Peter Ashby

Corticospinal projections to upper limb motoneurones in humans.

1. Magnetic stimulation was applied over the motor cortex in forty‐five normal human subjects and peristimulus time histograms (PSTHs) of the discharges of single motor units were used to record changes in the firing probability of individual spinal motoneurones of contralateral upper limb muscles. Recordings were obtained from 153 motor units from fourteen upper limb muscles. 2. For the majority of motor units the initial effect was a short latency facilitation. The estimated central conduction velocities and the rise times of the underlying excitatory postsynaptic potentials (EPSPs) were compatible with monosynaptic facilitation by a fast corticospinal pathway. In some motor units the initial effect was a short latency inhibition. Other units showed no statistically significant changes in firing probability. The proportion of the tested motor units in each of these categories depended on the muscle. All of the sampled units of first dorsal interosseous (1DI) showed short latency facilitation, as did the majority of units in the forearm and the biceps brachii. More than half of the sampled motor units of triceps brachii and deltoid showed either no effect or were inhibited. 3. To compare the net short latency actions of the neurones activated by magnetic stimulation on various motoneurone pools, the magnitude of the short latency facilitation or inhibition in a given motor unit was normalized to the magnitude of the short latency facilitation in the 1DI motor unit of the same subject at the same stimulus intensity, and these data were pooled for a number of subjects. 4. 1DI motoneurones received strong net facilitation (estimated mean EPSP amplitude 2.9 +/‐ 0.2 mV), the motoneurones of forearm muscles and biceps brachii received weaker net facilitation and triceps brachii and deltoid received no net effect. 5. It is concluded that the short latency corticospinal projections to upper limb motoneurones in humans have a distinct pattern which is similar to that in other primates.

Deep brain stimulation for Parkinson's disease: disrupting the disruption

Many people are disabled by Parkinsons disease (PD) despite the drug treatments that are currently available. For these patients, neurosurgery has the potential to help restore their function. The most effective neurosurgical procedures to date use electrical stimulation--deep brain stimulation (DBS)--of small targets in the brain by use of a pacemaker-like device to deliver constant stimulation. Although these operations can produce striking results, the mechanism by which delivery of electrical stimulation to targets deep in the brain can restore function in the motor system is not clear. This type of surgery probably works by interfering with and shutting down abnormal brain activity in areas where the current is delivered, such as the thalamus, globus pallidus, or the subthalamic nucleus. With this abnormal neuronal activity neutralised, motor areas of the brain can resume their function and normal movements are reinstated. Current research is aimed at elucidating how DBS works and using this information to develop better treatments for patients with PD and other neurological disorders.

SPTLC1 is mutated in hereditary sensory neuropathy, type 1

Hereditary sensory neuropathy type 1 (HSN1, MIM 162400; ref. 1) genetically maps to human chromosome 9q22 (refs. 2–4). We report here that the gene encoding a subunit of serine palmitoyltransferase is located within the HSN1 locus, expressed in dorsal root ganglia (DRG) and mutated in HSN1.

Inhibition in the human motor cortex is reduced just before a voluntary contraction

Objective: To examine inhibition in the human motor cortex before and during voluntary movements. Methods: The balance between the excitation and inhibition of corticospinal neurons in the human motor cortex was tested by conditioning the motor evoked potentials (MEP) evoked in forearm muscles by transcranial magnetic stimulation with a preceding subthreshold stimulus delivered through the same coil. Results: When normal individuals (n = 9) made a tonic wrist extension, inhibition of the forearm extensor MEP decreased, whereas that of the forearm flexors was unchanged. When these individuals made a tonic wrist flexion, inhibition of the forearm flexor MEP diminished, whereas that of the forearm extensors was unchanged. When normal individuals (n = 10) made a phasic wrist extension in response to an auditory signal, inhibition of the extensor MEP began to decline about 95 msec before the onset of the agonist EMG activity. Conclusions: The changes in balance of excitation and inhibition of corticospinal neurons associated with a voluntary movement precede the movement and are directed at the corticospinal neurons projecting to the agonists. These changes may help to select the population of cortical neurons responsible for the movement.

Does stimulation of the GPi control dyskinesia by activating inhibitory axons

A 69‐year‐old woman with Parkinsons disease and levodopa‐induced dyskinesias had a deep brain stimulation (DBS) electrode inserted into the right globus pallidus internus (GPi). During the operation, the GPi was mapped with dual microelectrode recordings. Stimulation through one microelectrode in GPi inhibited the firing of GPi neurons recorded with another microelectrode 600–1,000 μm distant. The inhibition could be obtained with pulse widths of 150 μs and intensities as low as 10 μA. Single stimuli inhibited GPi neurons for ∼50 ms. Trains of 300 Hz stimuli inhibited GPi neuron firing almost completely. Postoperatively, stimulation through macroelectrode contacts located in the posterior ventral pallidum controlled the patients dyskinesias. The effect could be obtained with pulse widths of 50 μs and frequencies as low as 70–80 Hz. We postulate stimulation of the ventral pallidum controls dyskinesias by activating large axons which inhibit GPi neurons.

