The impact of levamisole and alcohol on white matter microstructure in adult chronic cocaine users.

Previous brain imaging studies with chronic cocaine users (CU) using diffusion tensor imaging (DTI) mostly focused on fractional anisotropy to investigate white matter (WM) integrity. However, a quantitative interpretation of fractional anisotropy (FA) alterations is often impeded by the inherent limitations of the underlying tensor model. A more fine-grained measure of WM alterations could be achieved by measuring fibre density (FD). This study investigates this novel DTI metric comparing 23 chronic CU and 32 healthy subjects. Quantitative hair analysis was used to determine intensity of cocaine and levamisole exposure-a cocaine adulterant with putative WM neurotoxicity. We first assessed the impact of cocaine use, levamisole exposure and alcohol use on group differences in WM integrity. Compared with healthy controls, all models revealed cortical reductions of FA and FD in CU. At the within-patient group level, we found that alcohol use and levamisole exposure exhibited regionally different FA and FD alterations than cocaine use. We found mostly negative correlations of tract-based WM associated with levamisole and weekly alcohol use. Specifically, levamisole exposure was linked with stronger WM reductions in the corpus callosum than alcohol use. Cocaine use duration correlated negatively with FA and FD in some regions. Yet, most of these correlations did not survive a correction for multiple testing. Our results suggest that chronic cocaine use, levamisole exposure and alcohol use were all linked to significant WM impairments in CU. We conclude that FD could be a sensitive marker to detect the impact of the use of multiple substances on WM integrity in cocaine but also other substance use disorders.

Bilateral age-related atrophy in the planum temporale is associated with vowel discrimination difficulty in healthy older adults.

In this study we investigated the association between age-related brain atrophy and behavioural as well as electrophysiological markers of vowel perception in a sample of healthy younger and older adults with normal pure-tone hearing. Twenty-three older adults and 27 younger controls discriminated a set of vowels with altered second formants embedded in consonant-vowel syllables. Additionally, mismatch negativity (MMN) responses were recorded in a separate oddball paradigm with the same set of stimuli. A structural magnet resonance scan was obtained for each participant to determine cortical architecture of the left and right planum temporale (PT). The PT was chosen for its function as a major processor of auditory cues and speech. Results suggested that older adults performed worse in vowel discrimination despite normal-for-age pure-tone hearing. In the older group, we found evidence that those with greater age-related cortical atrophy (i.e., lower cortical surface area and cortical volume) in the left and right PT also showed weaker vowel discrimination. In comparison, we found a lateralized correlation in the younger group suggesting that those with greater cortical thickness in only the left PT performed weaker in the vowel discrimination task. We did not find any associations between macroanatomical traits of the PT and MMN responses. We conclude that deficient vowel processing is not only caused by pure-tone hearing loss but is also influenced by atrophy-related changes in the ageing auditory-related cortices. Furthermore, our results suggest that auditory processing might become more bilateral across the lifespan.

Use of levamisole-adulterated cocaine is associated with increased load of white matter lesions.

Background: Cocaine use has been associated with vascular pathologies, including cerebral white matter hyperintensities. Street cocaine is most often adulterated with levamisole, an anthelminthic drug that may also be associated with vascular toxicity. However, whether levamisole exposure from cocaine consumption further accelerates the development of white matter lesions remains unknown. Methods: We investigated the association of cocaine and levamisole exposure with white matter hyperintensities in 35 chronic cocaine users and 34 healthy controls. We measured cocaine and levamisole concentrations in hair samples, which reflected exposure up to 6 months previously. We assessed the number and total surface area of the white matter hyperintensities using structural MRI (FLAIR sequence). Using generalized linear models, we analyzed the contributions of cocaine and levamisole to the number and area of white matter hyperintensities, accounting for several confounding factors. Results: Analysis using generalized linear models revealed that cocaine users had more white matter hyperintensities in terms of total surface area, but not in terms of number. Further generalized linear models that included cocaine and levamisole hair concentrations (instead of group) as predictors indicated that levamisole exposure was strongly associated with more and larger white matter hyperintensities, suggesting that the elevated white matter hyperintensities in cocaine users were driven mainly by levamisole exposure. Finally, white matter hyperintensities in levamisole-exposed cocaine users were located primarily in the periventricular and juxtacortical white matter. Limitations: The sample size was moderate, and blood pressure was not systematically assessed. Conclusion: As an adulterant of cocaine, levamisole appears to increase the risk of white matter injury.

