Long-term Cortical Reorganization Research Articles

Spatial Relationship Perception is Not Affected by Short-term Cortical Reorganization

Aims: Long-term cortical reorganization after cortical damage can induce abnormal spatial relationship perception (spatial anisotropy) but there is also evidence of short-term, reversible cortical re-modulation even in the absence of cerebral damage: simulated hemianopic deprivation, in fact, is found to affect the positional judgment. This study investigates if the same occurs for spatial relationship perception.
 Study Design: Case series.
 Place and duration of Study: Service of Neuro-Ophthalmology, University of Turin, Italy, from January 2020 to July 2020.
 Methodology: Spatial relationship perception (SRP) of three subjects was measured in the presence of simulated homonymous hemianopia with a psychophysical procedure that estimates the discrimination threshold between elliptical and circular stimuli centered to the fixation point. The extent of the deprivation was graded as the distance of the proximal border of the nonresponsive area from the fixation point.
 Results: Overall, spatial relationship perception is not affected by the hemifield deprivation in terms of distance of the scotoma from the fixation point (P= 0.26), laterality (P= 0.07), and distance X laterality (P= 0.15). However, a significant effect of distance and laterality (P= 0.01 and P= 0.02, respectively) was found in the sole observer who showed an anisotropic perception in normal (no-simulated) condition.
 Conclusion: SRP appears to be robust toward the reversible spatial remapping induced by simulated hemianopia along the deprived area. However, the response of the visual system to artificial visual deprivation seems conditioned by pre-existing anisotropy.

Cortical Reorganization: Reallocated Responses without Rewiring

Summary Is the brain able to reorganise following loss of sensory input? New work on individuals with sight loss shows that, while brain areas normally allocated to vision respond to other sensory stimuli, those responses are unlikely to mean the brain has rewired.

Primary visual cortical remapping in patients with inherited peripheral retinal degeneration.

Human studies addressing the long-term effects of peripheral retinal degeneration on visual cortical function and structure are scarce. Here we investigated this question in patients with Retinitis Pigmentosa (RP), a genetic condition leading to peripheral visual degeneration. We acquired functional and anatomical magnetic resonance data from thirteen patients with different levels of visual loss and twenty-two healthy participants to study primary (V1) visual cortical retinotopic remapping and cortical thickness. We identified systematic visual field remapping in the absence of structural changes in the primary visual cortex of RP patients. Remapping consisted in a retinotopic eccentricity shift of central retinal inputs to more peripheral locations in V1. Importantly, this was associated with changes in visual experience, as assessed by the extent of the visual loss, with more constricted visual fields resulting in larger remapping. This pattern of remapping is consistent with expansion or shifting of neuronal receptive fields into the cortical regions with reduced retinal input. These data provide evidence for functional changes in V1 that are dependent on the magnitude of peripheral visual loss in RP, which may be explained by rapid cortical adaptation mechanisms or long-term cortical reorganization. This study highlights the importance of analyzing the retinal determinants of brain functional and structural alterations for future visual restoration approaches.

Interactive Effects Between Exercise and Serotonergic Pharmacotherapy on Cortical Reorganization After Spinal Cord Injury

Background. In rat models of spinal cord injury, at least 3 different strategies can be used to promote long-term cortical reorganization: (1) active exercise above the level of the lesion; (2) passive exercise below the level of the lesion; and (3) serotonergic pharmacotherapy. Whether and how these potential therapeutic strategies—and their underlying mechanisms of action—interact remains unknown. Methods. In spinally transected adult rats, we compared the effects of active exercise above the level of the lesion (treadmill), passive exercise below the level of the lesion (bike), serotonergic pharmacotherapy (quipazine), and combinations of the above therapies (bike+quipazine, treadmill+quipazine, bike+treadmill+quipazine) on long-term cortical reorganization (9 weeks after the spinal transection). Cortical reorganization was measured as the percentage of cells recorded in the deafferented hindlimb cortex that responded to tactile stimulation of the contralateral forelimb. Results. Bike and quipazine are “competing” therapies for cortical reorganization, in the sense that quipazine limits the cortical reorganization induced by bike, whereas treadmill and quipazine are “collaborative” therapies, in the sense that the reorganization induced by quipazine combined with treadmill is greater than the reorganization induced by either quipazine or treadmill. Conclusions. These results uncover the interactive effects between active/passive exercise and serotonergic pharmacotherapy on cortical reorganization after spinal cord injury, emphasizing the importance of understanding the effects of therapeutic strategies in spinal cord injury (and in other forms of deafferentation) from an integrated system-level approach.

