Motor planning ability is not related to lesion side or functional manual ability in children with hemiplegic cerebral palsy.

Optimal task performance requires anticipatory planning to select the most appropriate movement strategy. There is conflicting evidence for hemispheric specialisation of motor planning, with some suggesting left hemisphere dominance, claiming that children with right hemiplegic cerebral palsy (HCP) are therefore disproportionally affected. An alternative view is that there is a positive relationship between functional ability (rather than side of lesion) and motor planning skill. We aimed to compare children with right and left HCP on motor planning ability and to explore its relationship with functional manual ability. Participants were 76 children with HCP (40 left HCP; 30 female), aged 4-15 years (Mean 9.09, SD 2.94). Motor planning was assessed using a measure of end-state comfort, which involved turning a hexagonal handle 180° without readjusting grasp. This is difficult, or in some cases impossible, to achieve unless an appropriate initial grasp is adopted. Children completed 24 turns (12 clockwise), which were video recorded for offline scoring. Functional manual ability was assessed with the ABILHAND-Kids questionnaire, completed by parents. Contrary to the existing literature, no differences were observed between right and left HCP. However, a significant interaction between direction of turn and side of hemiplegia indicated a preferential bias for turns in the medial direction, consistent with the "medial over lateral advantage". There was no relationship between functional ability and motor planning. Therefore, motor planning may not be a priority for therapeutic intervention to improve functional ability in HCP.

The myth of the 'unaffected' side after unilateral stroke: is reorganisation of the non-infarcted corticospinal system to re-establish balance the price for recovery?

BACKGROUND: Bilateral changes in the hemispheric reorganisation have been observed chronically after unilateral stroke. Our hypotheses were that activity dependent competition between the lesioned and non-lesioned corticospinal systems would result in persisting asymmetry and be associated with poor recovery. METHODS: Eleven subjects (medium 6.5 years after stroke) were compared to 9 age-matched controls. The power spectral density (PSD) of the sensorimotor electroencephalogram (SM1-EEG) and electromyogram (EMG) and corticomuscular coherence (CMC) were studied during rest and isometric contraction of right or left opponens pollicis (OP). Global recovery was assessed using NIH score. FINDINGS: There was bilateral loss of beta frequency activity in the SM1-EEGs and OP-EMGs in strokes compared to controls. There was no difference between strokes and controls in symmetry indices estimated between the two corticospinal systems for SM1-EEG, OP-EMG and CMC. Performance correlated with preservation of beta frequency power in OP-EMG in both hands. Symmetry indices for the SM1-EEG, OP-EMG and CMC correlated with recovery. INTERPRETATION: Significant changes occurred at both cortical and spinomuscular levels after stroke but to the same degree and in the same direction in both the lesioned and non-lesioned corticospinal systems. Global recovery correlated with the degree of symmetry between corticospinal systems at all three levels - cortical and spinomuscular levels and their connectivity (CMC), but not with the absolute degree of abnormality. Re-establishing balance between the corticospinal systems may be important for overall motor function, even if it is achieved at the expense of the non-lesioned system.

Corticospinal tract development and its plasticity after perinatal injury.

The final pattern of the origin and termination of the corticospinal tract is shaped during development by the balance between projection and withdrawal of axons. In animals, unilateral inhibition of the sensorimotor cortex during development results in a sparse contralateral projection from this cortex and retention of a greater number of ipsilateral projections from the more active cortex. Similarly in subjects with hemiplegic cerebral palsy if transcranial magnetic stimulation (TMS) of the damaged motor cortex fails to evoke responses in the paretic upper limb, TMS of the undamaged ipsilateral motor cortex evokes abnormally large and short-onset responses. Rather than representing a "reparative plasticity in response to injury", this review presents evidence that increased ipsilateral projections from the non-infarcted motor cortex arise from perturbation of ongoing developmental processes, whereby reduced activity in the damaged hemisphere, leads to increased withdrawal of its surviving contralateral corticospinal projections because their terminals have been displaced by the more active ipsilateral projections of the undamaged hemisphere and thereby adding to the degree of long-term motor impairment.

Evidence of activity-dependent withdrawal of corticospinal projections during human development.

