Multidimensional sequence learning in patients with focal basal ganglia lesions

Parkinson's patients have been found to be impaired in learning movement sequences. In the current study, patients with unilateral basal ganglia lesions due to stroke were tested on a serial reaction time task in which responses were based on the spatial location of each stimulus. The spatial locations either followed a fixed sequence or were selected at random, with learning operationalized as the difference in reaction time between these two conditions. In addition, three response-to-stimulus intervals were used, and these either followed a fixed sequence or were randomized. Compared to control participants, the patients showed normal learning of the spatial and temporal sequences, as well as normal cross-dimensional learning. This was true for performance with either the contralesional or ipsilesional hand. Sequence learning was not correlated with maximum tapping rate, a simple measure of motor impairment. These results raise questions concerning the use of Parkinson's disease as a model for studying basal ganglia dysfunction.     

基底神经节损伤对知觉性启动效应影响的进一步研究

基底神经节的认知和记忆功能是近年认知神经科学研究的热点。该研究采用两项语义性启动效应（自由联想、偏好）和一项知觉性启动效应（字辨认）任务,发现基底神经节损伤、分别伴两侧海马或右侧丘脑损伤的两例患者的语义性启动效应正常,知觉性启动效应障碍。由于先前研究已经证实海马或丘脑结构与启动效应无关,因此该两例患者表现的知觉性启动效应障碍可归因于基底神经节损伤,进一步证实了王常生等人认为基底神经节可能具有或参与知觉性启动效应调节作用,与语义性启动效应无关的观点。     

The differential role of premotor frontal cortex and basal ganglia in motor sequence learning: evidence from focal basal ganglia lesions

There has been a growing interest in the differential role of various neural structures in implicit learning processes. The goal of our study was to clarify how focal lesions restricted to the basal ganglia interfere with different aspects of implicit visuo-motor sequence learning. A version of the Serial Reaction Time Task (SRTT) of Nissen and Bullemer using a 12-trial sequence was administered. A total of 20 subjects with focal basal ganglia lesions caused by ischemic or hemorrhagic infarction and 20 matched control subjects participated in this study. The results indicate that subjects with focal basal ganglia lesions showed unimpaired implicit learning of a 12-item motor sequence. Subjects with basal ganglia lesions, however, had more difficulties improving their general proficiency with the reaction-time task independent of sequence-specific learning. We observed a tendency toward smaller regional volumes in the cerebellum and left pre-supplementary motor area (pre-SMA) of subjects with basal ganglia lesions. Smaller cerebellar and pre-SMA volumes were related to lower implicit learning performance in the lesion group. The size of lesions in the basal ganglia was not related to sequence-specific implicit learning but had a significant influence on subjects' general proficiency for execution of the reaction-time task. We propose that implicit learning is achieved by a distributed network of cortical and subcortical structures. The basal ganglia seem to be responsible for adjusting to the general requirements of a task rather than for learning specific associations between stimuli that might be accomplished by premotor frontal areas and the cerebellum instead.     

Comparison of patients with Parkinson's disease or cerebellar lesions in the production of periodic movements involving event-based or emergent timing

We have hypothesized a distinction between the processes required to control the timing of different classes of periodic movements. In one class, salient events mark successive cycles. For these movements, we hypothesize that the temporal goal is a requisite component of the task representation, what we refer to as event-based timing. In the other class, the successive cycles are produced continuously. For these movements, alternative control strategies can optimize performance, allowing timing to be emergent. In a previous study, patients with cerebellar lesions were found to be selectively impaired on event-based timing tasks; they were unimpaired on a continuously produced task. In the present study, patients with Parkinson's disease were tested on repetitive movement tasks in which timing was either event-based or emergent. Temporal variability on either type of task did not differ between on- and off-medication sessions for the Parkinson's patients nor did patient performance differ from that of controls. These results suggest that the basal ganglia play a minimal role in movement timing and that impairments on event-based timing tasks are specific to cerebellar damage.     

Providing explicit information disrupts implicit motor learning after basal ganglia stroke

Despite their purported neuroanatomic and functional isolation, empirical evidence suggests that sometimes conscious explicit processes can influence implicit motor skill learning. Our goal was to determine if the provision of explicit information affected implicit motor-sequence learning after damage to the basal ganglia. Individuals with stroke affecting the basal ganglia (BG) and healthy controls (HC) practiced a continuous implicit motor-sequencing task; half were provided with explicit information (EI) and half were not (No-EI). The focus of brain damage for both BG groups was in the putamen. All of the EI participants were at least explicitly aware of the repeating sequence. Across three days of practice, explicit information had a differential effect on the groups. Explicit information disrupted acquisition performance in participants with basal ganglia stroke but not healthy controls. By retention (day 4), a dissociation was apparent--explicit information hindered implicit learning in participants with basal ganglia lesions but aided healthy controls. It appears that after basal ganglia stroke explicit information is less helpful in the development of the motor plan than is discovering a motor solution using the implicit system alone. This may be due to the increased demand placed on working memory by explicit information. Thus, basal ganglia integrity may be a crucial factor in determining the efficacy of explicit information for implicit motor-sequence learning.     

