Long-term motor cortex reorganization after facial nerve severing in newborn rats

Using the model of facial nerve injury, we have compared the effect of injury in newborn and adult rats on the adult rat motor cortex (M1). To this end, the facial nerve was severed in 10 newborn rats 2 days after birth (Newborn group) and in 10 adult rats (Adult group). In both the Control (contralateral to untouched nerve) and the Experimental (contralateral to severed nerve) hemisphere of each rat, the M1 output organization was assessed by intracortical microstimulation. Our findings demonstrated that: (i) there is no statistical difference in the percentage of movement sites and in current thresholds required to evoke movement in Control hemispheres between the Adult and Newborn groups of rats; (ii) in Adult Experimental hemispheres, neck sites expand in the medial part of the vibrissae representation more extensively than shown in Newborn Experimental hemispheres; (iii) in Newborn Experimental hemispheres eye sites expand in the medial part of the vibrissae representation more extensively than in Adult Experimental hemispheres (these sites overlap the cortical region where electrical stimulation evokes neck movement in Adult Experimental hemispheres) and (iv) in both Newborn and Adult Experimental hemispheres, forelimb sites expand similarly thereby overlapping the same cortical region, corresponding to the lateral part of the vibrissae representation. We conclude that, when the facial nerve injury is performed in the newborn rat, the pattern of movement representation differs from that obtained with the same lesion in the mature brain only in the frontal cortex corresponding to the medial part of the normal vibrissae representation.     

Short-term cortical reorganization by deafferentation of the contralateral sensory cortex

The topographic arrangement of the human primary somatosensory cortex following deafferentation of the contralateral cortex has been investigated by means of dipole source analysis. Somatosensory-evoked potentials were obtained by electrical stimulation of digit 1 and digit 5 of the left hand before and after anesthesia of digits 2-4 of the right hand during different terms of attention. Anesthesia induced an expansion of the three-dimensional distance between digits 1 and 5. This suggests intercortical plasticity modulated between bilateral primary somatosensory cortical areas, which is unaffected by spatial attention. These changes occur rapidly and are probably mediated by disinhibition of intercortical connections, leading to hyperexcitability of the primary sensory cortex that is contralateral to the region undergoing deafferentation.     

Physiological analysis of motor reorganization following lower limb amputation.

It is now known that amputation results in reorganization of central motor pathways, but the mechanism for the changes is unclear. One possibility is alteration of the excitability of the alpha motoneurons. We studied motor reorganization and excitability of alpha motoneurons to Ia input in 6 subjects with unilateral lower limb amputation. A Cadwell MES-10 stimulator was used to deliver transcranial magnetic stimuli through a circular coil centered on the sagittal axis 4 cm anterior to Cz and through an 8-shaped coil positioned over scalp locations 1 cm apart along the coronal axis. Surface EMG was recorded bilaterally from quadriceps femoris, the first muscle immediately proximal to the site of amputation. Excitability of the spinal alpha motoneuron pool to Ia afferents was assessed by determining the ratio of the maximal H reflex to the maximal M response (H/M ratio) elicited in the quadriceps femoris. Stimuli of equal intensity delivered to optimal scalp positions recruited a larger percentage of the alpha motoneuron pool in muscles ipsilateral to the stump than in those contralateral to the stump (P less than 0.01). Mean onset latencies of motor evoked potentials were shorter in ipsilateral muscles than in contralateral muscles (P less than 0.01). Muscles ipsilateral to the stump showed a trend toward activation from a larger number of scalp positions than those contralateral to the stump (P = 0.06). There was no difference in the quadriceps H/M ratios (7.2% ipsilateral vs. 10.9% contralateral). The absence of changes in the excitability of the alpha motoneuron pool in the presence of motor reorganization targeting muscles proximal to the stump suggests that reorganization occurs proximal to the alpha motoneuron level.     

