Ulrike Halsband

Motor learning in man: A review of functional and clinical studies

This chapter reviews results of clinical and functional imaging studies which investigated the time-course of cortical and subcortical activation during the acquisition of motor a skill. During the early phases of learning by trial and error, activation in prefrontal areas, especially in the dorsolateral prefrontal cortex, is has been reported. The role of these areas is presumably related to explicit working memory and the establishment of a novel association between visual cues and motor commands. Furthermore, motor associated areas of the right hemisphere and distributed cerebellar areas reveal strong activation during the early motor learning. Activation in superior-posterior parietal cortex presumably arises from visuospatial processes, while sensory feedback is coded in the anterior-inferior parietal cortex and the neocerebellar structures. With practice, motor associated areas of the left-hemisphere reveal increased activity. This shift to the left hemisphere has been observed regardless of the hand used during training, indicating a left-hemispheric dominance in the storage of visuomotor skills. Concerning frontal areas, learned actions of sequential character are represented in the caudal part of the supplementary motor area (SMA proper), whereas the lateral premotor cortex appears to be responsible for the coding of the association between visuo-spatial information and motor commands. Functional imaging studies which investigated the activation patterns of motor learning under implicit conditions identified for the first, a motor circuit which includes lateral premotor cortex and SMA proper of the left hemisphere and primary motor cortex, for the second, a cognitive loop which consists of basal ganglia structures of the right hemisphere. Finally, activity patterns of intermanual transfer are discussed. After right-handed training, activity in motor associated areas maintains during performance of the mirror version, but is increased during the performance of the original-oriented version with the left hand. In contrary, increased activity during the mirror reversed action, but not during the original-oriented performance of the untrained right hand is observed after left-handed training. These results indicate the transfer of acquired right-handed information which reflects the mirror symmetry of the body, whereas spatial information is mainly transferred after left-handed training. Taken together, a combined approach of clinical lesion studies and functional imaging is a promising tool for identifying the cerebral regions involved in the process of motor learning and provides insight into the mechanisms underlying the generalisation of actions.

Recognition and imitation of pantomimed motor acts after unilateral parietal and premotor lesions: a perspective on apraxia.

We compared gesture comprehension and imitation in patients with lesions in the left parietal lobe (LPAR, n=5) and premotor cortex/supplementary motor area (LPMA, n=8) in patients with damage to the right parietal lobe (RPAR, n=6) and right premotor/supplementary motor area (RPMA, n=6) and in 16 non-brain damaged control subjects. Three patients with left parietal lobe damage had aphasia. Subjects were shown 136 meaningful pantomimed motor acts on a videoscreen and were asked to identify the movements and to imitate the motor acts from memory with their ipsilesional and contralesional hand or with both hands simultaneously. Motor tasks included gestures without object use (e.g. to salute, to wave) pantomimed imitation of gestures on ones own body (e.g. to comb ones hair) and pantomimed imitation of motor acts which imply tool use to an object in extrapersonal space (e.g. to hammer a nail). Videotaped test performance was analysed by two independent raters; errors were classified as spatial errors, body part as object, parapraxic performance and non-identifiable movements. In addition, action discrimination was tested by evaluating whether a complex motor sequence was correctly performed. Results indicate that LPAR patients were most severely disturbed when imitation performance was assessed. Interestingly, LPAR patients were worse when imitating gestures on their own bodies than imitating movements with reference to an external object use with most pronounced deficits in the spatial domain. In contrast to imitation, comprehension was not or only slightly disturbed and no clear correlation was found between the severity of imitation deficits and gesture comprehension. Moreover, although the three patients with aphasia imitated the movements more poorly than non-aphasic LPAR patients, the severity of comprehension errors did not differ. Whereas unimanual imitating performance and gesture comprehension of PMA patients did not differ significantly from control subjects, bimanual tasks were severely disturbed, in particular when executing different movements simultaneously with the right and left hands.

Differential cerebral activation during observation of expressive gestures and motor acts

We compared brain activation involved in the observation of isolated right hand movements (e.g. twisting a lid), body-referred movements (e.g. brushing teeth) and expressive gestures (e.g. threatening) in 20 healthy subjects by using functional magnetic resonance imaging (fMRI). Perception-related areas in the occipital and inferior temporal lobe but also the mirror neuron system in the lateral frontal (ventral premotor cortex and BA 44) and superior parietal lobe were active during all three conditions. Observation of body-referred compared to common hand actions induced increased activity in the bilateral posterior superior temporal sulcus (STS), the left temporo-parietal lobe and left BA 45. Expressive gestures involved additional areas related to social perception (bilateral STS, temporal poles, medial prefrontal lobe), emotional processing (bilateral amygdala, bilateral ventrolateral prefrontal cortex (VLPFC), speech and language processing (Brocas and Wernickes areas) and the pre-supplementary motor area (pre-SMA). In comparison to body-referred actions, expressive gestures evoked additional activity only in the left VLPFC (BA 47). The valence-ratings for expressive gestures correlated significantly with activation intensity in the VLPFC during expressive gesture observation. Valence-ratings for negative expressive gestures correlated with right STS-activity. Our data suggest that both, the VLPFC and the STS are coding for differential emotional valence during the observation of expressive gestures.