Asymmetric control of force and symmetric control of timing in bimanual finger tapping

An experiment was conducted to examine the control of force and timing in bimanual finger tapping. Participants were trained to produce both unimanual (left or right hand) and bimanual finger-tapping sequences with a peak force of 200 g and an intertap interval (ITI) of 400 ms. During practice, visual force feedback was provided pertaining to the hand performing the unimanual tapping sequences and to either the dominant or the nondominant hand in the bimanual tapping sequences. After practice, the participants produced the learned unimanual and bimanual tapping sequences in the absence of feedback. In those trials the force produced by the dominant (right) hand was significantly larger than that produced by the nondominant (left) hand, in the absence of a significant difference between the ITIs produced by both hands. Furthermore, after unilateral feedback had been provided of the force produced by the nondominant hand, the force output of the dominant hand was significantly more variable than that of the nondominant hand. In contrast, after feedback had been provided of the force produced by the dominant hand, the variability of the force outputs of the two hands did not differ significantly. These results were discussed in the light of both neurophysiological and anatomical findings, and were interpreted to imply that the control of timing (in bimanual tasks) may be more tightly coupled in the motor system than the control of force.     

Basal ganglia, dopamine and temporal processing: performance on three timing tasks on and off medication in Parkinson's disease

A pervasive hypothesis in the timing literature is that temporal processing in the milliseconds and seconds range engages the basal ganglia and is modulated by dopamine. This hypothesis was investigated by testing 12 patients with Parkinson's disease (PD), both 'on' and 'off' dopaminergic medication, and 20 healthy controls on three timing tasks. In a seconds range (30-120 s) time production task, patients tested 'on' medication showed a significantly different accuracy profile compared to controls and when tested 'off' medication. However, no group or on vs off medication differences in accuracy were found on a time reproduction task and a warned reaction time task requiring temporal processing within the 250-2000 ms range. Variability was measured using the coefficient of variation, with the performance of the patient group on the time reproduction task violating the scalar property, suggesting atypical temporal processing mechanisms. The data suggest that the integrity of the basal ganglia is necessary for 'typical' time production in the seconds range as well as for time reproduction at shorter intervals. Exploratory factor analysis suggested that the time production task uses neural mechanisms distinct from those used in the other two timing tasks. The dissociation of the effects of dopaminergic medication and nature of task on performance in PD raises interesting questions about the pharmacological mediation and task-specificity of deficits in temporal processing.     

时间认知神经科学研究进展

当前对时间认知的脑机制探讨有三个模型：特异化计时模型、分布网络模型和定域计时模型。在这些模型的框架下,时间认知的神经心理学研究集中探讨了小脑、基底神经节、前额叶在时间信息加工中的作用和大脑两半球在时间认知中的不对称性。小脑作为内部计时系统对时间控制具有重要作用,在周期性动作任务中,小脑对不连续动作计时具有特异性。基底神经节在时间加工任务中与小脑存在明显的作用分离,其具体机制还有待深入研究。前额叶的计时功能可能与注意和工作记忆对时间信息的获得、维持和组织有关。此外,还发现大脑右半球与时问信息的加工关系密切。     

Ipsilesional Arm Aiming Movements After Stroke: Influence of the Degree of Contralesional Impairment

The authors examined the effects of the degree of impairment of the contralesional upper limb and the side of the hemispheric damage on ipsilesional upper limb performance in chronic stroke individuals. Right- and left-side stroke resulting in mild-to-severe impairment and healthy participants took part in simple and choice reaction time tasks involving aiming movements. The stroke individuals performed the aiming movements with the ipsilesional upper limb using a digitizing tablet to ipsi- or contralateral targets presented in a monitor. The global performance of the group with severe right hemispheric damage was worse than that of the other groups, indicating that the side of hemispheric damage and degree of motor impairment can adversely affect aiming movement performance.     

