Whisker motor cortex reorganization after superior colliculus output suppression in adult rats

The effect of unilateral superior colliculus (SC) output suppression on the ipsilateral whisker motor cortex (WMC) was studied at different time points after tetrodotoxin and quinolinic acid injections, in adult rats. The WMC output was assessed by mapping the movement evoked by intracortical microstimulation (ICMS) and by recording the ICMS‐evoked electromyographic (EMG) responses from contralateral whisker muscles. At 1 h after SC injections, the WMC showed: (i) a strong decrease in contralateral whisker sites, (ii) a strong increase in ipsilateral whisker sites and in ineffective sites, and (iii) a strong increase in threshold current values. At 6 h after injections, the WMC size had shrunk to 60% of the control value and forelimb representation had expanded into the lateral part of the normal WMC. Thereafter, the size of the WMC recovered, returning to nearly normal 12 h later (94% of control) and persisted unchanged over time (1–3 weeks). The ICMS‐evoked EMG response area decreased at 1 h after SC lesion and had recovered its baseline value 12 h later. Conversely, the latency of ICMS‐evoked EMG responses had increased by 1 h and continued to increase for as long as 3 weeks following the lesion. These findings provide physiological evidence that SC output suppression persistently withdrew the direct excitatory drive from whisker motoneurons and induced changes in the WMC. We suggest that the changes in the WMC are a form of reversible short‐term reorganization that is induced by SC lesion. The persistent latency increase in the ICMS‐evoked EMG response suggested that the recovery of basic WMC excitability did not take place with the recovery of normal explorative behaviour.     

Suppression of activity in the forelimb motor cortex temporarily enlarges forelimb representation in the homotopic cortex in adult rats

After forelimb motor cortex (FMC) damage, the unaffected homotopic motor cortex showed plastic changes. The present experiments were designed to clarify the electrophysiological nature of these interhemispheric effects. To this end, the output reorganization of the FMC was investigated after homotopic area activity was suppressed in adult rats. FMC output was compared after lidocaine-induced inactivation (L-group) or quinolinic acid-induced lesion (Q-group) of the contralateral homotopic cortex. In the Q-group of animals, FMC mapping was performed, respectively, 3 days (Q3D group) and 2 weeks (Q2W group) after cortical lesion. In each animal, FMC output was assessed by mapping movements induced by intracortical microstimulation (ICMS) in both hemispheres (hemisphere ipsilateral and contralateral to injections). The findings demonstrated that in the L-group, the size of forelimb representation was 42.2% higher than in the control group ( P  < 0.0001). The percentage of dual forelimb–vibrissa movement sites significantly increased over the controls ( P  < 0.0005). The dual-movement sites occupied a strip of the map along the rostrocaudal border between the forelimb and vibrissa representations. This form of interhemispheric diaschisis had completely reversed, with the recovery of the baseline map, 3 days after the lesion in the contralateral FMC. This restored forelimb map showed no ICMS-induced changes 2 weeks after the lesion in the contralateral FMC. The present results suggest that the FMCs in the two hemispheres interact continuously through predominantly inhibitory influences that preserve the forelimb representation and the border vs. vibrissa representation.     

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.     

Modulation of motor cortex excitability induced by pinch grip repetition

Summary. We examined the influence of right handed pinch grips and the effect of a motor training on motor cortex excitability of the left first dorsal interosseus muscle (FDI). TMS single and paired pulses were applied over the right human motor cortex (M1) during and after right handed pinch grips with low force. In another experiment, these stimulations were performed before and after a 30-minute right handed pinch grip training. Results: MEP amplitudes in left FDI were reduced when TMS single pulses were applied during the pinch grip. Simultaneously, motor cortex excitability was enhanced but returned to baseline after the training period. Conclusion: Phasic pinch grips of the right hand exert an inhibiting effect on the corticospinal excitability of the ipsilateral motor cortex and lead to an increase of intracortical excitability. These changes are distinct and independent of each other. Motor training has an interhemispheric effect on intracortical excitability.     