Intermanual transfer of proximal and distal motor engrams in humans

We studied intermanual motor transfer for right-to-left or left-to-right direction of transfer between either proximal or distal upper extremity muscle groups. The influence of previously acquired motor engrams (original learning, OL) on learning efficiency of the contralateral side (transfer learning, TL) was examined in 26 right-handed healthy subjects. The task consisted of the drawing of meaningless figures. During TL, OL figures had to be reproduced as vertical mirror reversals. Data revealed a benefit for right-to-left but not left-to-right direction of transfer for time to complete a figure as well as a left-to-right transfer benefit for spatial motor precision. Furthermore, a benefit for intermanual transfer of training between proximal but not distal muscle groups was found when movement time to complete a figure was evaluated. Of special interest was the observation of a disadvantage due to prior contralateral learning for performance at right distal effectors. The asymmetrical transfer benefits with respect to side are in line with previous findings and support the proficiency model and the cross-actiation model. Results further showed that intermanual transfer of training might differ with respect to muscle group involvement and suggest that, although primarily facilitating, previous opposite hand training may lead to inhibitory influences on subsequent contralateral reproduction.

Planning Abilities and the Tower of London: Is This Task Measuring a Discrete Cognitive Function?

The Tower of London (ToL) test is widely used for measuring planning and aspects of problem solving. The primary focus of this study was to assess the relationship among different performance measures on the ToL. A secondary purpose was to examine the putative relationship between intelligence and working memory with that of ToL performance. Analyses of the interrelation of several ToL parameters indicated that better ToL performance was associated with longer preplanning time and shorter movement execution time. Good performers showed a stronger increase in preplanning duration with task difficulty than intermediate or poor planners. Stepwise multiple regression analysis yielded fluid intelligence as the only significant predictor of ToL performance. These results suggest that the Tower of London assesses predominantly planning and problem solving and could not be sufficiently explained by other cognitive domains.

Lateralization of hippocampal activation differs between left and right temporal lobe epilepsy patients and correlates with postsurgical verbal learning decrement

We addressed the question whether lateralization of memory-related medial temporal lobe (MTL) activity in medial temporal lobe epilepsy (MTLE) patients is determined by pathology or sex, differentiating between two MTL subregions implicated in visuospatial memory as regions-of-interest (ROI) - the hippocampus (Hc) and the parahippocampal place area (PPA). We further assessed the relation between lateralization of hippocampal activation and postsurgical memory decline regarding performance in standardized neuropsychological tests of verbal and visuospatial learning. Functional magnetic resonance imaging (fMRI) data were acquired from unilateral MTLE patients performing an object location memory task in a virtual environment. Individual lateralization indices (LI) based on memory-related brain activation patterns were calculated for each subject and ROI. Correlational analyses were computed between pre- to postsurgical changes in learning and asymmetry in hippocampal activation. Results revealed that lateralization of hippocampal, memory-related activity in patients with MTLE was determined by the side of seizure focus, not sex. Laterality of activation in the PPA was neither influenced by side of pathology nor sex. Lateralization of hippocampal activation was significantly correlated with decline in verbal learning after surgery. We were able to demonstrate that asymmetry of hippocampal fMRI-activation in unilateral MTLE patients is determined by the side of seizure focus, thus indicating the relative functional integrity of the hippocampi. This is corroborated by the finding that greater activation of the to-be-resected hippocampus leads to stronger verbal memory decline after surgery.

Neuronal correlates of encoding and retrieval in episodic memory during a paired-word association learning task: a functional magnetic resonance imaging study.

