Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy

Purpose Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. The possibility of a paradoxical excitatory effect of GABA in epilepsy has been suggested, but has not been investigated in vivo. We investigated pre- and post-synaptic GABAergic mechanisms in patients with idiopathic generalised epilepsy (IGE). Method In 10 patients and 12 control subjects we explored short- and long-interval intracortical inhibition (SICI, LICI; post-synaptic GABAA and GABAB-mediated respectively) and long-interval intracortical facilitation (LICF; pre-synaptic disinhibition) using transcranial magnetic stimulation. Results While post-synaptic GABAB-mediated inhibition was unchanged in IGE (p = 0.09), LICF was reduced compared to controls (controls: 141 ± 17% of baseline; untreated patients: 107 ± 12%, p = 0.2; treated patients: 79 ± 10%, p = 0.003). GABAA-mediated inhibition was reduced in untreated patients (response amplitude 56 ± 4% of baseline vs. 26 ± 6% in controls, p = 0.004) and normalised with treatment (37 ± 12%, p = 0.5 vs. controls). When measured during LICI, GABAA-mediated inhibition became excitatory in untreated IGE (response amplitude 120 ± 10% of baseline, p = 0.017), but not in treated patients. Conclusion Pre- and post-synaptic GABA-mediated inhibitory mechanisms are altered in IGE. The findings lend in vivo support to evidence from experimental models and in vitro studies of human epileptic brain tissue that GABA may have a paradoxical excitatory role in ictogenesis

Presaccadic ‘spike’ potential: Investigation of topography and source

Approximately 15–30 ms before a saccade, a large-amplitude, relatively short duration potential whose source has not previously been determined with certainty, can be recorded from the scalp in man. We have measured the surface topography of this potential during horizontal saccades in normal subjects and have found it to be maximal near the eye on the side ipsilateral to the direction of the saccade. Dipole medelling predicts a source near the eye ipsilateral to the direction of gaze, and the application of source derivation supports such an origin. Measurements of the potential close to the orbits in normal subjects in patients with a unilateral abducens nerve palsy, exenterated orbit or ocular prosthesis suggest that it is a summation potential derived from the ipsilateral lateral rectus and contralateral medial rectus muscles. It is hypothesized that the potential may arise as a result of the synchronized recruitment of motor units in the extraocular muscles prior to the commencement of the saccade

Cerebral events preceding self-paced and visually triggered saccades. A study of presaccadic potentials

The cerebral potentials preceding self-paced and visually triggered saccadic eye movements were studied using multichannel recording and spatio-temporal mapping techniques, and the contribution to these potentials of stimulus-evoked activity and the electro-oculographic field was investigated. A premotor positivity (PMP) and negativity (PMN) comparable to those associated with movements of the extremities were found with both self-paced and triggered saccades, but there were differences in the amplitude, duration and topography of these potentials in the different types of eye movement. The slope of the PMP was greater for visually triggered than for self-paced saccades and its slope and duration were influenced by the predictability of the triggering stimulus, the slope being greater and the duration shorter with predictable than with unpredictable stimuli. The characteristics of this potential are compatible with an origin from saccade-related and visually sensitive neurons in parietal and occipital cortex and it is suggested that in a visually triggered eye movement, the PMP may be a correlate of visuomotor interactions. A PMN was associated with both self-paced and visually triggered saccades, and in the case of triggered saccades is thought to reflect anticipation of the cuing stimulus in addition to preparatory movement-related activity. When the precise timing of the cuing stimulus was not known by the subject, a PMN still developed but then plateaued until the arrival of the stimulus and execution of the movement. In this situation the PMN therefore appears to reflect an increasing level of arousal and preparedness to move which is then maintained pending the final motor command

Cortical activity preceding self-initiated and externally triggered voluntary movement

Letter to the Edito

Presaccadic spike potential. Relation to eye movement direction

The spike potential (SP) which precedes horizontal saccadic eye movement has been shown to arise in the agonist lateral and medial rectus muscles of the two eyes. To determine whether other extra-ocular muscles also generate an SP, recordings were carried out in normal subjects performing vertical and oblique as well as horizontal saccades. An SP was recorded before saccades in all directions. The potential was highest in amplitude with horizontal or oblique abducting saccades and was higher in amplitude with vertical upgoing than downgoing saccades

Presaccadic spike potential: A computer model based upon motor unit recruitment patterns in the extraocular muscles

Details are presented of a computer model of the presaccadic ‘spike’ potential based upon the discharge properties of motor units in the extraocular muscles. The model provides support for the hypothesis that the spike potential represents the summated electrical activity from the near-synchronous recruitment of motor units in the extraocular muscles by the presaccadic burst of motoneurone activity

Premotor negativity associated with saccadic eye movement and finger movement: A comparative study

The topography and time course of the premotor negativity (PMN) associated with horizontal saccadic eye movement and with thumb movement has been compared in a group of normal subjects. It was found that the time of onset, slope and distribution of the PMN was essentially the same for both types of movement. This finding suggests that the PMN may reflect primarily a non-movement-specific increase in attention or arousal processes common to both types of movement rather than activity in specific cortical areas concerned with the programming and execution of the movements

F-response studies: Computer analysis and recovery cycle

A computerized technique has been used for the analysis of F responses in normal subjects. Differences between the dominant and non-dominant upper limb have been found in some subjects and potentiation of the F response by the Jendrassik manoeuvre has been demonstrated. The recovery cycle of the F response has been studied in human subjects and in the rat and has been found to be similar to that of the H reflex. Such studies may be useful for studying alpha motor neurone excitability

An investigation of the late excitatory potential in the hand following magnetic stimulation of the motor cortex

Magnetic stimulation of the motor cortex gives rise to a motor evoked potential (MEP) followed by a silent period (SP) during which a late excitatory potential (LEP) may occur in the surface EMG. To elucidate the mechanism of the LEP we investigated the effect of muscle contraction, stimulus intensity and stimulation site on the LEP recorded from the abductor pollicis brevis muscle. The amplitude of the LEP increased with increasing levels of muscle contraction and decreased with increasing stimulus intensity. There was no direct relationship between the amplitude of the LEP and the MEP, but there was an inverse relationship between LEP amplitude and SP duration. The latency of the LEP was unaffected by the level of muscle contraction, but increased with increasing stimulus intensity. Topographic mapping with stimulation at multiple scalp sites yielded a LEP at sites partially encircling but not including the centre of the APB motor area. These results are consistent with the LEP being due to reflex alpha motoneurone firing as a result of gamma motoneurone activation or with a period of disinhibition at cortical level allowing breakthrough of voluntary activity

Computerised topographical mapping of scalp recorded event-related potentials

A technique is described for the recording of multichannel cerebral evoked potential data and their conversion to colour-coded displays of scalp electrical activity at up to 40 instants in time. Such mapping gives a more readily assimilated picture of the evolution of the potential changes over the scalp than the raw waveforms. The method employs a PDP 11/23 computer for data collection and surface topography calculation, and a Tektronix 4662 digital plotter with 8 colour option for the display of spatio-temporal maps