Apomorphine delays simple reaction time in Parkinsonian patients

BACKGROUND: Parkinsonian patients have difficulty in the preparation and execution of movements, which translate into delayed performance of simple reaction time (SRT) paradigms. OBJECTIVE: To examine short-term effects of an acute subcutaneous injection of the dopamine agonist apomorphine on the results of a SRT task. METHODS: We studied a SRT paradigm in 26 non-fluctuating idiopathic Parkinsonian patients, before and 30, 60, 90 min after administration of apomorphine. RESULTS: The reaction time (RT) was significantly delayed after apomorphine injection. We found no significant change in movement time (MT). CONCLUSION: Delay of RT and the lack of response of MT to apomorphine administration may result from the sedative effects of apomorphine, overstimulation of postsynaptic dopaminergic receptors with subsequent inhibition of prefrontal cholinergic neurotransmission, and at least partial binding of apomorphine to presynaptic dopaminergic autoreceptors, which cause inhibition of locomotor activity. We suggest that future studies testing the capacity for reaction in Parkinsonian patients should consider the exact timing of the delivery of dopamine substituting drugs prior to the test.     

Cognitive components of reaction time in Parkinson''s disease.

Studies of reaction time in Parkinson's disease (PD) have suggested a selective deficit in simple reaction time (SRT), compared with choice reaction time (CRT). This finding has been interpreted as a deficit in motor preprogramming but could involve other factors, such as attentional focussing and stimulus predictability. Moreover, not all studies show the same selective deficit, possibly because of differences in patient selection and treatment effects. The neurochemical basis of RT deficits in PD remains unclear. Accordingly, the contribution of cognitive factors to impaired RT was assessed in a large group of PD patients, including early untreated cases, and performance was examined in relation to clinical variables and the effect of treatment in longitudinal study. Motor output was constant in both SRT and CRT tasks. In the SRT task, all stimuli required a response; in the CRT task, subjects were required to respond to only one of the two possible stimuli. Attentional focussing on SRT was examined by variation of the interval between cue and stimulus; effects of stimulus uncertainty were evaluated from a comparison of SRT and CRT; temporal predictability of the stimulus was examined from a comparison of conditions in which the interval between warning signal and imperative stimulus was constant or variable. The PD patients showed similar deficits in SRT and CRT, but normal effects of cue-stimulus interval and temporal predictability. Reaction time correlated with measures of global cognitive capacity and frontal-lobe function, as well as motor disability. Treatment had no effect on SRT or CRT, despite clinical benefit. These findings indicate that RT deficits in PD are not due to impaired attentional focussing or stimulus predictability but are compatible with a deficit in higher-order processes concerned with the orientation of both cognitive and motor responses to a stimulus. These processes are not substantially dopamine-dependent but may be served by non-dopaminergic neurotransmission.     

Differential response in choice reaction time following apomorphine based on prior dopaminergic treatment

Choice reaction time (CRT) paradigms demonstrated deficits in the preparation and execution of movements in patients with Parkinson's Disease (PD). Predominantly these trials did not consider an influence of acute and long-term dopaminergic substitution. Objective was to determine the acute effect of apomorphine on the response to a repeatedly performed CRT task. We repeatedly executed the CRT paradigm before and after subcutaneous apomorphine injection in previously treated, untreated and long-term dopamine substituted PD patients, who took placebo. No significant change of CRT and movement time (MT) appeared in PD patients with chronic dopaminergic drug intake after apomorphine injection. CRT and MT both significantly worsened in untreated PD patients. Placebo application induced no significant alteration. Binding of apomorphine to presynaptic autoreceptors with subsequent sedation or inhibition of locomotor activity hypothetically explain our results in before untreated PD patients. Previous long-term dopaminergic substitution may cause a certain tolerance to this phenomenon.     

Effects of unilateral pallidotomy on voluntary movement, and simple and choice reaction times in Parkinson's disease.

