Decoding cerebro-spinal signatures of human behavior: Application to motor sequence learning.

Mapping the neural patterns that drive human behavior is a key challenge in neuroscience. Even the simplest of our everyday actions stem from the dynamic and complex interplay of multiple neural structures across the central nervous system (CNS). Yet, most neuroimaging research has focused on investigating cerebral mechanisms, while the way the spinal cord accompanies the brain in shaping human behavior has been largely overlooked. Although the recent advent of functional magnetic resonance imaging (fMRI) sequences that can simultaneously target the brain and spinal cord has opened up new avenues for studying these mechanisms at multiple levels of the CNS, research to date has been limited to inferential univariate techniques that cannot fully unveil the intricacies of the underlying neural states. To address this, we propose to go beyond traditional analyses and instead use a data-driven multivariate approach leveraging the dynamic content of cerebro-spinal signals using innovation-driven coactivation patterns (iCAPs). We demonstrate the relevance of this approach in a simultaneous brain-spinal cord fMRI dataset acquired during motor sequence learning (MSL), to highlight how large-scale CNS plasticity underpins rapid improvements in early skill acquisition and slower consolidation after extended practice. Specifically, we uncovered cortical, subcortical and spinal functional networks, which were used to decode the different stages of learning with a high accuracy and, thus, delineate meaningful cerebro-spinal signatures of learning progression. Our results provide compelling evidence that the dynamics of neural signals, paired with a data-driven approach, can be used to disentangle the modular organization of the CNS. While we outline the potential of this framework to probe the neural correlates of motor learning, its versatility makes it broadly applicable to explore the functioning of cerebro-spinal networks in other experimental or pathological conditions.

Early stages of sensorimotor map acquisition: neurochemical signature in primary motor cortex and its relation to functional connectivity.

The earliest stages of sensorimotor learning involve learning the correspondence between movements and sensory results-a sensorimotor map. The present exploratory study investigated the neurochemical underpinnings of map acquisition by monitoring 25 participants as they acquired a new association between movements and sounds. Functional magnetic resonance spectroscopy was used to measure neurochemical concentrations in the left primary motor cortex during learning. Resting-state functional magnetic resonance imaging data were also collected before and after training to assess learning-related changes in functional connectivity. There were monotonic increases in γ-aminobutyric acid (GABA) and decreases in glucose during training, which extended into the subsequent rest period and, importantly, in the case of GABA correlated with the amount of learning: participants who showed greater behavioral learning showed greater GABA increase. The GABA change was furthermore correlated with changes in functional connectivity between the primary motor cortex and a cluster of voxels in the right intraparietal sulcus: greater increases in GABA were associated with greater strengthening of connectivity. Transiently, there were increases in lactate and reductions in aspartate, which returned to baseline at the end of training, but only lactate showed a statistical trend to correlate with the amount of learning. In summary, during the earliest stages of sensorimotor learning, GABA levels are linked on a subject-level basis to both behavioral learning and a strengthening of functional connections that persists beyond the training period. The findings are consistent with the idea that GABA-mediated inhibition is linked to maintenance of newly learned information.NEW & NOTEWORTHY Learning the mapping between movements and their sensory effects is a necessary step in the early stages of sensorimotor learning. There is evidence showing which brain areas are involved in early motor learning, but their role remains uncertain. Here, we show that GABA, a neurotransmitter linked to inhibitory processing, rises during and after learning and is involved in ongoing changes in resting-state networks.

Multisession Anodal tDCS Protocol Improves Motor System Function in an Aging Population.

OBJECTIVES: The primary objective of this study was to investigate the effects of five consecutive, daily 20-minute sessions of M1 a-tDCS on motor learning in healthy, cognitively intact, aging adults. DESIGN: A total of 23 participants (51 to 69 years old) performed five consecutive, daily 20-minute sessions of a serial reaction time task (SRT task) concomitant with either anodal (n = 12) or sham (n = 11) M1 a-tDCS. RESULTS: We found a significant group × training sessions interaction, indicating that whereas aging adults in the sham group exhibited little-to-no sequence-specific learning improvements beyond the first day of training, reproducible improvements in the ability to learn new motor sequences over 5 consecutive sessions were the net result in age-equivalent participants from the M1 a-tDCS group. A significant main effect of group on sequence-specific learning revealed greater motor learning for the M1 a-tDCS group when the five learning sessions were averaged. CONCLUSION: These findings raise into prominence the utility of multisession anodal TDCS protocols in combination with motor training to help prevent/alleviate age-associated motor function decline.

