Stroke Induces Long-Lasting Deficits in the Temporal Fidelity of Sensory Processing in the Somatosensory Cortex

Abstract

Recovery from stroke is rarely complete as humans and experimental animals typically show lingering deficits in sensory function. One explanation for limited recovery could be that rewired cortical networks do not process sensory stimuli with the same temporal precision as they normally would. To examine how well peri-infarct and more distant cortical networks process successive vibrotactile stimulations of the affected forepaw (a measure of temporal fidelity), we imaged cortical depolarizations with millisecond temporal resolution using voltage-sensitive dyes. In control mice, paired forepaw stimulations (ranging from 50 to 200 milliseconds apart) induced temporally distinct depolarizations in primary forelimb somatosensory (FLS1) cortex, and to a lesser extent in secondary FLS (FLS2) cortex. For mice imaged 3 months after stroke, the first forepaw stimulus reliably evoked a strong depolarization in the surviving region of FLS1 and FLS2 cortex. However, depolarizations to subsequent forepaw stimuli were significantly reduced or completely absent (for stimuli p100 milliseconds apart) in the FLS1 cortex, whereas FLS2 responses were relatively unaffected. Our data reveal that stroke induces long-lasting impairments in how well the rewired FLS1 cortex processes temporal aspects of sensory stimuli. Future therapies directed at enhancing the temporal fidelity of cortical circuits may be necessary for achieving full recovery of sensory functions.

Stroke and the Connectome: How Connectivity Guides Therapeutic Intervention

“…These regions could include those that receive common thalamic input or send axonal projections to neighboring targets. For example, motor cortex, primary somatosensory cortex, and secondary somatosensory cortex all receive thalamic input (Hunnicutt et al, 2014;Oh et al, 2014), and function in secondary areas can be preserved after stroke to primary somatosensory areas (Sweetnam and Brown, 2013). In the rodent motor cortex, for example, the strongest intracortical connections are with the rest of the sensory-motor cortex in the same hemisphere, but strong interhemispheric connections also exist with homotopic areas (Bauer et al, 2014).…”

Rapid and Bihemispheric Reorganization of Neuronal Activity in Premotor Cortex after Brain Injury

“…These changes were also observed in iPMv and cPMv, and more pronounced with movements of the paretic hand. Similarly, stroke in the somatosensory cortex induces chronic impairments in the temporal fidelity of responses to peripheral stimulation ( Sweetnam and Brown, 2013 ), which could be because of a dysfunction of the corticothalamic feedback circuit involved in the inhibition of thalamocortical neurons ( Paz et al, 2010 ). In the visual system, corticothalamic feedback from the visual cortex to the lateral geniculate nucleus is involved in spike-timing precision of thalamic neurons' responses to incoming visual signals ( Hasse and Briggs, 2017 ).…”

“…However, most studies have used noninvasive imaging methods based on indirect metabolic measures ( Ward, 2015 ; Crofts et al, 2020 ). To date, direct in vivo recording of the impact of brain injury on neuronal activity has revealed that cortical inactivation or lesion profoundly alters processing of sensory information in the two hemispheres ( Meyer et al, 1985 ; Takatsuru et al, 2009 ; Sweetnam and Brown, 2013 ; Kokinovic and Medini, 2018 ), even within minutes after injury ( Sakatani et al, 1990 ; Ding et al, 2011 ; Mohajerani et al, 2011 ). Such rapid neuronal changes can be viewed as consequences of the lesion on the network's homeostasis ( von Monakow, 1914 ; Carrera and Tononi, 2014 ), with a questionable active involvement in motor function at this stage.…”

A review of novel optical imaging strategies of the stroke pathology and stem cell therapy in stroke

“…Both, VSDs and VSFPs respond to changes in transmembrane voltage in the millisecond time scale, by changing their fluorescence properties [but resolving single action potentials is still limited ( Akemann et al, 2009 )]. Several studies have recently applied VSDs on experimental models of stroke to image functional reorganization of forelimb cortex areas ( Brown et al, 2009 ; Figure 4A ) and long-lasting impairments on the processing of sensory stimuli by the forelimb somatosensory cortex ( Sweetnam and Brown, 2013 ). Weerakkody et al (2013) applied VSD imaging to study the cortical activity after implantation of NSCs into the ventricle of naïve mice.…”