Selective long‐term reorganization of the corticospinal projection from the supplementary motor cortex following recovery from lateral motor cortex injury

Brain injury affecting the frontal motor cortex or its descending axons often causes contralateral upper extremity paresis. Although recovery is variable, the underlying mechanisms supporting favorable motor recovery remain unclear. Because the medial wall of the cerebral hemisphere is often spared following brain injury and recent functional neuroimaging studies in patients indicate a potential role for this brain region in the recovery process, we investigated the long‐term effects of isolated lateral frontal motor cortical injury on the corticospinal projection (CSP) from intact, ipsilesional supplementary motor cortex (M2). After injury to the arm region of the primary motor (M1) and lateral premotor (LPMC) cortices, upper extremity recovery is accompanied by terminal axon plasticity in the contralateral CSP but not the ipsilateral CSP from M2. Furthermore, significant contralateral plasticity occurs only in lamina VII and dorsally within lamina IX. Thus, selective intraspinal sprouting transpires in regions containing interneurons, flexor‐related motor neurons, and motor neurons supplying intrinsic hand muscles, which all play important roles in mediating reaching and digit movements. After recovery, subsequent injury of M2 leads to reemergence of hand motor deficits. Considering the importance of the CSP in humans and the common occurrence of lateral frontal cortex injury, these findings suggest that spared supplementary motor cortex may serve as an important therapeutic target that should be considered when designing acute and long‐term postinjury patient intervention strategies aimed to enhance the motor recovery process following lateral cortical trauma. J. Comp. Neurol. 518:586–621, 2010. © 2009 Wiley‐Liss, Inc.     

Cortical reorganization following intradigital tendon transfer

We distinguish between two models of adult cortical reorganization, adaptive and constant somatotopy, using functional magnetic resonance imaging maps corresponding to individual thumb and fourth-finger digits in a patient with a right-hand fourth digit tendon transfer that salvaged impaired function of the right thumb. Comparison of motor and sensory maps for both digits and both hands was consistent with a model of 'adaptive somatotopy' in which thumb control was taken over by regions adjacent to the fourth finger control cluster rather than at the presurgical lateral region as predicted by a model of 'constant somatotopy'. These findings are the first to demonstrate that rerouting of peripheral input, in the absence of brain injury, is sufficient to drive cortical reorganization resulting in recovery of lost motor function, and further suggest an adaptive mechanism associated with brain tissue engaged in intact motor functions.     

Disinhibition of the contralateral motor cortex by low-frequency rTMS

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) results in a lasting decrease of motor evoked potentials (MEPs). Here we investigated the effects of supra-threshold rTMS (15 min, 1 Hz) to the left M1 on the excitability of the stimulated and homologous (unstimulated) M1 in healthy subjects by using single and double pulse TMS before and after rTMS. We found reduction of MEP amplitudes on the stimulated side and, most importantly, disinhibition of intracortical excitability of the homologous M1. This crossed effect of rTMS supports the concept of a physiological balance of reciprocal inhibitory projections and emphasizes that rTMS can induce remote effects that are relevant for the physiological interpretation of such interventions.     

Is it necessary to use the entire root as a donor when transferring contralateral C_7 nerve to repair median nerve?

If a partial contralateral C_7 nerve is transferred to a recipient injured nerve, results are not satisfactory. However, if an entire contralateral C_7 nerve is used to repair two nerves, both recipient nerves show good recovery. These findings seem contradictory, as the above two methods use the same donor nerve, only the cutting method of the contralateral C_7 nerve is different. To verify whether this can actually result in different repair effects, we divided rats with right total brachial plexus injury into three groups. In the entire root group, the entire contralateral C_7 root was transected and transferred to the median nerve of the affected limb. In the posterior division group, only the posterior division of the contralateral C_7 root was transected and transferred to the median nerve. In the entire root + posterior division group, the entire contralateral C_7 root was transected but only the posterior division was transferred to the median nerve. After neurectomy, the median nerve was repaired on the affected side in the three groups. At 8, 12, and 16 weeks postoperatively, electrophysiological examination showed that maximum amplitude, latency, muscle tetanic contraction force, and muscle fiber cross-sectional area of the flexor digitorum superficialis muscle were significantly better in the entire root and entire root + posterior division groups than in the posterior division group. No significant difference was found between the entire root and entire root + posterior division groups. Counts of myelinated axons in the median nerve were greater in the entire root group than in the entire root + posterior division group, which were greater than the posterior division group. We conclude that for the same recipient nerve, harvesting of the entire contralateral C_7 root achieved significantly better recovery than partial harvesting, even if only part of the entire root was used for transfer. This result indicates that the entire root should be used as a donor when transferring contralateral C_7 nerve.     

Residual function in motor cortex contralateral to amputated hand

OBJECTIVE: To investigate residual function of the motor cortex corresponding to the hand of the amputated arm (MCamp). METHODS: Focal transcranial magnetic stimulation (TMS) of MCamp was performed in 10 patients 22 to 52 years after arm amputation to inhibit tonic muscle contraction in the intact hand ipsilateral to cortex stimulation. RESULTS: In all patients, onset latency, degree, and duration of this inhibition were normal. CONCLUSION: The presence of motor inhibition in the residual hand of amputees originating from the hand motor representation of MCamp indicates residual cortical motor representation of the lost hand irrespective of whether the effect is mediated by commissural or ipsilateral corticospinal connections.     