Enhancing both motor and cognitive functioning in Parkinson's disease: Aerobic exercise as a rehabilitative intervention.

BACKGROUND: Aerobic exercise training (AET) has been shown to provide health benefits in individuals with Parkinson's disease (PD). However, it is yet unknown to what extent AET also improves cognitive and procedural learning capacities, which ensure an optimal daily functioning. OBJECTIVE: In the current study, we assessed the effects of a 3-month AET program on executive functions (EF), implicit motor sequence learning (MSL) capacity, as well as on different health-related outcome indicators. METHODS: Twenty healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike-training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+5 min/week up to 40 min) based on participant's maximal aerobic power. Before and after AET, EF tests assessed participants' inhibition and flexibility functions, whereas implicit MSL capacity was evaluated using a version of the Serial Reaction Time Task. RESULTS: The AET program was effective as indicated by significant improvement in aerobic capacity in all participants. Most importantly, AET improved inhibition but not flexibility, and motor learning skill, in both groups. CONCLUSION: Our results suggest that AET can be a valuable non-pharmacological intervention to promote physical fitness in early PD, but also better cognitive and procedural functioning.

Host behaviour manipulation as an evolutionary route towards attenuation of parasitoid virulence.

By definition, insect parasitoids kill their host during their development. Data are presented showing that ladybirds not only can survive parasitism by Dinocampus coccinellae, but also can retain their capacity to reproduce following parasitoid emergence. We hypothesize that host behaviour manipulation constitutes a preadaptation leading to the attenuation of parasitoid virulence. Following larval development, the parasitoid egresses from the host and spins a cocoon between the ladybird's legs. Throughout parasitoid pupation, the manipulated host acts as a bodyguard to protect the parasitoid cocoon from predation. The parasitoid has evolved mechanisms to avoid killing the host prematurely so that its own survival is not compromised. Bodyguard manipulation may thus constitute a selective trait for the evolution of true parasitism in some host-parasitoid associations.

Brown tumor of the iliac crest initially misdiagnosed as a giant cell tumor of the bone.

SUMMARY: Brown tumors (BTs) are expansile osteolytic lesions complicating severe primary hyperparathyroidism (PHPT). Clinical, radiological and histological features of BTs share many similarities with other giant cell-containing lesions of the bone, which can make their diagnosis challenging. We report the case of a 32-year-old man in whom an aggressive osteolytic lesion of the iliac crest was initially diagnosed as a giant cell tumor by biopsy. The patient was scheduled for surgical curettage, with a course of neoadjuvant denosumab. Routine biochemical workup prior to denosumab administration incidentally revealed high serum calcium levels. The patient was diagnosed with PHPT and a parathyroid adenoma was identified. In light of these findings, histological slices of the iliac lesion were reviewed and diagnosis of a BT was confirmed. Follow-up CT-scans performed 2 and 7 months after parathyroidectomy showed regression and re-ossification of the bone lesion. The aim of this case report is to underline the importance of distinguishing BTs from other giant cell-containing lesions of the bone and to highlight the relevance of measuring serum calcium as part of the initial evaluation of osteolytic bone lesions. This can have a major impact on patients' management and can prevent unnecessary invasive surgical interventions. LEARNING POINTS: Although rare, brown tumors should always be considered in the differential diagnosis of osteolytic giant cell-containing bone lesions. Among giant cell-containing lesions of the bone, the main differential diagnoses of brown tumors are giant cell tumors and aneurysmal bone cysts. Clinical, radiological and histological characteristics can be non-discriminating between brown tumors and giant cell tumors. One of the best ways to distinguish these two diagnoses appears to be through biochemical workup. Differentiating brown tumors from giant cell tumors and aneurysmal bone cysts is crucial in order to ensure better patient care and prevent unnecessary morbid surgical interventions.

Investigations on spinal cord fMRI of cats under ketamine.

