Colum D. MacKinnon

DEFINITION AND CLASSIFICATION OF HYPERKINETIC MOVEMENTS IN CHILDHOOD

Hyperkinetic movements are unwanted or excess movements that are frequently seen in children with neurologic disorders. They are an important clinical finding with significant implications for diagnosis and treatment. However, the lack of agreement on standard terminology and definitions interferes with clinical treatment and research. We describe definitions of dystonia, chorea, athetosis, myoclonus, tremor, tics, and stereotypies that arose from a consensus meeting in June 2008 of specialists from different clinical and basic science fields. Dystonia is a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. Chorea is an ongoing random‐appearing sequence of one or more discrete involuntary movements or movement fragments. Athetosis is a slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Myoclonus is a sequence of repeated, often nonrhythmic, brief shock‐like jerks due to sudden involuntary contraction or relaxation of one or more muscles. Tremor is a rhythmic back‐and‐forth or oscillating involuntary movement about a joint axis. Tics are repeated, individually recognizable, intermittent movements or movement fragments that are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movement. Stereotypies are repetitive, simple movements that can be voluntarily suppressed. We provide recommended techniques for clinical examination and suggestions for differentiating between the different types of hyperkinetic movements, noting that there may be overlap between conditions. These definitions and the diagnostic recommendations are intended to be reliable and useful for clinical practice, communication between clinicians and researchers, and for the design of quantitative tests that will guide and assess the outcome of future clinical trials.

Pathways mediating abnormal intracortical inhibition in Parkinson's disease.

Previous studies have used paired‐pulse transcranial magnetic stimulation to show that short‐interval intracortical inhibition (SICI) is reduced in patients with Parkinsons disease (PD). This study examined whether reduced SICI in PD is caused by an increase in the threshold of inhibitory pathways or a reduction in the threshold of excitatory pathways. Motor‐evoked potentials were recorded from a hand muscle in 12 patients with PD (7 patients were tested off and on antiparkinsonian medications) and 12 control subjects. SICI was tested at seven conditioning stimulus intensities (CSIs; 40–100% of resting motor threshold) and at interstimulus intervals (ISIs) of 2, 3, and 4 milliseconds. No differences were found between groups in resting or active motor threshold, SICI threshold, or the extent of SICI at CSIs at or below 80% of resting motor threshold. Significant differences between groups were observed at CSIs of 90% and 100% with an ISI of 3 milliseconds. Antiparkinsonian medication had no effect on SICI. These findings show that the low threshold inhibitory pathways mediating SICI are normal in PD. The suppression of SICI observed at higher CSIs suggests that the threshold of intracortical facilitatory pathways is decreased in PD. Ann Neurol 2005;58:516–524

Stimulation through electrodes implanted near the subthalamic nucleus activates projections to motor areas of cerebral cortex in patients with Parkinson's disease

High‐frequency electrical stimulation through electrodes implanted in the subthalamic nucleus (STN) has been shown to reduce significantly the cardinal symptoms of Parkinsons disease (PD). Despite the success of this treatment, the mechanisms of action of stimulation are poorly understood. To elucidate further the mechanisms of action of deep brain stimulation and its effects on cortical activity, we recorded electroencephalographic potentials from 61 scalp‐surface electrodes during low‐frequency (5–10 Hz) bipolar stimulation in 11 patients with advanced PD (14 implanted electrodes were tested). In all electrodes tested, stimulation through at least one of the four contacts produced a medium‐latency waveform with an average onset of 14 ± 3 ms and peak at 23 ± 4 ms. This potential typically increased in magnitude across contacts from ventral to dorsal. Within‐subject comparisons of median nerve somatosensory evoked potentials demonstrated that the generator of the medium‐latency potential was within the primary sensorimotor cortex or lateral premotor cortex ipsilateral to stimulation. The timing and topography of this potential were consistent with indirect activation of the cortex by excitation of pallido‐thalamic axons that traverse the dorsal aspect of the STN. The potential evoked by stimulation through the contact used for optimal clinical effect was highly variable across electrodes and frequently different from the medium‐latency potential described above, suggesting that the neuronal elements mediating the medium‐latency potential were different from those that mediate the clinical effects.

