A positron emission tomographic study of subthalamic nucleus stimulation in Parkinson disease: enhanced movement-related activity of motor-association cortex and decreased motor cortex resting activity.

BACKGROUND: Long-term high-frequency stimulation of the subthalamic nucleus (STN) improves akinesia in Parkinson disease. The neural correlates of STN stimulation are not well understood. Positron emission tomography can be applied to the in vivo study of the mechanisms of deep brain stimulation. OBJECTIVE: To study changes in regional cerebral blood flow as an index of synaptic activity in patients with Parkinson disease with effective STN stimulation on and off during rest and movement. METHODS: Eight patients with Parkinson disease who had electrodes implanted in the STN underwent 12 measurements of regional cerebral blood flow with water O 15 positron emission tomography at rest and during performance of paced freely selected joystick movements, both with and without STN stimulation (3 scans per experimental condition). Motor performance and reaction and movement times were monitored. Statistical parametric mapping was used to compare changes in regional cerebral blood flow between conditions and differences in activation. RESULTS: All patients showed improvement in reaction and movement times during scans with the stimulator on. As predicted, increases in activation of rostral supplementary motor area and premotor cortex ipsilateral to stimulation were observed when stimulation was on during contralateral movement (P<.001). Unpredicted observations included decreases in regional cerebral blood flow in primary motor cortex at rest induced by STN stimulation. CONCLUSION: Stimulation of the STN reduces the movement-related impairment of frontal motor association areas and the inappropriate motor cortex resting activity in Parkinson disease.

Comparison of various coils used for magnetic stimulation of peripheral motor nerves: physiological considerations and consequences for diagnostic use.

We compared the ability of 4 magnetic coils to activate peripheral nerves in healthy subjects. No differences in motor threshold intensities were found between the coils, but the intensities needed to elicit maximum compound muscle action potential (CMAP) amplitudes were different. For superficial nerves maximum CMAPs in comparison with electrical stimulation were usually but not always found. CMAPs were at their maximum only when the direction of induced current flowed from proximal to distal and when a certain part of the coil was over the nerve. Distal nerve stimulation was time consuming. Due to artifacts many stimuli were necessary and sometimes no maximum CMAP could be elicited. CMAPs were much less sensitive to position changes of the coil than to changes in an electrical stimulator. Small circular coils were superior to larger coils in terms of the lower intensities necessary to elicit maximum CMAPs, better focusing of the stimulus, and less artifacts. For deep nerves amplitudes were always submaximal. Coactivation of nearby nerves and underlying muscles was another main drawback especially at proximal sites and for coils of large diameter. Despite better focusing, double coils are less useful due to their great diameter. Magnetic stimulation cannot replace electrical neurography at the moment, even if different coils are used at different sites of stimulation.

Magnetically induced muscle contraction is caused by motor nerve stimulation and not by direct muscle activation.

When magnetically stimulating peripheral nerves, a local cocontraction of muscle under the coil is observed. We assessed whether this contraction results from: (1) magnetic stimulation of motor nerves, or (2) direct depolarization of the muscle membrane. Wrist extensor muscles of normal subjects were magnetically stimulated with the coil placed directly above the muscle. Neuromuscular transmission was then blocked by atracurium using a technique of local curarization. As a reference, the radial nerve was stimulated electrically. Magnetic and electrical stimuli were applied alternatingly every 10 s. Twitch force of wrist extension was measured isometrically over a period of about 70 min including the phase of complete neuromuscular block. Twitch amplitudes elicited by magnetic and electrical stimuli were equivalent during the whole experiment. These results suggest that muscle cocontraction following magnetic stimulation results from depolarization of terminal motor nerve branches.

Changes in the response to magnetic and electrical stimulation of the motor cortex following muscle stretch in man.

1. The effect of muscle stretch on the EMG response from the stretched muscle to transcranial magnetic stimulation of the motor cortex was studied in eight subjects. Muscle stretch was produced by increasing the torque of a motor acting through a lever which was held at constant position by a flexion force of the index and middle fingers. EMG responses were recorded from fine-wire electrodes inserted into flexor digitorum profundus muscle in the forearm. They consisted of a spinal latency component and a long-latency component which could in some subjects be separated into an early and a late phase. 2. In four subjects, four intervals between the stretch and the cortical stimulus were explored using three intensities of cortical stimulation. At all three intensities, when the magnetic cortical stimulus was timed to produce an EMG response in the period of the later part of the long-latency stretch reflex the response was larger than when it was timed to produce a response in the period of the short-latency spinal reflex or when superimposed on the tonic muscle activity used to resist the standing torque of the motor. 3. When the intensity of magnetic cortical stimulation was reduced so that it was just below threshold to produce an EMG response in the short-latency reflex period or on the background tonic EMG activity, it still was capable of producing a response when superimposed on the long-latency stretch reflex. 4. In four subjects the time course of this effect was studied in more detail using only one intensity of magnetic cortical stimulus set to be just above threshold to produce a response in tonically active muscles. The time course of the facilitatory effect was similar to the time course of the later part of the long-latency stretch reflex. From these data it was not possible to determine whether the early part of the long-latency stretch reflex also was accompanied by the facilitatory effect since this component was present in only one of the four subjects. 5. The facilitatory effect persisted after the ulnar and median nerves were totally blocked at the wrist by injections of local anaesthetic. This suggests that inputs from muscle receptors of the stretched muscle contribute to the effect.4=

Stereoencephalotomy and control of skeletal muscle tone.

Stereotactic interventions at the thalamic or subtalamic level for treatment of pathological hyperkinesias provide a good model for investigation of the systems controlling tonic innervation in the alert subject. It is suggested that the poststereotactic muscular hypotonia observed contralaterally to the lesion is due to changes in the tonic innervation pattern caused by interruption of a proprioceptive feedback loop.

Computer-assisted analysis of functional anatomy of human ventrolateral thalamus.

A three-dimensional map was created by a computer-assisted analysis of functional and somatotopic organization of the target area in the human ventrolateral thalamus. Stimulation in the target area mostly elicited increased tone in skeletal muscles, with a concomitant decrease or stop of tremor. Despite averaging of all responses, no clear somatotopic organization could be demonstrated for the tonifying stimulation effects. In addition, somatosensory-evoked potentials were recorded, indicating an afferent projection to the target area.

Somatosensory evoked potentials in the ventrolateral thalamus.

Within the target area (VL) used for the stereotactic treatment of parkinsonian tremor and spasmodic torticollis, electrical stimulation as well as recording of somatosensory evoked potential (SEP) was performed. The effects of stimulation in the target area are facilitation of muscle tone showing some degree of somatotopic distribution. The recorded SEPs indicate a projection of an afferent system (probably of muscle afferents) to the target area. We assume that the target area is a relay station involved in the control of muscle tone. The interruption of muscle afferents in combination with the correct somatotopic localization of the lesion is important for the therapeutic efficacy in parkinsonian tremor and spasmodic torticollis.