We studied the effects of unilateral pallidotomy on motor execution and reaction times in patients with moderately advanced Parkinson's disease (PD). Twelve consecutive patients (7 men, 5 women; all right-handed) underwent left-side microelectrode-guided pallidotomy. In addition to clinical rating, reaction time (RT) tests and repetitive movements of the contralesional hand/arm were carried out at baseline and 2 to 3 months after surgery while patients were on optimal medical regimens (on period). The initiation time in both simple reaction time (SRT) and choice reaction time (CRT) improved significantly after pallidotomy (P < 0.05), whereas no effect was observed on the choice processing time, which was calculated by subtracting the mean value of the onset of SRT from that of CRT. Pallidotomy resulted in significant improvement of repetitive movements such as hand pronation/supination and finger-tapping (P < 0.002, P < 0.005, respectively). Improvements in RT tests and repetitive movements suggest that pallidotomy may enhance attention and motor function. These effects are probably mediated through the pallido-thalamic-cortical neural circuitry.     

Fine and gross motor skills differ between healthy-weight and obese children

Within the obesity literature, focus is put on the link between weight status and gross motor skills. However, research on fine motor skills in the obese (OB) childhood population is limited. Therefore, the present study focused on possible weight related differences in gross as well as fine motor skill tasks. Thirty-four OB children (12 ♀ and 22 ♂, aged 7–13 years) were recruited prior to participating in a multidisciplinary treatment program at the Zeepreventorium (De Haan, Belgium). Additionally, a control group of 34 age and gender-matched healthy-weight (HW) children was included in the study. Anthropometric measures were recorded and gross and fine motor skills were assessed using the Bruininks–Oseretsky Test of Motor Proficiency, second edition (BOT-2). Results were analyzed by independent samples t-tests, multivariate analysis of variance, and a chi-squared test. Being OB was detrimental for all subtests evaluating gross motor skill performance (i.e., upper-limb coordination, bilateral coordination, balance, running speed and agility, and strength). Furthermore, OB children performed worse in fine motor precision and a manual dexterity task, when compared to their HW peers. No group differences existed for the fine motor integration task. Our study provides evidence that lower motor competence in OB children is not limited to gross motor skills alone; OB children are also affected by fine motor skill problems. Further investigation is warranted to provide possible explanations for these differences. It is tentatively suggested that OB children experience difficulties with the integration and processing of sensory information. Future research is needed to explore whether this assumption is correct and what the underlying mechanism(s) could be.     

Effects of subthalamic nucleus stimulation on characteristics of EMG activity underlying reaction time in Parkinson's disease.

We examined the effects of high-frequency deep brain stimulation of the subthalamic nucleus (STN-DBS) on characteristics of electromyographic (EMG) activity of the agonist muscle in 8 patients with Parkinson's disease (PD). Patients were examined during STN-DBS (ON), and 30 minutes after switching off both stimulators (OFF). They were asked to make a ballistic movement in paradigms of simple reaction time (SRT) and choice reaction time (CRT) tasks. Onset of movement (MOVonset) was measured as the latency of the initial displacement from baseline of the signal from an accelerometer attached to the dorsum of the hand. In the associated EMG activity, recorded from wrist extensor muscles, we measured onset latency (EMGonset), size of the first EMG burst (EMGsize), and number of EMG bursts (EMGbursts) counted between EMGonset and task execution. MOVonset and EMGonset were significantly shorter in ON than in OFF conditions in CRT. EMGsize was larger, EMGbursts were reduced, and peak of the acceleration profile was larger in ON compared with OFF conditions in both SRT and CRT. Our results indicate that STN-DBS induces a significant improvement in motor performance of reaction time tasks in PD patients. Such improvement is associated with a change in features of the EMG activity suggesting an increase in the excitability of the motor pathways engaged in ballistic movements.     

Impairment of willed actions and use of advance information for movement preparation in schizophrenia