Functional magnetic resonance imaging (fMRI) of the spinal cord has been the subject of intense research for the last ten years. An important motivation for this technique is its ability to detect non-invasively neuronal activity in the spinal cord related to sensorimotor functions in various conditions, such as after spinal cord lesions. Although promising results of spinal cord fMRI have arisen from previous studies, the poor reproducibility of BOLD activations and their characteristics remain a major drawback. In the present study we investigated the reproducibility of BOLD fMRI in the spinal cord of cats (N=9) by repeating the same stimulation protocol over a long period (approximately 2 h). Cats were anaesthetized with ketamine, and spinal cord activity was induced by electrical stimulation of cutaneous nerves of the hind limbs. As a result, task-related signals were detected in most cats with relatively good spatial specificity. However, BOLD response significantly varied within and between cats. This variability was notably attributed to the moderate intensity of the stimulus producing a low amplitude haemodynamic response, variation in end-tidal CO(2) during the session, low signal-to-noise ratio (SNR) in spinal fMRI time series and animal-specific vascular anatomy. Original contributions of the present study are: (i) first spinal fMRI experiment in ketamine-anaesthetized animals, (ii) extensive study of intra- and inter-subject variability of activation, (iii) characterisation of static and temporal SNR in the spinal cord and (iv) investigation on the impact of CO(2) end-tidal level on the amplitude of BOLD response.

Large-scale neural model validation of partial correlation analysis for effective connectivity investigation in functional MRI.

Recent studies of functional connectivity based upon blood oxygen level dependent functional magnetic resonance imaging have shown that this technique allows one to investigate large-scale functional brain networks. In a previous study, we advocated that data-driven measures of effective connectivity should be developed to bridge the gap between functional and effective connectivity. To attain this goal, we proposed a novel approach based on the partial correlation matrix. In this study, we further validate the use of partial correlation analysis by employing a large-scale, neurobiologically realistic neural network model to generate simulated data that we analyze with both structural equation modeling (SEM) and the partial correlation approach. Unlike real experimental data, where the interregional anatomical links are not necessarily known, the links between the nodes of the network model are fully specified, and thus provide a standard against which to judge the results of SEM and partial correlation analyses. Our results show that partial correlation analysis from the data alone exhibits patterns of effective connectivity that are similar to those found using SEM, and both are in agreement with respect to the underlying neuroarchitecture. Our findings thus provide a strong validation for the partial correlation method.

The use of dorsal distraction plating for severely comminuted distal radius fractures: A review and comparison to volar plate fixation.

INTRODUCTION: Optimal fixation for highly comminuted distal radius fractures remains a major treatment challenge for orthopaedic surgeons. Dorsal distraction plating can serve as an improved fixation technique by allowing reduction under ligamentotaxis, providing a dorsal buttress, addressing proximal comminution, and allowing for early weightbearing in polytrauma patients. The aim of this study was to review current literature regarding treatment of distal radius fractures treated with dorsal distraction plating. METHODS: We performed a literature search in Pubmed and EMBASE databases to identify all studies analyzing use of dorsal distraction plating. Case reports, biomechanical and anatomic cadaver studies were excluded from analysis. Primary outcome measures were range of motion (ROM) at final follow up, grip strength, and radiographic parameters. RESULTS: Eight studies were included in the final analysis. Pooled mean ROM after dorsal distraction plating was found to be 47.6° of flexion, 50.5° of extension, 76.0° of pronation, and 74.2° of supination. Pooled mean grip strength was 79.1% compared to the uninjured contralateral limb. Pooled mean volar tilt was 3.6°. Overall radial height was maintained at an average of 10.5 mm with a pooled mean loss of only 3.8 mm in length. Mean radial inclination was found to be 19.4 mm with patients having a mean ulnar variance of 0.5 mm. DISCUSSION & CONCLUSION: Treatment of comminuted intra-articular distal radius fractures with dorsal distraction plating yielded excellent outcomes with very low complication rates, and has several advantages over volar plating and/or external fixation for these fractures. Necessity of plate removal remains a negative feature of this technique.

Neural substrates of cognitive skill learning in Parkinson's disease.