Super-selective cervical nerve root stimulation in contralateral C7 transfer: An intraoperative study

Objective

We designed this study using super-selective intraoperative cervical nerve root stimulation aiming to support decision making about complete or partial contralateral C7 (cC7) nerve root transfer in patients with multiple cervical root avulsion injury.

Long-term reorganization of motor cortex outputs after arm amputation.

OBJECTIVE: To investigate the reorganization of the corticospinal system long after arm amputation at different levels. METHODS: Focal transcranial magnetic stimulation (TMS) was performed in 15 patients 21 to 65 years after arm amputation at the level of the forearm, upper arm, or shoulder. Cortically elicited electromyographic responses were investigated in muscles immediately proximal to the stump. TMS was performed on a skull surface grid overlying the motor cortex. The response threshold, number of effective stimulation sites, and the sum of the amplitudes elicited at these sites were evaluated for slightly contracted muscles. RESULTS: Seven of eight patients with forearm amputation had larger stimulation effects in the biceps supplied by the motor cortex contralateral to amputation, as indicated by variable patterns of lowered response thresholds, increased response amplitudes, or increased numbers of effective stimulation sites. In seven patients with a more proximal amputation, the motor responses were investigated in the deltoid and trapezoid muscle. In only two of them, the motor cortex contralateral to amputation showed an increased excitability. Three patients presented with a higher excitability of the motor cortex contralateral to the intact arm and two with a balanced type of excitability. CONCLUSION: Reorganization of the motor system can be present more than 20 years after amputation. Furthermore, differential patterns of reorganized corticospinal output were found for different stump muscles, which might be due to varying amounts of ipsilateral corticospinal projections.     

Temporal progression of cortical reorganization following nerve injury

Damage to peripheral nerves of adult mammals causes reorganization of somatosensory maps in the cerebral cortex. An understanding of the temporal progression of cortical changes is important for understanding the underlying mechanisms. The present experiments utilized neurophysiological recordings to analyze the time course of reorganization in the S-I cortical hindpaw area in adult rats. Following loss of sciatic inputs, the cortical area responding to low threshold inputs from the hindpaw saphenous nerve expands. A brief, early onset period of rapid expansion is followed by a prolonged period of slow increase. The temporal progression suggests that early onset changes condition the central nervous system for later changes.     

Complete reorganization of the motor cortex of adult rats following long‐term spinal cord injuries

Understanding brain reorganization following long‐term spinal cord injuries is important for optimizing recoveries based on residual function as well as developing brain‐controlled assistive devices. Although it has been shown that the motor cortex undergoes partial reorganization within a few weeks after peripheral and spinal cord injuries, it is not known if the motor cortex of rats is capable of large‐scale reorganization after longer recovery periods. Here we determined the organization of the rat (Rattus norvegicus) motor cortex at 5 or more months after chronic lesions of the spinal cord at cervical levels using intracortical microstimulation. The results show that, in the rats with the lesions, stimulation of neurons in the de‐efferented forelimb motor cortex no longer evokes movements of the forelimb. Instead, movements of the body parts in the adjacent representations, namely the whiskers and neck were evoked. In addition, at many sites, movements of the ipsilateral forelimb were observed at threshold currents. The extent of representations of the eye, jaw and tongue movements was unaltered by the lesion. Thus, large‐scale reorganization of the motor cortex leads to complete filling‐in of the de‐efferented cortex by neighboring representations following long‐term partial spinal cord injuries at cervical levels in adult rats.     

Tongue motor responses following transcranial magnetic stimulation of the motor cortex and proximal hypoglossal nerve in man