The early release of planned movement by acoustic startle can be delayed by transcranial magnetic stimulation over the motor cortex

Non‐technical summary  Reaction times of planned movements can be reduced to less than 100 ms when a startling acoustic stimulus (SAS) is presented immediately prior to, or coincident with, the imperative ‘go’ cue. Based on the short latency of these reaction times, it has been suggested that the early release of planned movements by a SAS is mediated by shorter pathways that pass through the brainstem instead of via the primary motor cortex. Here we show that the application of high intensity transcranial magnetic stimulation over the primary motor cortex, a method that suppresses the excitability of the motor cortex and blocks voluntary drive, caused a significant delay in the onset of SAS‐released movements. These findings provide evidence that the early release of planned movements by a SAS is mediated, in part, by pathways that pass through the primary motor cortex.

The effect of task instruction on the excitability of spinal and supraspinal reflex pathways projecting to the biceps muscle

There is controversy within the literature regarding the influence of task instruction on the size of the long-latency stretch reflex (M2) elicited by a joint displacement. The aim of this study was to investigate if the previously reported task-dependent modulation of the M2 is specific to the M2 or can be explained by an early release of the intended voluntary response. We took advantage of the fact that the M2 is absent when the duration of the applied perturbation is less than a critical time period. This allowed us to examine modulation of muscle activity with and without the contribution of the M2. In addition, we applied transcranial magnetic stimulation (TMS) over the primary motor cortex to examine the modulation of corticomotor excitability with task instruction. Elbow joint extension displacements were used to elicit a stretch reflex in the biceps muscle. Subjects were instructed to “do not intervene” (DNI) with the applied perturbation, or to oppose the perturbation by activating the elbow flexors in response to the perturbation (FLEX). Electromyographic (EMG) activity in the time period corresponding to the M2 was significantly facilitated in the FLEX task instruction both with and without the presence of the M2. Motor evoked potentials (MEPs) elicited by TMS were also facilitated during the FLEX condition in the absence of the M2. EMG and MEP responses were not facilitated until immediately prior to the onset of the M2. Paired-pulse TMS revealed a significant reduction in short-interval intracortical inhibition (SICI) during the M2 response, but the level of SICI was not altered by the task instruction. We conclude that the task-dependent modulation of the biceps M2 results, at least in part, from an early release of the prepared movement and is accompanied by an increase in corticospinal excitability that is not specific to the M2 pathway. Task-dependent modulation of the response cannot be explained by an alteration in the excitability of intracortical inhibitory circuits.

Postural preparation prior to stepping in patients with Parkinson's disease

People with Parkinsons disease (PD) frequently have difficulties with generating anticipatory postural adjustments (APAs) for forward propulsion and lateral weight transfer when initiating gait. This impairment has been attributed to deficits in motor planning and preparation. This study examined the preparation of APAs prior to an imperative cue to initiate forward stepping. A startling acoustic stimulus (SAS) was used to probe the state of preparation of the APA in eight PD (off medication) and seven matched control subjects. Subjects performed visually cued trials involving a pre-cue light instructing them to prepare to step, followed 3.5 s later by a go-cue light to rapidly initiate stepping. In random trials, a SAS (124 dB) was presented at -1,500, -1,000, -500, -250, -100, or 0 ms before the go-cue. Subjects also performed self-initiated steps. Ground reaction forces (GRFs), center of pressure (CoP) changes, and electromyographic (EMG) signals were recorded. The SAS triggered APAs in 94 ± 11% (PD) and 96 ± 8% (control) of trials at latencies 89 ± 4 ms (PD) and 97 ± 3 ms (control) earlier than Control trials. The temporal profile of APA preparation was similar between groups. However, peak EMG, GRF, and mediolateral CoP amplitudes were reduced in PD. SAS-evoked APAs at 0 ms matched Control trial APAs and were enhanced compared with self-initiated stepping. These results demonstrate that people with mild to moderate PD can plan and prepare the appropriate APA sequence prior to the expected cue to initiate gait; however, the prepared APAs are underscaled in magnitude.

