Cortical excitability changes induced by deafferentation of the contralateral hemisphere

Abstract

Short-term deprivation of sensory input by ischaemic nerve block (INB) leads to functional reorganization in the deafferented motor cortex. Here, we show that INB also elicits functional changes in homotopic regions of the cortex contralateral to the deafferented one. We measured motor evoked potential (MEP) amplitudes elicited by transcranial magnetic stimulation (TMS) in small hand and biceps brachii muscles before, during and after INB of the right hand. INB increased excitability of the cortical representation of (i) the intact hand and (ii) body parts proximal to the deafferented hand (upper arm), in the absence of excitability changes in other body part representations such as thorax or leg muscles. This effect persisted throughout the entire period of deafferentation and returned to baseline values afterward. Motor responses to brainstem electrical stimulation remained unchanged during INB, indicating that the effect is probably of cortical origin. Lorazepam, a GABA(A) receptor agonist, blocked this increased excitability. Interhemispheric inhibition between hand muscles decreased during INB. After chronic deafferentation in amputees, MEP amplitudes and motor output curves in small hand muscles were depressed and motor thresholds were elevated compared with aged-matched controls. These results indicate that acute hand deafferentation can elicit a focal increase in excitability in the hand motor representation contralateral to the deafferented cortex that is influenced by transcallosal interactions and GABAergic transmission, and is balanced in the setting of chronic deafferentation.

Optogenetic-guided cortical plasticity after nerve injury

“…Increases in cortical excitability were also shown to be accompanied by increases in AMPA receptor autoradiographic binding (53) and decreases in GABA staining in the deprived S1 (53,54). Moreover, increases in motor-evoked potential in the motor cortical representations contralateral and ipsilateral to the nerve injury in human subjects were blocked after administration of GABA agonists (24).…”

“…Additional evidence indicates that the increase of inhibitory neuronal activity in the deprived cortex may be the foundation of the poor recovery and pain observed in patients suffering from nerve injury (24,25,57). Moreover, previous studies suggested that these evoked increases in inhibitory activity are mediated through the transcallosal pathway (20,21).…”

“…Indeed, there are ongoing efforts to modify transcallosal activity in patients suffering from peripheral nerve injury. For instance, improvement in tactile discrimination of the injured hand was found after decreasing afferent inputs from the intact hand using constraint induced therapy (CIT) (22), using nerve blocking (23), and directly inhibiting neuronal networks through transcranial magnetic stimulation (TMS) (24,25). Still, these rehabilitation approaches are neither precise nor neuronalspecific, and they cannot be repeated often.…”

Use-Dependent Hemispheric Balance

“…In fact, an acute upper limb deafferentation induced a focal increase in the excitability of the non-deafferented hand motor cortex (Werhahn et al, 2002a;Floel et al, 2008) together with improvements in the non-deafferented hand in either tactile spatial acuity in healthy subjects (Werhahn et al, 2002b) and in hand motor performance in patients with stroke (Floel et al, 2008).…”

Intracortical inhibition and facilitation with unilateral dominant, unilateral nondominant and bilateral movement tasks in left- and right-handed adults

“…This occurs in healthy adults (20) and in stroke patients when the intact hand is anesthetized (21) and argues against activating the non-paretic arm and hand while training the paretic arm and hand. Furthermore, there is evidence that some patients with chronic stroke and larger impairments have an abnormally high interhemispheric inhibitory drive from M1 in the contralesional hemisphere to M1 in the ipsilesional hemisphere (22).…”