Bridging the brain structure-brain function gap in prosodic speech processing in older adults.

Age-related decline in speech perception may result in difficulties partaking in spoken conversation and potentially lead to social isolation and cognitive decline in older adults. It is therefore important to better understand how age-related differences in neurostructural factors such as cortical thickness (CT) and cortical surface area (CSA) are related to neurophysiological sensitivity to speech cues in younger and older adults. Age-related differences in CT and CSA of bilateral auditory-related areas were extracted using FreeSurfer in younger and older adults with normal peripheral hearing. Behavioral and neurophysiological sensitivity to prosodic speech cues (word stress and fundamental frequency of oscillation) was evaluated using discrimination tasks and a passive oddball paradigm, while EEG was recorded, to quantify mismatch negativity responses. Results revealed (a) higher neural sensitivity (i.e., larger mismatch negativity responses) to word stress in older adults compared to younger adults, suggesting a higher importance of prosodic speech cues in the speech processing of older adults, and (b) lower CT in auditory-related regions in older compared to younger individuals, suggesting neuronal loss associated with aging. Within the older age group, less neuronal loss (i.e., higher CT) in a right auditory-related area (i.e., the supratemporal sulcus) was related to better performance in fundamental frequency discrimination, while higher CSA in left auditory-related areas was associated with higher neural sensitivity toward prosodic speech cues as evident in the mismatch negativity patterns. Overall, our results offer evidence for neurostructural changes in aging that are associated with differences in the extent to which left and right auditory-related areas are involved in speech processing in older adults. We argue that exploring age-related differences in brain structure and function associated with decline in speech perception in older adults may help develop much needed rehabilitation strategies for older adults with central age-related hearing loss.

Longitudinal changes in cocaine intake and cognition are linked to cortical thickness adaptations in cocaine users.

BACKGROUND: Cocaine use has been consistently associated with decreased gray matter volumes in the prefrontal cortex. However, it is unclear if such neuroanatomical abnormalities depict either pre-existing vulnerability markers or drug-induced consequences. Thus, this longitudinal MRI study investigated neuroplasticity and cognitive changes in relation to altered cocaine intake. METHODS: Surface-based morphometry, cocaine hair concentration, and cognitive performance were measured in 29 cocaine users (CU) and 38 matched controls at baseline and follow-up. Based on changes in hair cocaine concentration, CU were classified either as Decreasers (n = 15) or Sustained Users (n = 14). Surface-based morphometry measures did not include regional tissue volumes. RESULTS: At baseline, CU displayed reduced cortical thickness (CT) in lateral frontal regions, and smaller cortical surface area (CSA) in the anterior cingulate cortex, compared to controls. In Decreasers, CT of the lateral frontal cortex increased whereas CT within the same regions tended to further decrease in Sustained Users. In contrast, no changes were found for CSA and subcortical structures. Changes in CT were linked to cognitive performance changes and amount of cocaine consumed over the study period. CONCLUSIONS: These results suggest that frontal abnormalities in CU are partially drug-induced and can recover with decreased substance use. Moreover, recovery of frontal CT is accompanied by improved cognitive performance confirming that cognitive decline associated with cocaine use is potentially reversible.

Cognitive and neuroanatomical impairments associated with chronic exposure to levamisole-contaminated cocaine.

Currently, levamisole is the most common cocaine adulterant worldwide and it is known to induce a variety of adverse side effects. Animal studies and human case reports suggest potential neurotoxicity of the compound but neither neuroanatomical nor cognitive effects of levamisole have been systematically investigated in cocaine users so far. We examined cognitive performance and cortical structural differences between chronic cocaine users with low and high recent exposure to levamisole objectively determined by quantitative toxicological hair analyses. In Study 1, we compared 26 chronic cocaine users with low levamisole exposure (lowLevCU), 49 matched cocaine users with high levamisole exposure (highLevCU), and 78 matched stimulant-naive controls regarding cognitive functioning employing a comprehensive neuropsychological test battery. In Study 2, we investigated cortical thickness by use of T1-weighted MRI in a subgroup of 12 lowLevCU, 17 highLevCU, and 38 stimulant-naive controls. In Study 1, both cocaine user groups showed significant impairments in the cognitive domains of attention and working memory as well as in the global cognitive index. However, highLevCU showed significantly worse executive functions compared to lowLevCU although both groups did not differ in severity of cocaine consumption and other clinical dimensions. Study 2 revealed that highLevCU, displayed reduced cortical thickness specifically in the middle frontal gyrus compared to both controls and lowLevCU. Our results suggest that levamisole exposure during the last months in cocaine users is associated with increased executive function impairments and pronounced thinning of the lateral prefrontal cortex. Consequently, prevention and drug policy-making should aim to reduce levamisole contamination of street cocaine.