OBJECTIVES: To assess willed actions in patients with schizophrenia using reaction time (RT) tasks that differ in the degree to which they involve volitionally controlled versus stimulus driven responses. METHODS: Ten patients diagnosed with schizophrenia and 13 normal controls of comparable age were tested. Subjects performed a visual simple RT (SRT), an uncued four choice reaction time (CRT), and a fully cued four choice RT task. A stimulus 1(S1)-stimulus 2(S2) paradigm was used. The warning signal/precue (S1) preceded the imperative stimulus (S2) by either 0 (no warning signal or precue) 200, 800, 1600, or 3200 ms. RESULTS: The patients with schizophrenia had significantly slower RTs and movement times than normal subjects across all RT tasks. The unwarned SRT trials were significantly faster than the uncued CRT trials for both groups. For both groups, fully cued CRTs were significantly faster than the uncued CRTs. However, the S1-S2 interval had a differential effect on CRTs in the two groups. For the normal subjects fully cued CRTs and SRTs were equivalent when S1-S2 intervals were 800 ms or longer. A similar pattern of effects was not seen in the patients with schizophrenia, for whom the fully cued CRT were unexpectedly equivalent to SRT for the 200 ms interval and expectedly for the 1600 ms S1-S2 interval, but not the 3200 or 800 ms intervals. CONCLUSIONS: Patients with schizophrenia were able to use advance information inherent in SRT or provided by the precue in fully cued CRT to speed up RT relative to uncued CRT. However, in the latter task, in which the volitional demands of preprogramming are higher since a different response has to be prepared on each trial, patients showed some unusual and inconsistent interval effects suggesting instability of attentional set. It is possible that future studies using RT tasks with higher volitional demands in patients with predominance of negative signs may disclose greater deficits in willed action in schizophrenia.     

Training reaction and movement times of moderately and severely mentally retarded persons in aiming movements

The effect of information feedback of movement components on the reaction time (RT) and movement time (MT) of mentally retarded adults performing a discrete movement aiming task was investigated. We anticipated that specific training and informational feedback on the RT portion of the RT-MT task would more effectively reduce RT, despite aiming requirements of the movement. Results suggested that specific training and feedback on RT decreased both RT and MT components of the task, whereas specific training on MT reduced only MT. The data were discussed with respect to the differential effects of training on subject populations at varying levels of intellectual capacity.     

Hand and gender differences in the organization of aiming in 5-year-old children.

The aim of the present study was to analyze the organization of aiming movements in right-handed children aged 5 years, depending on gender and hand used to perform the task. We first tested the hypothesis that aiming movements are predominantly organized in a feed-forward manner before the age of six. Using a direction pre-cueing protocol, we analyzed the effect of gender and hand used to perform the task on reaction time (RT), movement time (MT), spatial accuracy (SA) and acceleration profiles (APs) in children aged 5 years. Differences in RT between the uncued and pre-cued conditions suggest that the direction is actually specified prior to the execution of the movement at the age of five. However, the results also show significant hand and gender effects on MTs, spatial error and APs. Specifically, in girls, MT and kinematics profiles vary as a function of hand and target localization, whereas this is not the case in boys. In addition, SA is lower when aiming with the non-dominant hand in boys, but not in girls. These results suggest that multiple movement strategies are already available to the child at the age of five. Girls appear to be able to change movement strategy as a function of the constraints of the task, resulting in a stability of spatial accuracy (SA). On the contrary, the functional advantage of the right hand on MT and SA generally reported in right-handed males is not present in the boys at the age of five.     

Simple and choice reaction time in patients with human immunodeficiency virus infection

The performance of 56 homosexual men infected with human immunodeficiency virus (HIV) was compared to that of 23 HIV antibody-seronegative controls on simple (SRT) and choice (CRT) reaction time tasks. Patients were classified into 3 groups according to Centers for Disease Control clinical criteria. There were 18 patients who had acquired immunodeficiency syndrome (AIDS), 18 who had AIDS-related complex (ARC), and 20 who were HIV antibody-seropositive but otherwise asymptomatic (HIV-Ab+). The SRT task consisted of 5 trials, each containing 10 target stimuli. The CRT task consisted of 10 trials, each containing 5 target stimuli randomly interspersed with 5 nontarget stimuli. The mean response latency of each of the patient groups on the SRT task was not significantly different from that of controls. However, the performance of patients with AIDS or ARC on the CRT task was significantly lower than that of controls, whereas that of HIV-Ab+ patients was not. Analysis of the quality of RT task performance also indicated that the impairment of processing efficiency at higher levels of task difficulty reflected a disruption of processing prior to the response selection stage.     

