Modulation of 7 T fMRI Signal in the Cerebellar Cortex and Nuclei During Acquisition, Extinction, and Reacquisition of Conditioned Eyeblink Responses.

Classical delay eyeblink conditioning is likely the most commonly used paradigm to study cerebellar learning. As yet, few studies have focused on extinction and savings of conditioned eyeblink responses (CRs). Saving effects, which are reflected in a reacquisition after extinction that is faster than the initial acquisition, suggest that learned associations are at least partly preserved during extinction. In this study, we tested the hypothesis that acquisition-related plasticity is nihilated during extinction in the cerebellar cortex, but retained in the cerebellar nuclei, allowing for faster reacquisition. Changes of 7 T functional magnetic resonance imaging (fMRI) signals were investigated in the cerebellar cortex and nuclei of young and healthy human subjects. Main effects of acquisition, extinction, and reacquisition against rest were calculated in conditioned stimulus-only trials. First-level ß values were determined for a spherical region of interest (ROI) around the acquisition peak voxel in lobule VI, and dentate and interposed nuclei ipsilateral to the unconditioned stimulus. In the cerebellar cortex and nuclei, fMRI signals were significantly lower in extinction compared to acquisition and reacquisition, but not significantly different between acquisition and reacquisition. These findings are consistent with the theory of bidirectional learning in both the cerebellar cortex and nuclei. It cannot explain, however, why conditioned responses reappear almost immediately in reacquisition following extinction. Although the present data do not exclude that part of the initial memory remains in the cerebellum in extinction, future studies should also explore changes in extracerebellar regions as a potential substrate of saving effects. Hum Brain Mapp 38:3957-3974, 2017. © 2017 Wiley Periodicals, Inc.

Cerebellar cortex and cerebellar nuclei are concomitantly activated during eyeblink conditioning: a 7T fMRI study in humans.

There are controversies whether learning of conditioned eyeblink responses primarily takes place within the cerebellar cortex, the interposed nuclei, or both. It has also been suggested that the cerebellar cortex may be important during early stages of learning, and that there is a shift to the cerebellar nuclei during later stages. As yet, human studies have provided little to resolve this question. In the present study, we established a setup that allows ultra-high-field 7T functional magnetic resonance imaging (fMRI) of the cerebellar cortex and interposed cerebellar nuclei simultaneously during delay eyeblink conditioning in humans. Event-related fMRI signals increased concomitantly in the cerebellar cortex and nuclei during early acquisition of conditioned eyeblink responses in 20 healthy human subjects. ANOVAs with repeated-measures showed significant effects of time across five blocks of 20 conditioning trials in the cortex and nuclei (p < 0.05, permutation corrected). Activations were most pronounced in, but not limited to, lobules VI and interposed nuclei. Increased activations were most prominent at the first time the maximum number of conditioned responses was achieved. Our data are consistent with a simultaneous and synergistic two-site model of learning during acquisition of classically conditioned eyeblinks. Because increased MRI signal reflects synaptic activity, concomitantly increased signals in the cerebellar nuclei and cortex are consistent with findings of learning related potentiation at the mossy fiber to nuclear cell synapse and mossy fiber to granule cell synapse. Activity related to the expression of conditioned responses, however, cannot be excluded.

Structural and functional MRI abnormalities of cerebellar cortex and nuclei in SCA3, SCA6 and Friedreich's ataxia.

Spinocerebellar ataxia type 3, spinocerebellar ataxia type 6 and Friedreich's ataxia are common hereditary ataxias. Different patterns of atrophy of the cerebellar cortex are well known. Data on cerebellar nuclei are sparse. Whereas cerebellar nuclei have long been thought to be preserved in spinocerebellar ataxia type 6, histology shows marked atrophy of the nuclei in Friedreich's ataxia and spinocerebellar ataxia type 3. In the present study susceptibility weighted imaging was used to assess atrophy of the cerebellar nuclei in patients with spinocerebellar ataxia type 6 (n = 12, age range 41-76 years, five female), Friedreich's ataxia (n = 12, age range 21-55 years, seven female), spinocerebellar ataxia type 3 (n = 10, age range 34-67 years, three female), and age- and gender-matched controls (total n = 23, age range 22-75 years, 10 female). T1-weighted magnetic resonance images were used to calculate the volume of the cerebellum. In addition, ultra-high field functional magnetic resonance imaging was performed with optimized normalization methods to assess function of the cerebellar cortex and nuclei during simple hand movements. As expected, the volume of the cerebellum was markedly reduced in spinocerebellar ataxia type 6, preserved in Friedreich's ataxia, and mildy reduced in spinocerebellar ataxia type 3. The volume of the cerebellar nuclei was reduced in the three patient groups compared to matched controls (P-values < 0.05; two-sample t-tests). Atrophy of the cerebellar nuclei was most pronounced in spinocerebellar ataxia type 6. On a functional level, hand-movement-related cerebellar activation was altered in all three disorders. Within the cerebellar cortex, functional magnetic resonance imaging signal was significantly reduced in spinocerebellar ataxia type 6 and Friedreich's ataxia compared to matched controls (P-values < 0.001, bootstrap-corrected cluster-size threshold; two-sample t-tests). The difference missed significance in spinocerebellar ataxia type 3. Within the cerebellar nuclei, reductions were significant when comparing spinocerebellar ataxia type 6 and Friedreich's ataxia to matched controls (P < 0.01, bootstrap-corrected cluster-size threshold; two-sample t-tests). Susceptibility weighted imaging allowed depiction of atrophy of the cerebellar nuclei in patients with Friedreich's ataxia and spinocerebellar ataxia type 3. In spinocerebellar ataxia type 6, pathology was not restricted to the cerebellar cortex but also involved the cerebellar nuclei. Functional magnetic resonance imaging data, on the other hand, revealed that pathology in Friedreich's ataxia and spinocerebellar ataxia type 3 is not restricted to the cerebellar nuclei. There was functional involvement of the cerebellar cortex despite no or little structural changes.