OBJECTIVE: To characterize the development of ipsilateral corticospinal projections from birth and compare to 1) development of contralateral projections in the same subjects and 2) ipsilateral corticospinal projections in subjects with unilateral lesions of the corticospinal system acquired perinatally or in adulthood. METHOD: Transcranial magnetic stimulation excited the motor cortex, and responses were recorded bilaterally in pectoralis major, biceps brachii, and the first dorsal interosseus muscles. Subjects studied included 9 neonates recruited at birth, studied longitudinally for 2 years; 85 healthy subjects aged from birth to adulthood; 10 subjects with hemiplegic cerebral palsy; and 8 with hemiplegia after stroke. RESULTS: In neonates, ipsilateral responses had significantly shorter onsets than contralateral responses but similar thresholds and amplitudes. Thresholds within both pathways increased in the first 3 months. Differential development was present from 3 months so that by 18 months ipsilateral responses were significantly smaller and had significantly higher thresholds and longer onset latencies than contralateral responses. A similar pattern of smaller and later ipsilateral responses was observed after transcranial magnetic stimulation of the intact cortex in subjects with stroke. In contrast, subjects with hemiplegic cerebral palsy had ipsilateral responses with onsets, thresholds and amplitudes similar to those of contralateral responses. Significant branching of contralateral corticospinal axons from the intact motor cortex was excluded by cross-correlation analysis. CONCLUSIONS: These data, together with previously published anatomic and radiologic studies, are consistent with activity-dependent corticospinal axonal withdrawal during development and maintenance of increased corticomotoneuronal projections from the intact hemisphere after unilateral perinatal lesions.

Abnormal corticospinal function but normal axonal guidance in human L1CAM mutations.

L1 cell adhesion molecule (L1CAM) gene mutations are associated with X-linked 'recessive' neurological syndromes characterized by spasticity of the legs. L1CAM knock-out mice show hypoplasia of the corticospinal tract and failure of corticospinal axonal decussation and projection beyond the cervical spinal cord. The aim of this study was to determine if similar neuropathology underlies the spastic diplegia of males hemizygous for L1CAM mutations. Studies were performed on eight carrier females and 10 hemizygous males. Transcranial magnetic stimulation excited the corticospinal tract and responses were recorded in biceps brachii and quadriceps femoris. In contralateral biceps and quadriceps the responses had high thresholds and delayed onset compared with normal subjects. Ipsilateral responses in biceps were smaller, with higher thresholds and delayed onsets relative to contralateral responses. Subthreshold corticospinal conditioning of the stretch reflex of biceps and quadriceps was abnormal in both hemizygous males and carrier females suggesting there may also be a reduced projection to inhibitory interneurones. Histological examination of post-mortem material from a 2-week-old male with an L1CAM mutation revealed normal corticospinal decussation and axonal projections to lumbar spinal segments. These data support a role for L1CAM in corticospinal tract development in hemizygous males and 'carrier' females, but do not support a critical role for L1CAM in corticospinal axonal guidance.

Comparison of spinal myotatic reflexes in human adults investigated with cross-correlation and signal averaging methods.

A cross-correlation method for recording spinal myotatic reflexes has been developed to meet the need for brief test periods in babies and children and subjects with central neurological pathology. In normal adult subjects the method has been validated by comparing excitatory and inhibitory reflexes obtained with cross-correlation with those obtained with conventional signal averaging. In the cross-correlation method a pseudo-random binary sequence of 64 brief tendon taps was delivered in <1.5 s, and in the averaging method 20-150 taps at one per second. The reflexes were expressed as unit impulse responses to enable direct, quantitative comparisons to be made. With cross-correlation the responses were slightly expanded in time, had lower peak amplitudes, and onset latencies advanced by 10 ms, the clock period of the pseudo-random binary sequence. The amplitude of biceps phasic stretch reflex increased with muscle contraction in a similar manner with both methods. In tests for stationarity the amplitude of biceps phasic stretch reflex varied <10% in the first six repeats of the pseudo-random binary sequence. The tap force required at threshold for cross-correlation was approximately half that for averaging, but with both methods the magnitude of biceps phasic stretch reflex varied linearly with tap force over the range of one to two times threshold. The validity of responses obtained with cross-correlation was assessed by a statistical procedure. In conclusion, the cross-correlation method is robust and gives similar results to those obtained with averaging.

Reciprocal and Renshaw (recurrent) inhibition are functional in man at birth.

