The Tyneside Pegboard Test: development, validation, and observations in unilateral cerebral palsy.

AIM: The aims of this study were twofold: first, to develop and validate a timed test of unimanual and bimanual dexterity suitable for those with disability affecting hand function; second, to explore relationships between unimanual and bimanual completion times. METHOD: We developed the Tyneside Pegboard Test (TPT), an electronically timed test with three peg sizes, incorporating an asymmetrical bimanual task. Nine hundred and seventy-four participants (455 males, 519 females; age range 4-80y) provided normative data. Test-retest reliability and construct validity were assessed (50 adults: 14 males, 36 females; 15-73y) on two occasions 2 weeks apart. Bimanual and unimanual completion times were measured in 87 children (51 males, 36 females) with unilateral cerebral palsy (CP) and 498 individuals in a comparison group (238 males, 260 females; 5-15y). RESULTS: The comparison group showed an asymmetrical U-shaped relationship between completion times and age. Intraclass correlation coefficients ranged from 0.74 to 0.91, indicating moderate test-retest reliability. There was a negative relationship between average TPT bimanual times and Purdue pegboard bimanual scores (Spearman's rho -0.611, degrees of freedom 44, p<0.001). Children with unilateral CP had greater prolongation of bimanual than unimanual completion times compared with the comparison group (mean difference 20.31s, 95% confidence interval 18.13-22.49, p<0.001). INTERPRETATION: The TPT is accessible for those with impaired hand function. Children with unilateral CP demonstrated disproportionate bimanual deficits, even allowing for unimanual dexterity: this has implications for therapy. WHAT THIS PAPER ADDS: We developed an adapted, electronically timed 9-hole pegboard test. Our modifications facilitate use by those with disability affecting hand function. The test incorporates an asymmetrical bimanual task. Children with unilateral cerebral palsy showed disproportionate bimanual dexterity deficits even allowing for unimanual dexterity.

Developmental tuning and decay in senescence of oscillations linking the corticospinal system.

There is increasing evidence of the importance of synchronous activity within the corticospinal system for motor control. We compared oscillatory activity in the primary sensorimotor cortex [EEG of sensorimotor cortex (SMC-EEG)] and a motor neuronal pool [surface electromyogram of opponens pollicis (OP-EMG)], and their coherence in children (4-12 years of age), young adults (20-35 years of age), and elderly adults (>55 years of age). The ratio between lower (2-13 Hz) and higher (14-32 Hz) frequencies in both SMC-EEG and OP-EMG decreased with age, correlating inversely with motor performance. There was evidence for larger, more distributed cortical networks in the children and elderly compared with young adults. Corticomuscular coherence (CMC) was present in all age groups and shifted between frontal and parietal cortical areas. In children, CMC was smaller and less stationary in amplitude and frequency than in adults. Young adults had single peaks of CMC clustered near the modal frequency (23 Hz); multiple peaks with a broad spread of frequencies occurred in children and the elderly; the further the frequency of the maximum peak CMC was from 23 Hz, the poorer the performance. CMC amplitude was inversely related to performance in young adults but was not modulated in relation to performance in children and the elderly. We propose that progressive fine-tuning of the frequency coding and stabilization of the dynamic properties within and between corticospinal networks occurs during adolescence, refining the capacity for efficient dynamic communication in adulthood. In old age, blurring of the tuning between networks and breakdown in their integration occurs and is likely to contribute to a decrement in motor control.

Developmental plasticity connects visual cortex to motoneurons after stroke.

We report motor cortical function in the left occipital cortex of a subject who suffered a left middle cerebral artery stroke early in development. Transcranial magnetic stimulation of the left occipital cortex evoked contraction of right hand muscles. Electroencephalogram recorded over the left occipital cortex showed: 1) coherence with electromyogram from a right hand muscle; 2) a typical sensorimotor Mu rhythm at rest that was suppressed during contraction of right hand muscles. This is the first evidence that cortical plasticity extends beyond reshaping of primary sensory cortical fields to respecification of the cortical origin of subcortically projecting pathways.

Progressive loss of PAX6, TBR2, NEUROD and TBR1 mRNA gradients correlates with translocation of EMX2 to the cortical plate during human cortical development.

