Cortical reorganization in NT3-treated experimental spinal cord injury: Functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) studies were performed for visualizing ongoing brain plasticity in Neurotrophin-3 (NT3)-treated experimental spinal cord injury (SCI). In response to the electrical stimulation of the forepaw, the NT3-treated animals showed extensive activation of brain structures that included contralateral cortex, thalamus, caudate putamen, hippocampus, and periaqueductal gray. Quantitative analysis of the fMRI data indicated significant changes both in the volume and center of activations in NT3-treated animals relative to saline-treated controls. A strong activation in both ipsi- and contralateral periaqueductal gray and thalamus was observed in NT3-treated animals. These studies indicate ongoing brain reorganization in the SCI animals. The fMRI results also suggest that NT3 may influence nociceptive pathways.     

Neurofunctional maps of the ‘maternal brain’ and the effects of oxytocin: A multimodal voxel‐based meta‐analysis

Several studies have tried to understand the possible neurobiological basis of mothering. The putative involvement of oxytocin, in this regard, has been deeply investigated. Performing a voxel‐based meta‐analysis, we aimed at testing the hypothesis of overlapping brain activation in functional magnetic resonance imaging (fMRI) studies investigating the mother–infant interaction and the oxytocin modulation of emotional stimuli in humans. We performed two systematic literature searches: fMRI studies investigating the neurofunctional correlates of the ‘maternal brain’ by employing mother–infant paradigms; and fMRI studies employing oxytocin during emotional tasks. A unimodal voxel‐based meta‐analysis was performed on each database, whereas a multimodal voxel‐based meta‐analytical tool was adopted to assess the hypothesis that the neurofunctional effects of oxytocin are detected in brain areas implicated in the ‘maternal brain.’ We found greater activation in the bilateral insula extending to the inferior frontal gyrus, basal ganglia and thalamus during mother–infant interaction and greater left insular activation associated with oxytocin administration versus placebo. Left insula extending to basal ganglia and frontotemporal gyri as well as bilateral thalamus and amygdala showed consistent activation across the two paradigms. Right insula also showed activation across the two paradigms, and dorsomedial frontal cortex activation in mothers but deactivation with oxytocin. Significant activation in areas involved in empathy, emotion regulation, motivation, social cognition and theory of mind emerged from our multimodal meta‐analysis, supporting the need for further studies directly investigating the neurobiology of oxytocin in the mother–infant relationship.     

Anatomical Functional Changes in a Patient Presenting a Complex Malformation of Cortical Development

The authors describe a case of right fronto‐parietal micropoligyria associated with small schizencephaly clefts and the presence of a frontal open‐lip schizencephaly with corpus callosum agenesis. A functional magnetic resonance imaging (fMRI) study was performed to evaluate the possible reorganization of cortical functions in a patient presentinga complex malformation pattern and to investigate which cortical areas were activated during left finger movements. An fMRI study was performed during the execution of a repetitive index finger‐to‐thumb opposition movement with the right hand and the left hand in 2 separate sessions. Movement of the right hand induced a normal motor activation pattern involving the contralateral left sensory‐motor cortex. Movement of the left hand produced significant activation of brain cortex. This fMRI study highlights the compensatory role of the ipsilateral cortical pathways in hand movements in the case of a complex brain malformation that involves the main motor activation areas.     

Reorganization in the primary motor cortex after spinal cord injury - A functional Magnetic Resonance (fMRI) study

Activation maps in the primary motor cortex (M1) were investigated in three patients with complete spinal cord injury (SCI) at level TH3, TH7 and TH9 and in one patient with an incomplete spinal cord injury at level L1 during right elbow (4 patients), right thumb (4 patients), bilateral lip (2 patients) and right foot (3 patients during imagined, 1 patient during executed) movements using functional Magnetic Resonance Imaging (fMRI). Compared to controls fMRI activation maps of patients with complete paraplegia showed a cranial displacement of the activation maxima in the contralateral primary motor cortex during elbow movement of 13.3mm, whereas the maxima of thumb and lip movements were not altered. The patient with an incomplete spinal cord injury revealed no displacement of elbow activation maxima. The reorganization is likely to occur on the cortical and not on the spinal level.     

