Intrinsic functional organization of putative language networks in the brain following left cerebral hemispherectomy.

In rare cases of severe and intractable epilepsy, cerebral hemispherectomy is performed to arrest seizure activity and improve quality of life. The remaining hemisphere is often capable of supporting many cognitive functions post-surgery, although the outcome depends on the underlying etiology, hemisphere removed, and age of resection. The mechanisms underlying this massive reorganization are at present unknown. Here we examined intrinsic functional connectivity of putative language brain networks in four children after left cerebral hemispherectomy using resting-state functional magnetic resonance imaging (rsfMRI). We compared these functional systems to intrinsic language networks in 15 neurotypical controls using region-of-interest (ROI)-based functional connectivity analyses. In three out of four hemispherectomy patients, the ROI placed in the right inferior gyrus revealed a functional network that strongly resembled the right-hemisphere intrinsic language network observed in controls. This network typically comprised inferior frontal gyrus, superior temporal sulcus, and premotor regions. Quantitative ROI-to-ROI analyses revealed that functional connectivity between major nodes of the language network was significantly altered in all 4 examined patients. Overall, our data demonstrate that the pattern of functional connectivity within language networks is at least partially preserved in the intact right hemisphere of patients who underwent left hemispherectomy.

When left-hemisphere reading is compromised: Comparing reading ability in participants after left cerebral hemispherectomy and participants with developmental dyslexia.

OBJECTIVE: We investigated reading skills in individuals who have undergone left cerebral hemispherectomy and in readers with developmental dyslexia to understand diverse characteristics contributing to reading difficulty. Although dyslexia is a developmental disorder, left hemispherectomy requires that patients (re)establish the language process needed to perform the language-based tasks in the nondominant (right) hemisphere to become readers. METHODS: Participants with developmental dyslexia (DD; n = 11) and participants who had undergone left hemispherectomy (HEMI; n = 11) were matched on age and gender, and were compared on timed and untimed measures of single word and pseudo-word reading. The hemispherectomy group was subdivided into prenatal (in utero) and postnatal (>3 years) insult groups, indicating the timing of the primary lesion that ultimately required surgical intervention. RESULTS: On an untimed reading measure, the readers with DD were comparable to individuals who had undergone left hemispherectomy due to prenatal insult, but both scored higher than the postnatal hemispherectomy group. Timed word reading differed across groups. The hemispherectomy prenatal subgroup had low average scores on both timed and untimed tests. The group with dyslexia had average scores on untimed measures and below average scores on timed reading. The hemispherectomy postnatal group had the lowest scores among the groups by a significant margin, and the most pronounced reading difficulty. SIGNIFICANCE: Patients with prenatal lesions leading to an isolated right hemisphere (RH) have the potential to develop reading to a degree comparable to that in persons with dyslexia for single word reading. This potential sharply diminishes in individuals who undergo hemispherectomy due to postnatal insult. The higher scores of the prenatal hemispherectomy group on timed reading suggest that under these conditions, individuals with an isolated RH can compensate to a significant degree.

Complex syntax in the isolated right hemisphere: Receptive grammatical abilities after cerebral hemispherectomy.

OBJECTIVES: In this study, we explored the syntactic competence of the right hemisphere (RH) after left cerebral hemispherectomy, on the premise that it (syntactic competence) is known to be one of the most strongly left-lateralized language functions. As basic syntactic development for individuals in this subject pool has already been extensively explored, we focused instead on the investigation of complex syntactic constructions that are normally acquired later in childhood, i.e., between 7 and 9years of age. METHODS: Grammatical competence in 10 participants who had undergone left cerebral hemispherectomy was compared to that of a group of normally developing children, with the two groups matched by the size of their vocabulary. The two tests we used for this research were created by the 1st language acquisition linguists and were designed to test sets of constructions categorized and differentiated by the order in which they are normally acquired and by the type of grammatical competence that they involve. RESULTS: We found that both groups followed the same developmental sequence of syntactic development with five (50%) postsurgical participants (all with prenatal etiologies) reaching nearly mature command of sentence grammar. Seizures negatively impacted performance on all tests. CONCLUSIONS: The isolated RH has the potential to support the complex grammatical categories that emerge relatively late in the normal acquisition of English by native speakers. Successful performance may be related to the timing of the initial insult and seizure control following hemispherectomy.

