Time course for the reappearance of vibrissal motor representation following botulinum toxin injection into the vibrissal pad of the adult rat

The present study investigates the time course and pattern of movement representation recovery in the motor cortex during the recovery after a peripheral paralysis. To this end a transitory flaccid paralysis of the vibrissae muscle was induced in adult rats that underwent two unilateral injections of 8 U of botulinum toxin (BTX) into a vibrissal pad, at a duration of 12 days from one another. The compound muscle action potential (MAP) of the vibrissae muscle began to reappear 4 weeks after the first BTX injection. Intracortical microstimulation (ICMS) was used to map rat motor cortices 4, 5, 6, 7 and 8 weeks after the first BTX injection. Findings demonstrated that: (i) contralateral vibrissae movement reappears in the medial part of its normal cortical territory when the MAP is almost 10% of the control value; in the remaining part, ICMS elicits eye, ipsilateral vibrissae, neck and forelimb movements; (ii) the contralateral vibrissae movement reappears in sites where ipsilateral vibrissae and/or neck movement are co-represented; (iii) as MAP recovers, the vibrissae representation expands until it recovers the 90.8% of its territory after 7 weeks, when the MAP was almost 43.4% of the control value; (iv) from 4 to 7 weeks, the ICMS-evoked contralateral vibrissae movement shows a significantly higher electrical threshold vs. the control group; (v) recovery of the baseline excitability uniformly involves the vibrissae representation 1 week later, after its cortical territory has recovered 93.1% of the control value and the MAP has returned to 78.8% of the baseline value.     

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.     

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.     

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.     

Functional reorganization of adult raccoon somatosensory cerebral cortex following neonatal digit amputation

Amputation of a forepaw digit in raccoons 2–8 weeks of age produced dramatic changes in the functional organization of somatosensory cortex examined electrophysiologically 9–12 months later. The cortical region normally representing the digit that was amputated received widely overlapping input from the entire forepaw, with local disruption of somatotopic organization. Compared with normal animals, the receptive fields of cortical neurons in amputated animals were larger, often included both glabrous and hairy skin, sometimes involved discontinuous skin regions, and were much more variable in peripheral location as a function of recording distance across the cortex and of depth within the cortex.     

A second forelimb motor area exists in rat frontal cortex

Intracortical microstimulation of 40–50 points in the frontal cortex of ketamine-anesthetized rats using perpendicular penetrations has demonstrated a second forelimb area located rostrally near the frontal pole as well as confirming the existence of a more caudally located forelimb area just anterior to bregma. Cortex where neck and/or vibrissae movements were evoked separated the two forelimb areas. The rostral and caudal forelimb areas defined by microstimulation correspond with patches of corticospinal neurons labeled with HRP following injections of this tracer into the cervical enlargement. Digit movements were commonly evoked from the rostral forelimb area but were rarely elicited from the caudal forelimb area. The question of whether the rostral forelimb region is part of primary or supplementary motor cortex is not yet able to be answered.     

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.     

Two whisker motor areas in the rat cortex: Evidence from thalamocortical connections

In primates, the motor cortex consists of at least seven different areas, which are involved in movement planning, coordination, initiation, and execution. However, for rats, only the primary motor cortex has been well described. A rostrally located second motor area has been proposed, but its extent, organization, and even definitive existence remain uncertain. Only a rostral forelimb area (RFA) has been definitively described, besides few reports of a rostral hindlimb area. We have previously proposed existence of a second whisker area, which we termed the rostral whisker area (RWA), based on its differential response to intracortical microstimulation compared with the caudal whisker area (CWA) in animals under deep anesthesia (Tandon et al. [2008] Eur J Neurosci 27:228). To establish that RWA is distinct from the caudally contiguous CWA, we determined sources of thalamic inputs to the two proposed whisker areas. Sources of inputs to RFA, caudal forelimb area (CFA), and caudal hindlimb region were determined for comparison. The results show that RWA and CWA can be distinguished based on differences in their thalamic inputs. RWA receives major projections from mediodorsal and ventromedial nuclei, whereas the major projections to CWA are from the ventral anterior, ventrolateral, and posterior nuclei. Moreover, the thalamic nuclei that provide major inputs to RWA are the same as for RFA, and the nuclei projecting to CWA are same as for CFA. The results suggest that rats have a second rostrally located motor area with RWA and RFA as its constituents. J. Comp. Neurol. 522:528–545, 2014. © 2013 Wiley Periodicals, Inc.     