The vibrissal motor output following severing and repair of the facial nerve in the newborn rat reorganises less than in the adult

This study examined the ability of facial motoneurons and motor cortex to reorganise their relationship with the somatic musculature following the severing and repair of the facial nerve in rats at birth. In each adult rat, the organisation of the facial nucleus and the cortical motor output corresponding to the normal side were compared with those corresponding to the reinnervated side. Labelling was used to reveal reinnervation-induced long-term changes in the motoneuron pool supplying vibrissal muscles. Cortical motor output was assessed by mapping the vibrissal movement area extension and thresholds evoked by intracortical microstimulation. After facial nerve reinnervation: (i) the proportion of labelled cell profiles decreased by 85.2% of that in the control side and cortical representation of vibrissal movement decreased by 66.3% of that in control hemispheres; (ii) the reorganised vibrissal representation was shrunken to the medialmost portion of the normal vibrissal representation and there was a medial extension of the forelimb representation, and a more modest lateral extension of eye representation, into the vibrissal territory; (iii) the normal pattern of contralateral vibrissal movement was observed in only 10% of the vibrissal sites, whereas ipsilateral vibrissal movement was found in 53% of the vibrissal sites; (iv) there was an increase in the mean threshold required to evoke contralateral vibrissal movement (32.5+/-11.1 vs. 20.5+/-6.9 microA). Thresholds to evoke other types of movement were similar to normal. These changes indicate that an incomplete motor axon regeneration at birth does not restore normal innervation and normal cortical control over the vibrissal muscles.     

Ipsilateral cortical inputs to the rostral and caudal motor areas in rats

Rats have a complete body representation in the primary motor cortex (M1). Rostrally there are additional representations of the forelimb and whiskers, called the rostral forelimb area (RFA) and the rostral whisker area (RWA). Recently we showed that sources of thalamic inputs to RFA and RWA are similar, but they are different from those for the caudal forelimb area (CFA) and the caudal whisker area (CWA) of M1 (Mohammed and Jain [2014] J Comp Neurol 522:528–545). We proposed that RWA and RFA are part of a second motor area, the rostral motor area (RMA). Here we report ipsilateral cortical connections of whisker representation in RMA, and compare them with connections of CWA. Connections of RFA, CFA, and the caudally located hindlimb area (CHA), which is a part of M1, were determined for comparison. The most distinctive features of cortical inputs to RWA compared with CWA include lack of inputs from the face region of the primary somatosensory cortex (S1), and only about half as much inputs from S1 compared with the lateral somatosensory areas S2 (second somatosensory area) and the parietal ventral area (PV). A similar pattern of inputs is seen for CFA and RFA, with RFA receiving smaller proportion of inputs from the forepaw region of S1 compared with CFA, and receiving fewer inputs from S1 compared with those from S2. These and other features of the cortical input pattern suggest that RMA has a distinct, and more of integrative functional role compared with M1. J. Comp. Neurol. 524:3104–3123, 2016. © 2016 Wiley Periodicals, Inc.     

Effects of incisor extraction on jaw and tongue motor representations within face sensorimotor cortex of adult rats

Loss of teeth is associated with changes in somatosensory inputs and altered patterns of mastication, but it is unclear whether tooth loss is associated with changes in motor representations within face sensorimotor cortex of rats. We used intracortical microstimulation (ICMS) and recordings of cortically evoked muscle electromyographic (EMG) activities to test whether changes occur in the ICMS‐defined motor representations of the left and right jaw muscles [masseter, anterior digastric (LAD, RAD)] and tongue muscle [genioglossus (GG)] within the cytoarchitectonically defined face primary motor cortex (face‐M1) and adjacent face primary somatosensory cortex (face‐S1) 1 week following extraction of the right mandibular incisor in anesthetized (ketamine‐HCl) adult male Sprague‐Dawley rats. Under local and general anesthesia, an “extraction” group (n = 8) received mucoalveolar bone surgery and extraction of the mandibular right incisor. A “sham‐extraction” group (n = 6) received surgery with no extraction. A “naive” group (n = 6) had neither surgery nor extraction. Data were compared by using mixed‐model repeated‐measures ANOVA. Dental extraction was associated with a significantly increased number of sites within face‐M1 and face‐S1 from which ICMS evoked RAD EMG activities, a lateral shift of the RAD and LAD centers of gravity within face‐M1, shorter onset latencies of ICMS‐evoked GG activities within face‐M1 and face‐S1, and an increased number of sites within face‐M1 from which ICMS simultaneously evoked RAD and GG activities. Our novel findings suggest that dental extraction may be associated with significant neuroplastic changes within the rat's face‐M1 and adjacent face‐S1 that may be related to the animal's ability to adapt to the altered oral state. J. Comp. Neurol. 518:1030–1045, 2010. © 2009 Wiley‐Liss, Inc.     