Literacy after cerebral hemispherectomy: Can the isolated right hemisphere read?

OBJECTIVES: Cerebral hemispherectomy, a surgical procedure undergone to control intractable seizures, is becoming a standard procedure with more cases identified and treated early in life [33]. While the effect of the dominant hemisphere resection on spoken language has been extensively researched, little is known about reading abilities in individuals after left-sided resection. Left-lateralized phonological abilities are the key components of reading, i.e., grapheme-phoneme conversion skills [1]. These skills are critical for the acquisition of word-specific orthographic knowledge and have been shown to predict reading levels in average readers as well as in readers with mild cognitive disability [26]. Furthermore, impaired phonological processing has been implicated as the cognitive basis in struggling readers. Here, we explored the reading skills in participants who have undergone left cerebral hemispherectomy. METHODS: Seven individuals who have undergone left cerebral hemispherectomy to control intractable seizures associated with perinatal infarct have been recruited for this study. We examined if components of phonological processing that are shown to reliably separate average readers from struggling readers, i.e., phonological awareness, verbal memory, speed of retrieval, and size of vocabulary, show the same relationship to reading levels when they are mediated by the right hemisphere [2]. RESULTS: We found that about 60% of our group developed both word reading and paragraph reading in the average range. Phonological processing measured by both phonological awareness and nonword reading was unexpectedly spared in the majority of participants. Phonological awareness levels strongly correlated with word reading. Verbal memory, a component of phonological processing skills, together with receptive vocabulary size, positively correlated with reading levels similar to those reported in average readers. Receptive vocabulary, a bilateral function, was preserved to a certain degree similar to that of strongly left-lateralized phonological skills [3]. Later seizure onset was associated with better reading levels. CONCLUSIONS: When cerebral hemispherectomy is performed to control seizures associated with very early (in utero) insult, it has been found that the remaining right hemisphere is still able to support reading and phonological processing skills that are normally mediated by the left hemisphere. Our results also suggest the existence of variability in individuals after hemispherectomy, even within groups having the same etiology and similar timing of insult.

Neonatal neuroimaging predicts recruitment of contralesional corticospinal tracts following perinatal brain injury.

AIM: Unilateral perinatal brain injury may result in recruitment of ipsilateral projections originating in the unaffected hemisphere and development of unilateral spastic cerebral palsy (USCP). The aim of this study was to assess the predictive value of neonatal neuroimaging following perinatal brain injury for recruitment of ipsilateral corticospinal tracts. METHOD: Neonatal magnetic resonance imaging (MRI) and cranial ultrasound scans of 37 children (20 males, 17 females; median [range] gestational age 36 wks(+4) [26(+6) -42wks(+5) ] and birthweight 2312 g ([770-5230g]) with unilateral perinatal arterial ischaemic stroke (n=23) or periventricular haemorrhagic infarction (n=14) were reviewed and scored for involvement of the corticospinal trajectory. Hand function was assessed using the Assisting Hand Assessment (AHA) and transcranial magnetic stimulation (TMS) was performed (age range 7y 4mo-18y and 7mo) to determine the type of cortical motor organization (normal, mixed or ipsilateral). Neuroimaging scores were used to predict TMS patterns. RESULTS: Eighteen children developed USCP with ipsilateral corticospinal tract projections in 13 children (eight mixed, five ipsilateral). AHA scores decreased with increased ipsilateral projections. Asymmetry of the corticospinal tracts seen on neonatal MRI was predictive of development of USCP and recruitment of ipsilateral tracts (positive and negative predictive value of 73% and 91%). INTERPRETATION: Neonatal neuroimaging can predict recruitment of ipsilateral corticospinal tracts. Early knowledge of the expected pattern of cortical motor organization will allow early identification of children eligible for early therapy.