The transcription factors Emx2 and Pax6 are expressed in the proliferating zones of the developing rodent neocortex, and gradients of expression interact in specifying caudal and rostral identities. Pax6 is also involved in corticoneurogenesis, being expressed by radial glial progenitors that give rise to cells that also sequentially express Tbr2, NeuroD and Tbr1, genes temporally downstream of Pax6. In this study, using in situ hybridization, we analysed the expression of EMX2, PAX6, TBR2, NEUROD and TBR1 mRNA in the developing human cortex between 8 and 12 postconceptional weeks (PCW). EMX2 mRNA was expressed in the ventricular (VZ) and subventricular zones (SVZ), but also in the cortical plate, unlike in the rodent. However, gradients of expression were similar to that of the rodent at all ages studied. PAX6 mRNA expression was limited to the VZ and SVZ. At 8 PCW, PAX6 was highly expressed rostrally but less so caudally, as has been seen in the rodent, however this gradient disappeared early in corticogenesis, by 9 PCW. There was less restricted compartment-specific expression of TBR2, NEUROD and TBR1 mRNA than in the rodent, where the gradients of expression were similar to that of PAX6 prior to 9 PCW. The gradient disappeared for TBR2 by 10 PCW, and for NEUROD and TBR1 by 12 PCW. These data support recent reports that EMX2 but not PAX6 is more directly involved in arealization, highlighting that analysis of human development allows better spatio-temporal resolution than studies in rodents.

Is hemiplegic cerebral palsy equivalent to amblyopia of the corticospinal system?

OBJECTIVE: Subjects with severe hemiplegic cerebral palsy have increased ipsilateral corticospinal projections from their noninfarcted cortex. We investigated whether their severe impairment might, in part, be caused by activity-dependent, competitive displacement of surviving contralateral corticospinal projections from the affected cortex by more active ipsilateral corticospinal projections from the nonaffected cortex, thereby compounding the impairment. METHODS: Transcranial magnetic stimulation (TMS) characterized corticospinal tract development from each hemisphere over the first 2 years in 32 healthy children, 14 children with unilateral stroke, and 25 with bilateral lesions. Magnetic resonance imaging and anatomic studies compared corticospinal tract growth in 13 patients with perinatal stroke with 46 healthy subjects. RESULTS: Infants with unilateral lesions initially had responses after TMS of the affected cortex, which became progressively more abnormal, and seven were eventually lost. There was associated hypertrophy of the ipsilateral corticospinal axons projecting from the noninfarcted cortex. Magnetic resonance imaging and anatomic studies demonstrated hypertrophy of the corticospinal tract from the noninfarcted hemisphere. TMS findings soon after the stroke did not predict impairment; subsequent loss of responses and hypertrophy of ipsilateral corticospinal axons from the noninfarcted cortex predicted severe impairment at 2 years. Infants with bilateral lesions maintained responses to TMS from both hemispheres with a normal pattern of development. INTERPRETATION: Rather than representing "reparative plasticity," increased ipsilateral projections from the noninfarcted cortex compound disability by competitively displacing surviving contralateral corticospinal projections from the infarcted cortex. This may provide a pathophysiological explanation for why signs of hemiplegic cerebral palsy appear late and progress over the first 2 years of life.

Greater intermanual transfer in the elderly suggests age-related bilateral motor cortex activation is compensatory.

Hemispheric lateralization of movement control diminishes with age; whether this is compensatory or maladaptive is debated. The authors hypothesized that if compensatory, bilateral activation would lead to greater intermanual transfer in older subjects learning tasks that activate the cortex unilaterally in young adults. They studied 10 young and 14 older subjects, learning a unimanual visuomotor task comprising a feedforward phase, where there is unilateral cortical activation in young adults, and a feedback phase, which activates the cortex bilaterally in both age groups. Increased intermanual transfer was demonstrated in older subjects during feedforward learning, with no difference between groups during feedback learning. This finding is consistent with bilateral cortical activation being compensatory to maintain performance despite declining computational efficiency in neural networks.

High-energy and -protein diet increases brain and corticospinal tract growth in term and preterm infants after perinatal brain injury.

OBJECTIVE: Our hypothesis was that infants with perinatal brain injury fail to thrive in the first postnatal year because of increased energy and protein requirements from deficits that accumulated during neonatal intensive care. Our aim was to assess whether dietary energy and protein input was a rate-limiting factor in brain and body growth in the first year after birth. METHODS: We conducted a prospective, double-blind and randomized, 2-stage group sequential study and controlled for gestation, gender, and brain lesion. Neonates with perinatal brain damage were randomly allocated to receive either a high- (120% recommended average intake) or average (100% recommended average intake) energy and protein diet. The study began at term and continued for 12 months. Three-day dietary diaries estimated energy and protein intake. The primary outcome measure was growth of occipitofrontal circumference. Other measures were growth of axonal diameters in the corticospinal tract, which were estimated by using transcranial magnetic stimulation, weight gain, and length. RESULTS: The study was terminated at the first analysis when the 16 subjects had completed the protocol, because the predetermined stopping criterion of >1 SD difference in occipitofrontal circumference at 12 months' corrected age in those receiving the higher-energy and -protein diet had been demonstrated. Axonal diameters in the corticospinal tract, length, and weight were also significantly increased. CONCLUSIONS: These data support our hypothesis that infants with significant perinatal brain damage have increased nutritional requirements in the first postnatal year and suggest that decreased postnatal brain growth may exacerbate their impairment. There are no measures of cognitive ability at 12 months of age, and whether there will be any improvement in the status of these children, therefore, remains to be shown.