Longitudinal fMRI measures of cortical reactivation and hand use with and without training after sensory loss in primates

Abstract

In a series of previous studies, we demonstrated that damage to the dorsal column in the cervical spinal cord deactivates the contralateral somatosensory hand cortex and impairs hand use in a reach-to-grasp task in squirrel monkeys. Nevertheless, considerable cortical reactivation and behavioral recovery occurs over the following weeks to months after lesion. This timeframe may also be a window for targeted therapies to promote cortical reactivation and functional reorganization, aiding in the recovery process. Here we asked if and how task specific training of an impaired hand would improve behavioral recovery and cortical reorganization in predictable ways, and if recovery related cortical changes would be detectable using noninvasive functional magnetic resonance imaging (fMRI). We further asked if invasive neurophysiological mapping reflected fMRI results. A reach-to-grasp task was used to test impairment and recovery of hand use before and after dorsal column lesions (DC-lesion). The activation and organization of the affected primary somatosensory cortex (area 3b) was evaluated with two types of fMRI – either blood oxygenation level dependent (BOLD) or cerebral blood volume (CBV) with a contrast agent of monocrystalline iron oxide nanocolloid (MION) – before and after DC-lesion. At the end of the behavioral and fMRI studies, microelectrode recordings in the somatosensory areas 3a, 3b and 1 were used to characterize neuronal responses and verify the somatotopy of cortical reactivations. Our results indicate that even after nearly complete DC lesions, monkeys had both considerable post-lesion behavioral recovery, as well as cortical reactivation assessed with fMRI followed by extracellular recordings. Generalized linear regression analyses indicate that lesion extent is correlated with the behavioral outcome, as well as with the difference in the percent signal change from pre-lesion peak activation in fMRI. Monkeys showed behavioral recovery and nearly complete cortical reactivation by 9–12 weeks post-lesion (particularly when the DC-lesion was incomplete). Importantly, the specific training group revealed trends for earlier behavioral recovery and had higher magnitude of fMRI responses to digit stimulation by 5–8 weeks post-lesion. Specific kinematic measures of hand movements in the selected retrieval task predicted recovery time and related to lesion characteristics better than overall task performance success. For measures of cortical reactivation, we found that CBV scans provided stronger signals to vibrotactile digit stimulation as compared to BOLD scans, and thereby may be the preferred non-invasive way to study the cortical reactivation process after sensory deprivations from digits. When the reactivation of cortex for each of the digits was considered, the reactivation by digit 2 stimulation as measured with microelectrode maps and fMRI maps was best correlated with overall behavioral recovery.

Decreased but diverse activity of cortical and thalamic neurons in consciousness-impairing rodent absence seizures

“…The unanesthetized GAERS model therefore shows cortical fMRI signal decreases and thalamic increases during SWDs, similar to the changes associated with human absence seizures. The magnitude of the changes, at ~1%, are comparable to the ~0.5% changes observed in humans 14 , 20 and at the upper end of the general 0–1% expected range for normal (non-noise-induced) fMRI signal dynamics across species 46 , 47 . The relatively large changes in GAERS may be due to their selective breeding for the expression of robust, widespread SWDs.…”

Regressive changes in sizes of somatosensory cuneate nucleus after sensory loss in primates

“…These data include six adult monkeys that experienced a task-specific training regimen of hand use before and after the dorsal column lesion. Although analysis suggested performance benefits of the behavioral task training ( 24 ), the Cu size did not show signs of greater preservation. In this set of cases, we also included nine monkeys with chondroitinase ABC (chABC) treatments, which was expected to promote tissue repair and axon sprouting after a spinal cord injury by digesting scar components (e.g., refs.…”

“…However, we do not know if hand use effects the size of Cu or if the Cu for each hand differs in size in humans based on handedness. We do know that sensory loss impacts hand use, especially during the first few months after the loss, with considerable recovery due to plasticity within the somatosensory system emerging after 4 to 6 mo ( 24 , 39 ).…”

“…A small sample of DCL cases in our study received the intervention of task-specific training with the affected arm ( 24 ) or treatment with the enzyme chABC in native form ( 28 ) or modified in an affinity release hydrogel ( 29 , 30 ). The interventions may have increased the reactivation of Cu, but they did not prevent Cu size reduction.…”

Sensory Circuit Remodeling and Movement Recovery After Spinal Cord Injury

“…In chronic injury, this leads to afferent information from neighboring regions activating neurons in deafferented cortex and driving phantom sensations rather than functional recovery ( Jain et al, 1997 ). Rehabilitation may be used to effectively shape S1 remodeling as fMRI imaging in non-human primates trained on a reach-to-grasp task shows reactivation of somatosensory cortex after unilateral dorsal column lesion S1 ( Qi et al, 2021 ). In this study, cortex rendered unresponsive to vibrotactile stimulation by injury began to respond to stimuli as hand use improved.…”