Spinal Cord Injury and Loss of Cortical Inhibition

Abstract

After spinal cord injury (SCI), the destruction of spinal parenchyma causes permanent deficits in motor functions, which correlates with the severity and location of the lesion. Despite being disconnected from their targets, most cortical motor neurons survive the acute phase of SCI, and these neurons can therefore be a resource for functional recovery, provided that they are properly reconnected and retuned to a physiological state. However, inappropriate re-integration of cortical neurons or aberrant activity of corticospinal networks may worsen the long-term outcomes of SCI. In this review, we revisit recent studies addressing the relation between cortical disinhibition and functional recovery after SCI. Evidence suggests that cortical disinhibition can be either beneficial or detrimental in a context-dependent manner. A careful examination of clinical data helps to resolve apparent paradoxes and explain the heterogeneity of treatment outcomes. Additionally, evidence gained from SCI animal models indicates probable mechanisms mediating cortical disinhibition. Understanding the mechanisms and dynamics of cortical disinhibition is a prerequisite to improve current interventions through targeted pharmacological and/or rehabilitative interventions following SCI.

The human pupil and face encode sound affect and provide objective signatures of tinnitus and auditory hypersensitivity disorders

“…One general limitation of observational research on human sensory disorders relates to uncertainty about the underlying precipitators of tinnitus and sound sensitivity in our subjects. Hearing loss, age, and certain medications can directly impact central gain and tinnitus [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] , motivating us to strictly screen and match these variables in NT and DH cohorts to control for a confounding influence.…”

“…Most evidence suggests that disinhibition in auditory processing centers of the brain is a proximal cause of tinnitus and sound sensitivity [3][4][5][6][7] . Central auditory disinhibition related to tinnitus and sound sensitivity can arise from normal aging 8,9 , as a compensatory response to hearing loss and auditory nerve degeneration [10][11][12][13][14][15][16][17][18][19] , from traumatic injury of the brain or cervical ganglia [20][21][22] , or simply from the abrupt cessation of prescription GABA agonists 23,24 . Whatever the source, the Excess Central Gain model posits that disinhibition has the knock-on effect of increasing the synchrony and activity rate of local excitatory neurons in silence (the basis of the phantom sound) as well as disproportionately strong responses to moderately intense sound (the basis of loudness hypersensitivity) [25][26][27][28][29] .…”

“…Most evidence suggests that disinhibition in auditory processing centers of the brain is a proximal cause of tinnitus and sound sensitivity [3][4][5][6][7] . Central auditory disinhibition related to tinnitus and sound sensitivity can arise from normal aging 8,9 , as a compensatory response to hearing loss and auditory nerve degeneration [10][11][12][13][14][15][16][17][18][19] , from traumatic injury of the brain or cervical ganglia [20][21][22] , or . CC-BY-NC-ND 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

The role of arousal and motivation in emotional conflict resolution: Implications for spinal cord injury

“…As the primary relay center of neural transmission, a SCI interrupts the communication of the afferent and efferent systems between the brain and the rest of the body ( Leemhuis et al, 2019 , 2022 ), via the spinal projections ( Bican et al, 2013 ; Rupp, 2020 ). The axotomy after SCI has thus implications for the motor, sensory, autonomic physiology of the cortical and corticospinal network ( Nagendran et al, 2017 ; Michael et al, 2019 ; Benedetti et al, 2022 ). Accordingly, patients with SCI represent an ideal model for studying the role of physiological arousal in resolving emotional conflict, given their distinct pathophysiological autonomic profile.…”

Brain Activation Evoked by Motor Imagery in Pediatric Patients with Complete Spinal Cord Injury

“…T raumatic spinal cord injury is a sudden and unpredictable incident that can destroy the spinal cord, leading to sensory and motor dysfunction. 1 It can occur at any age, including childhood, not only causing a heavy burden on the families but also having serious consequences for children's physical and mental well-being. 2 The most common rehabilitation strategy used in patients with incomplete spinal cord injury is physical training, which is intended to promote cortical plasticity by driving motor neural networks and facilitating functionally relevant muscle activity below the injury level.…”