Sex differences in cerebellar mechanisms involved in pain-related safety learning.

Recent studies have suggested that the cerebellum contributes to the central processing of pain, including pain-related learning and memory processes. As a complex experience with multiple emotional and cognitive facets, the response to pain and its underlying neural correlates differ between men and women. However, it remains poorly understood whether and to what extent sex differences exist in the cerebellar contribution to pain-related associative learning processes. In the present conditioning study with experimental abdominal pain as unconditioned stimuli (US), we assessed sex-dependent differences in behavioral and neural responses to conditioned warning and safety cues in healthy volunteers. The results revealed that in response to visual stimuli signaling safety from abdominal pain (CS(-)), women showed enhanced cerebellar activation in lobules I-IV, V, VI, VIIIa, IX and X as well as Crus II and the dentate nucleus, which are mostly representative of somatomotor networks. On the other hand, men showed enhanced neural activation in lobules I-IV, VI, VIIb, VIIIb, IX as well as Crus I and II in response to CS(-), which are representative of frontoparietal and ventral attention networks. No sex differences were observed in response to pain-predictive warning signals (CS(+)). Similarly, men and women did not differ in behavioral measures of conditioning, including conditioned changes in CS valence and contingency awareness. Together, we could demonstrate that the cerebellum is involved in associative learning processes of conditioned anticipatory safety from pain and mediates sex differences in the underlying neural processes. Given the high prevalence of chronic pain conditions in women, these results may contribute to improve our understanding of the acquisition and manifestation of chronic abdominal pain syndromes.

Experience with magnetic resonance imaging of human subjects with passive implants and tattoos at 7 T: a retrospective study.

OBJECT: Over the last decade, the number of clinical MRI studies at 7 T has increased dramatically. Since only limited information about the safety of implants/tattoos is available at 7 T, many centers either conservatively exclude all subjects with implants/tattoos or have started to perform dedicated tests for selected implants. This work presents our experience in imaging volunteers with implants/tattoos at 7 T over the last seven and a half years. MATERIALS AND METHODS: 1796 questionnaires were analyzed retrospectively to identify subjects with implants/tattoos imaged at 7 T. For a total of 230 subjects, the type of local transmit/receive RF coil used for examination, imaging sequences, acquisition time, and the type of implants/tattoos and their location with respect to the field of view were documented. These subjects had undergone examination after careful consideration by an internal safety panel consisting of three experts in MR safety and physics. RESULTS: None of the subjects reported sensations of heat or force before, during, or after the examination. None expressed any discomfort related to implants/tattoos. Artifacts were reported in 52% of subjects with dental implants; all artifacts were restricted to the mouth area and did not affect image quality in the brain parenchyma. CONCLUSION: Our initial experience at 7 T indicates that a strict rejection of subjects with tattoos and/or implants is not justified. Imaging can be conditionally performed in carefully selected subjects after collection of substantial safety information and evaluation of the detailed exposure scenario (RF coil/type and position of implant). Among the assessed subjects with tattoos, no side effects from the exposure to 7 T MRI were reported.

Activation of the cerebellar cortex and the dentate nucleus in a prism adaptation fMRI study.