Response Channel Activation and the Temporoparietal Junction

When we learn to make one motor response to one visual stimulus and a different motor response to another, representations of these stimulus–response associations must be maintained to efficiently transduce perception into action. When an irrelevant distractor is presented adjacent to a target stimulus, interference is observed when the two stimuli are associated with conflicting responses, presumably due to response channel activation by the incompatible information. We have explored the neural bases of these interference effects. In a previous study, patients with hemispatial neglect showed normal interference from contralesional flankers. In another study, patients with lesions of the lateral prefrontal cortex were found not to show interference from distractors presented in the contralesional hemifield. The current study provided a more anatomically detailed investigation of the effects of posterior association cortex lesions on flanker interference. Patients with chronic, unilateral lesions involving the temporoparietal junction (TPJ), two of whom had hemispatial neglect, were compared with patients with lesions of the posterior association cortex not involving the TPJ. All patients performed a color discrimination task at fixation while a congruent or incongruent colored flanker was briefly presented (16.7 ms) in the adjacent contralesional or ipsilesional hemifield. Patients with TPJ lesions showed no interference effects from the contralesional flankers. These results suggest that the TPJ, in combination with the dorsolateral prefrontal cortex, is involved in transducing perception into action.     

Lesions of the basal ganglia, thalamus, and deep white matter: Differential effects on language functions

Forty-five patients with unilateral demarcated vascular lesions in the basal ganglia, the thalamus and the deep white matter were investigated with an "aphasia battery." Patients with basal ganglia lesions performed worse than both other groups in tests of articulation, syntax, and lexical functions. The deficit of patients with basal ganglia lesions on all expressive language modalities was lateralized to the left hemisphere. Patients with left thalamic lesions showed impairments of speech fluency and in the Token Test. Patients with white matter lesions alone showed no effect of laterality in tests of language functions. The results are discussed on the basis of a recent theory of the participation of the deep nuclei in language processing.     

Circle drawing does not exhibit auditory-motor synchronization

Differences in timing control processes between tapping and circle drawing have been extensively documented during continuation timing. Differences between event and emergent control processes have also been documented for synchronization timing using emergent tasks that have minimal event-related information. However, it is not known whether the original circle-drawing task also behaves differently than tapping during synchronization. In this experiment, 10 participants performed a table-tapping and a continuous circle-drawing task to an auditory metronome. Synchronization performance was assessed via the value and variability of asynchronies. Synchronization was substantially more difficult in circle drawing than in tapping. Participants drawing timed circles exhibited drift in synchronization error and did not maintain a consistent phase relationship with the metronome. An analysis of temporal anchoring revealed that timing to the timing target was not more accurate than timing to other locations on the circle trajectory. The authors conclude that participants were not able to synchronize movement with metronome tones in the circle-drawing task despite other findings that cyclical tasks do exhibit auditory motor synchronization, because the circle-drawing task is unique and absent of event and cycle position information.     

Adolescents with Down syndrome exhibit greater force and delay in onset of tapping movements

This study examined the control of force and timing during finger tapping sequences of adolescents with Down syndrome. Participants performed both unimanual and bimanual tapping tasks with one self-paced test trial after three audible-synchronized practice trials with concurrent feedback of force output. All tasks consisted of a target force of 2N and a target intertap interval of 500 msec. Adolescents with Down syndrome exhibited a greater magnitude of positive constant error and variable error for peak force than typical adolescents. They also exhibited a greater magnitude of negative constant error and variable error for intertap interval than typical adolescents. Although normally developing comparison adolescents exhibited a linear relationship between peak force and press duration or time-to-peak force, the relationship was not familiar to adolescents with Down's syndrome. This may suggest differences in the manner of motor unit recruitment between the group with Down's syndrome and comparison adolescents.     

Time but not force is transferred between ipsilateral upper and lower limbs

The authors compared the force and time endpoint accuracy of goal-directed ipsilateral upper and lower limb isometric contractions and determined the components of motor performance that can be transferred from 1 limb to the other after practice. Ten young adults (27.4 +/- 4.4 years) performed 100 trials that involved their matching peak force to a force-time target with ankle dorsiflexor and elbow flexor muscles. The peak force error and variability was greater for ankle dorsiflexor contractions than for elbow flexor contractions, whereas the timing error and variability did not significantly vary with limb. There was transfer of timing, but not force, of motor output between upper and lower limbs. The timing error of the elbow flexor contractions decreased by 23% when those contractions were preceded by ankle dorsiflexor contractions, and the timing error of the ankle dorsiflexors decreased by 24% when those contractions were preceded by elbow flexor contractions. These finding therefore suggest that timing of an aiming isometric contraction may be organized at a common part of the brain for the upper and lower limbs.     

Deficits of motor intention following parietal lesions

Patients with lesions to the right parietal lobe were tested on their ability to reach to targets, or to respond verbally to targets. The targets occurred at the same two spatial locations--to the left and right of the patient--with the task being cued by the color of the target. Patients were able to perform both tasks separately rapidly and without error. However, when the two tasks were interleaved, they had difficulty making a response in the left (contralesional) field when this was different to a response that they had just made. These results suggest that lesions to the parietal cortex may cause a deficit in the coding for motor intention, as well as attention in the contralesional field.     

