Giovanna Pari

Deficits in saccadic eye-movement control in Parkinson's disease

In contrast to their slowed limb movements, individuals with Parkinsons disease (PD) produce rapid automatic eye movements to sensory stimuli and show an impaired ability to generate voluntary eye movements in cognitive tasks. Eighteen PD patients and 18 matched control volunteers were instructed to look either toward (pro-saccade) or away from (anti-saccade) a peripheral stimulus as soon as it appeared (immediate, gap and overlap conditions) or after a variable delay; or, they made sequential saccades to remembered targets after a variable delay. We found that PD patients made more express saccades (correct saccades in the latency range of 90-140 ms) in the immediate pro-saccade task, more direction errors (automatic pro-saccades) in the immediate anti-saccade task, and were less able to inhibit saccades during the delay period in all delay tasks. PD patients also made more directional and end-point errors in the memory-guided sequential task. Their inability to plan eye movements to remembered target locations suggests that PD patients have a deficit in spatial working memory which, along with their deficit in automatic saccade suppression, is consistent with a disorder of the prefrontal-basal ganglia circuit. Impairment of this pathway may release the automatic saccade system from top-down inhibition and produce deficits in volitional saccade control. Parallel findings across various motor, cognitive and oculomotor tasks suggest a common mechanism underlying a general deficit in automatic response suppression.

Executive impairment in Parkinson's disease: Response automaticity and task switching

Patients with Parkinsons disease (PD) show slowed movement initiation and can have deficits in executive function, leading to impairments in controlling involuntary behavior. This results in difficulties performing an antisaccade, which requires one to suppress an automatic eye movement (a prosaccade) to a visual stimulus, and execute a voluntary eye movement in the opposite direction. Antisaccade deficits are similar to those seen in task switching, whereby one is required to change a response after performing a different behavior. Both antisaccade (Hood et al., 2007) and task switching (Cools, Barker, Sahakian, & Robbins, 2001) deficits in PD have been attributed to fronto-basal ganglia (BG) dysfunction. Previously, we demonstrated with functional magnetic resonance imaging that BG circuitry is important to both task switching and voluntary saccade generation, as greater caudate activation was seen when healthy young adults first prepared a prosaccade, but then switched to an antisaccade (Cameron, Coe, et al., 2009). Therefore, we hypothesized that PD patients would have difficulty switching from one saccade response to the other, with particular impairment in switching from a pro to an antisaccade. Here, we not only confirmed this prediction, but also showed that PD patients performed better than controls in switching from an anti to a prosaccade. This suggests that task switching deficits in PD are particularly pronounced when more automatic behavior needs to be overridden with alternative behavior. We suggest that this occurs primarily at the level of establishing the appropriate task set, which is an internalized rule that governs how to respond.

The effect of inertial loading on wrist postural tremor in essential tremor

OBJECTIVES Determine the effect of inertial loading on the strength of motor unit entrainment and the synergistic/competitive interaction between central and mechanical reflex tremor components in subjects with essential tremor (ET). METHODS Twenty-three subjects with ET and 22 controls held their hand in an outstretched position while supporting sub-maximal loads (no-load, 5%, 15% and 25% 1-repetition maximum). Hand postural tremor and wrist extensor neuromuscular activity were recorded. RESULTS Inertial loading resulted in a reduction in postural tremor in all ET subjects. The largest reduction in tremor amplitude occurred between 5% and 15% loads, which was associated with spectral separation of the mechanical reflex and central tremor components in a large number of ET subjects. Despite an increase in overall neuromuscular activity with inertial loading, EMG tremor spectral power did not increase with loading. CONCLUSIONS The effect of inertial loading on postural tremor amplitude appears to be mediated in large part by its effect on the interaction between mechanical reflex and central tremor components. Also, ET is associated with a constant absolute level of motor unit entrainment. SIGNIFICANCE The amplitude of postural tremor is dependent on both central and peripheral factors, with proportionally greater motor unit entrainment occurring at low contraction intensities.

Disruption of pupil size modulation correlates with voluntary motor preparation deficits in Parkinson's disease.

Pupil size is an easy-to-measure, non-invasive method to index various cognitive processes. Although a growing number of studies have incorporated measures of pupil size into clinical investigation, there have only been limited studies in Parkinsons disease (PD). Convergent evidence has suggested PD patients exhibit cognitive impairment at or soon after diagnosis. Here, we used an interleaved pro- and anti-saccade paradigm while monitoring pupil size with saccadic eye movements to examine the relationship between executive function deficits and pupil size in PD patients. Subjects initially fixated a central cue, the color of which instructed them to either look at a peripheral stimulus automatically (pro-saccade) or suppress the automatic response and voluntarily look in the opposite direction of the stimulus (anti-saccade). We hypothesized that deficits of voluntary control should be revealed not only on saccadic but also on pupil responses because of the recently suggested link between the saccade and pupil control circuits. In elderly controls, pupil size was modulated by task preparation, showing larger dilation prior to stimulus appearance in preparation for correct anti-saccades, compared to correct pro-saccades, or erroneous pro-saccades made in the anti-saccade condition. Moreover, the size of pupil dilation correlated negatively with anti-saccade reaction times. However, this profile of pupil size modulation was significantly blunted in PD patients, reflecting dysfunctional circuits for anti-saccade preparation. Our results demonstrate disruptions of modulated pupil responses by voluntary movement preparation in PD patients, highlighting the potential of using low-cost pupil size measurement to examine executive function deficits in early PD.