Corticospinal projections to lower limb motoneurons in man

SummaryThe projections of cortical neurons activated by transcranial magnetic stimulation to single lower limb spinal motoneurons were examined in 34 normal subjects. Peristimulus time histograms of the discharge times of single, voluntarily activated motor units were used to derive information about postsynaptic potentials in single spinal motoneurons produced by magnetic stimuli applied over the contralateral scalp. All tibialis anterior motor units and the majority of motoneurons innervating the small muscles of the foot showed strong short latency facilitation. About half of the motoneurons of proximal lower limb muscles showed this facilitation. Short latency facilitation of the motoneurons of soleus and medial gastrocnemius was only rarely observed and when present was weak. The short latency facilitation is attributed to the projections of the fast corticospinal pathway with monosynaptic projections to motoneurons. The relative strength of the facilitation in different motoneuron pools is considered to reflect the density of corticospinal projections to that motoneuron pool. The observed pattern of projections in man shows some differences from the pattern of projections in subhuman primates that might reflect the different use of the limb.

Segmental reflex pathways in spinal shock and spinal spasticity in man

Activity in three segmental pathways was compared in normal subjects, patients with spinal shock, and patients with established spinal spasticity. The Achilles tendon reflex (ATR) was used to estimate transmission in the Ia monosynaptic pathway. Evidence is produced implying that vibration activates motoneurones principally through a polysynaptic pathway. The tonic vibration reflex (TVR) was used to estimate transmission in this Ia polysynaptic pathway. The percentage of the motoneurone pool (M-response) that could be activated by these pathways was used as a measure of transmission. The H reflex (vibration)/H reflex (control) ratio was used as an estimate of the degree of presynaptic inhibition of the Ia monosynaptic pathway. The findings led to the following conclusions. (1) In spinal shock presynaptic inhibition is greater than normal, transmission in the Ia monosynaptic pathway is reduced, and in the Ia polysynaptic pathway virtually abolished. (2) In established spasticity presynaptic inhibition is impaired, transmission in the Ia monosynaptic pathway is increased, but transmission in the Ia polysynaptic pathway never recovers. (3) The failure of presynaptic inhibition associated with spasticity is a gradual process. A hypothesis to explain these findings is proposed.

Evidence that a long latency stretch reflex in humans is transcortical.

1. The hypothesis that the long latency reflex response to muscle stretch in humans uses a transcortical pathway was tested by looking for convergence onto cortical neurones in eleven normal subjects. 2. Postsynaptic events in single flexor pollicis longus (FPL) motoneurones were derived from changes in the firing probability of individual FPL motor units. 3. Extension of the terminal phalynx of the thumb resulted in both short latency and long latency facilitations of individual FPL motoneurones. These were not reproduced by electrical stimulation of afferents in the terminal phalynx. Magnetic stimulation over the contralateral motor cortex produced strong, short latency facilitation of FPL motoneurones. 4. When the facilitation produced by stimulation over the cortex was superimposed on the long latency facilitation produced by extension of the thumb, the facilitation produced by both stimuli was greater than the sum of the individual facilitations produced by either stimulus given alone. This was not the case when the superimposition occurred on the short latency response to stretch. 5. We conclude that afferent systems excited by the stretch of FPL converge onto cortical neurones which are known to facilitate motoneurones. Thus the cortex is likely to contribute to the long latency stretch reflex in humans.

Potentials recorded at the scalp by stimulation near the human subthalamic nucleus

OBJECTIVE To record the potentials evoked at the scalp by stimulation through electrodes targeted at the human subthalamic nucleus (STN) and to determine whether the responsible pathways continue to be excited or become blocked with high frequency stimulation. METHODS We recorded the potentials evoked at the scalp in response to single and multiple stimuli delivered through STN contacts in 6 patients with Parkinsons disease. RESULTS On 9/11 sides tested, single stimuli elicited a negative potential with latency of approximately 3 ms which was largest over the frontal region. Its short chronaxie (50 micros) and refractory period imply that it arose from the activation of low threshold neural elements, possibly myelinated axons. This potential could follow at 100 Hz. This early potential was sometimes followed by later negative potentials at approximately 5 ms (6/11 sides) and approximately 8 ms (8/11 sides). The responsible neural elements had the same short chronaxie. These potentials were augmented by paired stimuli at separations of 2-7 ms and by trains of stimuli at 200 Hz. CONCLUSIONS Trains of stimuli delivered to the STN may excite low threshold neural elements which can transmit impulses at frequencies >100 Hz without blocking and which may produce postsynaptic facilitation at the cortex.

Parietal Pick's disease mimicking cortical-basal ganglionic degeneration

We report a patient with pathologically proven asymmetric Picks disease involving the parietal lobe who displayed a combination of parkinsonism, myoclonus, and other motor disturbances more typical of cortical-basal ganglionic degeneration.