contrast, internal capsule lesions produced delayed recovery with no evidence of long-term ipsilesional cortical reorganization. These findings challenge the relevance of cortical reorganization for recovery from subcortical lesions and indicate that post-stroke recovery mechanisms are lesion-specific and that models targeting subcortical white matter are essential for maximizing translational relevance.

neuroscience↗

bioRxiv2025

Motor impairment and adaptation in a novel non-human primate model of internal capsule infarct

Loss of distal hand and finger control is among the most disabling consequences of stroke. Functional outcomes are typically worse when infarcts involve subcortical white matter tracts, particularly the internal capsule, yet most preclinical stroke models target cortical regions. To address this gap, we developed a non-human primate model of internal capsule infarct using stereotactically guided endothelin-1 injections to disrupt descending fibers from the primary motor cortex hand area. Serial structural and diffusion MRI, along with histology, confirmed subcortical infarcts centered on the targeted white matter region with no apparent cortical involvement. Motor function was assessed pre- and post-infarct using a joystick-based center-out task (proximal forelimb control) and a Kluver board task (distal forelimb control). Animals exhibited variable impairments in proximal function and consistent post-infarct deficits in distal function, including reduced contralesional hand use, longer retrieval time, and increased in-well digit flexions. One animal showed mild post-infarct impairment and the smallest lesion, highlighting that this model reflects inter-individual differences in infarct size and functional outcome as seen in human subcortical stroke. In contrast, the other two animals developed a compensatory wrist-extended posture on the Kluver board task by 4 weeks post-infarct, which stabilized the hand and enabled improved digit flexion. Incorporating this behavioral adaptation into statistical models improved prediction of motor performance. The observed adaptation may have drawn on spared corticospinal output pathways, allowing animals to re-engage pre-existing motor routines to perform the retrieval. While future studies may benefit from ethologically relevant tasks to further elucidate such adaptations, findings from this study recapitulate key features of human subcortical stroke, including persistent distal motor deficits and emergence of adaptive motor strategies. By combining precise lesioning, longitudinal imaging, and detailed behavioral analysis, this model provides a translationally oriented platform for studying white matter stroke mechanisms and evaluating interventions that promote functional recovery.

neuroscience↗

bioRxiv2022

Mesoscale corticocortical connectivity corresponds with intracortical microstimulation-evoked neural activity

BackgroundCortical electrical stimulation has been a versatile technique for examining the structure and function of cortical regions as well as for implementing novel therapies. While electrical stimulation has been used to examine the local spread of neural activity, it may also enable longitudinal examination of mesoscale interregional connectivity. Recent studies have used focal intracortical microstimulation (ICMS) with optical imaging to show cross-region spread of neural activity, but techniques are limited to utilizing hemodynamic responses within anesthetized preparations. ObjectiveHere, we sought to use ICMS in conjunction with recordings of multi-unit action potentials to assess the mesoscale effective connectivity within sensorimotor cortex. MethodsNeural recordings were made from multielectrode arrays placed into sensory, motor, and premotor regions during surgical experiments in three squirrel monkeys. During each recording, single-pulse ICMS was repeatably delivered to a single region. Mesoscale effective connectivity was calculated from ICMS-evoked changes in multi-unit firing. ResultsMulti-unit action potentials were able to be detected on the order of 1 ms after each ICMS pulse. Across sensorimotor regions, short-latency (< 2.5 ms) ICMS-evoked neural activity strongly correlated with known anatomic connections. Additionally, ICMS-evoked responses remained stable across the experimental period, despite small changes in electrode locations and anesthetic state. ConclusionsThese results show that monitoring ICMS-evoked neural activity, in a technique we refer to as Stimulation-Evoked Effective Connectivity (SEEC), is a viable way to longitudinally assess effective connectivity enabling studies comparing the time course of connectivity changes with the time course of changes in behavioral function. HighlightsO_LIShort-latency neural responses to ICMS were evaluated in multiple cortical regions. C_LIO_LINeural responses strongly correlated with known anatomical connections. C_LIO_LIStimulation-evoked neural responses were maintained across repeated tests. C_LIO_LIICMS-evoked activity can show longitudinal changes in effective connectivity. C_LI

neuroscience↗