Reorganization in the primary motor cortex after spinal cord injury - A functional Magnetic Resonance (fMRI) study

Activation maps in the primary motor cortex (M1) were investigated in three patients with complete spinal cord injury (SCI) at level TH3, TH7 and TH9 and in one patient with an incomplete spinal cord injury at level L1 during right elbow (4 patients), right thumb (4 patients), bilateral lip (2 patients) and right foot (3 patients during imagined, 1 patient during executed) movements using functional Magnetic Resonance Imaging (fMRI). Compared to controls fMRI activation maps of patients with complete paraplegia showed a cranial displacement of the activation maxima in the contralateral primary motor cortex during elbow movement of 13.3mm, whereas the maxima of thumb and lip movements were not altered. The patient with an incomplete spinal cord injury revealed no displacement of elbow activation maxima. The reorganization is likely to occur on the cortical and not on the spinal level.     

Adaptation in the motor cortex following cervical spinal cord injury

BACKGROUND: The nature of the adaptive changes that occur in the cerebral cortex following injury to the cervical spinal cord are largely unknown. OBJECTIVE: To investigate these adaptive changes by examining the relationship between the motor cortical representation of the paretic right upper extremity compared with that of the tongue. The tongue was selected because the spinal cord injury (SCI) does not affect its movement and the cortical representation of the tongue is adjacent to that of the paretic upper extremity. METHODS: FMRI was used to map cortical representations associated with simple motor tasks of the right upper extremity and tongue in 14 control subjects and 9 patients with remote (>5.5 months) cervical SCI. RESULTS: The mean value for the site of maximum cortical activation during upper limb movement was identical between the two groups. The site of maximum left hemispheric cortical activation during tongue movement was 12.8 mm (p < 0.01) medial and superior to that of control subjects, indicating the presence of a shift in cortical activation. CONCLUSION: The findings indicate that the adult motor cortex does indeed adapt following cervical SCI. The nature of the adaptation and the underlying biological mechanisms responsible for this change require further investigation.     

Hand somatosensory cortex activity following selective dorsal rhizotomy: report of three cases with fMRI

Introduction Selective dorsal rhizotomy (SDR) is an effective treatment for lower extremity spasticity in cerebral palsy. Cortical organization in sensory cortex may be abnormal in cerebral palsy, and deafferentation is known to lead to cortical reorganization in many situations.Methods We used functional magnetic resonance imaging (fMRI) of hand sensory stimulation to determine if the partial deafferentation of the lower extremity sensory system, associated with SDR, led to any alterations in the cortical somatosensory representation for the upper limbs. Three patients with spastic diplegia were studied with blood oxygen level-dependent (BOLD)-fMRI before and after SDR. fMRI during tactile stimulation of the digits of the right hand was used to map hand somatosensory cortex. Comparison of the cortical maps devoted to the hand before and after SDR assessed for cortical reorganization following partial deafferentation of the lower extremity.Results In the one patient with upper extremity involvement, the hand sensory representation was markedly enhanced following SDR. In the other two patients, a normal pattern, but with diminished activity, was seen compared with preoperative findings. SDR for lower limb spastic diplegia does not lead to extensive reorganization of cortex dedicated to the representation of the upper limb. An essentially normal pattern of activation was seen both before and after SDR.Conclusion The relief of attention demands associated with spasticity may explain the modulation in intensity seen after SDR in the patients who exhibited no upper extremity involvement despite lower limb spasticity.     

Outcome‐dependent coactivation of lip and tongue primary somatosensory representation following hypoglossal–facial transfer after peripheral facial palsy

A hypoglossal–facial transfer is a common surgical strategy for reanimating the face after persistent total hemifacial palsy. We were interested in how motor recovery is associated with cortical reorganization of lip and tongue representation in the primary sensorimotor cortex after the transfer. Therefore, we used functional magnetic resonance imaging (fMRI) in 13 patients who underwent a hypoglossal–facial transfer after unilateral peripheral facial palsy. To identify primary motor and somatosensory tongue and lip representation sites, we measured repetitive tongue and lip movements during fMRI. Electromyography (EMG) of the perioral muscles during tongue and lip movements and standardized evaluation of lip elevation served as outcome parameters. We found an association of cortical representation sites in the pre‐ and postcentral gyrus (decreased distance of lip and tongue representation) with symmetry of recovered lip movements (lip elevation) and coactivation of the lip during voluntary tongue movements (EMG‐activity of the lip during tongue movements). Overall, our study shows that hypoglossal–facial transfer resulted in an outcome‐dependent cortical reorganization with activation of the cortical tongue area for restituded movement of the lip. Hum Brain Mapp 35:638–645, 2014. © 2012 Wiley‐Periodicals, Inc.     