Cerebral hemispherectomy: sensory scores before and after intensive mobility training.

PURPOSE: It is unclear whether sensory modalities can be modified by rehabilitation and if sensory functions vary on the affected side many years after cerebral hemispherectomy. This pilot, proof-of-concept study assessed light touch and proprioception before and after 10 days of intensive mobility training in individuals after hemispherectomy. METHODS: Light touch and proprioception of the upper and lower extremity was measured using the Fugl-Meyer sensory subtest on the paretic side in 18 individuals with hemispherectomy before and after mobility training. Sensory scores and differences related to mobility training were compared with clinical variables. RESULTS: Patients were 7.1±5.7 years from time of surgery to sensory assessment and mobility training. Light touch scores were 81±22% and proprioception values were 64±23% of normal (p=0.0022). Light touch did not correlate with proprioception scores, and differences comparing after with before mobility training did not correlate. In multivariate analysis, younger age at seizure onset correlated with better light touch scores, and older age at onset correlated with improvements in light touch scores with mobility training. By comparison, proprioception scores were better in individuals with perinatal infarcts compared with Rasmussen encephalitis and Sturge-Weber. Post-training, proprioception scores were better in Sturge-Weber cases. CONCLUSION: Light touch was less affected than proprioception on the paretic side after cerebral hemispherectomy. Improvements with mobility training correlated with older age at seizure onset and etiology. These findings suggest that many years after epilepsy surgery sensory functions are not static supporting the notion of existing developmental neuroplasticity of the remaining cerebral cortex along with brain stem and spinal cord pathways.

Constraint-induced movement therapy for individuals after cerebral hemispherectomy: a case series.

BACKGROUND AND PURPOSE: This case report describes the feasibility and efficacy of the use of constraint-induced movement therapy (CIMT) in 4 individuals (aged 12-22 years) who underwent cerebral hemispherectomy (age at time of surgery=4-10 years). The aims of this case series were: (1) to evaluate the feasibility of this therapeutic approach involving a shortened version of CIMT, (2) to examine improvements that occurred within the upper extremity of the hemiparetic side, (3) to investigate the feasibility of conducting brain imaging in individuals with depressed mental ages, and (4) to examine changes in the sensorimotor cortex following intervention. CASE DESCRIPTION: The patients received a shortened version of CIMT for 3 hours each day for a period of 10 days. In addition, a standard resting splint was used for the unimpaired hand for an 11-day period. Each patient was encouraged to wear the splint for 90% of his or her waking hours. The following outcome measures were used: the Actual Amount of Use Test (AAUT), the Box and Block Test (BBT), and the upper-extremity grasping and motor portions of the Fugl-Meyer Assessment of Motor Recovery (FM). OUTCOMES: Immediately after therapy, improvements were found in AAUT and BBT scores, but no improvements were found in FM scores. Three patients underwent brain imaging before and after therapy and showed qualitative changes consistent with reorganization of sensorimotor cortical representations of both paretic and nonparetic hands in one isolated hemisphere. DISCUSSION: The findings suggest that CIMT may be a feasible method of rehabilitation in individuals with chronic hemiparesis, possibly leading to neuroplastic therapy-related changes in the brain.

Asymmetry of temporal processing in listeners with normal hearing and unilaterally deaf subjects.