Functional reorganization of the forepaw cortical representation immediately after thoracic spinal cord hemisection in rats

Spinal cord injury may produce long-term reorganization of cortical circuits. Little is known, however, about the early neurophysiological changes occurring immediately after injury. On the one hand, complete thoracic spinal cord transection of the spinal cord immediately decreases the level of cortical spontaneous activity and increases the cortical responses to stimuli delivered to the forepaw, above the level of the lesion. On the other hand, a thoracic spinal cord hemisection produces an immediate cortical hyperexcitability in response to preserved spinothalamic inputs from stimuli delivered to the hindpaw, below the level of the lesion. Here we show that a thoracic spinal cord hemisection also produces a bilateral increase of the responses evoked in the forepaw cortex by forepaw stimuli, associated with a bilateral decrease of cortical spontaneous activity. Importantly, the increased cortical forepaw responses are immediate in the cortex contralateral to the hemisection (significant within 30min after injury), but they are progressive in the cortex ipsilateral to the hemisection (reaching significance only 2.5h after injury). Conversely, the decreased cortical spontaneous activity is progressive both ipsilaterally and contralaterally to the hemisection (again reaching significance only 2.5h after injury). In synthesis, the present work reports a functional reorganization of the forepaw cortical representation immediately after thoracic spinal cord hemisection, which is likely important to fully understand the mechanisms underlying long-term cortical reorganization after incomplete spinal cord injuries.

Long-term cortical reorganization following stroke in a single subject with severe motor impairment

Stroke continues to be a major public health concern in the United States. Motor recovery in the post-acute stages of stroke is possible due to neuroplasticity, or the capacity of the brain to reorganize. This case study tracks neuroplastic and motor change in a subject with severe hemiparesis following an extensive middle cerebral artery stroke. He had absence of ipsilesional motor evoked potentials in early evaluations. This report is unique in that the duration of follow-up evaluation extends nearly 2 years, with evaluations being performed at 7, 9, 10, 13, 20, and 21 months post-stroke. At each evaluation we used transcranial magnetic stimulation to track neuroplastic change and the Fugl-Meyer Assessment and the Wolf Motor Function Test to evaluate upper extremity motor performance. The contralesional hemisphere showed dynamic change throughout the study period. In contrast, the ipsilesional hemisphere demonstrated notable change only between 13 and 21 months post-stroke, with the most dramatic change occurring between 20 and 21 months post-stroke. Motor performance generally improved throughout the study period. Our findings demonstrate that substantial neuroplasticity-mediated motor recovery can occur nearly 2 years after stroke in an individual with severe post-stroke motor impairment.

A prolonged experimental febrile seizure results in motor map reorganization in adulthood

Introduction Clinical studies have suggested that children experiencing a febrile seizure (FS) before the age of 1 year have persistent deficits, but it is unknown whether these seizures lead to permanent cortical reorganization and alterations in function. A FS on the background of increased genetic seizure susceptibility may also lead to negative long-term consequences. Alterations in neocortical motor map expression provide a measure of neocortical reorganization and have been reported in both adults with frontal lobe epilepsy and following seizure induction in experimental models. The objectives of the present study were to determine whether 1) an infantile FS leads to changes to motor map expression in adulthood; 2) long-term cortical reorganization is a function of the age at FS or genetic seizure susceptibility; and 3) different levels of GABA A or glutamate receptor subunits or cation-chloride-co-transporters (CCCs) at the time of FS correlate with alterations to motor map expression. Materials and methods FSs were induced in postnatal day 10 (P10) or P14 Long–Evans (LE) rats or in P14 seizure-prone FAST rats by the administration of the bacterial endotoxin lipopolysaccharide (LPS) and a subconvulsant dose of kainic acid. Ten weeks later intracortical microstimulation was performed to generate motor maps of forelimb movement representations. Sensorimotor neocortex samples were also dissected from naïve P10 FAST and P10 and P14 LE pups for western blotting with antibodies against various GABA A, NMDA, and AMPA receptor subunits and for CCCs. Results Adult FAST rats had larger motor maps with lower stimulation thresholds after a FS at P14, while adult LE rats had significantly lower map stimulation thresholds but similar sized maps after a FS at P10 compared to controls. There were no differences in neocortical motor map size or stimulation thresholds in adult LE rats after a FS at P14. Both P10 LE and P14 FAST rats had significantly lower levels of the GABA A receptor α1 subunit, higher levels of the α2 subunit, and a higher NKCC1/KCC2 ratio in the sensorimotor cortex compared with the P14 LE rat. In addition, the P14 FAST rats had lower levels of the GluR2 and NR2A receptor subunits in the sensorimotor cortex compared with the P14 LE rats. Conclusions A single infantile FS can have long-term effects on neocortical reorganization in younger individuals and those with underlying seizure susceptibility. These changes may be related to an increased level of excitability in the neocortex of younger or genetically seizure-prone rats, as suggested by immaturity of their GABAergic and CCC systems. Given the high incidence of FSs in children, it will be important to gain a better understanding of how age and genetic seizure predisposition may contribute to the long-term sequelae of these events.