Interhemispheric differences of hand muscle representation in human motor cortex

Focal magnetic transcranial stimulation (TCS) is employed for mapping of the motor cortical output to abductor digiti minimi (ADM) muscle. The aim of this study was to evaluate the interhemispheric asymmetries in normals. Motor maps were obtained through motor evoked potentials (MEPs) recordings from ADM muscle in 20 healthy subjects in right and left hemispheres TCS. Measurement of several indexes such as excitability threshold, MEPs amplitude, MEPs latency, and silent period duration did not show differences between the hemispheres. Moreover, no interhemispheric asymmetries were found when the amplitude ratio values were analyzed. The hand motor cortical area, as represented by the number of responsive sites (3.6 vs. 3.5) and the “hot spot” site localization presented a fairly symmetrical organization. Absolute values displayed a relatively wide intersubject variability, while their interhemispheric differences were extremely restricted. This observation can offer a new tool in diagnosing and following up neurological disorders affecting the central motor system, mainly for those concerning monohemispheric lesions. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 535–542, 1997.     

Single-cell study of motor cortex projections to the barrel field in rats

In freely moving rats, whisking is associated with a slow modulation of neuronal excitability in the primary somatosensory cortex. Because it persists after the blockade of vibrissa input, it was suggested that the slow modulation might be mediated by motor-sensory corticocortical connections and perhaps result from the corollary discharges of corticofugal cells. In the present study, we identified motor cortical cells that project to the barrel field and reconstructed their axonal projections after juxtacellularly staining single cells with a biotinylated tracer. On the basis of the final destination of main axons, two groups of neurons contribute to motor-sensory projections: callosal cells (87.5%) and corticofugal cells (12.5%). Axon collaterals of callosal cells arborize in layers five to six of the granular and dysgranular zones and give off several branches that ascend between the barrels to ramify in the molecular layer. In contrast, the axon collaterals of corticofugal cells do not ramify in the infragranular layers but in layer 1. The origin of the majority of motor sensory projections from callosally projecting cells does not support the notion that the slow modulation results from the corollary discharges of corticofugal axons. It would rather originate from a separate population of cells, which could output the slow signal to the barrel field in parallel with the corticofugal commands to a brainstem pattern generator. As free whisking is characterized by bilateral concerted movements of the vibrissae, the transcallosal contribution of motor-sensory axons represents a substrate for synchronizing the slow modulation across both hemispheres.     

Vibrissectomy induced changes in GAP-43 immunoreactivity in the adult rat barrel cortex.

Within the rat primary somatosensory cortex, neurons responding principally to movement of each individual mystacial vibrissa are grouped together in structures termed barrels. Previous studies have examined changes in the area of cortex showing increased 2-deoxyglucose uptake in response to vibrissal stimulation. These studies have shown that chronic removal of all but the central (C3) vibrissa in adult rats induces an enlarged representation of the remaining C3 barrel in the contralateral cortex. This increase is prevented by cortical norepinephrine depletion. The major question raised by such studies is whether such plasticity is due to structural rearrangement or unmasking of otherwise silent synapses. In this study, antibodies to GAP-43, a presynaptic protein whose synthesis is related to neuronal development and regeneration, were used to investigate this issue. In adult rat brain, tangential sections through layer IV of the barrel receptor field normally show moderate levels of GAP-43 immunoreactivity (GAP-IR) in the inter-barrel septa and low levels within the barrels themselves. The present study examined changes in the pattern of GAP-IR from 1 to 8 weeks after vibrissectomy with sparing of C3 as an index of possible physical reorganization of cortical circuits. Quantitative analysis of the cortices of animals with unilateral vibrissectomy with sparing of C3 showed that the area of low GAP-IR within the barrels surrounding C3 was decreased at 1 week (8.4% shrinkage; P less than 0.01) and 8 weeks (12.0% shrinkage; P less than 0.015), relative to the cortex ipsilateral to the surgery. Both bilateral vibrissectomy with sparing of C3 and ibotenic acid lesions of the ventrobasal thalamus produced similar results. Some evidence was also seen that the area of low GAP-IR in the C3 barrel shrank to a similar degree after such manipulations. Cortical norepinephrine depletion had no apparent effect on vibrissectomy-induced GAP-IR changes. These results suggest that removal of vibrissal input to the adult rat barrel cortex produces transynaptic induction of axonal sprouting within the barrel cortex.     