OBJECTIVES: In general, auditory cortex on the left side of the brain is specialized for processing of acoustic stimuli with complex temporal structure including speech, and the right hemisphere is primary for spectral processing and favors tonal stimuli and music. This asymmetry in processing is further emphasized when hemisphere-favored stimuli are presented to the contralateral ear. The purpose of the first experiment is to further investigate the properties that dictate lateralized processing of auditory stimuli by ear and the relationship between auditory task and stimulus type. Next, it is not clear what compensation may exist for the loss of function of one ear and consequently, reduced access to functions primary performed in the opposite hemisphere, in the case of early unilateral profound hearing loss. The purpose of experiment 2 is to determine if any compensation for loss of function is seen in persons with early unilateral deafness. DESIGN: Experiment 1: Gap detection thresholds were determined in 30 right-handed listeners with normal hearing using wide-band noise markers (temporally complex), 400 and 4000 Hz pure tones presented individually to the left and right ears. Experiment 2: The same procedure was administered to listeners with early-onset, severe-to-profound unilateral deafness (seven left ear deaf and five right ear deaf) in the hearing ear alone. RESULTS: A significant right ear advantage was found for gap detection threshold using noise markers and a smaller left ear advantage was found for tonal stimuli. Listeners with unilateral deafness demonstrated that the hearing ear, left or right, performed in a manner similar to listeners with normal hearing. CONCLUSIONS: Results indicate that (1) gap marker, more than task, was the salient feature in determining laterality of processing in this experiment, (2) the two ears have distinct processing capacity based on stimulus type, and (3) compensation for loss is not apparent in persons with congenital unilateral deafness.

Dichotic listening after cerebral hemispherectomy: methodological and theoretical observations.

We examined two commonly used dichotic listening tests for measuring the degree of hemispheric specialization for language in individuals who had undergone cerebral hemispherectomy: the consonant-vowel (CV) nonsense syllables and the fused words (FW) tests, using the common laterality indices f and lambda. Hemispherectomy on either side resulted in a massive contralateral ear advantage, demonstrating nearly complete ipsilateral suppression of the left ear in the right hemispherectomy group but slightly less complete suppression of the right ear in the left hemispherectomy group. The results are consistent with the anatomical model of the ear advantage [Kimura, D. (1961). Most syllables or words are reported for the ear contralateral to the remaining hemisphere, while few or none are reported for the ear ipsilateral to the remaining hemisphere. In the presence of competing inputs to the two ears, the stronger contralateral ear-hemisphere connection dominates/suppresses the weaker ipsilateral ear-hemisphere connection. The lambda index was similar in the two tests but the index f was higher in the CV than the FW test. Both indices of the CV test were sensitive to side of resection, higher in the right hemispherectomy than in the left hemispherectomy groups.

Locomotor training remodels fMRI sensorimotor cortical activations in children after cerebral hemispherectomy.

PURPOSE: This study examined whether locomotor training, which included body weight-supported treadmill therapy, improved walking and induced cortical representational adaptations using functional magnetic resonance imaging in the remaining sensorimotor network after cerebral hemispherectomy. METHODS: Hemispherectomy patients (n = 12) underwent 2 weeks of gait training for at least 30 hours each. They were tested pre- and posttraining with the Fugl-Meyer Motor Assessment, unassisted single-limb stance time, and usual and fastest walking speeds. Three patients performed voluntary ankle movements as the functional magnetic resonance imaging activation task pre- and posttraining. Control subjects included 5 healthy children tested 2 weeks apart, 2 of whom trained on the treadmill, and 2 hemispherectomy patients who received upper extremity rehabilitation and no gait therapy. RESULTS: Although patients reported improvements with gait training, behavioral outcomes did not significantly change. Training was associated with increased volume and intensity of cortical activation in the primary sensorimotor (S1M1), supplementary motor, motor cingulate, and secondary somatosensory cortex for the paretic foot, along with greater overlap in the representation for each moving foot in S1M1 and the supplementary motor area of the remaining hemisphere. Control subjects showed a decrease in activation in these cortical regions after training. CONCLUSIONS: Locomotor training of hemispherectomy patients improved mobility subjectively in association with functional magnetic resonance imaging evidence of cortical remodeling with ankle dorsiflexion. These findings support the notion that hemispherectomy patients may respond to rehabilitation interventions through mechanisms of activity-dependent cortical plasticity. The authors hypothesize that developmentally persistent descending ipsilateral and contralateral corticospinal tracts may allow the remaining hemisphere to maintain bilateral lower extremity motor control after surgery.