The aims were (1) to determine when in human postnatal development Group Ia reciprocal and Renshaw inhibition can be demonstrated; (2) to explore the relationship between the expression reciprocal inhibition and the disappearance of Group Ia excitatory reflexes between agonist and antagonist muscles. Studies were performed on 99 subjects, aged 1 day to 31 years, of whom 53 were neonates. A longitudinal study was also performed on 29 subjects recruited at birth and studied 3 monthly until 12 months of age. Reciprocal inhibitory and excitatory reflexes were recorded in the surface EMG of contracting biceps brachii (Bi), evoked by taps applied to the tendon of triceps brachii (Tri). Reciprocal excitatory reflexes were recorded in all but one neonate. Reciprocal inhibition was observed in 25% of neonates; evidence is provided that it was likely to have been masked by low threshold reciprocal excitation in the remaining neonates. Reciprocal inhibition was demonstrated in all subjects after 9 months of age. In four neonates there was depression of inhibition of Bi during co-contraction of Bi and Tri implying that Group Ia interneurones may be under segmental and suprasegmental control at birth. Renshaw cells, identified in human postmortem cervical spinal cord by their morphology, location and calbindin D28K immunoreactivity, were present at 11 weeks post-conceptional age (PCA) and by 35 weeks PCA had mature morphological characteristics. In four neonates reciprocal inhibitory responses in Bi disappeared when the tap to Tri evoked its own homonymous phasic stretch reflex, providing neurophysiological evidence for Renshaw inhibition of Group Ia inhibitory interneurones.

Short latency heteronymous excitatory and inhibitory reflexes between antagonist and heteronymous muscles of the human shoulder and upper limb.

The aims were (i) to investigate heteronymous excitatory and inhibitory Group Ia reflexes linking agonist/antagonist muscle pairs acting at the shoulder and elbow; clavicular pectoralis major (Pmajor) and posterior deltoid (Pdeltoid); biceps brachii (Bi) and Tri brachii (Tri), and linking muscles acting at the elbow (Bi and Tri) with muscles acting at the shoulder (Pmajor and Pdeltoid). (ii) To test the hypothesis that the excitability of the reflexes would vary between different tasks in a functionally relevant manner. The study was performed on 45 adults. Reflexes were recorded in the surface EMG when the target muscle was contracting at 10% maximum voluntary contraction. Reflexes were recorded in Bi and Tri with the elbow joint in one of three positions: 105 degrees, 80 degrees, or 55 degrees from full extension. Group Ia reflexes were evoked using a small, brief tap to the tendon of the muscle being stimulated. Reflexes were recorded by cross-correlation of the surface EMG and pseudo-random series of taps. All subjects demonstrated short latency inhibition and excitation between agonist/antagonist muscle pairs; inhibition was significantly more frequent than excitation. Excitation and inhibition occurred with equal frequency between muscle pairs acting between elbow and shoulder. Minimum central delays for excitatory reflexes were 1 ms, consistent with monosynaptic projections and for inhibitory responses were 2 ms consistent with disynaptic linkage. Later excitatory and inhibitory reflexes with central delays of up to 15 ms also occurred. The probability of evoking excitation or inhibition in Tri or Bi changed with the different elbow positions.

Visual impairment in children with acute nontraumatic coma.

PURPOSE: To determine the incidence and severity of visual impairment in children following acute nontraumatic coma. METHODS: An 18-month prospective epidemiologic study of acute nontraumatic coma was undertaken in the former Northern NHS Region of England. Children aged >1 month and <16 years were included in the study if they had a Glasgow Coma Score of < or = 12 for >6 hours or if they died within 6 hours of the onset of decreased levels of consciousness. For survivors, ophthalmologic assessments were performed 6 weeks and 12 months after presentation. RESULTS: Two hundred eighty-seven children were included in the study, of whom 127 died. Of the 137 examined survivors, 35 had visual abnormalities suspected by the examining neurologist during the ophthalmic assessment. Of these, visual impairment was confirmed in 10 children at the 6-week assessment by the pediatric ophthalmologist. At the 1 2-month assessment, visual impairment remained stable in 9 children and improved in 1. CONCLUSION: In this study, 6.6% of children surviving acute nontraumatic coma had visual impairment that persisted at the 12-month follow-up examination. Incidence of visual impairment in acute nontraumatic coma is 0.97 per 100,000 children per year.

