James G. Colebatch

INterhemispheric inhibition of the human motor cortex

1. Using two magnetic stimulators, we investigated the effect of a conditioning magnetic stimulus over the motor cortex of one hemisphere on the size of EMG responses evoked in the first dorsal interosseous (FDI) muscle by a magnetic test stimulus given over the opposite hemisphere. 2. A single conditioning shock to one hemisphere produced inhibition of the test response evoked from the opposite hemisphere when the conditioning‐test interval was 5‐6 ms or longer. We shall refer to this as interhemispheric inhibition. However, the minimum latency of inhibition observed using surface EMG responses may have underestimated the true interhemispheric conduction time. Single motor unit studies suggested values 4‐7 ms longer than the minimum interval observed with surface EMG. 3. Interhemispheric inhibition was seen when the test muscle was active or relaxed. Increasing the intensity of the conditioning stimulus increased the duration of inhibition: increasing the intensity of the test stimulus reduced the depth of inhibition. 4. The conditioning coil had to be placed on the appropriate area of scalp for inhibition to occur. The effect of the conditioning stimulus was maximal when it was applied over the hand area of motor cortex, and decreased when the stimulus was moved medial or lateral to that point. 5. The inhibitory effect on the test stimulus probably occurred at the level of the cerebral cortex. In contrast to the inhibition of test responses evoked by magnetic test stimuli, test responses evoked in active FDI by a small anodal electric shock were not significantly inhibited by a contralateral magnetic conditioning stimulus. Similarly, H reflexes in relaxed forearm flexor muscles were unaffected by conditioning stimuli to the ipsilateral hemisphere. However, inhibition was observed if the experiment was repeated with the muscles active.

Myogenic potentials generated by a click-evoked vestibulocollic reflex.

Electromyograms (EMGs) were recorded from surface electrodes over the sternomastoid muscles and averaged in response to brief (0.1 ms) clicks played through headphones. In normal subjects, clicks 85 to 100 dB above our reference (45 dB SPL: close to perceptual threshold for normal subjects for such clicks) evoked reproducible changes in the averaged EMG beginning at a mean latency of 8.2 ms. The earliest potential change, a biphasic positive-negativity (p13-n23), occurred in all subjects and the response recorded from over the muscle on each side was predominantly generated by afferents originating from the ipsilateral ear. Later potentials (n34, p44), present in most but not all subjects, were generated bilaterally after unilateral ear stimulation. The amplitude of the averaged responses increased in direct proportion to the mean level of tonic muscle activation during the recording period. The p13-n23 response was abolished in patients who had undergone selective section of the vestibular nerve but was preserved in subjects with severe sensorineural hearing loss. It is proposed that the p13-n23 response is generated by activation of vestibular afferents, possibly those arising from the saccule, and transmitted via a rapidly conducting oligosynaptic pathway to anterior neck muscles. Conversely, the n34 and p44 potentials do not depend on the integrity of the vestibular nerve and probably originate from cochlear afferents.

CORTICAL AREAS AND THE SELECTION OF MOVEMENT : A STUDY WITH POSITRON EMISSION TOMOGRAPHY

SummaryRegional cerebral blood flow was measured in normal subjects with positron emission tomography (PET) while they performed five different motor tasks. In all tasks they had to moved a joystick on hearing a tone. In the control task they always pushed it forwards (fixed condition), and in four other experimental tasks the subjects had to select between four possible directions of movement. These four tasks differed in the basis for movement selection. A comparison was made between the regional blood flow for the four tasks involving movement selection and the fixed condition in which no selection was required. When selection of a movement was made, significant increases in regional cerebral blood flow were found in the premotor cortex, supplementary motor cortex, and superior parietal association cortex. A comparison was also made between the blood flow maps generated when subjects performed tasks based on internal or external cues. In the tasks with internal cues the subjects could prepare their movement before the trigger stimulus, whereas in the tasks with external cues they could not. There was greater activation in the supplementary motor cortex for the tasks with internal cues. Finally a comparison was made between each of the selection conditions and the fixed condition; the greatest and most widespread changes in regional activity were generated by the task on which the subjects themselves made a random selection between the four movements.