Functional magnetic resonance imaging for assessment of language and memory in clinical practice

PURPOSE OF REVIEW: There has been considerable interest in the role that functional magnetic resonance imaging (fMRI) may play in the assessment of patients with epilepsy. This review considers recent progress in this field and the current role of fMRI in the preoperative assessment of language and memory function. RECENT FINDINGS: Many studies have compared fMRI with the intracarotid amytal test for establishing language dominance, with most showing over 90% concordance between the two tests. Atypical dominance is greater in patients with left temporal lobe epilepsy and has been shown to be associated with increased epileptic activity. Preoperative fMRI has been used to predict language deficits following left anterior temporal lobe resection. A variety of paradigms have been used to assess memory function, and novel paradigms have demonstrated robust medial temporal lobe activation. Different patterns of encoding activity have been observed between patients with unilateral temporal lobe epilepsy and control individuals. SUMMARY: The application of fMRI paradigms used in cognitive neuroscience to patients with epilepsy is complicated by several factors. Although fMRI is increasingly being used clinically to establish language dominance, further work is required to localize accurately those specific language functions that are most at risk following surgery. Memory paradigms are not yet validated for use in surgical planning, although methodological and technical advances should make this possible in the near future. Further studies looking at the reorganization of language and memory function after surgery are also required.     

New evidence for preserved somatosensory pathways in complete spinal cord injury: A fMRI study

Trauma to the spinal cord rarely results in complete division of the cord with surviving nerves sometimes remaining silent or failing to function normally. The term motor or sensory discomplete has been used to describe this important but unclassified subgroup of complete SCI. Importantly, silent motor or sensory pathways may contribute to aversive symptoms (spasticity, pain) or improved treatment success. To demonstrate more objectively the presence of subclinical preserved somatosensory pathways in clinically complete SCI, a cross‐sectional study using functional MRI (fMRI) was undertaken. The presence of brain activation following innocuous brushing of an insensate region below‐injury (great toe) was analyzed in 23 people (19 males (83%), mean ± SD age 43 ± 13 years) with clinically complete (AIS A) SCI with (n = 13) and without (n = 10) below‐level neuropathic pain and 21 people without SCI or pain (15 males (71%); mean ± SD age 41 ± 14 years). Location appropriate, significant fMRI brain activation was detected in 48% (n = 11/23) of subjects with clinically complete SCI from below‐injury stimulation. No association was found between the presence of subclinical sensory pathways transmitting innocuous mechanical stimuli (dorsal column medical lemniscal) and below‐level neuropathic pain (χ² = 0.034, P = 0.9). The high prevalence of sensory discomplete injuries (～50% complete SCI) strengthens the case to explore inclusion of this category into the international SCI taxonomy (ISNCSCI). This would ensure more widespread inclusion of discomplete SCI in ongoing pain and motor recovery research. Neurophysiological tests such as fMRI may play a role in this process. Hum Brain Mapp 39:588–598, 2018. © 2017 Wiley Periodicals, Inc.     

Motor recovery at 6 months after admission is related to structural and functional reorganization of the spine and brain in patients with spinal cord injury

This study aimed to explore structural and functional reorganization of the brain in the early stages of spinal cord injury (SCI) and identify brain areas that contribute to motor recovery. We studied 25 patients with SCI, including 10 with good motor recovery and 15 with poor motor recovery, along with 25 matched healthy controls. The mean period post‐SCI was 9.2 ± 3.5 weeks in good recoverers and 8.8 ± 2.6 weeks in poor recoverers. All participants underwent structural and functional MRI on a 3‐T magnetic resonance system. We evaluated differences in cross‐sectional spinal cord area at the C2/C3 level, brain cortical thickness, white matter microstructure, and functional connectivity during the resting state among the three groups. We also evaluated associations between structural and functional reorganization and the rate of motor recovery. After SCI, compared with good recoverers, poor recoverers had a significantly decreased cross‐sectional spinal cord area, cortical thickness in the right supplementary motor area and premotor cortex, and fractional anisotropy (FA) in the right primary motor cortex and posterior limb of the internal capsule. Meanwhile, poor recoverers showed decreased functional connectivity between the primary motor cortex and higher order motor areas (supplementary motor area and premotor cortex), while good recoverers showed increased functional connectivity among these regions. The structural and functional reorganization of the spine and brain was associated with motor recovery rate in all SCI patients. In conclusion, structural and functional reorganization of the spine and brain directly affected the motor recovery of SCI. Less structural atrophy and enhanced functional connectivity are associated with good motor recovery in patients with SCI. Multimodal imaging has the potential to predict motor recovery in the early stage of SCI. Hum Brain Mapp 37:2195–2209, 2016. © 2016 Wiley Periodicals, Inc.     