While cognitive skill learning is normally acquired implicitly through frontostriatal circuitry in healthy individuals, neuroimaging studies suggest that patients with Parkinson's disease (PD) do so by activating alternate, intact brain areas associated with explicit memory processing. To further test this hypothesis, 10 patients with PD and 12 healthy controls were tested on a modified, learning version of the Tower of London task while undergoing positron emission tomography at four different time points over the course of learning. Despite having less accurate problem solving abilities than controls, PD patients were able to acquire the skill learning task. However, as compared to controls, they maintained higher levels of cerebral blood flow activity in the dorsolateral prefrontal cortex and hippocampus and showed an increase in activity in the frontopolar cortex and posterior cingulate over the course of learning. These findings reflect a shift to the explicit memory system in PD patients, enabling them to learn this cognitive skill, which is normally acquired by control subjects using implicit learning strategies and frontostriatal circuitry.

Activation detection in diffuse optical imaging by means of the general linear model.

Due to its non-invasive nature and low cost, diffuse optical imaging (DOI) is becoming a commonly used technique to assess functional activation in the brain. When imaging with DOI, two major issues arise in the data analysis: (i) the separation of noise of physiological origin and the recovery of the functional response; (ii) the tomographic image reconstruction problem. This paper focuses on the first issue. Although the general linear model (GLM) has been extensively used in functional magnetic resonance imaging (fMRI), DOI has mostly relied on filtering and averaging of raw data to recover brain functional activation. This is mainly due to the high temporal resolution of DOI which implies a new design of the drift basis modelling physiology. In this paper, we provide (i) a filtering method based on cosine functions that is more adapted than standard averaging techniques for DOI specifically; (ii) a new mode-locking technique to recover small signals and locate them temporally with high precision (shift method). Results on real data show the capability of the shift method to retrieve HbR and HbO(2) peak locations.

Muscular responses during motor imagery as a function of muscle contraction types.

This study was designed to gain more insight into the mechanisms underlying motor imagery (MI). While there is ample evidence that motor performance and MI share common central neural mechanisms, the question whether MI is accompanied by subliminal electromyographic (EMG) activity remained unsolved. Thirty right-handed volunteers were asked to lift or to imagine lifting a weighted dumbbell using different types of muscle contraction, i.e. heavy concentric, light concentric, isometric and eccentric contractions. EMG activity from 9 muscles of the dominant arm (agonist, antagonist, synergist and fixator muscles) was monitored. Autonomic nervous system responses were also recorded on the non-dominant hand, thus attesting mental activity at the peripheral level. A significant increased pattern of EMG activity was recorded in all muscles during MI, when compared to the rest condition, while the goniometric data did not reveal any movement. Although being subliminal, the magnitude of this activation was found to be correlated to the mental effort required to lift a weight mentally, as more EMG activity was recorded during imaginary lifting of heavy than light concentric contractions. When considering the different types of contraction, our results provided evidence of selective changes in EMG activity. Especially, the imagined eccentric condition elicited a significant weaker muscular activity than all other conditions. In addition, the changes in the EMG pattern mirrored those usually observed during physical movement. These findings support the hypotheses of a selective effect of MI at the level of muscular activity and of incomplete inhibition of the motor command during MI.

Influence of aerobic exercise training on the neural correlates of motor learning in Parkinson's disease individuals.

BACKGROUND: Aerobic exercise training (AET) has been shown to provide general health benefits, and to improve motor behaviours in particular, in individuals with Parkinson's disease (PD). However, the influence of AET on their motor learning capacities, as well as the change in neural substrates mediating this effect remains to be explored. OBJECTIVE: In the current study, we employed functional Magnetic Resonance Imaging (fMRI) to assess the effect of a 3-month AET program on the neural correlates of implicit motor sequence learning (MSL). METHODS: 20 healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+ 5 min/week up to 40 min) based on participant's maximal aerobic power. Before and after the AET program, participants' brain was scanned while performing an implicit version of the serial reaction time task. RESULTS: Brain data revealed pre-post MSL-related increases in functional activity in the hippocampus, striatum and cerebellum in PD patients, as well as in the striatum in HC individuals. Importantly, the functional brain changes in PD individuals correlated with changes in aerobic fitness: a positive relationship was found with increased activity in the hippocampus and striatum, while a negative relationship was observed with the cerebellar activity. CONCLUSION: Our results reveal, for the first time, that exercise training produces functional changes in known motor learning related brain structures that are consistent with improved behavioural performance observed in PD patients. As such, AET can be a valuable non-pharmacological intervention to promote, not only physical fitness in early PD, but also better motor learning capacity useful in day-to-day activities through increased plasticity in motor related structures.