A reappraisal of rat motor cortex organization by intracortical microstimulation

The organization of the motor cortex was reinvestigated with intracortical microstimulation, in light-anaesthetized (ketamine) rats. A posterolateral (PL) vibrissae area was found in addition to the rostral one, and blinks of the contralateral eyelids were elicited from a part of this PL area. Several cortical representations such as neck or tail were largely overlapping with neighbouring areas. Vegetative effects (mainly myosis and swallowing) were obtained from a medial cortical strip. Within the PL vibrissae area, a topical arrangement related to the vibrissal rows was observed, whereas in the leg areas, no individual representation of muscles could be evidenced. These results are compared with the maps previously published, and discussed in terms of specificity, musculotopy and overlapping of motor areas.     

The organization of the rat motor cortex: A microstimulation mapping study

In conclusion, the rat primary motor cortex appears to be organized into irregularly shaped patches of cortex devoted to particular movements. The location of major subdivisions such as the forelimb or hindlimb areas is somatotopic and is consistent from animal to animal, but the internal organization of the pattern of movements represented within major subdivisions varies significantly between animals. The motor cortex includes both agranular primary motor cortex (AgL) and, in addition, a significant amount of the bordering granular somatic sensory cortex (Gr(SI)), as well as the rostral portion of the taste sensory insular or claustrocortex (Cl). The rat frontal cortex also contains a second, rostral motor representation of the forelimb, trunk and hindlimb, which is somatotopically organized and may be the rat's supplementary motor area. Both of these motor representations give rise to direct corticospinal projections^21,42,51,57, some of which may make monosynaptic connections with cervical enlargement motorneurons¹⁶. Medial to the primary motor cortex, in cytoarchitectonic field AgM, is what appears to be part of the rat's frontal eye fields, a region which also includes the vibrissae motor representation. The somatic motor cortical output organization pattern in the rat is remarkably similar to that seen in the primate, whose primary, supplementary and frontal eye field cortical motor regions have been extensively studied.     

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.     

Motor mapping of the hand muscles using peripheral innervation-based navigated transcranial magnetic stimulation to identify functional reorganization of primary motor regions in malignant tumors

Tumor-related motor reorganization remains unclear. Navigated transcranial magnetic stimulation (nTMS) can investigate plasticity non-invasively. nTMS-induced motor-evoked potentials (MEPs) of different muscles are commonly used to measure the center of gravity (CoG), the location with the highest density of corticospinal neurons in the precentral gyrus. We hypothesized that a peripheral innervation-based MEP analysis could outline the tumor-induced motor reorganization with a higher clinical and oncological relevance. Then, 21 patients harboring tumors inside the left corticospinal tract (CST) or precentral gyrus were enrolled in group one (G1), and 24 patients with tumors outside the left CST or precentral gyrus were enrolled in Group 2 (G2). Median- and ulnar-nerve-based MEP analysis combined with diffusion tensor imaging fiber tracking was used to explore motor function distribution. There was no significant difference in CoGs or size of motor regions and underlying tracts between G1 and G2. However, G1 involved a sparser distribution of motor regions and more motor-positive sites in the supramarginal gyrus—tumors inside motor areas induced motor reorganization. We propose an “anchor-and-ship theory” hypothesis for this process of motor reorganization: motor CoGs are stably located in the cortical projection area of the CST, like a seated anchor, as the core area for motor output. Primary motor regions can relocate to nearby gyri via synaptic plasticity and association fibers, like a ship moving around its anchor. This principle can anticipate functional reorganization and be used as a neuro-oncological tool for local therapy, such as radiotherapy or surgery.     

Plastic changes in the vibrissa motor cortex in adult rats after output suppression in the homotopic cortex

After motor cortex damage, the unaffected homotopic cortex shows changes in motor output. The present experiments were designed to clarify the nature of these interhemispheric effects. We investigate the vibrissa motor cortex (VMC) output after activity suppression of the homotopic area in adult rats. Comparison was made of VMC output after lidocaine inactivation (L-group) or quinolinic acid lesion (Q-group) of the homotopic cortex. In the Q-group, VMC mapping was performed 3 days (Q3Ds group), 2 weeks (Q2Ws group) and 4 weeks (Q4Ws group) after cortical lesion. In each animal, VMC output was assessed by mapping movements induced by intracortical microstimulation (ICMS) in both hemispheres (hemisphere ipsilateral and contralateral to injections). Findings demonstrated that, in the L-group, the size of vibrissal representation was 39.5% smaller and thresholds required to evoke vibrissa movement were 46.3% higher than those in the Control group. There was an increase in the percentage of ineffective sites within the medial part of the VMC and an increase in the percentage of forelimb sites within the lateral part. Both the Q3Ds group and the L-group led to a similar VMC reorganization (Q3Ds vs. L-group, P > 0.05). In the Q2Ws group the VMC representation showed improvement in size (83.4% recovery compared with controls). The VMC showed recovery to normal output at 4 weeks after lesion (Control vs. Q4Ws group, P > 0.05). These results suggest that the VMC of the two hemispheres continuously interact through excitatory influences, preserving the normal output and inhibitory influences defining the border with the forelimb representation.     