Responses of guinea pig primary vestibular neurons to clicks

Responses of single neurons in the vestibular nerve to high-intensity clicks were studied by extracellular recording in anaesthetised guinea pigs. One hundred and two neurons in the posterior division of the superior branch or in the inferior branch of the vestibular nerve were activated at short latency by intense clicks. The latency of activation was short (median 0.9 ms) and the threshold was high: the click intensity for evoking the response of these cells was around 60 dB above the auditory brainstem response threshold. Animals were tilted and rotated to identify physiologically the sensory region of the labyrinth from which the activated neurons originated. Seventeen neurons responded to static tilt as well as clicks. These results show that vestibular receptors, probably the otoliths, respond to clicks at intensities corresponding to those used in a new clinical test of the vestibulo-collic pathway.

Characteristics and clinical applications of vestibular-evoked myogenic potentials

A recent technique of assessing vestibular function, the vestibular-evoked myogenic potential (VEMP), is an otolith-mediated, short-latency reflex recorded from averaged sternocleidomastoid electromyography in response to intense auditory clicks delivered via headphones. Since their first description 10 years ago, VEMPs are now being used by investigators worldwide, and characteristic changes observed with aging and in a variety of peripheral and central vestibulopathies have been described. Additional methods of evoking VEMPs, which use air- and bone-conducted short-tone bursts, forehead taps, and short-duration transmastoid direct current (DC) stimulation, have been described, and these complement the original technique. Click-evoked VEMPs are attenuated or absent in a proportion of patients with vestibular neuritis, herpes zoster oticus, late Ménière disease, and vestibular schwannomas; their amplitudes are increased and thresholds are pathologically lowered in superior semicircular canal dehiscence presenting with the Tullio phenomenon. VEMPs evoked by clicks and DC are useful when monitoring the efficacy of intratympanic gentamicin therapy used for chemical vestibular ablation. Prolonged p13 and n23 peak latencies and decreased amplitudes have been observed in association with central vestibulopathy. VEMPs evoked by clicks are a robust, reproducible screening test of otolith function. DC stimulation enables differentiation of labyrinthine from retrolabyrinthine lesions; bone-conducted stimuli permit VEMP recording despite conductive hearing loss and deliver a relatively larger vestibular stimulus for a given level of auditory perception.

Decreases in Regional Cerebral Blood Flow with Normal Aging

Positron emission tomographic (PET) images of regional cerebral blood flow (rCBF) from 30 normal, resting volunteers aged 30 to 85 years were analysed to identify areas where rCBF fell with age. Images were anatomically normalised, and a pixel-by-pixel linear regression was performed to remove differences in global CBF between subjects. Pixels at which rCBF then showed a significant (p < 0.01) negative correlation with age were identified. They were displayed as a statistical parametric map (SPM) of correlations. We demonstrate an age-related decrease in adjusted rCBF in the cingulate, parahippocampal, superior temporal, medial frontal, and posterior parietal cortices bilaterally, and in the left insular and left posterior prefrontal cortices (omnibus significance, χ2 = 2,291, p < 0.0001, df = 1). Decreases in rCBF suggest a regionally specific loss of cerebral function with age. The affected areas were all limbic, or association, cortices. Therefore, these decreases may constitute the cerebral substrate of the cognitive changes that occur during normal aging.

Ocular vestibular evoked myogenic potentials (OVEMPs) produced by air-and bone-conducted sound