Surface recordings of EMG responses were performed bilaterally from the tongue following transcranial magnetic cortex (TCS) and nerve stimulation (TNS) to characterize the activated corticonuclear pathways and to obtain normative data for a diagnostic use. TCS over the face-associated motor cortex with 1.3 times the response threshold for relaxed muscles produced bilateral tongue responses with similar latencies and amplitudes for ipsi- (8.3±1.1 ms, 1.3±0.7 mV) and contralateral responses (8.5±1.0 ms, 1.7±0.8 mV, n=20, 10 subjects). In individual subjects maximal ipsilateral and contralateral responses were elicited by stimulation over about the same cortex area which lay 2–4 cm lateral and 0–2 cm anterior to the center of the hand motor representation area. Magnetic stimulation of the hypoglossal nerve with 70% of the maximal stimulator output and a circular coil placed over the posterior lateral skull produced a more proximal nerve excitation than electrical stimulation at the mandible, as reflected by the response latencies (3.4±0.9 ms vs. 2.1±0.7 ms). The effect of magnetic TNS was independent of the direction of the coil currents. Central motor latencies as calculated by subtracting the response latencies after TNS from the overall latency after TCS were 4.8±1.2 ms and 5.0±1.1 ms for ipsi- and contralateral responses, respectively. The findings suggest the existence of a direct and fast conducting connection between motor cortex and brainstem tongue motor nuclei on both sides in man.     

Stable ratio of ipsilateral to contralateral sensory motor cortex activity despite varying effort and peripheral nerve block.

BACKGROUND: Ipsilateral sensory motor cortex (SMC) activation can occur during hand movements following cerebral injury. We studied the effect of increasing task difficulty and temporary peripheral paralysis on patterns of motor system activation.METHODS: Six healthy subjects completed a functional MRI paradigm of right finger abduction with four stages; light resistance, strong resistance, imagined movement and attempted abduction after ulnar nerve blockade. Activation maps compared images acquired during rest and task, while region of interest analysis measured numbers of activated pixels.RESULTS: All subjects showed some ipsilateral SMC activation. Across all subjects and all tasks involving hand movement, contralateral activation was proportional to ipsilateral activation (2.1:1; r=0.86).CONCLUSIONS: The relationship between ipsilateral and contralateral SMC activation remained stable despite differing effort or hand paralysis. The contralateral and ipsilateral SMC appear to act in a coordinated fashion during unilateral hand movements.     

Time course of motor cortex reorganization following botulinum toxin injection into the vibrissal pad of the adult rat

The present experiment studies representation patterns in the motor cortex (M1) of adult rats, 1, 3, 6, and 12 days after unilateral injection of Botulinum Toxin (BTX) into the vibrissa pad. Intracortical microstimulation (ICMS) was used to evidence changes in the representation over time and in the current thresholds required to evoke movements inside the disconnected vibrissa region. After 1 day, isolated as well as contiguous negative sites were observed within the motor cortex corresponding to the disconnected vibrissa region. Thereafter the percentage of unresponsive sites decreased so that after 6 days, the number of unresponsive sites was not significantly higher than those in the control hemispheres. Within the disconnected vibrissa region, electrical stimulation elicited forelimb, eye, ipsilateral vibrissa and neck movements. Following BTX injection, the enlargement of the forelimb representation into the disconnected vibrissa representation began during the first day and stabilized during the second week after injection. In the first days, stimulation thresholds in expanded forelimb sites were higher than those required for similar movement in normal M1 forelimb representation. These thresholds then declined so that in approximately 6 days they were similar to normal. There was no clear evidence that stimulation of sites in the medial part of disconnected vibrissa-cortex evoked eye movements during the first 6 days after BTX injection. After this time, thresholds required to evoke eye movement in expanded sites were generally similar to, and never higher than, those needed to evoke this movement in control sites. Intermingled ipsilateral vibrissa and neck movement occupies part of the medial vibrissa region. Over the 12 days, extension of the ipsilateral vibrissa representation shrank while the representation of neck movement remained unchanged. Throughout the entire time there was no change in the excitability of these sites and the thresholds remained higher than that needed to elicit the vibrissa movement normally represented in this cortical region. No significant differences in threshold were found over time for any of the other movement categories represented in M1. These results indicate that, over time, the new movements inside the disconnected vibrissa region develop differently in M1 following peripheral motor disconnection. The implications for mechanisms involved in cortical plasticity are discussed.     

Organization of adult motor cortex representation patterns following neonatal forelimb nerve injury in rats