Somatosensory system in two types of motor reorganization in congenital hemiparesis: topography and function

This study investigates the (re-)organization of somatosensory functions following early brain lesions. Using functional magnetic resonance imaging (fMRI), passive hand movement was studied. Transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) were used as complementary methods. fMRI data was analyzed on the first level with regard to topographical variability; second-level group effects as well as the overall integrity of the somatosensory circuitry were also assessed. Subjects with unilateral brain lesions occurring in the third trimester of pregnancy or perinatally with different types of motor reorganization were included: patients with regular, contralateral motor organization following middle cerebral artery strokes (CONTRA(MCA), n = 6) and patients with reorganized, ipsilateral motor functions due to periventricular lesions (IPSI(PL), n = 8). Motor impairment was similar, but sensory impairment was more pronounced in the CONTRA(MCA) group. Using fMRI and MEG, both groups showed a normal pattern with a contralateral somatosensory representation, despite the transhemispherically reorganized primary motor cortex in the IPSI(PL) group, as verified by TMS. Activation topography for the paretic hands was more variable than for the nonparetic hand in both groups. The cortico-cerebellar circuitry was well-preserved in almost all subjects. We conclude that in both models of motor reorganization, no interhemispheric reorganization of somatosensory functions occurred. Also, no relevant intrahemispheric reorganization was observed apart from a higher topographical variability of fMRI activations. This preserved pattern of somatosensory organization argues in favor of a differential lesion effect on motor and somatosensory functions and demonstrates a limited compensatory potential for the latter.     

Transhemispheric cortical reorganization in rat SmI and involvement of central noradrenergic system

Responses of single units in the hindpaw representational area of the left primary somatosensory cortex to electrical stimulation of both hindpaws and the right forepaw were recorded under urethane anaesthesia in three groups of adult male rats: a control group and two groups in which the right hindpaw representational area had been ablated 3–4 weeks previously, immediately after intraperitoneal injection of saline vehicle or DSP4, to destroy cortical noradrenergic terminals arising from the locus coeruleus. The lesion increased the overall number of neurones responding within 500 ms after the stimulation of the contralateral hindpaw (from 64 to 91%), and the proportion exhibiting short-latency response increased from 41 to 61%. Interestingly, the proportion of neurones with bilateral representation increased from 3 to 10% after the cortical lesioning. The changes were prevented by injection of DSP4 prior to lesioning and therefore depended on an intact central noradrenergic system. The increase in bilateral representation could not have been due to direct interhemispheric connections between corresponding representational areas because it occurred after lesioning of the homologous area in the contralateral hemisphere. The phenomenon was termed ‘transhemispheric reorganization’ and because it was somatotopically oriented (e.g. to either hindpaw); its function may be to ensure that when a sensory cortical area is damaged, its basic sensory functions are ‘taken over’ by the corresponding contralateral area.     

Sensorimotor corticocortical projections from rat barrel cortex have an anisotropic organization that facilitates integration of inputs from whiskers in the same row

We used a dual anterograde-tracing paradigm to characterize the organization of corticocortical projections from primary somatosensory (SI) barrel cortex. In one group of rats, biotinylated dextran amine (BDA) and Fluoro-Ruby (FR) were injected into separate barrel columns that occupied the same row of barrel cortex; in the other group, the tracers were deposited into barrel columns residing in different rows. The labeled corticocortical terminals in the primary motor (MI) and secondary somatosensory (SII) cortices were plotted, and digital reconstructions of these plots were quantitatively analyzed. In all cases, labeled projections from focal tracer deposits in SI barrel cortex terminated in elongated, row-like strips of cortex that corresponded to the whisker representations of the MI or SII cortical areas. When both tracers were injected into separate parts of the same SI barrel row, FR- and BDA-labeled terminals tended to merge into a single strip of labeled MI or SII cortex. By comparison, when the tracers were placed in different SI barrel rows, both MI and SII contained at least two row-like FR- and BDA-labeled strips that formed mirror image representations of the SI injection sites. Quantitative analysis of these labeling patterns revealed three major findings. First, labeled overlap in SII was significantly greater for projections from the same barrel row than for projections from different barrel rows. Second, in the infragranular layers of MI but not in the supragranular layers, labeled overlap was significantly higher for projections from the same SI barrel row. Finally, in all layers of SII and in the infragranular layers of MI, the amount of labeled overlap was proportional to the proximity of the tracer injection sites. These results indicate that SI projections to MI and SII have an anisotropic organization that facilitates the integration of sensory information received from neighboring barrels that represent whiskers in the same row.     