Identification of the transmembrane dimer interface of the bovine papillomavirus E5 protein.

We have developed a genetic method to determine the active orientation of dimeric transmembrane protein helices. The bovine papillomavirus E5 protein, a 44-amino acid homodimeric protein that appears to traverse membranes as a left-handed coiled-coil, transforms fibroblasts by binding and activating the platelet-derived growth factor (PDGF) beta receptor. A heterologous dimerization domain was used to force E5 monomers to adopt all seven possible symmetric coiled-coil registries relative to one another within the dimer. Focus formation assays demonstrated that dimerization of the E5 protein is required for transformation and identified a single preferred orientation of the monomers. The essential glutamine residue at position 17 resided in the dimer interface in this active orientation. The active chimera formed complexes with the PDGF beta receptor and induced receptor tyrosine phosphorylation. We also identified E5-like structures that underwent non-productive interactions with the receptor.

Speech acquisition predicts regions of enhanced cortical response to auditory stimulation in autism spectrum individuals.

A continuum of phenotypes makes up the autism spectrum (AS). In particular, individuals show large differences in language acquisition, ranging from precocious speech to severe speech onset delay. However, the neurological origin of this heterogeneity remains unknown. Here, we sought to determine whether AS individuals differing in speech acquisition show different cortical responses to auditory stimulation and morphometric brain differences. Whole-brain activity following exposure to non-social sounds was investigated. Individuals in the AS were classified according to the presence or absence of Speech Onset Delay (AS-SOD and AS-NoSOD, respectively) and were compared with IQ-matched typically developing individuals (TYP). AS-NoSOD participants displayed greater task-related activity than TYP in the inferior frontal gyrus and peri-auditory middle and superior temporal gyri, which are associated with language processing. Conversely, the AS-SOD group only showed enhanced activity in the vicinity of the auditory cortex. We detected no differences in brain structure between groups. This is the first study to demonstrate the existence of differences in functional brain activity between AS individuals divided according to their pattern of speech development. These findings support the Trigger-threshold-target model and indicate that the occurrence of speech onset delay in AS individuals depends on the location of cortical functional reallocation, which favors perception in AS-SOD and language in AS-NoSOD.

Increased cortico-striatal connectivity during motor practice contributes to the consolidation of motor memory in writer's cramp patients.

Sensorimotor representations of movements are created in the sensorimotor network through repeated practice to support successful and effortless performance. Writer's cramp (WC) is a disorder acquired through extensive practice of finger movements, and it is likely associated with the abnormal acquisition of sensorimotor representations. We investigated (i) the activation and connectivity changes in the brain network supporting the acquisition of sensorimotor representations of finger sequences in patients with WC and (ii) the link between these changes and consolidation of motor performance 24 h after the initial practice. Twenty-two patients with WC and 22 age-matched healthy volunteers practiced a complex sequence with the right (pathological) hand during functional MRI recording. Speed and accuracy were measured immediately before and after practice (day 1) and 24 h after practice (day 2). The two groups reached equivalent motor performance on day 1 and day 2. During motor practice, patients with WC had (i) reduced hippocampal activation and hippocampal-striatal functional connectivity; and (ii) overactivation of premotor-striatal areas, whose connectivity correlated with motor performance after consolidation. These results suggest that patients with WC use alternative networks to reach equiperformance in the acquisition of new motor memories.

Role of the right temporal lobe in visual-cue learning during repeated pattern discriminations.

The ability to acquire visual cues for discriminating between two targets against a background of visually similar items was examined in 64 patients with unilateral temporal- or frontal-lobe excisions and 20 normal control subjects. The subjects were tested on two versions (letters and abstract designs) of a visual cue-learning task that was an adaptation and extension of RABBITT's (Am. J. Psychol. 80, 1-13, 1967) visual-search paradigm. For both versions, the material consisted of two packs of cards, each containing a different set of background letters or designs. Subjects were required to sort the cards into two piles according to which of two targets was present on the card. On the letter task, all groups took longer to sort when the background letters were changed after three learning trials. With abstract designs, patients with right temporal-lobe lesions failed to show this interference effect after three learning trials, but they, like other groups, did so after six. This slowness in learning was related neither to the extent of hippocampal removal nor to visual-field defects. It is argued that the right temporal neocortex plays a role in incremental learning of visual cues during repeated pattern discriminations.