Neuroanatomical and resting state EEG power correlates of central hearing loss in older adults.

To gain more insight into central hearing loss, we investigated the relationship between cortical thickness and surface area, speech-relevant resting state EEG power, and above-threshold auditory measures in older adults and younger controls. Twenty-three older adults and 13 younger controls were tested with an adaptive auditory test battery to measure not only traditional pure-tone thresholds, but also above individual thresholds of temporal and spectral processing. The participants' speech recognition in noise (SiN) was evaluated, and a T1-weighted MRI image obtained for each participant. We then determined the cortical thickness (CT) and mean cortical surface area (CSA) of auditory and higher speech-relevant regions of interest (ROIs) with FreeSurfer. Further, we obtained resting state EEG from all participants as well as data on the intrinsic theta and gamma power lateralization, the latter in accordance with predictions of the Asymmetric Sampling in Time hypothesis regarding speech processing (Poeppel, Speech Commun 41:245-255, 2003). Methodological steps involved the calculation of age-related differences in behavior, anatomy and EEG power lateralization, followed by multiple regressions with anatomical ROIs as predictors for auditory performance. We then determined anatomical regressors for theta and gamma lateralization, and further constructed all regressions to investigate age as a moderator variable. Behavioral results indicated that older adults performed worse in temporal and spectral auditory tasks, and in SiN, despite having normal peripheral hearing as signaled by the audiogram. These behavioral age-related distinctions were accompanied by lower CT in all ROIs, while CSA was not different between the two age groups. Age modulated the regressions specifically in right auditory areas, where a thicker cortex was associated with better auditory performance in older adults. Moreover, a thicker right supratemporal sulcus predicted more rightward theta lateralization, indicating the functional relevance of the right auditory areas in older adults. The question how age-related cortical thinning and intrinsic EEG architecture relates to central hearing loss has so far not been addressed. Here, we provide the first neuroanatomical and neurofunctional evidence that cortical thinning and lateralization of speech-relevant frequency band power relates to the extent of age-related central hearing loss in older adults. The results are discussed within the current frameworks of speech processing and aging.

Executive Functions in Healthy Older Adults Are Differentially Related to Macro- and Microstructural White Matter Characteristics of the Cerebral Lobes.

Aging is associated with microstructural white matter (WM) changes. WM microstructural characteristics, measured with diffusion tensor imaging (DTI), are different in normal appearing white matter (NAWM) and WM hyperintensities (WMH). It is largely unknown how the microstructural properties of WMH are associated with cognition and if there are regional effects for specific cognitive domains. We therefore examined within 200 healthy older participants (a) differences in microstructural characteristics of NAWM and WMH per cerebral lobe; and (b) the association of macrostructural (WMH volume) and microstructural characteristics (within NAWM and WMH separately) of each lobe with measures of executive function and processing speed. Multi-modal imaging (i.e., T1, DTI, and FLAIR) was used to assess WM properties. The Stroop and the Trail Making Test were used to measure inhibition, task-switching (both components of executive function), and processing speed. We observed that age was associated with deterioration of white matter microstructure of the NAWM, most notably in the frontal lobe. Older participants had larger WMH volumes and lowest fractional anisotropy values within WMH were found in the frontal lobe. Task-switching was associated with cerebral NAWM volume and NAWM volume of all lobes. Processing speed was associated with total NAWM volume, and microstructural properties of parietal NAWM, the parietal WMH, and the temporal NAWM. Task-switching was related to microstructural properties of WMH of the frontal lobe and WMH volume of the parietal lobe. Our results confirm that executive functioning and processing speed are uniquely associated with macro- and microstructural properties of NAWM and WMH. We further demonstrate for the first time that these relationships differ by lobar region. This warrants the consideration of these distinct WM indices when investigating cognitive function.

Regional cerebellar volumetric correlates of manual motor and cognitive function.