RECOVERY OF SWALLOWING FUNCTION IS ACCOMPANIED BY THE EXPANSION OF THE CORTICAL MAP

To determine whether multiple sessions of electrical stimulation (ES) applied to neck muscles improve swallowing function and whether this improvement is accompanied by cortical reorganization in patients with dysphagia, before-after trials were performed on eight subjects. ES was applied for 1 hour, 5 days a week for 2 weeks. Swallowing function significantly improved after 2 weeks of ES, and this change was found to correlate with cortical reorganization measured by corticobulbar output maps. This study suggests that multiple sessions of ES applied to the neck muscles improve swallowing function via a mechanism involving long-term cortical reorganization.

Lack of long-term cortical reorganization after macaque retinal lesions

Several aspects of cortical organization are thought to remain plastic into adulthood, allowing cortical sensorimotor maps to be modified continuously by experience. This dynamic nature of cortical circuitry is important for learning, as well as for repair after injury to the nervous system. Electrophysiology studies suggest that adult macaque primary visual cortex (V1) undergoes large-scale reorganization within a few months after retinal lesioning, but this issue has not been conclusively settled. Here we applied the technique of functional magnetic resonance imaging (fMRI) to detect changes in the cortical topography of macaque area V1 after binocular retinal lesions. fMRI allows non-invasive, in vivo, long-term monitoring of cortical activity with a wide field of view, sampling signals from multiple neurons per unit cortical area. We show that, in contrast with previous studies, adult macaque V1 does not approach normal responsivity during 7.5 months of follow-up after retinal lesions, and its topography does not change. Electrophysiology experiments corroborated the fMRI results. This indicates that adult macaque V1 has limited potential for reorganization in the months following retinal injury.

Lack of long-term cortical reorganization after macaque retinal lesions

Several aspects of cortical organization are thought to remain plastic into adulthood, allowing cortical sensorimotor maps to be modified continuously by experience. This dynamic nature of cortical circuitry is important for learning, as well as for repair after injury to the nervous system. Electrophysiology studies suggest that adult macaque primary visual cortex (V1) undergoes large-scale reorganization within a few months after retinal lesioning, but this issue has not been conclusively settled. Here we applied the technique of functional magnetic resonance imaging (fMRI) to detect changes in the cortical topography of macaque area V1 after binocular retinal lesions. fMRI allows non-invasive, in vivo, long-term monitoring of cortical activity with a wide field of view, sampling signals from multiple neurons per unit cortical area. We show that, in contrast with previous studies, adult macaque V1 does not approach normal responsivity during 7.5 months of follow-up after retinal lesions, and its topography does not change. Electrophysiology experiments corroborated the fMRI results. This indicates that adult macaque V1 has limited potential for reorganization in the months following retinal injury.

Filling-in of retinal scotomas

In this study we examined the perception of one- and two-dimensional patterns across central retinal scotomas, caused by age-related macular degeneration. In contrast with previous studies of disrupted visual input that used the blind spot and artificial scotomas, the current study used large central scotomas caused by physical retinal damage. Such damage is associated with atrophy and long-term cortical reorganization, and it was therefore unclear whether perceptual completion in the damaged system will be similar to that reported for artificial scotomas and the blind spot. In addition, the scotomas under study were much larger and more central than artificial scotomas for which perceptual completion has been reported. For 1-D line and grating patterns, we found perceptual completion across large central scotomas (up to radius of 7°), which is significantly beyond the range of perceptual completion in artificial scotomas. Gratings completion was better than that of a single line, and increased with bars density. The use of central scotomas allowed us to test the completion of 2-D patterns that are difficult to study in peripheral vision. We found completion of two-dimensional dot arrays over large regions that improved with pattern density and regularity. The results show that in the physically damaged system the range of perceptual completion is increased compared with artificial scotomas, they strongly support the view of an active filling-in process rather than simply ignoring the damaged location, and they show that perceptual completion of physical scotomas is likely to involve cortical processing at multiple levels. We finally discuss implications of the results to the possible use of image enhancement techniques to facilitate the perception of low-vision individuals.