Time-frequency analysis of movement-related spectral power in EEG during repetitive movements: A comparison of methods

During dynamic voluntary movements, power in the alpha- and beta-bands resulting from synchronized neuronal activity is modulated in a manner that is time-locked to movement onset. These signals can be readily recorded from the scalp surface using electroencephalography. Abnormalities in the magnitude and timing of these oscillations are present in a wide variety of movement disorders including Parkinsons disease and dystonia. Most studies have examined movement-related oscillations in the context of single discrete movements, yet marked impairments are often seen during the performance of repetitive movements. For this reason, there is considerable need for analysis methods that can resolve the modulation of these oscillations in both the frequency and time domains. Presently, there is little consensus on which is the most appropriate method for this purpose. In this paper, a comparison of commonly used time-frequency methods is presented for the analysis of movement-related power in the alpha- and beta-bands during repetitive movements. The same principles hold, however, for any form of repetitive or rhythmic input-output processes in the brain. In particular, methods based on band-pass filtering, the short-time Fourier transform (STFT), continuous wavelet transform and reduced interference distributions are discussed. The relative merits and limitations in terms of spectral or temporal resolution of each method are shown with the use of simulated and experimental data. It is shown that the STFT provides the best compromise between spectral and temporal resolution and thus is the most appropriate approach for the analysis and interpretation of repetitive movement-related oscillations in health and disease.

Effect of movement frequency on repetitive finger movements in patients with Parkinson's disease

Performance of repetitive hand movements in patients with Parkinsons disease (PD) is characterized by slowness, reduced movement amplitude, and hesitation or arrests in ongoing movement. Currently, the factors and mechanisms contributing to impaired performance of these types of movement remain poorly understood. This study examined the effects of movement frequency and medication on the performance of unconstrained index finger flexion movements in patients with PD and matched control subjects. Movements were synchronized with an auditory tone as the frequency of the tone was increased from 1 to 3 Hz in 0.25 Hz increments. Movement performance was quantified based upon finger kinematics and electromyography (EMG) recorded from the index finger flexors and extensors. The principal finding was that patients with PD showed a dramatic reduction in movement amplitude, an increase in movement frequency, and a loss of phase when the movement frequency reached or exceeded 2 Hz. This deficit was not significantly improved with medications. In contrast, all control subjects could synchronize to 3 Hz. These findings show that movement frequency is a major determinant of hypokinesia during repetitive movements and may contribute to hesitations and movement arrest during clinical testing of bradykinesia in the upper limb of patients with PD.

Role of brainstem–spinal projections in voluntary movement

Previous studies have emphasised the role of brainstem–spinal pathways in presetting reflex sensitivity (for example of stretch or flexion reflexes) or in reflex contributions to movement (for example, vestibulospinal control of neck or trunk position). However, little is known about the possible role of these pathways in volitional movements. Given the extensive projections from cortex onto areas of origin of brainstem–spinal tracts, such a role seems to be a reasonable anatomical possibility. This role is supported by two sets of data involving rapid voluntary movements in healthy subjects.

Co-contraction modifies the stretch reflex elicited in muscles shortened by a joint perturbation

Simultaneous contraction of agonist and antagonist muscles acting about a joint influences joint stiffness and stability. Although several studies have shown that reflexes in the muscle lengthened by a joint perturbation are modulated during co-contraction, little attention has been given to reflex regulation in the antagonist (shortened) muscle. The goal of the present study was to determine whether co-contraction gives rise to altered reflex regulation across the joint by examining reflexes in the muscle shortened by a joint perturbation. Reflexes were recorded from electromyographic activity in elbow flexors and extensors while positional perturbations to the elbow joint were applied. Perturbations were delivered during isolated activation of the flexor or extensor muscles as well as during flexor and extensor co-contraction. Across the group, the shortening reflex in the elbow extensor switched from suppression during isolated extensor muscle activation to facilitation during co-contraction. The shortening reflex in the elbow flexor remained suppressive during co-contraction but was significantly smaller compared to the response obtained during isolated elbow flexor activation. This response in the shortened muscle was graded by the level of activation in the lengthened muscle. The lengthening reflex did not change during co-contraction. These results support the idea that reflexes are regulated across multiple muscles around a joint. We speculate that the facilitatory response in the shortened muscle arises through a fast-conducting oligosynaptic pathway involving Ib interneurons.