Interplay between intra- and interhemispheric remodeling of neural networks as a substrate of functional recovery after stroke: adaptive versus maladaptive reorganization.

Brain injuries such as focal stroke initiate a myriad of neural events leading to local and remote alterations in cerebral networks. The neurochemical and neurophysiological mechanisms underlying these postlesion changes raise the question of their beneficial or adverse effects on functional recovery. In this review, we aim to reconcile findings from animal and patients studies using a "from cellular-to network-levels" perspective to gain further insights into the neuroplasticity mechanisms underlying recovery of sensorimotor functions. Ultimately, an integrative view of the multiple facets of poststroke changes should give an impetus to novel neurorehabilitation strategies by providing evidence of how neuroscience findings can be translated and operationalized within the context of restorative stroke.

Neuronal substrates of haptic shape encoding and matching: a functional magnetic resonance imaging study.

We used functional magnetic resonance imaging to differentiate cerebral areas involved in two different dimensions of haptic shape perception: encoding and matching. For this purpose, healthy right-handed subjects were asked to compare pairs of complex 2D geometrical tactile shapes presented in a sequential two-alternative forced-choice task. Shape encoding involved a large sensorimotor network including the primary (SI) and secondary (SII) somatosensory cortex, the anterior part of the intraparietal sulcus (IPA) and of the supramarginal gyrus (SMG), regions previously associated with somatosensory shape perception. Activations were also observed in posterior parietal regions (aSPL), motor and premotor regions (primary motor cortex (MI), ventral premotor cortex, dorsal premotor cortex, supplementary motor area), as well as prefrontal areas (aPFC, VLPFC), parietal-occipital cortex (POC) and cerebellum. We propose that this distributed network reflects construction and maintenance of sensorimotor traces of exploration hand movements during complex shape encoding, and subsequent transformation of these traces into a more abstract shape representation using kinesthetic imagery. Moreover, haptic shape encoding was found to activate the left lateral occipital complex (LOC), thus corroborating the implication of this extrastriate visual area in multisensory shape representation, besides its contribution to visual imagery. Furthermore, left hemisphere predominance was shown during encoding, whereas right hemisphere predominance was associated with the matching process. Activations of SI, MI, PMd and aSPL, which were predominant in the left hemisphere during the encoding, were shifted to the right hemisphere during the matching. In addition, new activations emerged (right dorsolateral pre-frontal cortex, bilateral inferior parietal lobe, right SII) suggesting their specific involvement during 2D geometrical shape matching.

Influence of the postlesion environment and chronic piracetam treatment on the organization of the somatotopic map in the rat primary somatosensory cortex after focal cortical injury.

The influence of housing in an enriched or impoverished environment and anti-ischemic treatment (piracetam) on the organization of the intact regions of the somatosensory cortical maps adjacent to a focal cortical injury were investigated in adult rats. Response properties of small clusters of neurons were recorded in the area of the primary somatosensory cortex (SI) devoted to the contralateral forepaw representation. Electrophysiological maps were elaborated on the basis of the sensory "submodality" (cutaneous or noncutaneous) and the location of the receptive fields (RFs) of layer IV neurons. Recordings were made before, and 3 weeks after induction of a focal neurovascular lesion to the SI cortex. The main results were: 1) the focal ischemic injury induced a cellular loss which was less severe in the piracetam treated rats, regardless of the housing conditions; 2) the lesion resulted in a compression of the remaining forepaw map, a fragmentation of the representational zones serving the cutaneous surfaces (low-threshold inputs) and an enlargement of noncutaneous zones (high-threshold inputs) in the spared cortical sectors surrounding the lesion. These changes were found in all placebo rats, with the most detrimental effects in the animals exposed to an impoverished environment, and in the piracetam-plus-impoverished rats. In contrast, a limited compression of the forepaw map and a preservation of most representational sectors were observed in the piracetam-plus-enriched animals, 3) the size of the cutaneous RFs of the neurons within the intact cortical zones remained unchanged, regardless of environment or treatment; 4) consistent with the map changes, the skin surfaces lacking low-threshold cutaneous RFs increased after the lesion in all animal groups but the piracetam-plus-enriched rats; 5) cortical responsiveness as assessed with mechanical threshold evaluation was diminished in the placebo rats, whatever the environment, and in the piracetam-impoverished rats, but was not significantly affected in the piracetam-enriched animals. Our findings, based on the first double electrophysiological mapping in the rat SI cortex, highlight the protective effects of an environmental therapy associated with an anti-ischemic treatment on the neurophysiological properties of cortical neurons following a focal neurovascular injury to the neocortex.

Vestibular compensation: role of visual motion cues in the recovery of posturo-kinetic functions in the cat.

Vision has long been recognized as a sensorimotor system which plays a major role in substitution for functional deficits induced by unilateral or bilateral exclusion of primary vestibular afferents. Little is known, however, about the post-lesion influence of visual inputs on the recovery of posturo-kinetic balance in a situation where fine, well-coordinated locomotor adjustments are required. The present study was carried out in order to gain some insight into the role played by motion vision in the restoration of fine posturo-kinetic balance in adult cats subjected to unilateral vestibular neurectomy. Prior to the lesion, 15 adult animals were trained to cross a beam rotating at various speeds. Their best global balance performance (highest beam rotation speed that did not provoke falling) and their average locomotion speed were evaluated. After the lesion, the cats were separated into three groups: (1) five animals were placed in a normal environment (animal house) (NV cats); (2) four animals were exposed to stroboscopic illumination which eliminated visual motion cues (SV cats) for 2 weeks following the lesion; and (3) three animals were placed in a normal environment and their training was interrupted for the same period as in the SV cats (NVI cats). The possible influence of the 2-week deprivation of visual motion cues on posturo-kinetic balance was also examined in three intact cats. The present behavioral study showed that: (1) early sensory deprivation caused suspension of the posturo-kinetic balance recovery process as long as it was maintained; (2) complete restoration of global balance capacities developed following the vestibular neurectomy after a significant delay in half of the SV cats; (3) the lack of motion cues resulted in severe alterations of fine posturo-kinetic balance (inappropriate dynamic motor adjustments and irregular locomotion speed regulation) in all SV cats; and (4) the visual deprivation induced a 2-week delay in the restoration of fine locomotor balance. These findings provide evidence for a defect in the visual sensory substitution processes that normally take place within the first few weeks following exclusion of primary vestibular afferents.