A validation of event-related FMRI comparisons between users of cocaine, nicotine, or cannabis and control subjects

OBJECTIVE: Noninvasive brain imaging techniques are a powerful tool for researching the effects of drug abuse on brain activation measures. However, because many drugs have direct vascular effects, the validity of techniques that depend on blood flow measures as a reflection of neuronal activity may be called into question. This may be of particular concern in event-related functional magnetic resonance imaging (fMRI), where current analytic techniques search for a specific shape in the hemodynamic response to neuronal activity. METHOD: To investigate possible alterations in task-related activation as a result of drug abuse, fMRI scans were conducted on subjects in four groups as they performed a simple event-related finger-tapping task: users of cocaine, nicotine, or cannabis and control subjects. RESULTS: Activation measures, as determined by two different analytic methods, did not differ between the groups. A comparison between an intravenous saline and an intravenous cocaine condition in cocaine users found a similar null result. Further in-depth analyses of the shape of the hemodynamic responses in each group also showed no differences. CONCLUSIONS: This study demonstrates that drug groups may be compared with control subjects using event-related fMRI without the need for any post hoc procedures to correct for possible drug-induced cardiovascular alterations. Thus, fMRI activation differences reported between these drug groups can be more confidently interpreted as reflecting neuronal differences.     

Parametric fMRI of paced motor responses uncovers novel whole‐brain imaging biomarkers in spinocerebellar ataxia type 3

Machado‐Joseph Disease, inherited type 3 spinocerebellar ataxia (SCA3), is the most common form worldwide. Neuroimaging and neuropathology have consistently demonstrated cerebellar alterations. Here we aimed to discover whole‐brain functional biomarkers, based on parametric performance‐level‐dependent signals. We assessed 13 patients with early SCA3 and 14 healthy participants. We used a combined parametric behavioral/functional neuroimaging design to investigate disease fingerprints, as a function of performance levels, coupled with structural MRI and voxel‐based morphometry. Functional magnetic resonance imaging (fMRI) was designed to parametrically analyze behavior and neural responses to audio‐paced bilateral thumb movements at temporal frequencies of 1, 3, and 5 Hz. Our performance‐level‐based design probing neuronal correlates of motor coordination enabled the discovery that neural activation and behavior show critical loss of parametric modulation specifically in SCA3, associated with frequency‐dependent cortico/subcortical activation/deactivation patterns. Cerebellar/cortical rate‐dependent dissociation patterns could clearly differentiate between groups irrespective of grey matter loss. Our findings suggest functional reorganization of the motor network and indicate a possible role of fMRI as a tool to monitor disease progression in SCA3. Accordingly, fMRI patterns proved to be potential biomarkers in early SCA3, as tested by receiver operating characteristic analysis of both behavior and neural activation at different frequencies. Discrimination analysis based on BOLD signal in response to the applied parametric finger‐tapping task significantly often reached >80% sensitivity and specificity in single regions‐of‐interest.Functional fingerprints based on cerebellar and cortical BOLD performance dependent signal modulation can thus be combined as diagnostic and/or therapeutic targets in hereditary ataxia. Hum Brain Mapp 37:3656–3668, 2016. © 2016 Wiley Periodicals, Inc .     