SRT lengthening: role of an alertness deficit in frontal damaged patients

Numerous studies have documented the lengthening of reaction time (RT) following brain damage. However, the origin of response retardation and its anatomical basis still remain unknown. This study assessed simple RT (SRT) and choice RT (CRT) in patients with frontal or posterior damage. It showed (i) that RTs were longer in frontal damaged patients; (ii) with a constant response retardation across SRT and CRT tests; (iii) that minimum and percentile 25th SRTs of the frontal group were within normal ranges, indicating that they were able to produce fast responses; (iv) that percentiles 50 and 75th SRTs of the frontal group were longer, indicating that they produced a lower proportion of fast responses; (v) an interpretation supported by the decrement of the peak of SRT distribution. Such a pattern is highly suggestive of a disorder of an attentional process required to trigger the same response as fast as possible throughout the test. According to Posner’s model of attention, this function is devoted to the alerting network and the present study supports the key role of the frontal lobes for alertness.     

Surround inhibition is modulated by task difficulty

ObjectiveThe aim of this study was to further characterize surround inhibition (SI) in the primary motor cortex (M1) by comparing its magnitude and time course during a simple reaction time task (SRT) and a choice reaction time task (CRT).MethodsIn both the SRT and the CRT, subjects performed the same right index finger flexion in response to an acoustic signal. For CRT, the alternative choice was a similar movement using the left index finger, as distinguished by a different tone. In both tasks, single pulse transcranial magnetic stimulation (TMS) was applied at rest, 75 ms (T1) and 25 ms before EMG onset (T2), and during the first peak of EMG (T3) in the right first dorsal interosseous muscle (FDI). Motor evoked potentials (MEPs) were recorded from both FDIs, which act as synergists in the task, and the right surrounding, relaxed abductor pollicis brevis muscle (APB).ResultsFor right hand movement, SI started earlier and was more pronounced for CRT compared to SRT. For left hand movement in the CRT, SI was similar to that of right hand movement.ConclusionsWe conclude that SI occurs earlier and stronger with increasing task difficulty.SignificanceThe timing as well as the bilateral effect of the inhibition suggests that motor areas involved in motor planning, proximate to the motor cortex, contribute to the genesis of surround inhibition.     

Corpus callosum size, reaction time speed and variability in mild cognitive disorders and in a normative sample

Intra-individual variability in reaction time increases with age and with neurological disorders, but the neural correlates of this increased variability remain uncertain. We hypothesized that both faster mean reaction time (RT) and less intra-individual RT variability would be associated with larger corpus callosum (CC) size in older adults, and that these associations would be stronger in adults with mild cognitive disorders. A normative sample (n=432) and a sample with mild cognitive disorders (n=57) were compared on CC area, RT mean and RT variability adjusting for age, sex, education, APOE genotype, smoking, alcohol consumption, grip strength, visual acuity, handedness and lung function. Samples did not differ in CC area or intra-cranial volume. In the normative sample, simple RT (SRT) and choice RT (CRT) were negatively associated with CC area but there were minimal associations between CC area and intra-individual RT variability. In the mild cognitive disorders sample, SRT, CRT and intra-individual variability on the SRT task were associated with CC area. Increased RT variability explained up to 12.7 percent of the variance in CC area in the sample with mild cognitive disorders, but less than 1 percent of the variance in CC area in the normative sample. There were no associations with APOE genotype. We conclude that intra-individual variability is associated with CC area in mild cognitive disorders, but not in normal aging. We propose that biological limits on reserve capacity must occur in mild cognitive disorders that result in stronger brain-behavior relationships being observed.     

The effect of withdrawal of dopaminergic medication on simple and choice reaction time and the use of advance information in Parkinson''s disease.

Eight patients with Parkinson's disease performed simple reaction time (SRT), uncued, partially and fully cued four choice (CRT) tasks. They were tested on two occasions; on their normal dose of dopaminergic medication and following withdrawal of such medication for an average of 14.4 hours. Disability as rated on the Webster scale was greater in the drug reduced state. Although RTs were generally slower when tested in the drug reduced state than when on medication, few differences emerged. Withdrawal of dopaminergic medication had no effect on unwarned SRT and unwarned and uncued CRT performance. Both on and off medication, the patients benefited from a warning signal presented before the imperative stimulus. In both medication states, the speeding up of RT was greatest with a warning signal presented 200 ms before S2. When the imperative stimulus was unwarned, the temporal predictability of its occurrence speeded RT more when on medication than when off. Advance movement parameter information was used by patients to pre-programme responses both on and off medication. In both medication states, the fully cued CRT was the same as SRT only with the 3200 ms S1-S2 interval. Medication state had no effect on movement time or the number of errors. It is suggested that slowness in motor readiness and motor programming may not be specific to striatal dopamine deficiency but rather a nonspecific concomitant of brain damage.     