Cerebellar volume declines with aging. Few studies have investigated age differences in regional cerebellar volume (RCV) and their association with motor and cognitive function. In 213 healthy older adults, we investigated the association of age with motor skills, cognition and RCV. Subsequently, we studied the association of RCV with motor skills and cognition. RCVs were derived from T1-weighted MRI scans using the automated SUIT segmentation method and clustered using principal component analysis (PCA). Motor skill (manual dexterity, tapping speed, bimanual visuomotor coordination, grip force) and cognition (mental rotation, verbal memory, inhibition, mental flexibility) were assessed. Behavioral measures were clustered into compounds using PCA: left hand motor skill, right hand motor skill, verbal memory and mental flexibility, and mental rotation & inhibition. Volume of the rostral middle frontal gyri (rMFG) and premotor areas (PMA) were related to performance for reference. Analyses were adjusted for age, sex, and education. Volume of the cerebellar anterior lobe and top of the superior posterior lobe were positively associated with motor skill. Volume of the bottom part of the posterior superior lobe and the inferior posterior lobe was positively associated with cognition. PMA volume was associated with cognition and motor skill and rMFG volume with motor skill. Although these results did not survive FDR correction, their effect sizes suggest that regional cerebellar volume selectively contributes to cognitive and motor skill. Effect sizes of cerebellar associations with performance were similar to those of rMFG/PMA and performance suggesting parallel contributions to performance.

Structural and functional connectivity in healthy aging: Associations for cognition and motor behavior.

Age-related behavioral declines may be the result of deterioration of white matter tracts, affecting brain structural (SC) and functional connectivity (FC) during resting state. To date, it is not clear if the combination of SC and FC data could better predict cognitive/motor performance than each measure separately. We probed these relationships in the cingulum bundle, a major white matter pathway of the default mode network. We aimed to attain deeper knowledge about: (a) the relationship between age and the cingulum's SC and FC strength, (b) the association between SC and FC, and particularly (c) how the cingulum's SC and FC are related to cognitive/motor performance separately and combined. We examined these associations in a healthy and well-educated sample of 165 older participants (aged 64-85). SC and FC were acquired using probabilistic tractography to derive measures to capture white matter integrity within the cingulum bundle (fractional anisotropy, mean, axial and radial diffusivity) and a seed-based resting-state functional MRI correlation approach, respectively. Participants performed cognitive tests measuring processing speed, memory and executive functions, and motor tests measuring motor speed and grip force. Our data revealed that only SC but not resting state FC was significantly associated with age. Further, the cingulum's SC and FC showed no relation. Different relationships between cognitive/motor performance and SC/FC separately were found, but no additive effect of the combined analysis of cingulum's SC and FC for predicting cognitive/motor performance was apparent.

Improving sleep and cognition by hypnotic suggestion in the elderly.

Sleep quality markedly declines across the human lifespan. Particularly the amount of slow-wave sleep (SWS) decreases with age and this decrease is paralleled by a loss of cognitive functioning in the elderly. Here we show in healthy elderly females that the amount of SWS can be extended by a hypnotic suggestion "to sleep deeper" before sleep. In a placebo-controlled cross-over design, participants listened to hypnotic suggestions or a control tape before a midday nap while high density electroencephalography was recorded. After the hypnotic suggestion, we observed a 57% increase in SWS in females suggestible to hypnosis as compared to the control condition. Furthermore, left frontal slow-wave activity (SWA), characteristic for SWS, was significantly increased, followed by a significant improvement in prefrontal cognitive functioning after sleep. Our results suggest that hypnotic suggestions might be a successful alternative for widely-used sleep-enhancing medication to extend SWS and improve cognition in the elderly.

Cerebellar gray and white matter volume and their relation with age and manual motor performance in healthy older adults.

OBJECTIVES: Functional neuroimaging and voxel-based morphometry studies have confirmed the important role of the cerebellum in motor behavior. However, little is known about the relationship between cerebellar gray (GMv) and white matter (WMv) volume and manual motor performance in aging individuals. This study aims to quantify the relationship between cerebellar tissue volume and manual motor performance. EXPERIMENTAL DESIGN: To gain more insight into cerebellar function and how it relates to the role of the primary motor cortex (M1), we related cerebellar GMv, WMv, and M1v to manual motor performance in 217 healthy older individuals. Left and right cerebellar GMv and WMv, and M1v were obtained using FreeSurfer. The following motor measures were obtained: grip force, tapping speed, bimanual visuomotor coordination, and manual dexterity. PRINCIPAL OBSERVATIONS: Significant positive relationships were observed between cerebellar GMv and WMv and grip strength, right cerebellar WMv and right-hand tapping speed, right cerebellar WMv and dexterity, M1v and grip strength, and right M1v and left-hand dexterity, though effect sizes were small. CONCLUSIONS: Our results show that cerebellar GMv and WMv are differently associated with manual motor performance. These associations partly overlap with the brain-behavior associations between M1 and manual motor performance. Not all observed associations were lateralized (i.e., ipsilateral cerebellar and contralateral M1v associations with motor performance), which could point to age-related neural dedifferentiation. The current study provides new insights in the role of the cerebellum in manual motor performance. In consideration of the small effect sizes replication studies are needed to validate these results.