Chronic, selective forebrain responses to excitotoxic dorsal horn injury

Intraspinal injection of the AMPA/metabotropic receptor agonist quisqualic acid (QUIS) results in excitotoxic injury which develops pathological characteristics similar to those associated with ischemic and traumatic spinal cord injury (SCI) (R. P. Yezierski et al., 1998, Pain 75: 141-155; R. P. Yezierski et al., 1993, J. Neurotrauma 10: 445-456). Since spinal injury can lead to partial or complete deafferentation of ascending supraspinal structures, it is likely that secondary to the disruption of spinal pathways these regions could undergo significant reorganization. Recently, T. J. Morrow et al. (Pain 75: 355-365) showed that autoradiographic estimates of regional cerebral blood flow (rCBF) can be used to simultaneously identify alterations in the activation of multiple forebrain structures responsive to noxious formalin stimulation. Accordingly, we examined whether excitotoxic SCI produced alterations in the activation of supraspinal structures using rCBF as a marker of neuronal activity. Twenty-four to 41 days after unilateral injection of QUIS into the T12 to L3 spinal segments, we found significant increases in the activation of 7 of 22 supraspinal structures examined. As compared to controls, unstimulated SCI rats exhibited a significant bilateral increase in rCBF within the arcuate nucleus (ARC), the hindlimb region of S1 cortex (HL), parietal cortex (PAR), and the thalamic posterior (PO), ventral lateral (VL), ventral posterior lateral (VPL), and ventral posterior medial (VPM) nuclei. All structures showing significantly altered rCBF are associated with the processing of somatosensory information. These changes constitute remote responses to injury and suggest that widespread functional changes occur within cortical and subcortical regions following injury to the spinal cord.     

Massive somatic deafferentation and motor deefferentation of the lower part of the body impair its visual recognition: a psychophysical study of patients with spinal cord injury

Embodied cognition theories postulate that perceiving and understanding the body states of other individuals are underpinned by the neural structures activated during first‐hand experience of the same states. This suggests that one’s own sensorimotor system may be used to identify the actions and sensations of others. Virtual and real brain lesion studies show that visual processing of body action and body form relies upon neural activity in the ventral premotor and the extrastriate body areas, respectively. We explored whether visual body perception may also be altered in the absence of damage to the above cortical regions by testing healthy controls and spinal cord injury (SCI) patients whose brain was unable to receive somatic information from and send motor commands to the lower limbs. Participants performed tasks investigating the ability to visually discriminate changes in the form or action of body parts affected by somatosensory and motor disconnection. SCI patients showed a specific, cross‐modal deficit in the visual recognition of the disconnected lower body parts. This deficit affected both body action and body form perception, hinting at a pervasive influence of ongoing body signals on the brain network dedicated to visual body processing. Testing SCI patients who did or did not practise sports allowed us to test the influence of motor practice on visual body recognition. We found better upper body action recognition in sport‐practising SCI patients, indicating that motor practice is useful for maintaining visual representation of actions after deafferentation and deefferentation. This may be a potential resource to be exploited for rehabilitation.     

Non-invasive brain mapping of motor-related areas of four limbs in patients with clinically isolated syndrome compared to healthy normal controls

Functional MRI studies on patients with multiple sclerosis (MS) have demonstrated widespread cortical reorganization of the motor network. However, few functional studies have addressed cortical plasticity in patients with clinically isolated syndrome (CIS). The activity of the lower limb motor system, despite its highlighted involvement in patients with CIS and MS, has been little studied. Thus, brain activation was compared in CIS patients with clinically intact motor systems with that in healthy control participants while they were performing motor tasks with four limbs. A total of 26 right-handed patients with CIS with clinically intact motor systems and 28 right-handed age and sex-matched controls participated in the functional MRI (fMRI) motor task. Patients with CIS showed greater activation in the ipsilateral secondary somatosensory cortex, cingulate gyrus and precuneus cortex while performing the ankle movement task compared to healthy controls. In the finger-tapping task, patients with CIS showed greater activity in the contralateral thalamus, ipsilateral premotor and superior temporal gyrus. In addition, the left inferior frontal gyrus was activated more in patients with CIS, regardless of the hand used. Therefore, despite having clinically intact motor systems, patients with CIS had different motor networks. All novel recruited regions were adjacent to the somatotopy of the primary motor areas of the limbs. Our finding confirm that brain reorganization precedes clinical manifestation, as no patient had any clinical manifestation that suggested involvement of the motor system.     