Incidence, aetiology, and outcome of non-traumatic coma: a population based study.

AIM: To determine the incidence, presentation, aetiology, and outcome of non-traumatic coma in children aged between 1 month and 16 years. METHODS: In this prospective, population based, epidemiological study in the former Northern NHS region of the UK, cases were notified following any hospital admission or community death associated with non-traumatic coma. Coma was defined as a Glasgow Coma Score below 12 for more than six hours. RESULTS: The incidence of non-traumatic coma was 30.8 per 100 000 children under 16 per year (6.0 per 100 000 general population per year). The age specific incidence was notably higher in the first year of life (160 per 100 000 children per year). CNS specific presentations became commoner with increasing age. In infants, nearly two thirds of presentations were with non-specific, systemic signs. Infection was the commonest overall aetiology. Aetiology remained unknown in 14% despite extensive investigation and/or autopsy. Mortality was highly dependent on aetiology, with aetiology specific mortality rates varying from 3% to 84%. With follow up to approximately 12 months, overall series mortality was 46%.

Cognitive and adaptive outcomes and age at insult effects after non-traumatic coma.

Cognitive and adaptive behavioural outcome were studied in the identified survivors of a population based study of non-traumatic coma (NTC) in childhood. Children were assessed early (six weeks) and late (12 months) after NTC. At least 7% of those children in whom no suspicions of prior neurodevelopmental morbidity existed showed moderate or severe disability following NTC. Children over 2 years of age at insult showed some improvement between early and late assessments; however, children below 2 years showed no improvement. Differing age at insult effects were observed between aetiological groups. A relation between early age at first insult and poor outcome was particularly evident among children experiencing NTC caused by epilepsy.

Functional corticospinal projections are established prenatally in the human foetus permitting involvement in the development of spinal motor centres.

From studies of subhuman primates it has been assumed that functional corticospinal innervation occurs post-natally in man. We report a post-mortem morphological study of human spinal cord, and neurophysiological and behavioural studies in preterm and term neonates and infants. From morphological studies it was demonstrated that corticospinal axons reach the lower cervical spinal cord by 24 weeks post-conceptional age (PCA) at the latest. Following a waiting period of up to a few weeks, it appears they progressively innervate the grey matter such that there is extensive innervation of spinal neurons, including motor neurons, prior to birth. Functional monosynaptic corticomotoneuronal projections were demonstrated neurophysiologically from term, but are also likely to be present from as early as 26 weeks PCA. At term, direct corticospinal projections to Group Ia inhibitory interneurons were also confirmed. Independent finger movements developed much later, between 6 and 12 months post-natally. These data do not support the proposal that in man, establishment of functional corticomotoneuronal projections occurs immediately prior to and provides the capacity for the expression of fine finger movement control. We propose instead that such early corticospinal innervation occurs to permit cortical involvement in activity dependent maturation of spinal motor centres during a critical period of perinatal development. Spastic cerebral palsy from perinatal damage to the corticospinal pathway secondarily involves disrupted development of spinal motor centres. Corticospinal axons retain a high degree of plasticity during axon growth and synaptic development. The possibility therefore exists to promote regeneration of disrupted corticospinal projections during the perinatal period with the double benefit of restoring corticospinal connectivity and normal development of spinal motor centres.

Statistical method for the estimation of cerebral blood flow using the Kety-Schmidt technique.

The Kety-Schmidt technique for the measurement of cerebral blood flow (CBF) has been in use for many years, but efficient statistical methods for producing estimates of CBF have received little attention. This paper proposes simple statistical models for this problem and explores their properties using data from a recent study of severe head injury in children. The method, which can readily be implemented on a personal computer, allows the uncertainty in the estimate of CBF to be quantified.

Specific attention and executive function deficits in the long-term outcome of severe closed head injury.

Twenty-eight children (mean age= 10.9 years, SD= 1.9 years) who had experienced a severe closed head injury were assessed for outcome on tests of intelligence, attention and executive function at 1 year post-injury. The children with closed head injury were matched with children from a normative sample for age and intellectual ability. Specific deficits in attention and executive function were found in the closed head injury sample. The importance of including these outcome variables in child neuropsychological assessment is supported.

Abnormal development of biceps brachii phasic stretch reflex and persistence of short latency heteronymous reflexes from biceps to triceps brachii in spastic cerebral palsy.