Reliability and statistical power analysis of cortical and subcortical FreeSurfer metrics in a large sample of healthy elderly.

FreeSurfer is a tool to quantify cortical and subcortical brain anatomy automatically and noninvasively. Previous studies have reported reliability and statistical power analyses in relatively small samples or only selected one aspect of brain anatomy. Here, we investigated reliability and statistical power of cortical thickness, surface area, volume, and the volume of subcortical structures in a large sample (N=189) of healthy elderly subjects (64+ years). Reliability (intraclass correlation coefficient) of cortical and subcortical parameters is generally high (cortical: ICCs>0.87, subcortical: ICCs>0.95). Surface-based smoothing increases reliability of cortical thickness maps, while it decreases reliability of cortical surface area and volume. Nevertheless, statistical power of all measures benefits from smoothing. When aiming to detect a 10% difference between groups, the number of subjects required to test effects with sufficient power over the entire cortex varies between cortical measures (cortical thickness: N=39, surface area: N=21, volume: N=81; 10mm smoothing, power=0.8, α=0.05). For subcortical regions this number is between 16 and 76 subjects, depending on the region. We also demonstrate the advantage of within-subject designs over between-subject designs. Furthermore, we publicly provide a tool that allows researchers to perform a priori power analysis and sensitivity analysis to help evaluate previously published studies and to design future studies with sufficient statistical power.

Associations between age, motor function, and resting state sensorimotor network connectivity in healthy older adults.

Aging is associated with impaired motor performance across a range of tasks. Both primary neural representations of movement and potential compensatory cognitive mechanisms appear to be disrupted in older age. Here we determined how age is associated with resting state sensorimotor functional connectivity, and whether connectivity strength is associated with motor performance. We investigated the association between age and resting state functional connectivity of several sensorimotor networks in 191 healthy older, right-handed individuals. Regions of interest were defined in the left motor cortex, left putamen, and right cerebellar lobules V and VIII. Analyses were adjusted for head motion, gray matter volume, diastolic blood pressure, and smoker status; we then evaluated whether connectivity is associated with participants' manual motor performance. We found both increased and decreased connectivity within portions of the motor cortical and cerebellar networks after adjusting for covariates. We observed that connectivity increased with age for the motor cortex and cerebellar lobule VIII with the putamen, providing evidence of greater interactivity across networks with age. Higher tapping frequency and greater grip force were associated with stronger connectivity between the motor cortex during resting state, putamen, cerebellar lobule VIII and the insular cortex, suggesting that greater network interactivity may protect against age declines in performance.

Longitudinal reliability of tract-based spatial statistics in diffusion tensor imaging.

Relatively little is known about reliability of longitudinal diffusion-tensor imaging (DTI) measurements despite growing interest in using DTI to track change in white matter structure. The purpose of this study is to quantify within- and between session scan-rescan reliability of DTI-derived measures that are commonly used to describe the characteristics of neural white matter in the context of neural plasticity research. DTI data were acquired from 16 cognitively healthy older adults (mean age 68.4). We used the Tract-Based Spatial Statistics (TBSS) approach implemented in FSL, evaluating how different DTI preprocessing choices affect reliability indices. Test-Retest reliability, quantified as ICC averaged across the voxels of the TBSS skeleton, ranged from 0.524 to 0.798 depending on the specific DTI-derived measure and the applied preprocessing steps. The two main preprocessing steps that we found to improve TBSS reliability were (a) the use of a common individual template and (b) smoothing DTI data using a 1-voxel median filter. Overall our data indicate that small choices in the preprocessing pipeline have a significant effect on test-retest reliability, therefore influencing the power to detect change within a longitudinal study. Furthermore, differences in the data processing pipeline limit the comparability of results across studies.

Cortical surface area and cortical thickness demonstrate differential structural asymmetry in auditory-related areas of the human cortex.