Plasticity of the human motor system following muscle reconstruction: a magnetic stimulation and functional magnetic resonance imaging study

OBJECTIVE: Although motor system plasticity in response to neuromuscular injury has been documented, few studies have examined recovered and functioning muscles in the human. We examined brain changes in a group of patients who had a muscle transfer. METHODS: Transcranial magnetic stimulation (TMS) was used to study a unique group of 9 patients who had upper extremity motor function restored using microneurovascular transfer of the gracilis muscle. The findings from the reconstructed muscle were compared to the homologous muscle of the intact arm. One patient was also studied with functional magnetic resonance imaging (fMRI). RESULTS: TMS showed that the motor threshold and short interval intracortical inhibition was reduced on the transplanted side while at rest but not during muscle activation. The difference in motor threshold decreased with the time since surgery. TMS mapping showed no significant difference in the location and size of the representation of the reconstructed muscle in the motor cortex compared to the intact side. In one patient with reconstructed biceps muscle innervated by the intercostal nerves, both TMS mapping and fMRI showed that the upper limb area rather than the trunk area of the motor cortex controlled the reconstructed muscle. CONCLUSIONS: Plasticity occurs in cortical areas projecting to functionally relevant muscles. Changes in the neuronal level are not necessarily accompanied by changes in motor representation. Brain reorganization may involve multiple processes mediated by different mechanisms and continues to evolve long after the initial injury. SIGNIFICANCE: Central nervous system plasticity following neuromuscular injury may have functional relevance.     

Impaired corticomuscular coherence during isometric elbow flexion contractions in humans with cervical spinal cord injury

After spinal cord injury (SCI), the reorganization of the neuromuscular system leads to increased antagonist muscles’ co‐activation—that is, increased antagonist vs. agonist muscles activation ratio—during voluntary contractions. Increased muscle co‐activation is supposed to result from reduced cortical influences on spinal mechanisms inhibiting antagonist muscles. The assessment of the residual interactions between cortical and muscles activity with corticomuscular coherence (CMC) in participants with SCI producing different force levels may shed new lights on the regulation of muscle co‐activation. To achieve this aim, we compared the net joint torque, the muscle co‐activation and the CMC ~ 10 and ~ 20 Hz with both agonist and antagonist muscles in participants with SCI and healthy participants performing actual isometric elbow flexion contractions at three force levels. For all participants, overall CMC and muscle co‐activation decreased with the increase in the net joint torque, but only CMC ~ 10 Hz was correlated with muscle co‐activation. Participants with SCI had greater muscle co‐activation and lower CMC ~ 10 Hz, at the highest force levels. These results emphasize the importance of CMC as a mechanism that could take part in the modulation of muscle co‐activation to maintain a specific force level. Lower CMC ~ 10 Hz in SCI participants may reflect the decreased cortical influence on spinal mechanisms, leading to increased muscle co‐activation, although plasticity of the corticomuscular coupling seems to be preserved after SCI to modulate the force level. Clinically, the CMC may efficiently evaluate the residual integrity of the neuromuscular system after SCI and the effects of rehabilitation.     

Cerebral plasticity and recovery of function after childhood prefrontal cortex damage

Objective: Recovery of function after early brain injury depends upon both reparative and compensatory processes that are minimally understood. Using functional magnetic resonance imaging (fMRI), this study investigated the reorganization of hemispheric brain activity of a 24 year old male who suffered right prefrontal cortex damage at 7 years of age related to ruptured arteriovenous malformation. His pattern of recovery has been examined and tracked over the past 17 years and evolved from initial significant impairments in executive, spatial and attentional abilities from the brain lesion to remarkable recovery of function.

Methods: High field fMRI studies were completed with experimental cognitive tasks sensitive to right prefrontal functions, including visuospatial relational reasoning, spatial working memory, go no-go, emotional face recognition, and coin calculation. Results were compared to a matched control group for total hemispheric activity patterns.

Results: Analyses revealed that on fMRI activation tasks where the patient scored similar to controls, he activated a broader network of bilateral cortical regions than controls. On tasks where he scored lower than controls, there was under-activation of prefrontal cortical regions in comparison to controls.

Conclusion: Recovery of function after prefrontal cortex damage in childhood can occur and be associated with significant functional reorganization of hemispheric activity patterns (i.e. developmental cerebral plasticity). Although not all tasks showed recovery to the same extent in this case, those tasks with the most robust recovery entailed compensatory activation of additional cortical regions on fMRI. Further studies are needed to confirm and extend these findings.