Synaptic reorganization in the dorsal lateral geniculate nucleus following damage to visual cortex in newborn or adult cats

We have studied the effects of making large lesions of visual cortex on the synaptic organization of the dorsal lateral geniculate nucleus (LGN) in the cat. Visual cortex was removed at birth in one group of cats and during adulthood in a second group. Following survival periods of 6 months to 2 years, the organization of synapses made by afferents from the retina in the LGN was investigated quantitatively with the electron microscope. In single thin sections we determined the percentage of retinal axon terminals that made synapses in the LGN, the average number of synapses made by each retinal axon terminal, and the identity of each postsynaptic process. These measurements were made separately for retinogeniculate connections in the A and C laminae of the LGN. For comparison, similar sets of measurements were made in adult cats that had been reared normally. When single thin sections from the A or C laminae of the LGN in normal cats are examined, about 60% of the axon terminals from the retina are seen to make at least one synaptic contact. These contacts can be with dendrites or F profiles or both. On average, each retinogeniculate terminal makes approximately 1.4 synapses in the plane of a single section and contacts dendrites three times as often as F profiles. In the A laminae of the LGN in cats that received a visual cortex lesion at birth or in adulthood, the percentage of retinal terminals that make synapses is the same as in normal cats. Similarly, the average number of synaptic contacts made by each retinogeniculate terminal is not changed by a lesion of visual cortex. In contrast, the number of contacts made with dendrites is reduced markedly, by about 29% after a lesion at birth and 53% after a lesion as an adult. However, these reductions are offset by compensatory increases in the number of contacts made with F profiles, and thus the mean number of contacts made by each retinogeniculate terminal is stabilized at a normal value. In the C laminae of the LGN, retinogeniculate terminals also reapportion their synaptic contacts. In cats with a lesion during adulthood, the redistribution of synapses is compensatory, as in the A laminae. When a lesion is made at birth, however, the number of new retinal contacts made with F profiles exceeds the number of dendritic contacts that are lost. As a result, each retinogeniculate terminal makes about 26% more synapses, in total, than normal.(ABSTRACT TRUNCATED AT 400 WORDS)     

Assessment of the effect of continuous theta burst stimulation of the motor cortex on manual dexterity in non‐human primates in a direct comparison with invasive intracortical pharmacological inactivation

Non‐invasive reversible perturbation techniques of brain output such as continuous theta burst stimulation (cTBS), commonly used to modulate cortical excitability in humans, allow investigation of possible roles in functional recovery played by distinct intact cortical areas following stroke. To evaluate the potential of cTBS, the behavioural effects of this non‐invasive transient perturbation of the hand representation of the primary motor cortex (M1) in non‐human primates (two adult macaques) were compared with an invasive focal transient inactivation based on intracortical microinfusion of GABA‐A agonist muscimol. The effects on the contralateral arm produced by cTBS or muscimol were directly compared based on a manual dexterity task performed by the monkeys, the “reach and grasp” drawer task, allowing quantitative assessment of the grip force produced between the thumb and index finger and exerted on the drawer's knob. cTBS only induced modest to moderate behavioural effects, with substantial variability on manual dexterity whereas the intracortical muscimol microinfusion completely impaired manual dexterity, producing a strong and clear cortical inhibition of the M1 hand area. In contrast, cTBS induced mixed inhibitory and facilitatory/excitatory perturbations of M1, though with predominant inhibition. Although cTBS impacted on manual dexterity, its effects appear too limited and variable in order to use it as a reliable proof of cortical vicariation mechanism (cortical area replacing another one) underlying functional recovery following a cortical lesion in the motor control domain, in contrast to potent pharmacological block generated by muscimol infusion, whose application is though limited to an animal model such as non‐human primate.     

Primary somatosensory cortex hand representation dynamically modulated by motor output

The brain’s primary motor and primary somatosensory cortices are generally viewed as functionally distinct entities. Here we show by means of magnetoencephalography with a phantom-limb patient, that movement of the phantom hand leads to a change in the response of the primary somatosensory cortex to tactile stimulation. This change correlates with the described conscious perception and suggests a greater degree of functional unification between the primary motor and somatosensory cortices than is currently realized. We suggest that this may reflect the evolution of this part of the human brain, which is thought to have occurred from an undifferentiated sensorimotor cortex.     

Role of adaptive plasticity in recovery of function after damage to motor cortex.

Based upon neurophysiologic, neuroanatomic, and neuroimaging studies conducted over the past two decades, the cerebral cortex can now be viewed as functionally and structurally dynamic. More specifically, the functional topography of the motor cortex (commonly called the motor homunculus or motor map), can be modified by a variety of experimental manipulations, including peripheral or central injury, electrical stimulation, pharmacologic treatment, and behavioral experience. The specific types of behavioral experiences that induce long-term plasticity in motor maps appear to be limited to those that entail the development of new motor skills. Moreover, recent evidence demonstrates that functional alterations in motor cortex organization are accompanied by changes in dendritic and synaptic structure, as well as alterations in the regulation of cortical neurotransmitter systems. These findings have strong clinical relevance as it has recently been shown that after injury to the motor cortex, as might occur in stroke, post-injury behavioral experience may play an adaptive role in modifying the functional organization of the remaining, intact cortical tissue.     