Force and timing variability in rhythmic unimanual tapping

In 3 experiments the interdependencies between timing and force production in unimanual paced and self-paced rhythmic tapping tasks were examined as participants (N = 6 in each experiment) tapped (a) to 1 of 3 target periods (333 ms, 500 ms, and 1,000 ms), while they simultaneously produced a constant peak force (PF) over a 50-s trial; (b) to produce 1 of 3 target forces (5, 10, and 15 N) at their preferred frequency, while keeping their rhythm as invariant as possible; and (c) to all combinations of target force and period. The results showed that (a) magnitudes of force and period were largely independent; (b) variability in timing increased proportionally with tapping period, and the variability in force increased with peak force; (c) force variability decreased at faster tapping rates; and (d) timing variability decreased with increasing force levels. (e) Analysis of tap-to-tap variability revealed adjustments over sequences of taps and an acceleration in the tapping rate in unpaced conditions. The interdependencies of force and time are discussed with respect to the challenges they provide for an oscillator-based account.     

Force and Timing Variability in Rhythmic Unimanual Tapping

In 3 experiments the interdependencies between timing and force production in unimanual paced and self-paced rhythmic tapping tasks were examined as participants (N = 6 in each experiment) tapped (a) to 1 of 3 target periods (333 ms, 500 ms, and 1,000 ms), while they simultaneously produced a constant peak force (PF) over a 50-s trial; (b) to produce 1 of 3 target forces (5, 10, and 15 N) at their preferred frequency, while keeping their rhythm as invariant as possible; and (c) to all combinations of target force and period. The results showed that (a) magnitudes of force and period were largely independent; (b) variability in timing increased proportionally with tapping period, and the variability in force increased with peak force; (c) force variability decreased at faster tapping rates; and (d) timing variability decreased with increasing force levels, (e) Analysis of tap-to-tap variability revealed adjustments over sequences of taps and an acceleration in the tapping rate in unpaced conditions. The interdependencies of force and time are discussed with respect to the challenges they provide for an oscillator-based account.     

Emotional processing following cortical and subcortical brain damage: contribution of the fronto-striatal circuitry

The present study examined the differential contribution of cortical and subcortical brain structures in emotional processing by comparing patients with focal cortical lesions (n = 32) to those with primarily subcortical dysregulation of the basal ganglia (Parkinson's disease n = 14). A standardized measure of emotional perception (Tübingen Affect Battery) was used. Only patients in the more advanced stages of Parkinson's disease and patients with focal damage to the (right) frontal lobe differed significantly from controls in both facial expression and affective prosody recognition. The findings imply involvement of the fronto-striatal circuitry in emotional processing.     

Coordination deficits on the ipsilesional side after unilateral stroke: the effect of practice on nonisodirectional ipsilateral coordination

Previous studies have identified motor deficits on the ipsilesional side of patients recovering from a cerebro-vascular accident (CVA), including deficits in interlimb coordination. In the present study, unilateral stroke patients and a control group of healthy age-matched controls performed nonisodirectional coordination of the ipsilateral limbs across two days of practice with feedback. Findings revealed that control subjects were already quite successful at initiation of practice but further improved the coordination pattern across both days. The group of CVA patients also showed some improvement but problems with coordination of the ipsilateral limb segments persisted across practice. Variability in both timing and amplitude of both limb segments did improve with practice in both groups but these measures remained significantly higher in the CVA patients. Even though isodirectional and nonisodirectional coordination of the ipsilateral limb segments are normally considered to be part of the intrinsic motor repertoire, the present study suggests that nonisodirectional ipsilesional limb coordination poses considerable difficulties for CVA patients that are not easily overcome with feedback-assisted practice.     

Descending control to the nonparetic limb degrades the cyclic activity of paretic leg muscles

During anti-phased locomotor tasks such as cycling or walking, hemiparetic phasing of muscle activity is characterized by inappropriate early onset of activity for some paretic muscles and prolonged activity in others. Pedaling with the paretic limb alone reduces inappropriate prolonged activity, suggesting a combined influence of contralesional voluntary commands and movement-related sensory feedback. Five different non-target leg movement state conditions were performed by 15 subjects post-stroke and 15 nonimpaired controls while they pedaled with the target leg and EMG was recorded bilaterally. Voluntary engagement of the non-lesioned motor system increased prolonged paretic vastus medialis (VM) activity and increased phase-advanced rectus femoris (RF) activity. We suggest bilateral descending commands are primarily responsible for the inappropriate activity in the paretic VM during anti-phase pedaling, and contribute to the dysfunctional motor output in the paretic RF. Findings from controls suggest that even an undamaged motor system can contribute to this phenomenon.