Right temporal-lobe contribution to global visual processing.

The performance of 92 patients with unilateral temporal- or frontal-lobe excisions and 35 normal control subjects was tested under two experimental conditions (global, local) of a Stroop-type reaction-time task, employing either hierarchically structured letters or abstract designs as stimuli. In the local condition, subjects were asked to focus their attention on the small forms and to ignore the large form, whereas they were instructed to do the reverse in the global condition. The results showed that, in the local condition, the patients with right temporal-lobe lesions were less affected than the other groups by interference from the global aspect of the stimulus. This reduced sensitivity to the overall configuration of the stimulus was unrelated to the extent of hippocampal removal or to the presence of visual-field defects. These findings support the hypothesis that the human right temporal neocortex contributes to the global processing of visual information.

Mental representation of knowledge following frontal-lobe or postrolandic lesions.

The aims of this study were to examine the role of the prefrontal cortex in the representation of familiar activities using scripts, and to compare both Shallice's [Phil. Trans. Roy. Soc. Lond. B. Vol. 298, pp. 199-209, 1982] and Grafman's [Integrating Theory and Practice in Clinical Neuropsychology, pp. 93-138, Lawrence Erlbaum, Hillsdale, New Jersey, 1989] models of schematic representation of knowledge. Twelve patients with frontal-lobe damage, nine with postrolandic lesions, and 13 normal control subjects were asked to generate actions belonging to six different scripts in a forward condition, and to two others in a backward condition. The latter condition was included to test Shallice's hypothesis that damage to the frontal lobes would only affect the execution of non-routine tasks. The results showed that patients with frontal-lobe lesions produced scripts that were deprived of contextual elements and made more sequencing errors in the forward condition than matched normal control subjects, hence suggesting that the frontal cortex contributes to the production of an adequate mental representation of routine events. By contrast, the performance of the two clinical groups did not differ from the control subjects in their ability to generate scripts in the backward condition, although these three groups of subjects generated fewer actions in the latter condition. Further qualitative analyses demonstrated that patients with parietal-, but not with temporal-lobe lesions, produced sequencing errors in both forward and backward conditions. The latter findings suggest that the frontal lobes, together with the parietal cortex, may play a special role in establishing the spatio-temporal position of events within a script. The results of this study are discussed in terms of the recent models developed by Shallice and Grafman concerning the contribution of the frontal lobes in the mental representation of knowledge.

Role of the striatum, cerebellum and frontal lobes in the automatization of a repeated visuomotor sequence of movements.

Recently, Doyon et al. [20] demonstrated that lesions to both the striatum and to the cerebellum in humans produce a similar deficit in the learning of a repeated visuomotor sequence, which occurs late in the acquisition process. We now report the results of two experiments that were designed to examine whether this impairment was due to a lack of automatization of the repeating sequence of finger movements by using a dual-task paradigm and by testing for long-term retention of this skill. In Experiment 1, the performance of groups of patients with Parkinson's disease, or with damage to the cerebellum or to the frontal lobes, was compared to that of matched control subjects on the Repeated Sequence Test (primary task) and the Brooks' Matrices Test (secondary task). These two tests were administered concomitantly in both early and late learning phases of the visuomotor sequence. Overall, the groups did not differ in their ability to execute the primary task. By contrast, in accordance with the predictions, patients in Stages 2-3 of Parkinson's disease or with a cerebellar lesion failed to reveal the expected increase in performance on the secondary task seen with learning, suggesting that the latter groups of patients did not have access to the same level of residual cognitive resources to complete the matrices compared to controls. In Experiment 2, the same groups of patients and control subjects were retested again 10-18 months later. They were given four blocks of 100 trials each of the repeating sequence task, followed by a questionnaire and a self-generation task that measured their declarative knowledge of that sequence. The results revealed a long-term retention impairment only in patients who changed from Stage I to Stage II of the disease (suggesting further striatal degeneration) during the one-year interval, or who had a cerebellar lesion. By contrast, performance of the three clinical groups did not differ from controls on declarative memory tests. These findings suggest that both the striatum and the cerebellum participate to the automatization process during the late (slow) learning stage of a sequence of finger movements and that these structures also play a role in the neuronal mechanism subserving long-term retention of such a motor sequence behavior.