Co-contraction of antagonist muscles is characteristic of spasticity arising from perinatal brain damage but not in spasticity occurring after brain damage in adulthood. Such co-contraction is a normal feature of early post-natal motor development. Heteronymous, monosynaptic Group Ia projections from biceps brachii to both the antagonist triceps brachii and to other synergist and non-synergist muscles of the upper limb occur in the newborn baby and become restricted during the first 4 years to motor neurons of primarily synergistic muscles. Longitudinal and cross-sectional studies have been performed to test the hypothesis that inappropriate heteronymous excitatory projections persist in children with perinatal brain damage who develop spasticity. Subjects with spasticity, from brain damage acquired in adulthood were also studied to determine if these projections simply become unmasked as part of spasticity, independent of the age of occurrence of the brain damage. Twenty-nine healthy newborn babies and 29 at high risk for cerebral palsy, 12 of whom developed spastic quadriparesis, were studied longitudinally for 4 years. Thirty-eight subjects, aged 8-30 years, with spasticity of perinatal origin (11 hemiplegic, 11 quadriplegic, 16 with Rett syndrome) and 11 subjects with stroke in adulthood and spastic hemiplegia were also studied. The results were compared with those obtained in 372 normal subjects aged from birth to 55 years. Small taps were delivered to the tendon of biceps brachii using an electromechanical tapper. Surface EMG was recorded from biceps and triceps brachii, pectoralis major and deltoid. In the longitudinal study, those developing spastic quadriparesis showed persistent low thresholds for the homonymous phasic stretch reflex, which had abnormally short onset latencies. There was persistence of short onset heteronymous excitatory responses in triceps brachii, while a normal pattern of restriction of heteronymous responses to pectoralis major and deltoid occurred. The same pattern was observed in older subject groups with spasticity of perinatal origin. In adults with hemiplegia following stroke the threshold of the homonymous phasic stretch reflex was low, but it had a normal onset latency. There was no evidence of abnormal heteronymous excitatory responses. In conclusion, exaggerated excitatory responses to primary muscle afferent input were observed in the homonymous (biceps brachii) and antagonist (triceps brachii) motor neurons in subjects with spasticity arising from perinatal brain damage. They are likely to play an important role in the predominant co-contraction of agonist/antagonist muscles during voluntary movement observed in subjects with spastic cerebral palsy.

Comparison of activation of corticospinal neurons and spinal motor neurons by magnetic and electrical transcranial stimulation in the lumbosacral cord of the anaesthetized monkey.

To illuminate the action of non-invasive stimuli on the human cerebral cortex, responses of corticospinal axons and of plantar alpha-motor neurons following transcranial magnetic (TMS) and electrical stimulation (TES) were recorded in the lumbosacral cord in the anaesthetized macaque monkey. A round coil was used for TMS, and the anode was located at the vertex for TES. The responses of 175 identified corticospinal axons (conduction velocities of 24-95 m/s) were recorded from the lateral corticospinal tract at the T12-L3 spinal level. A single magnetic or electrical stimulus could evoke an early spike corresponding to the direct (D) wave in surface recorded volleys and was termed a D response. In the same axon, up to four further spikes, termed indirect (I) responses, could also be evoked. At a given intensity of stimulation, D responses had clear thresholds and fixed latencies, whereas I responses were labile in both respects. For TMS and TES, the thresholds of both D and I responses were inversely correlated with axonal conduction velocity. For TMS, fast conducting axons (> 75 m/s) had lower thresholds for D responses, while more slowly conducting axons (< 55 m/s) had lower thresholds for I responses. Very few of the axons with a conduction velocity of < 40 m/s (three out of 23) gave a D response to TMS. For TES, the majority of axons had lower thresholds for D responses or a similar threshold for both D and I responses. At threshold, the latencies of D responses evoked by TMS and TES were consistent with activation within the cortex, while TES also excited some corticospinal axons deep to the cortex. At 2.5 times threshold for the D response, TMS still excited axons mostly within the cortex, but with TES the site of activation shifted by as much as 65 mm below the cortex (mode 20 mm). Intracellular responses were recorded in 23 plantar alpha motor neurons supplying intrinsic muscles of the foot. All showed monosynaptic excitatory post-synaptic potentials (EPSPs) to both TMS and TES with no significant differences in the rise times of the evoked EPSPs. At threshold for a surface corticospinal volley, the average EPSP to TES began 0.5 ms earlier than that to TMS, and 1.0 ms earlier at 2.5 times this threshold. The different sites of activation of corticospinal neurons by TMS and TES, as well as the different distribution of D and I responses that they evoke, may both contribute to the differences in the onset latencies of the EMG responses evoked by these methods in human subjects.