The effect of contraction intensity on force fluctuations and motor unit entrainment in individuals with essential tremor

OBJECTIVES Quantify the effect of increasing contraction intensity on the amplitude of force fluctuations and neuromuscular and force tremor spectral power. METHODS Twenty-one subjects with essential tremor (ET) and 22 healthy controls applied isometric wrist extension contractions. Various sub-maximal contraction intensities were evaluated (5%-, 10%-, 20%- and 30%-MVC). Force fluctuations and wrist extensor neuromuscular activity were recorded using a load cell and electromyography (EMG). RESULTS Higher contraction intensities were associated with larger amplitude force fluctuations and greater neuromuscular activation. However, spectral power associated with tremor peaks remained relatively constant (EMG) or decreased (force) with increasing contraction intensity. CONCLUSIONS Motor unit entrainment associated with centrally generated oscillatory inputs does not increase with greater levels of muscle activation. SIGNIFICANCE Rather than influencing a constant proportion of active motor units, abnormal oscillatory drive influences a relative constant number of total motor units. When combined with the findings from our previous study on postural tremor, the present results provide preliminary evidence that abnormal stretch reflex activity may contribute to this motor unit entrainment.

The effect of inertial loading on wrist kinetic tremor and rhythmic muscle activity in individuals with essential tremor

OBJECTIVES Determine the effect of concentric and eccentric movement and contraction intensity on the strength of rhythmic muscle activity in individuals with essential tremor (ET). METHODS 21 ET subjects and 22 healthy controls produced wrist flexion-extension movements while supporting sub-maximal loads (no-load, 5%, 15% and 25% 1-repetition maximum). Kinetic tremor and wrist extensor neuromuscular activity were recorded using an angular displacement sensor and electromyography (EMG). RESULTS Rhythmic muscle activity was twice as big during movement compared to previous results involving postural or isometric tasks. ET subjects with greater rhythmic muscle activity had (1) larger overall kinetic tremor amplitude, (2) greater tremor spectral power during eccentric compared to concentric movement and (3) a reduction in overall kinetic tremor amplitude and the percentage of EMG spectral power accounted for by the tremor spectral peak in the presence of inertial loading. CONCLUSIONS Greater than normal kinetic tremor amplitude appears to be limited to ET subjects with higher levels of rhythmic muscle activity. Furthermore, rhythmic muscle activity is much greater during movement compared to during postural or closed-kinetic tasks. SIGNIFICANCE The strength of rhythmic muscle activity in ET is influenced by the type of contraction (i.e., static vs. dynamic) being performed. Clinicians and researchers should include measures of simple kinetic tremor as part of their assessments.

Tremor during movement correlates well with disability in people with essential tremor.

Essential tremor is the most common movement disorder, typically characterized by the presence of both postural and kinetic tremor of the hand. In recent studies, we described the effects of altering force and load conditions on tremor amplitude and power in people with essential tremor. In the same participants, we also measured tremor‐related functional disability. In this article we report on the current study on correlations of measures of tremor severity with those of tremor‐related functional disability. Twenty‐one participants with essential tremor had tremor measured in their more tremorous hand. Power spectral and amplitude measures of tremor were calculated for each of 16 conditions: force tremor at 4 submaximal force levels, postural tremor in unloaded and 3 submaximal load conditions, and kinetic tremor in unloaded and 3 submaximal load conditions for each of concentric and eccentric contractions of the wrist extensors. Participants were rated on the hand items of the Fahn‐Tolosa‐Marin rating scale and timed on the unilateral hand tasks of the Test Évaluant la Performance des Membres supérieurs des Personnes Âgées. The most consistently high and significant correlations were found between kinetic tremor measures and the hand task scores and tremor‐B scores (r = 0.548–0.780, P < .01). Postural tremor measures correlated with disability measures only in loaded conditions, most consistently with the hand task measures (r = 0.640–0.725, P < .01). Thus, measures of kinetic tremor and loaded postural tremor, but not unloaded postural tremor or force tremor, relate well to disability captured with dynamic tasks.

Metronidazole-induced encephalopathy: case report and review of MRI findings.

A 74-year-old man presented with a four week history of behavioural disturbances, upper and lower extremity numbness and impaired balance. He had been treated with metronidazole for six months for osteomyelitis of the right hallux. Examination revealed encephalopathy, and glove-and-stocking sensory loss to pinprick with reduced vibration threshold at the toe. The gait was wide based and ataxic. Nerve conduction studies showed a large fibre sensory-motor axonal polyneuropathy. Magnetic resonance imaging (MRI) revealed a solitary restricted diffusion lesion in the splenium of the corpus callosum (Figure A, B) with subtle prolongation of T2 (Figure C). The radiographic differential diagnosis included hypoglycaemia, viral encephalitis, antiepileptic drug toxicity/withdrawal and metronidazole toxicity1. The combination of the imaging finding with the history of prolonged metronidazole use suggested metronidazole induced encephalopathy. Metronidazole was discontinued based