Acute and separate modulation of motor and cognitive performance in parkinsonian rats by bilateral stimulation of the subthalamic nucleus

The subthalamic nucleus (STN) is involved in motor and cognitive performance through its key role in the basal ganglia-thalamocortical circuits, but how these different modalities (motor and cognition) are controlled (similar vs. dissimilar) has not yet been elucidated. In the present study, the effects of bilateral STN deep brain stimulation (DBS) on motor and cognitive performance were investigated in a rat model of Parkinson disease (PD). After being trained in a choice reaction time (CRT) task, rats received bilateral injections of 6-hydroxydopamine (6-OHDA) into the striatum. One group of 6-OHDA animals was implanted bilaterally with stimulation electrodes at the level of the STN. Stimulations were performed at 130 Hz (frequency), 60 μs (pulse width), and varying amplitudes of 1, 3, 30, and 150 μA during the CRT task. Finally, rats were sacrificed and the brains processed for staining to determine the dopaminergic lesion (TH immunohistochemistry) and localization of the electrode tip (HE histochemistry). Bilateral 6-OHDA infusion significantly decreased (70%) the number of dopaminergic cells in the substantia nigra pars compacta (SNc) and increased motor time (MT), proportion of premature responding (PR), and reaction time (RT). Bilateral STN stimulation with an amplitude of 3 μA normalized 6-OHDA-induced deficits in PR and RT. Simulation with an amplitude of 30 μA reversed the lesion-induced deficits in MT and RT. Our data show for the first time that bilateral STN stimulation differentially affected the 6-OHDA-induced motor and cognitive deficits. This means that basal ganglia-thalamocortical motor and associative circuits responsible for specific motor and cognitive performance, which are processed through the STN, have unique physiological properties that can acutely and separately be modulated by specific electrical stimuli.     

A comparative study of simple and choice reaction time in Parkinson's, Huntington's and cerebellar disease.

The aim of the study was to compare the quantitative and qualitative similarities and differences in the performance of patients with Parkinson's disease, Huntington's disease and cerebellar disease on a number of reaction time tasks. Simple reaction time (SRT), uncued and fully cued four choice (CRT) tasks were performed by eight patients with Parkinson's disease after withdrawal of dopaminergic medication for an average of 14.4 hours; by seven non-demented patients with Huntington's disease and by eight patients with cerebellar disease. An S1 (warning signal/precue)-S2 (imperative stimulus) paradigm was used in all tasks, with the S1-S2 interval randomly varying between 0, 200, 800, 1600 and 3200 ms across trials. The patients with Huntington's disease had a significantly longer SRT than those with Parkinson's disease. None of the other group differences in uncued and unwarned SRT and CRT was significant. For the patients with Parkinson's disease and those with cerebellar disease, unwarned SRT was faster than uncued and unwarned CRT. For the patients with Huntington's disease, this CRT/SRT difference was not significant. A warning signal before the imperative stimulus resulted in a reduction of reaction time in all three groups. Advance information provided by S1 about the response that would be required by S2 was used by patients in all three groups, evident from reaction times in the fully cued CRT task being faster than those in the uncued CRT condition. Patients with cerebellar disease had slower movement times in the SRT and CRT conditions compared with the patients with Parkinson's disease and Huntington's disease, whose times did not differ. In one SRT condition, when the absence of a warning signal was predictable, patients with cerebellar disease, and to a lesser extent those with Huntington's disease, were able to maintain a general motor readiness before the imperative stimulus. This was not the case for the patients with Parkinson's disease who seemed more dependent on the presence of a warning signal to reduce their reaction time. With a few exceptions, the pattern of results of the three groups were qualitatively similar. It may be concluded that similar reaction time deficits are found in Parkinson's disease, in patients with other disorders of the basal ganglia (Huntington's disease), as well as those with a disease sparing the basal ganglia (cerebellar disease). The non-specific slowness observed at the behavioural level may, however, have diverse central mechanisms.     