Modified hormonal effects on fat metabolism after severe head injury in children.

Previous studies within our research group have indicated that the hormonal influences on whole body energy expenditure may be modified in severely head-injured children. The aim of this study was to examine plasma concentrations of nonesterified fatty acids (NEFA) and the hormonal and metabolic mediators which influence these to determine whether there is a similarly modified effect on fat metabolism. A total of 64 serial measurements were made in 21 fasting severely head-injured children aged 2-15 y (Glasgow Coma Score < or = 8) who were receiving neurointensive care. Circulating NEFA, ketone bodies, and lactate concentrations were analyzed using microenzymatic or electrochemical techniques. Plasma concentrations of adrenaline and insulin were measured using radioenzymatic and RIA techniques, respectively. Net fat oxidation rates were determined using indirect calorimetry. Plasma NEFA concentrations showed a significant positive relationship with both net fat oxidation rates (p = 0.02) and log ketone body concentrations (p = 0.008), indicating that NEFA concentrations were significantly related with utilization. When compared with reference values for normal resting adults, 59 (92%) adrenaline measurements were elevated, whereas only 8 (12%) NEFA values lay above the reference range. Surprisingly, between children, there was a significant negative relationship between NEFA and adrenaline concentrations, even after allowing for the effects of insulin and lactate (p = 0.015). Both plasma NEFA and adrenaline concentrations were significantly related with Glasgo Coma Score (p = 0.04, p = 0.007, respectively), the most severely injured children having the lowest NEFA and highest adrenaline concentrations. The mechanisms underlying these metabolic changes may be related to the severity of head injury and may involve changes in triglyceride/NEFA cycling and/or peripheral effects on adrenergic receptors. If children are to be treated effectively after trauma, it is important to discover the mechanism of these changes which must reflect a fundamental alteration in metabolism.

Changes in cerebral oxygen consumption are independent of changes in body oxygen consumption after severe head injury in childhood.

This study examines the relation between cerebral O2 consumption (CMRO2) and the O2 consumption of the rest of the body (BVO2) after severe head injury. Seventy nine serial measurements of whole body O2 consumption, CMRO2, plasma adrenaline, T3, and glucagon concentrations were made in 15 children with severe head injuries receiving neurointensive care. Body O2 consumption was measured with indirect calorimetry and CMRO2 with the Kety-Schmidt technique. There was no evidence of a significant relation between CMRO2 and BVO2. Within each child there were statistically significant positive relations between BVO2 and adrenaline, T3, and glucagon. By contrast, there was only a weak significant positive relation between CMRO2 and T3. In conclusion, CMRO2 and BVO2 seem to be determined independently after severe head injury. Thus therapeutic measures aiming to reduce CMRO2 need to be specific to the brain and it should not be assumed that measures which decrease whole body energy expenditure will necessarily have the same effect on CMRO2.

Temperature response to severe head injury and the effect on body energy expenditure and cerebral oxygen consumption.

This study examines the relationship between core temperature and whole body energy expenditure, cerebral oxygen consumption (CMRO2), cerebral blood flow (CBF), and intracranial pressure (ICP) in severely head injured children. A total of 107 serial measurements of temperature, energy expenditure, CMRO2, CBF, and ICP were made in 18 head injured children receiving neurointensive care. Energy expenditure was measured using indirect calorimetry, and CMRO2 and CBF using the Kety-Schmidt technique. The mean rectal temperature was 37.8 degrees C (34-39.1 degrees C) despite modification with paracetamol. Within each child there was a positive relationship between rectal temperature and energy expenditure, energy expenditure increasing by a mean of 7.4% per degree C. There was no evidence of significant relationships between rectal temperature and CMRO2, CBF, or ICP. Mild induced hypothermia in two children did not result in decreased CMRO2 or CBF measurements. The efficacy of interventions aiming to modify cerebral energy metabolism by changing core temperature cannot be readily assessed by the response of the whole body.