This investigation provides an analysis of structural asymmetries in 5 anatomically defined regions (Heschl's gyrus, HG; Heschl's sulcus, HS; planum temporale, PT; planum polare, PP; superior temporal gyrus, STG) within the human auditory-related cortex. Volumetric 3-dimensional T1-weighted magnetic resonance imaging scans were collected from 104 participants (52 males). Cortical volume (CV), cortical thickness (CT), and cortical surface area (CSA) were calculated based on individual scans of these anatomical traits. This investigation demonstrates a leftward asymmetry for CV and CSA that is observed in the HG, STG, and PT regions. As regards CT, we note a rightward asymmetry in the HG and HS. A correlation analysis of asymmetry indices between measurements for distinct regions of interest (ROIs) yields significant correlations between CT and CV in 4 of 5 ROIs (HG, HS, PT, and STG). Significant correlation values between CSA and CV are observed for all 5 ROIs. The findings suggest that auditory-related cortical areas demonstrate larger leftward asymmetry with respect to the CSA, while a clear rightward asymmetry with respect to CT is salient in both the primary and the secondary auditory cortex only. In addition, we propose that CV is not an ideal neuromarker for anatomical measurements. CT and CSA should be considered independent traits of anatomical asymmetries in the auditory-related cortex.

The integration of size and weight cues for perception and action: evidence for a weight-size illusion.

Humans routinely estimate the size and weight of objects. Yet, when lifting two objects of equal weight but different size, they often perceive the smaller object as being heavier. This size-weight illusion (SWI) is known to have a lesser effect on motor control of object lifting. How the nervous system combines "weight" and "size" cues with prior experience and whether these cues are differentially integrated for perception and sensorimotor action is still not fully understood. Therefore, we assessed not only whether the experience of size biases weight perception, but also if experience of weight biases the size perception of objects. Further, to investigate differences between perceptual and motor systems for cue-experience integration, participants haptically explored the weight of an object with one hand and then shaped the aperture of their other hand to indicate its perceived size. Results-First, next to a SWI, healthy adults (N = 21) perceived lighter objects as being smaller and heavier objects as being larger, demonstrating a weight-size illusion (WSI). Second, participants were more susceptible to either the SWI or WSI. Third, aperture of the non-exploring hand was scaled to perceived weight and not to physical size. Hand openings were consistently smaller than physical size, with SWI-sensitive participants being significantly more affected than WSI-sensitive subjects. We conclude: first, both size and weight perceptions are biased by prior experience. Weight perception is biased by expectations of size, while size perception is influenced by the expectancy of weight. Second, humans have the tendency to use one cue predominantly for both types of perception. Third, combining perceived weight with expected size influenced hand motor control, while online haptic feedback was largely ignored. Finally, we present a processing model underlying the size-weight cue integration for the perceptual and motor system.

Recovery of upper limb function after cerebellar stroke: lesion symptom mapping and arm kinematics.

BACKGROUND AND PURPOSE: Loss of movement coordination is the main postacute symptom after cerebellar infarction. Although the course of motor recovery has been described previously, detailed kinematic descriptions of acute stage ataxia are rare and no attempt has been made to link improvements in motor function to measures of neural recovery and lesion location. This study provides a comprehensive assessment of how lesion site and arm dysfunction are associated in the acute stage and outlines the course of upper limb motor recovery for the first 4 months after the infarction. METHODS: Sixteen adult patients with cerebellar stroke and 11 age-matched healthy controls participated. Kinematics of goal-directed and unconstrained finger-pointing movements were measured at the acute stage and in 2-week and 3-month follow-ups. MRI data were obtained for the acute and 3-month follow-up sessions. A voxel-based lesion map subtraction analysis was performed to examine the effect of ischemic lesion sites on kinematic performance. RESULTS: In the acute stage, nearly 70% of patients exhibited motor slowing with hand velocity and acceleration maxima below the range of the control group. MRI analysis revealed that in patients with impaired motor performance, lesions were more common in paravermal lobules IV/V and affected the deep cerebellar nuclei. Stroke affecting the superior cerebellar artery led to lower motor performance than infractions of the posterior cerebellar artery. By the 2-week-follow-up, hand kinematics had improved dramatically (gains in acceleration up to 86%). Improvements between the 2-week and the 3-month-follow-ups were less pronounced. CONCLUSIONS: In the acute stage, arm movements were mainly characterized by abnormal slowness (bradykinesia) and not dyscoordination (ataxia). The motor signs were associated with lesions in paravermal regions of lobules IV/V and the deep cerebellar nuclei. Motor recovery was fast, with the majority of gains in upper limb function occurring in the first 2 weeks after the acute phase.