Anatomical and physiological properties of the projection from the sensory cortex to the motor cortex in normal cats: the difference between corticocortical and thalamocortical projections

Details of the distribution of terminal sites of the projection fibers from area 2 of the sensory cortex to the motor cortex were studied and compared with the distribution of terminals from the ventrolateral (VL) nucleus of the thalamus to the motor cortex. The results obtained were as follows: Intracortical microstimulation (ICMS) in area 2 produced measurable short-latency EPSPs only in neurons located in layers II and III of the motor cortex, whereas VL stimulation produced short-latency EPSPs in neurons throughout the depths of the motor cortex. The time from the beginning to the peak of the EPSPs was not significantly different for area 2- and VL-elicited EPSPs suggesting that there was no systematic difference between effective terminal sites for both inputs. However, there was a difference when a given neuron received both inputs suggesting that there was a segregation between the two inputs within a given cell. The majority of area 2-elicited EPSPs were smooth and monophasic, but some (40%) of them showed double peaks indicating that some neurons received mono- and disynaptic inputs from area 2. Intracellular injections of HRP suggested that neurons receiving input from area 2 were predominantly multipolar non-pyramidal neurons in layers II and III whereas neurons receiving thalamic input were pyramidal as well as non-pyramidal cells. Field potentials in the motor cortex evoked by area 2 stimulation did not change polarity in the depths of the cortex and therefore, differed from the VL-evoked potentials suggesting differences in the mechanisms of generating the electrical fields. It is concluded that association fibers effective for producing EPSPs terminate primarily on non-pyramidal cells in layer II and III whereas VL fibers terminate not only on pyramidal but also on non-pyramidal cells in layers III and V. This study provided a basis for examining the modifiability of association fibers after elimination of VL input to the motor cortex which is reported in the following paper.     

Modification of the projection from the sensory cortex to the motor cortex following the elimination of thalamic projections to the motor cortex in cats

Examination of the projection from area 2 of the sensory cortex to the motor cortex revealed substantial changes following lesion of the ventrolateral nucleus of the thalamus. These observed changes were as follows. (1) The polarity of the evoked potentials elicited by area 2 stimulation reversed in the depth of the motor cortex whereas in normal animals, there was no reversal. (2) The amplitude of area 2-elicited EPSPs in the motor cortical neurons became greater following the lesion of VL. (3) The shape of the observed EPSPs was characterized by multiple peaks whereas in normal animals, the EPSPs were generally smooth and monophasic. (4) Neurons receiving a short-latency input from area 2 were distributed throughout the depths of the motor cortex whereas in normal animals, they were located only in the upper layers (layers II and III). (5) Intracellular injection of HRP revealed that the neurons receiving short-latency input were not restricted to typical stellate type cells, but also included bipolar or bitufted neurons with elongated cell bodies and polarized arborizations. These neurons were located in the superficial (II and III) as well as in the deep (V) layer. It is concluded that the elimination of thalamic input resulted in the reinforcement of the corticocortical input to the motor cortex. The subsequently observed corticocortical projection extended to neurons did not originally innervated by the association fibers. The results suggested that functional recovery following thalamic lesion is partly due to reorganization of projections from the sensory cortex to the motor cortex.     

Mechano‐ and metabosensitive alterations after injection of botulinum toxin into gastrocnemius muscle

This study was designed to investigate effects of motor denervation by Clostridium botulinum toxin serotype A (BoNT/A) on the afferent activity of fibers originating from the gastrocnemius muscle of rats. Animals were randomized in two groups, 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle. Locomotor activity was evaluated once per day during 12 days with a test based on footprint measurements of walking rats (sciatic functional index). At the end of the functional assessment period, electrophysiological tests were used to measure muscle properties, metabosensitive afferent fiber responses to chemical (KCl and lactic acid) injections, electrically induced fatigue (EIF), and mechanosensitive responses to tendon vibrations. Additionally, ventilatory response was recorded during repetitive muscle contractions. Then, rats were sacrificed, and the BoNT/A‐injected muscles were weighed. Twelve days postinjection we observed a complete motor denervation associated with a significant muscle atrophy and loss of force to direct muscle stimulation. In the BoNT/A group, the metabosensitive responses to KCl injections were unaltered. However, we observed alterations in responses to EIF and to 1 mM of lactic acid (which induces the greatest activation). The ventilatory adjustments during repetitive muscle activation were abolished, and the mechanosensitive fiber responses to tendon vibrations were reduced. These results indicate that BoNT/A alters the sensorimotor loop and may induce insufficient motor and physiological adjustments in patients in whom a motor denervation with BoNT/A was performed. © 2014 Wiley Periodicals, Inc.