Role of Inhibition in Cortical Reorganization of the Adult Raccoon Revealed by Microiontophoretic Blockade of GABAAReceptors

Cortical reorganization was induced by amputation of the 4th digit in 11 adult raccoons. Animals were studied at various intervals, ranging from 2 to 37 wk, after amputation. Recordings were made from a total of 129 neurons in the deafferented cortical region using multibarrel micropipettes. Several types of receptive fields were described in reorganized cortex: restricted fields were similar in size to the normal receptive fields in nonamputated animals; multi-regional fields included sensitive regions on both adjacent digits and/or the underlying palm and were either continuous over the entire field or consisted of split fields. The proportion of neurons with restricted fields increased with time after amputation and was greater than previously found in subcortical regions. A GABA(A) receptor antagonist (bicuculline methiodide), glutamate, and GABA were administered iontophoretically to these neurons while determining their receptive fields and thresholds. Bicuculline administration resulted in expansion of the receptive field in 60% of the 93 neurons with cutaneous fields. In most cases (33 neurons) this consisted of a simple expansion around the borders of the predrug receptive field, and the average expansion (426%) was not different from that seen in nonamputated animals. In some neurons (n = 4), bicuculline produced an expansion from one digit onto the adjacent palm or another digit, an effect never seen in control animals. Bicuculline also changed the split fields of seven neurons into continuous fields by exposing a responsive region between the split fields. Finally, bicuculline changed the internal receptive field organization of 10 neurons by revealing subfields with reduced thresholds. In contrast to the situation in nonamputated animals, iontophoretic administration of glutamate also produced receptive field expansion in some neurons (n = 6), but the size and/or shape of the change was different from that produced by bicuculline, indicating that the effects of bicuculline were not due to an overall facilitation of neuronal activity. These results are consistent with the hypotheses that an important component of long-term cortical reorganization is the gradual reduction in effective receptive field size and that intracortical inhibitory networks are partially responsible for these changes.

Reorganization of cortical motor area in prior polio patients

Objective: Focal transcranial magnetic stimulation (TMS) was used to study the motor maps of upper limb muscles in 7 adult patients with a history of paralytic poliomyelitis. The aim of the study was to verify the potential for long-term cortical reorganization of a selective peripheral motor neuron lesion suffered early in life. Methods: Patient selection was based on the prevalent involvement of proximal muscles in only one of the upper limbs. Motor evoked potentials (MEPs) were recorded from deltoid and abductor pollicis brevis (APB) muscles. Each muscle map was characterized by area (no. of excitable positions), volume (the sum of MEP amplitudes at all scalp positions), maximal amplitude (the highest MEP recorded). Results: In the patients, the mean area, volume and maximal amplitude were significantly greater in affected vs. contralateral deltoid ( P<0.05) and vs. controls ( P<0.01). No significant differences were found in APB map parameters. The APB/deltoid ratio for area was lower in the affected compared with the unaffected side and controls ( P=0.06). Cortical reorganization was not significantly correlated with motor performance. Conclusion: These findings are consistent with a rearrangement in human motor pathways targeting muscles affected by a lower motor neuron lesion.

Monocular focal retinal lesions induce short-term topographic plasticity in adult cat visual cortex.

Electrophysiological recording in primary visual cortex (VI) was performed both prior to and in the hours immediately following the creation of a discrete retinal lesion in one eye with an argon laser. Lesion projection zones (LPZs; 21-64 mm2) were defined in the visual cortex by mapping the extent of the lesion onto the topographic representation in cortex. There was no effect on neuronal responses to the unlesioned eye or on its topographic representation. However, within hours of producing the retinal lesion, receptive fields obtained from stimulation of the lesioned eye were displaced onto areas surrounding the scotoma and were enlarged compared with the corresponding field obtained through the normal eye. The proportion of such responsive recording sites increased during the experiment such that 8-11 hours post-lesion, 56% of recording sites displayed neurons responsive to the lesioned eye. This is an equivalent proportion to that previously reported with long-term recovery (three weeks to three months). Responsive neurons were evident as far as 2.5 mm inside the border of the LPZ. The reorganization of the lesioned eye representation produced binocular disparities as great as 15 degrees, suggesting interactions between sites in VI up to 5.5 mm apart.

Sustained attention modulates the immediate effect of de-afferentation on the cortical representation of the digits: source localization of somatosensory evoked potentials in humans

Long-term cortical reorganization of the somatotopic arrangement of the digits after alterations of the peripheral input is well established. Studies on the immediate effects of manipulating peripheral input have shown conflicting results indicating that additional factors might modulate cortical reorganization. We present a source localization study using somatosensory evoked potentials (SEP) following electric stimulation of digits one and five before and during anaesthesia of digits two, three and four in 10 normal volunteers. When attention was directed to a stimulus at the dorsal hand, the 3D-distance between digits one and five decreased during as compared to before anaesthesia. In contrast, this distance enlarged when subjects were not attending a particular stimulus. In this condition most subjects focused their attention on the clear sensation of the de-afferented hand region. These results indicate that attention modulates the effect of immediate cortical reorganization of the hand area during partial de-afferentation. As an hypothesis: it may be speculated that the sensation of the de-afferentation results in increased synchronized activity of the de-afferented somatosensory cortex and, thus, to its enlarged representation. Conversely, if attention is directed to a different hand region, the representations of the neighboring digits may expand into the de-afferented cortex.