During prism adaptation two types of learning processes can be distinguished. First, fast strategic motor control responses are predominant in the early course of prism adaptation to achieve rapid error correction within few trials. Second, slower spatial realignment occurs among the misaligned visual and proprioceptive sensorimotor coordinate system. The aim of the present ultra-highfield (7T) functional magnetic resonance imaging (fMRI) study was to explore cerebellar cortical and dentate nucleus activation during the course of prism adaptation in relation to a similar visuomotor task without prism exposure. Nineteen young healthy participants were included into the study. Recently developed normalization procedures were applied for the cerebellar cortex and the dentate nucleus. By means of subtraction analysis (early prism adaptation > visuomotor, early prism adaptation > late prism adaptation) we identified ipsilateral activation associated with strategic motor control responses within the posterior cerebellar cortex (lobules VIII and IX) and the ventro-caudal dentate nucleus. During the late phase of adaptation we observed pronounced activation of posterior parts of lobule VI, although subtraction analyses (late prism adaptation > visuomotor) remained negative. These results are in good accordance with the concept of a representation of non-motor functions, here strategic control, within the ventro-caudal dentate nucleus.

Cerebellar contributions to different phases of visceral aversive extinction learning.

The cerebellum is increasingly recognized to contribute to non-motor functions, including cognition and emotion. Although fear conditioning has been studied for elucidating the pathophysiology of anxiety, the putative role of the cerebellum is still unknown. Fear conditioning could also be important in the etiology of chronic abdominal pain which often overlaps with anxiety. Hence, in this exploratory analysis, we investigated conditioned anticipatory activity in the cerebellum in a visceral aversive fear conditioning paradigm using functional magnetic resonance imaging. We extended and reanalyzed a previous dataset for different learning phases, i.e., acquisition, extinction, and reinstatement, utilizing an advanced normalizing method of the cerebellum. In 30 healthy humans, visual conditioned stimuli (CS(+)) were paired with painful rectal distensions as unconditioned stimuli (US), while other visual stimuli (CS(-)) were presented without US. During extinction, all CSs were presented without US, whereas during reinstatement, a single, unpaired US was presented. During acquisition, posterolateral cerebellar areas including Crus I, Crus II, and VIIb and parts of the dentate nucleus were activated in response to the CS(+) compared to the CS(-). During extinction, activation related to CS(+) presentation was detected in Crus I, Crus II, IV, V, VI, VIIb, IX, and vermis. Neural correlates of reinstatement were found in Crus I, Crus II, IV, V, and IX. We could show for the first time that the cerebellum is involved in abdominal pain-related associative learning processes. Together, these findings contribute to our understanding of the cerebellum in aversive learning and memory processes relevant to the pathophysiology of chronic abdominal pain.

Consensus paper: Language and the cerebellum: an ongoing enigma.

In less than three decades, the concept "cerebellar neurocognition" has evolved from a mere afterthought to an entirely new and multifaceted area of neuroscientific research. A close interplay between three main strands of contemporary neuroscience induced a substantial modification of the traditional view of the cerebellum as a mere coordinator of autonomic and somatic motor functions. Indeed, the wealth of current evidence derived from detailed neuroanatomical investigations, functional neuroimaging studies with healthy subjects and patients and in-depth neuropsychological assessment of patients with cerebellar disorders shows that the cerebellum has a cardinal role to play in affective regulation, cognitive processing, and linguistic function. Although considerable progress has been made in models of cerebellar function, controversy remains regarding the exact role of the "linguistic cerebellum" in a broad variety of nonmotor language processes. This consensus paper brings together a range of different viewpoints and opinions regarding the contribution of the cerebellum to language function. Recent developments and insights in the nonmotor modulatory role of the cerebellum in language and some related disorders will be discussed. The role of the cerebellum in speech and language perception, in motor speech planning including apraxia of speech, in verbal working memory, in phonological and semantic verbal fluency, in syntax processing, in the dynamics of language production, in reading and in writing will be addressed. In addition, the functional topography of the linguistic cerebellum and the contribution of the deep nuclei to linguistic function will be briefly discussed. As such, a framework for debate and discussion will be offered in this consensus paper.

Storage of a naturally acquired conditioned response is impaired in patients with cerebellar degeneration.

Previous findings suggested that the human cerebellum is involved in the acquisition but not the long-term storage of motor associations. The finding of preserved retention in cerebellar patients was fundamentally different from animal studies which show that both acquisition and retention depends on the integrity of the cerebellum. The present study investigated whether retention had been preserved because critical regions of the cerebellum were spared. Visual threat eye-blink responses, that is, the anticipatory closure of the eyes to visual threats, have previously been found to be naturally acquired conditioned responses. Because acquisition is known to take place in very early childhood, visual threat eye-blink responses can be used to test retention in patients with adult onset cerebellar disease. Visual threat eye-blink responses were tested in 19 adult patients with cerebellar degeneration, 27 adult patients with focal cerebellar lesions due to stroke, 24 age-matched control subjects, and 31 younger control subjects. High-resolution structural magnetic resonance images were acquired in patients to perform lesion-symptom mapping. Voxel-based morphometry was performed in patients with cerebellar degeneration, and voxel-based lesion-symptom mapping in patients with focal disease. Visual threat eye-blink responses were found to be significantly reduced in patients with cerebellar degeneration. Visual threat eye-blink responses were also reduced in patients with focal disease, but to a lesser extent. Visual threat eye-blink responses declined with age. In patients with cerebellar degeneration the degree of cerebellar atrophy was positively correlated with the reduction of conditioned responses. Voxel-based morphometry showed that two main regions within the superior and inferior parts of the posterior cerebellar cortex contributed to expression of visual threat eye-blink responses bilaterally. Involvement of the more inferior parts of the posterior lobe was further supported by voxel-based lesion symptom mapping in focal cerebellar patients. The present findings show that the human cerebellar cortex is involved in long-term storage of learned responses.