OBJECTIVE To determine the origin and properties of short latency extraocular potentials produced by activation of the vestibular apparatus using two modes of acoustic stimulation. METHODS Extraocular potentials were measured in 10 normal subjects using a bipolar montage to increase selectivity. Three dimensional eye movements were also recorded in five subjects. The subjects were stimulated with both air-conducted (AC) and bone-conducted (BC) sound using a single cycle of a 500Hz sine wave. RESULTS Short latency positive and negative potentials that peaked at 8.1-12.7ms for AC and 7.5-13.9ms for BC stimulation were recorded, which were distinct for the two eyes and for the two modes of stimulation. The extraocular potentials began prior to the onset of eye movements, which peaked at 16.5-20.1ms for AC, 17.8-25.0ms for BC stimulation. CONCLUSIONS The pattern of short latency eye movements and extraocular potentials induced by AC and BC vestibular stimulation are distinct. As the potentials preceded the eye movements and were not correlated morphologically with them, the source of the observed potentials is not an eye movement and thus we refer to them as ocular vestibular evoked myogenic potentials (OVEMPs). SIGNIFICANCE The potentials had properties consistent with modulation of the electromyogenic activity of the extraocular muscles and if interpreted as originating from displacement of the eye will give misleading results. AC and BC acoustic stimulation are likely to activate differing profiles of vestibular end organs.

Head taps evoke a crossed vestibulo-ocular reflex

Taps to the forehead on the midline, at the hairline (Fz), with a reflex hammer or powerful bone conduction vibrator caused short-latency surface potentials from beneath both eyes in all healthy subjects. The earliest negative responses were invariably absent from the eye contralateral to the side of a previous vestibular nerve section but were preserved despite sensorineural hearing loss. These responses probably reflect vestibular function via crossed otolith–ocular pathways.

Vestibulocollic reflexes: normal values and the effect of age

OBJECTIVES To define normal values and examine the influence of ageing on vestibulocollic reflexes (VCR). METHODS Vestibulocollic responses to 100 dB (normal hearing level; NHL) clicks, forehead taps and galvanic stimulation were measured in 70 healthy adults aged 25-85 years. RESULTS Click- and galvanic-evoked responses were present bilaterally in all subjects below 60. Average click-evoked response amplitudes decreased with age, with a pronounced decline of 25-30% per decade from the 6th decade. The average click thresholds increased from 85 dB in the third decade to 96.5 dB in the 8th and 9th decades. Average galvanic-evoked VCR amplitudes decreased sharply from the seventh decade. Tap-evoked reflex amplitudes showed a milder decrease. When side to side differences in amplitude were expressed as asymmetry ratios (AR) in subjects below the age of 60, values of up to 35 and 46% were obtained for click amplitudes corrected and uncorrected for background electromyogram (EMG), up to 61% for both corrected and uncorrected tap response amplitudes, and up to 41 and 55% for corrected and uncorrected galvanic-evoked responses. CONCLUSIONS A normative range of values can be specified for click- and galvanic-evoked VCRs for subjects up to the age of 60. Click- and galvanic-evoked VCR amplitudes decrease rapidly thereafter while tap-evoked responses are less affected. These changes are probably due to morphological changes in the vestibular system occurring with ageing and are more marked than in several previous reports of age-related changes in caloric responses and vestibulo-ocular reflexes.

Regional cerebral blood flow during volitional breathing in man

1. Positron emission tomographic imaging of brain blood flow was used to identify areas of motor activation associated with volitional inspiration in six normal male subjects. 2. Scans were performed using intravenous infusion of H2(15)O during voluntary targeted breathing and positive pressure passive ventilation at the same level. 3. Regional increases in brain blood flow, due to active inspiration, were derived using a pixel by pixel comparison of images obtained during the voluntary and passive ventilation phases. 4. Pooling data from all subjects revealed statistically significant increases in blood flow bilaterally in the primary motor cortex (left, 5.4%; right, 4.3%), in the right pre‐motor cortex (7.6%), in the supplementary motor area (SMA; 3.1%) and in the cerebellum (4.9%). 5. The site of increased neural activation in the motor cortex, associated with volitional inspiration, is consistent with an area which when stimulated, either directly during neurosurgery or transcranially with a magnetic stimulus, results in activation of the diaphragm. 6. The presence of additional sites of neural activation in the pre‐motor cortex and SMA appears analogous to the results of studies on voluntary limb movement. The site of the increase in the SMA was posterior to that previously reported for arm movements. These areas are believed to have a role ‘upstream’ of the motor cortex in the planning and organization of movement. 7. This technique provides a means of studying the volitional motor control of respiratory related tasks in man.