Residual motor control and cortical representations of function following hemispherectomy: effects of etiology.

Fifteen posthemispherectomy children were examined to assess residual motor function of the paretic side using the 74-point Fugl-Meyer Assessment of Motor Recovery scale. The degree of residual motor control differed for upper and lower extremities, with hand function being most severely impaired. Posthemispherectomy motor outcomes also differed as a function of etiology: cortical dysplasia, perinatal infarct, and Rasmussen's encephalitis. Children whose intractable seizures resulted from perinatal middle cerebral artery stroke demonstrated the most spared motor function. To detect cortical areas that represented motor control of the hemiparetic side, we focused on voluntary control of the affected lower extremity. Seven of our patients were able to carry out a foot dorsiflexion paradigm during functional magnetic resonance imaging, and these results were compared with activations found in normal controls. All children showed activations in the sensorimotor network ipsilateral to the affected side. The perinatal infarct group demonstrated greater activity in the cingulate cortex, whereas the Rasmussen's encephalitis group had significant activations in the insula, suggesting etiology-specific differences in reorganization. These findings are discussed in the framework of our understanding of mechanisms of cortical plasticity in the injured brain and its relevance to neurologic rehabilitation. We suggest that imaging techniques are important tools in identifying cortical regions underlying functional reorganization. Furthermore, detection of such areas might become a basis for specific training promoting the optimal reorganization of cortical networks to enhance motor control.

Modulations of 'late' event-related brain potentials in humans by dynamic audiovisual speech stimuli.

Lipreading reliably improve speech perception during face-to-face conversation. Within the range of good dubbing, however, adults tolerate some audiovisual (AV) discrepancies and lipreading, then, can give rise to confusion. We used event-related brain potentials (ERPs) to study the perceptual strategies governing the intermodal processing of dynamic and bimodal speech stimuli, either congruently dubbed or not. Electrophysiological analyses revealed that non-coherent audiovisual dubbings modulated in amplitude an endogenous ERP component, the N300, we compared to a 'N400-like effect' reflecting the difficulty to integrate these conflicting pieces of information. This result adds further support for the existence of a cerebral system underlying 'integrative processes' lato sensu. Further studies should take advantage of this 'N400-like effect' with AV speech stimuli to open new perspectives in the domain of psycholinguistics.

How normal is grammatical development in the right hemisphere following hemispherectomy? The root infinitive stage and beyond.

We examined the morphosyntax of eight left hemispherectomized children at two different stages and compared it to MLU-matched normals. We found that the language of the hemispherectomies paralleled that of their MLU matches with respect to the specific morphosyntactic characteristics of each stage. Our findings provide strong evidence for the presence of functional categories in all early grammars and demonstrate that grammatical development, regardless of its neural substrate, is highly constrained by UG and follows a narrowly determined course. We discuss our findings within a neurobiological framework in which etiology defines the integrity of the remaining hemisphere, which in turn, determines its potential for linguistic reorganization and/or acquisition.

Evidence of a visual-to-auditory cross-modal sensory gating phenomenon as reflected by the human P50 event-related brain potential modulation.

We investigated the existence of a cross-modal sensory gating reflected by the modulation of an early electrophysiological index, the P50 component. We analyzed event-related brain potentials elicited by audiovisual speech stimuli manipulated along two dimensions: congruency and discriminability. The results showed that the P50 was attenuated when visual and auditory speech information were redundant (i.e. congruent), in comparison with this same event-related potential component elicited with discrepant audiovisual dubbing. When hard to discriminate, however, bimodal incongruent speech stimuli elicited a similar pattern of P50 attenuation. We concluded to the existence of a visual-to-auditory cross-modal sensory gating phenomenon. These results corroborate previous findings revealing a very early audiovisual interaction during speech perception. Finally, we postulated that the sensory gating system included a cross-modal dimension.