Abstract The investigation of memory function using functional magnetic resonance imaging (fMRI) is an expanding field of research. The aim of this study was to demonstrate brain-activity patterns related to a word-pair association task employing a whole-brain EPI sequence. Six right-handed, healthy male volunteers (mean age: 27.5 years) took part in the study. fMRI was performed at a field strength of 1.5 Tesla with 26–32 slices parallel to the AC-PC line, depending on individual brain size. Distributed brain regions were activated in episodic encoding and retrieval with similarities, but also (distinct) differences in activation patterns. Bilateral prefrontal cortical areas were involved when comparing encoding as well as retrieval to the reference condition (nonsense words). Furthermore, activation was observed in cerebellar areas during encoding, and activation in bilateral parietal areas (precuneus and inferior parietal cortex) was differentially more pronounced during retrieval. The activation of left dorsomedial thalamus during retrieval of high imagery-content word-pair associates may point to the role of this structure in episodic retrieval. The direct cognitive subtraction of encoding minus retrieval yielded a differentially larger left prefrontal activation. There was a differentially higher right prefrontal activation during retrieval than during encoding, underlining the proposed right/left asymmetry for episodic memory processes.

The Tower of London: the impact of instructions, cueing, and learning on planning abilities

The Tower of London (ToL) is a well-known test of planning ability, and commonly used for the purpose of neuropsychological assessment and cognitive research. Its widespread application has led to numerous versions differing in a number of respects. The present study addressed the question whether differences in instruction, cueing, and learning processes systematically influence ToL performance across five difficulty levels (three to seven moves). A total of 81 normal adults were examined in a mixed design with the between-subject factor instruction (online versus mental preplanning) and the within-subject factors cueing (cue versus non-cue test version) and learning processes (first block and second block). We also assessed general intelligence for further analyses of differences between instruction groups. In general, there was a significant main effect across the difficulty levels indicating that the rate of incorrect solutions increased with problem difficulty. The participants who were instructed to make full mental plans before beginning to execute movements (preplanning) solved significantly more problems than people who started immediately with task-related movements (online). As for the cueing conditions, participants with the minimum number of moves predetermined (cue) could solve more trials than people who were only instructed to solve the problems in as few moves as possible (non-cue). Participants generally increased performance in the second part of the test session. However, an interaction of presentation order of the cueing condition with learning indicated that people who started the tasks with the non-cue version showed significantly better performance in the following cue condition, while participants who started with the cue condition stayed at the same performance level for both versions. These findings suggest that instruction, cueing conditions, and learning processes are important determinants of ToL performance, and they stress the necessity of standardized application in research and clinical practice.

Prism adaptation improves visual search in hemispatial neglect

Visuomotor prism adaptation has been found to induce a lateral bias of spatial attention in chronic hemispatial neglect patients. Here, two experiments were conducted to explore the effects of 10 degrees prism adaptation on visual search tasks and standard visual inattention tests. Baselines and intervention effects were measured on separate days for all patients. The first experiment explored whether prism adaptation affects performance on a time restricted visual search task (maximum 3500ms presentation followed by visual and auditory feedback). No positive effects of prism adaptation were found on accuracy in visual search nor on traditional neglect tests. These results accord well with previous studies showing that increased cognitive load can lead to prism de-adaptation or unchanged performance following prism adaptation. Response times in visual search became faster following intervention but this was not the case for the standard neglect tests. In the second experiment, the same single-featured search task was used, but the participants had unlimited search time and received no feedback on their response. This time, the patients showed accuracy improvements in visual search and all four on regular neglect tests. Therapeutic effects lasted for at least 90-120min. Response times on all tasks became faster after prism adaptation. The results are consistent with studies showing effects of prism adaptation on neuropsychological neglect tests and other attentional tasks that are not speeded or time restricted, where feedback is not provided, or are performed following non-feedback-based tasks. The current findings show that prism adaptation improves visual search in neglect and that these beneficial effects can disappear with feedback.

The reliability of fMRI activations in the medial temporal lobes in a verbal episodic memory task.

The test-retest reliability of activation patterns elicited by encoding and recognition of word-pair associates within the whole brain and a predefined medial temporal region of interest (ROI) was investigated. Twenty healthy right-handed subjects were studied within two sessions, either on the same day or 210-308 days later. Three quantitative measures of reliability were calculated for the contrasts encoding and recognition versus a control condition within the ROI and also for the whole brain: A group correlational analysis between the lateralization indices of the first and second session, correlations of the individual SPM(t) maps of the first and the second run, and overlap ratios between both sessions. For the ROI, correlational analysis of lateralization indices during both encoding trials was significant. Eighty percent of the individual positive correlation coefficients of SPM(t) maps during encoding, and 75% during recognition reached significance. The mean percentage of overlapping voxels was 18% during encoding and 19% during recognition. The reproducibility measures evaluated for the whole brain demonstrated significantly higher values compared to the ROI. For the group that stayed inside the scanner, better whole brain test-retest reliability was observed, and no influence of the memory process (encoding or recognition) on reproducibility was found.