Somatotopic representation patterns in the motor cortex (MI) of rats that had a unilateral forelimb amputation on the first postnatal day were examined after 2-4 months of survival. Intracortical electrical stimulation and recording techniques were used to map the somatic representation in MI and in the somatic sensory cortex (SI). In normal rats, vibrissa, forelimb, and hindlimb areas comprise the bulk of the MI representation. Stimulation within the forelimb area elicits elbow, wrist, or digit movements at the lowest current intensities. The proximal limb representation appears to be contained within the distal forelimb area, since shoulder movements are nearly always evoked by stimulating at higher current intensities at some distal forelimb sites. In agreement with previous studies, the distal forelimb representation overlapped the adjacent part of the granular SI cortex. Following removal of the forelimb at birth, 3 novel features of MI organization were observed. First, the areas from which stimulation evoked movements of the vibrissa or the shoulder musculature were larger than normal. Stimulation thresholds were lower than those required for comparable movements in normal rats throughout these areas, suggesting that nerve section had not simply unmasked a high-threshold representation. Second, vibrissa movements were more commonly paired with movements of the proximal forelimb muscles at the same site. Third, stimulation in the adjacent granular SI cortex failed to evoke shoulder or trunk movements, although receptive-field mapping in this region showed that cells were responsive to cutaneous stimulation of the trunk and shoulder region. These results indicate that several organizational features develop differently in MI following perinatal nerve injury: certain remaining muscle groups have enlarged cortical representations, there is a strengthening of some normally weak connections from MI to the proximal musculature, and muscles are grouped in unusual combinations. These data demonstrate that the formation of MI representation patterns is strongly influenced by nerve injury during the perinatal period.     

Rapid motor cortical reorganization following subacute spinal cord dysfunction

ObjectiveDamage to the spinal cord is known to be associated with a posterior shift of the motor cortical upper limb representation, i.e. towards the somatosensory cortex. Due to missing pre-traumatic data, knowledge resulted from comparing findings between patients and healthy subjects. Here, we present a case of transient spinal cord injury resulting in a left-sided hemiparesis for 4 weeks. By chance, this patient had a pre-lesional navigated transcranial magnetic stimulation (nTMS) motor mapping 2 years before. Hence, nTMS mapping was repeated during the acute (after 1 day), sub-acute (after 10 days) and chronic (after 2 years) phase to trace the cortical reorganization following this incident.MethodsAcute clinical work-up included magnetic resonance imaging and navigated transcranial magnetic stimulation (nTMS). Motor mapping was performed with 110% of the abductor pollicis brevis muscle (APB) resting motor threshold (rMT). Amplitudes and latencies of the motor-evoked potential (MEPs) were recorded and analyzed. In addition, motor function was evaluated by the Medical Research Council (MRC) scale, a standard Purdue Pegboard test and by a reaction time (RT) task.ResultsMRI revealed no aberrant findings. nTMS mapping, however, showed a posterior shift of the APB representation from the anatomical hand knob towards the somatosensory cortex in the acute in comparison to the pre-lesional phase. Concomitantly, there was an increase of rMT (6%). Within 10 days, there was an incomplete reversal of the posterior shift in parallel with improvement of the clinical motor function. Long-term follow-up revealed a complete restitution of nTMS cortical mapping and motor function.ConclusionThe present case report thoroughly documents a rapid cortical reorganization within a few days after a transient spinal shock. Our data adds further evidence to the literature suggesting a posterior shift of motor cortical representation following spinal cord injury. For the first time, 52 cortical reorganization was shown idiosyncratically in a single patient arising from the fortuitous fact of having a pre - lesional nTMS map.     

Stereological analysis of the reorganization of the dentate gyrus following entorhinal cortex lesion in mice

Denervation of the dentate gyrus by entorhinal cortex lesion has been widely used to study the reorganization of neuronal circuits following central nervous system lesion. Expansion of the non-denervated inner molecular layer (commissural/associational zone) of the dentate gyrus and increased acetylcholinesterase-positive fibre density in the denervated outer molecular layer have commonly been regarded as markers for sprouting following entorhinal cortex lesion. However, because this lesion extensively denervates the outer molecular layer and causes tissue shrinkage, stereological analysis is required for an accurate evaluation of sprouting. To this end we have performed unilateral entorhinal cortex lesions in adult C57BL/6J mice and have assessed atrophy and sprouting in the dentate gyrus using modern unbiased stereological techniques. Results revealed the expected increases in commissural/associational zone width and density of acetylcholinesterase-positive fibres on single brain sections. Yet, stereological analysis failed to demonstrate concomitant increases in layer volume or total acetylcholinesterase-positive fibre length. Interestingly, calretinin-positive fibres did grow beyond the border of the commissural/associational zone into the denervated layer and were regarded as sprouting axons. Thus, our data suggest that in C57BL/6J mice shrinkage of the hippocampus rather than growth of fibres underlies the two morphological phenomena most often cited as evidence of regenerative sprouting following entorhinal cortex lesion. Moreover, our data suggest that regenerative axonal sprouting in the mouse dentate gyrus following entorhinal cortex lesion may be best assessed at the single-fibre level.