Contrasting properties of neurons in two parts of the primary motor cortex of the awake rat

Features of neuronal activity in two subdivisions of primary motor cortex (MI) were recorded in awake rats. Neurons in the caudal part of MI, which overlaps part of the somatic sensory cortex, discharge with brief bursts in conjunction with isometric bar pressing with the forelimb. Cells in this caudal region are activated by cutaneous stimuli. In the rostral part of MI, neurons discharge prior to and during forelimb force changes, begin to discharge earlier than in the caudal zone, and have non-cutaneous or unidentifiable receptive fields. These results suggest separate motor control functions for rostral and caudal parts of rat MI.     

Amphetamine enhances training-induced motor cortex plasticity

OBJECTIVES: Repetitive synchronized movements lead to short-term plastic changes in the primary motor cortex, which can be assessed by transcranial magnetic stimulation (TMS). Drugs which enhance such plastic changes could be of therapeutical interest, e.g. in patients with cerebral lesions. MATERIAL AND METHODS: We studied the effect of amphetamine on motor performance and plastic changes in the motor cortex as revealed by TMS mapping in healthy humans, who had to train a repetitive synchronized movement over 1 h. RESULTS: Cortical plastic changes observed after 1 h of training were more pronounced with amphetamine, whereas motor performance did not differ between training sessions with and without amphetamine. CONCLUSION: We conclude that amphetamine is able to enhance training-induced motor cortex plasticity. This effect could be due to its known influence on the GABAergic and glutamatergic system, but might also result from its role as an indirect catecholaminergic agonist.     

The dual nature of time preparation: neural activation and suppression revealed by transcranial magnetic stimulation of the motor cortex

Single-pulse transcranial magnetic stimulations (TMSs) of the motor cortex (M1) were performed in order to decipher the neural mechanisms of time preparation. We varied the degree to which it was possible to prepare for the response signal in a choice reaction time (RT) task by employing either a short (500 ms) or a long (2500 ms) foreperiod in separate blocks of trials. Transcranial magnetic stimulations were delivered during these foreperiods in order to study modulations in both the size of the motor evoked potential (MEP) and the duration of the silent period (SP) in tonically activated response agonists. Motor evoked potential area and silent period duration were assumed to reflect, respectively, the excitability of the cortico-spinal pathway and the recruitment of inhibitory cortical interneurons. Shorter reaction times were observed with the shorter foreperiod, indicating that a better level of preparation was attained for the short foreperiod. Silent period duration decreased as time elapsed during the foreperiod and this decrement was more pronounced for the short foreperiod. This result suggests that time preparation is accompanied by a removal of intracortical inhibition, resulting in an activation. Motor evoked potential area decreased over the course of the short foreperiod, but not over the long foreperiod, revealing that time preparation involves the inhibition of the cortico-spinal pathway. We propose that cortico-spinal inhibition secures the development of cortical activation, preventing erroneous premature responding.     

Evaluation of the motor cortical excitability changes after ischemic stroke

Background:

We evaluated progressive changes in excitability of motor cortex following ischemic stroke using Transcranial Magnetic Stimulation (TMS).

Materials and Methods:

Thirty-one patients (24 men, 7 women; age 37.3 ± 8.2 years) were recruited and TMS was performed using Magstim 200 stimulator and a figure-of-eight coil. Resting motor threshold (RMT) was recorded from affected and unaffected hemispheres and motor evoked potential (MEP) was recorded from contralateral FDI muscle. Central motor conduction time (CMCT) was calculated using F wave method. All measurements were done at baseline (2^nd), 4^th, and 6^th week of stroke.

Results: Affected hemisphere:

MEP was recordable in 3 patients at baseline (all had prolonged CMCT). At 4 weeks, MEP was recordable in one additional patient and CMCT remained prolonged. At 6 weeks, CMCT normalized in one patient. RMT was recordable (increased) in 3 patients at baseline, in one additional patient at 4 weeks, and reduced marginally in these patients at 6 weeks.

Unaffected hemisphere:

MEP was recordable in all patients at baseline, and reduced significantly over time (2^nd week 43.52 ± 9.60, 4^th week 38.84 ± 7.83, and 6^th week 36.85 ± 7.27; P < 0.001). The CMCT was normal and remained unchanged over time.

Conclusion:

The increase in excitability of the unaffected motor cortex suggests plasticity in the post-stroke phase.