Effects of practice and unpredictable distractors on planning and executing aiming after stroke

The primary purpose of this study was to examine practice effects on the planning and execution of an aiming movement after right versus left stroke. A secondary purpose was to investigate the effects of a distractor that appeared randomly on motor performance after stroke. Right-hand dominant individuals, 15 with right stroke (right-sided brain damage), 16 with left stroke, and 30 without stroke, performed aiming movements to targets. Those with stroke used the ipsilesional upper extremity (UE). Right and left comparison groups used the right and left UE, respectively. Reaction time (RT) and movement time (MT) were collected to represent movement planning and execution, respectively. Individuals with right stroke improved RT with practice. Individuals with left stroke did not improve RT with practice and made more errors than their comparison group. Those with left stroke achieved faster MT with practice, but MT remained slower than their comparison group. There were no effects of the distractor on RT or MT. Adults with left stroke have persistent deficits in movement planning and execution. Further studies are needed to determine how the performance of older adults, with or without stroke, is affected by an unpredictable visual distractor.     

Implicit Learning in Parkinson's Disease: Evidence from a Verbal Version of the Serial Reaction Time Task

Evidence suggests that patients suffering from Parkinson's Disease (PD) demonstrate less sequence learning in the serial reaction time (SRT) task devised by Nissen and Bullemer (1987). One of the problems with this task is that it is motor intensive and, given the motor difficulties which characterize Parkinson's disease (e.g., tremor, impaired facility of movement, rigidity, and loss of postural reflexes), allows the possibility that patients with PD are capable of sequence learning but are simply unable to demonstrate this through a decrease in reaction time over trials. The present study examined the performance of patients with PD and healthy controls, matched for verbal fluency, on a verbal version of the SRT task where the standard button-pressing response was replaced by a spoken response. Thirteen nondementing patients with PD and 11 healthy controls were administered the SRT task. The PD group demonstrated less sequence learning than the controls and this was independent of age and severity of illness. The results add support to those studies which have found impaired sequence learning using the standard form of the SRT task.     

Anticipatory postural adjustments under simple and choice reaction time conditions

Two different schemes of the central organization of anticipatory postural adjustments (APAs) have been proposed: one of them assumes that postural and focal components of an action are results of a single control process (single-process hypothesis) while the other one suggests that these two components result from two relatively independent control processes (dual-process hypothesis). To distinguish between the two hypotheses, we investigated changes in the relative timing of the postural and focal components under self-paced, simple reaction time (SRT) and choice reaction conditions (CRT). Standing subjects performed one of four small arm movements resulting in a standard postural perturbation (dropping a load). APAs were quantified as changes in the background muscle activity as well as shifts of the center of pressure. APAs occurred at a larger delay prior to the focal movement under the self-paced condition than under the SRT condition. Under the CRT condition, actual RTs were longer than under SRT, but APAs were more similar to those under self-paced conditions. A negative correlation between the reaction time and APA onset was found. The findings demonstrate that the focal and APA components of an action can be decoupled, thus supporting the dual-process hypothesis. Changes in APAs with action suggest a possibility of modifications of a function that transforms two parallel control signals into a single command to the focal and postural muscles, based on postural requirements and behavioral constraints.     

Motor and non-motor sequence learning in children and adolescents with cerebellar damage.

Cerebellar involvement in motor and non-motor sequence learning was examined with serial reaction time tasks (SRT). Our sample consisted of 8 children and adolescents who had undergone surgical removal of a benign posterior fossa tumor (PFT) during childhood. None of them had undergone chemotherapy or cranial radiation therapy (CRT). Ages ranged from 1-11 years at surgery and 9-17 years at testing. The children were tested not earlier than 2.5 years after surgery (M = 5.9 years), enabling brain plasticity and recovery of functions. Their performance was compared with a matched control sample. The PFT group was not impaired in the implicit learning of sequences, as reflected in their performance in blocks with a repeated sequence, both before and after a random block. However, in the perceptual task, their performance deteriorated more than that of the control group when a random block was introduced, suggesting that it was more difficult for the patients to respond flexibly or change their response set when encountering changing task demands. These results are in line with another study by our group on task switching with the same patients.