Visual experience during a sensitive period plays a critical role in vestibular compensation: neuronal substrates within Deiters' nucleus in the alert cat.

In a previous study [31], we showed that Deiters' neurons ipsilateral to a vestibular neurectomy temporarily exhibit increased sensitivity to visual cues about fast movement. It was proposed that this change in the deafferented vestibular neuron response observed only during the first 3 weeks post-lesion plays an important role in the vestibular compensation process. The present study was aimed at analyzing the potential influence over the first 2 weeks post-lesion of visual motion cue deprivation (cats housed in stroboscopic light) and passive visual experience (visual information not correlated to head or body movement) on the visually induced activity of Deiters' cells. The extra-cellular response of single units was recorded during sinusoidal translation of a whole field optokinetic stimulus in six alert cats. Following the deprivation of visual motion cues, vestibular unit responses were found to be tuned to low frequencies of visual stimulation, as in intact cats, and to display a phase lag re. velocity during rapid visual stimulation. Passive visual stimulation was also found to impede the increase in neuronal sensitivity to visual input, although the cats had benefited from normal vision from the 15th day post-lesion. These results are discussed in relation to the functional implication of interactive visual experience within the early stages (sensitive period) of the vestibular compensation process.

Visual sensory substitution in vestibular compensation: neuronal substrates in the alert cat.

The purpose of this study was to investigate adaptive changes in the activity of vestibular nuclei neurons unilaterally deprived of their primary afferent inputs when influenced by visual motion cues. These neuronal changes might account for the established role that vision plays in the compensation for posturo-kinetic deficits after the loss of vestibular inputs. Neuronal recordings were made in alert, non-paralysed cats that had undergone unilateral vestibular nerve sections. The unit responses collected in both Deiters' nuclei were compared to those previously recorded in intact cats. We analysed the extracellular activity of Deiters' nucleus neurons, as well as the optokinetic reflex (OKR) evoked during sinusoidal translation of a whole-field optokinetic stimulus in the vertical plane. In intact cats, we found the unit firing rate closely correlated with the visual surround translation velocity, and the relationship between the discharge rate and the motion frequency was tuned around an optimal frequency. The maximum firing rate modulation was generally below the 0.25 Hz stimulus frequency; unit responses were weak or even absent above 0.25 Hz. From the 4th day to the end of the 3rd week after ipsilateral deafferentation, a majority of cells was found to display maximum discharge modulation during vertical visual stimulation at 0.50 Hz, and even at 0.75 Hz, indicating that the frequency bandwidth of the visually induced responses of deafferented vestibular nuclei neurons had been extended. Consequently, the frequency-dependent attenuation in the sensitivity of vestibular neurons to visual inputs was much less pronounced. After the first 3 weeks post-lesion, the unit response characteristics were very similar to those observed prior to the deafferentation. On the nucleus contralateral to the neurectomy, the maximum modulation of most cells was tuned to the low frequencies of optokinetic stimulation, as also seen prior to the lesion. We found, however, a subgroup of cells displaying well-developed responses above 0.50 Hz. Under all experimental conditions, the neuronal response phase still remained closely correlated with the motion velocity of the vertical sinusoidal visual pattern. We hypothesize that Deiters' neurons deprived of their primary afferents may transiently acquire the ability to code fast head movements on the basis of visual messages, thus compensating, at least partially, for the loss of dynamic vestibular inputs during the early stages of the recovery process.(ABSTRACT TRUNCATED AT 400 WORDS)

Recovery of head postural control following unilateral vestibular neurectomy in the cat. Neck muscle activity and neuronal correlates in Deiters' nuclei.

Recovery of head postural control after unilateral vestibular neurectomy was investigated in the alert cat by chronically recording the spontaneous neck muscle EMG activity from splenius capitis on both sides and the vestibulocollic reflexes evoked during roll and pitch tilts. Neuronal correlates occurring within the lateral (Deiters) vestibular nuclei (LVN) were also recorded during the time-course of recovery. During the acute phase (1-2 weeks), the cats exhibited strong imbalance in spontaneous neck muscle activity, characterized by increased muscular tone in the ipsilateral splenius capitis muscle and hypoactivity in the contralateral one. At the same time, the mean resting activity of Deiters' neurons strongly decreased on the deafferented side, while a slight but significant decrease was observed on the intact side. Vestibulocollic reflexes were totally lacking during the acute phase, whatever the direction and the amplitude of tilt. Recovery developed in the following weeks, leading to complete rebalance of spontaneous EMG activity as well as near to normal static vestibulocollic reflexes 5 weeks after the lesion. However, compensation remained sub-normal during roll tilts while overcompensation was found during pitch tilts, suggesting that the intact labyrinth would play a leader role in the recovery process but that bilateral cooperation of the two labyrinths is required for proper head postural control. Five weeks are also needed for a partial rebalancing of resting activity between both LVN. These results indicate that changes in neck muscle activity observed in the acute cats and that recovery found in the compensated animals could result from modifications in neural networks controlling neck musculature, such as the LVN.