Contributions of the cerebellum to disturbed central processing of visceral stimuli in irritable bowel syndrome.

There is evidence to support that the cerebellum contributes to the neural processing of both emotions and painful stimuli. This could be particularly relevant in conditions associated with chronic abdominal pain, such as the irritable bowel syndrome (IBS), which are often also characterized by affective disturbances. We aimed to test the hypothesis that in IBS, symptoms of anxiety and depression modulate brain activation during visceral stimulation within the cerebellum. We reanalyzed a previous data set from N = 15 female IBS patients and N = 12 healthy women with a specific focus on the cerebellum using advanced normalization methods. Rectal distension-induced brain activation was measured with functional magnetic resonance imaging using non-painful and painful rectal distensions. Symptoms of anxiety and depression, assessed with the Hospital Anxiety and Depression scale, were correlated with cerebellar activation within IBS patients. Within IBS, depression scores were associated with non-painful distension-induced activation in the right cerebellum primarily in Crus II and lobule VIIIb, and additionally in Crus I. Depression scores were also associated with painful distension-induced activation predominantly in vermal lobule V with some extension to the intermediate cerebellum. Anxiety scores correlated significantly with non-painful induced activation in Crus II. Symptoms of anxiety and depression, which are frequently found in chronic pain conditions like IBS, modulate activation during visceral sensory signals not only in cortical and subcortical brain areas but also in the cerebellum.

Evidence for a motor somatotopy in the cerebellar dentate nucleus--an FMRI study in humans.

Previous anatomical studies in monkeys have shown that forelimb motor representation is located caudal to hindlimb representation within the dorso-rostral dentate nucleus. Here we investigate human dentate nucleus motor somatotopy by means of ultra-highfield (7 T) functional magnetic brain imaging (fMRI). Twenty five young healthy males participated in the study. Simple finger and foot movement tasks were performed to identify dentate nucleus motor areas. Recently developed normalization procedures for group analyses were used for the cerebellar cortex and the cerebellar dentate nucleus. Cortical activations were in good accordance with the known somatotopy of the human cerebellar cortex. Dentate nucleus activations following motor tasks were found in particular in the ipsilateral dorso-rostral nucleus. Activations were also present in other parts of the nucleus including the contralateral side, and there was some overlap between the body part representations. Within the ipsilateral dorso-rostral dentate, finger activations were located caudally compared to foot movement-related activations in fMRI group analysis. Likewise, the centre of gravity (COG) for the finger activation was more caudal than the COG of the foot activation across participants. A multivariate analysis of variance (MANOVA) on the x, y, and z coordinates of the COG indicated that this difference was significant (P = 0.043). These results indicate that in humans, the lower and upper limbs are arranged rostro-caudally in the dorsal aspect of the dentate nucleus, which is consistent with studies in non-human primates.

Structural and functional magnetic resonance imaging of the human cerebellar nuclei.

The present review focuses on recent developments in structural and functional magnetic resonance imaging (MRI) of the deep cerebellar nuclei (DCN), the main output structure of the cerebellum. The high iron content in the DCN allows for their visibility in T2*-weighted images. Spatial resolution has improved allowing the identification of DCN in individual cerebellar patients and healthy subjects. Based on findings in larger groups of healthy subjects, probabilistic MRI-based atlases of the deep cerebellar nuclei have been developed, which are important tools in human lesion and functional imaging studies. High iron content in the DCN, on the other hand, decreases the blood oxygenation level dependent-signal making functional imaging a difficult challenge. Compared to the vast amount of studies reporting activation of the cerebellar cortex, the number of studies demonstrating activation of the DCN is much less. Most studies report activation of the dentate nucleus. Dentate activations appear to be more reliable in more complex tasks for reasons currently unknown. As yet, few studies tried to show activations of functional subunits of the dentate nucleus. Increased signal-to-noise ratio and better spatial resolution using higher MR field strength together with recent progress in dentate normalization methods will allow identification of functional subunits and their interactions with the cerebellar cortex in future studies.

Impaired prehension is associated with lesions of the superior and inferior hand representation within the human cerebellum.

Impairment of patients with cerebellar disease in prehension is well recognized. So far specific localizations within the human cerebellum associated with the impairment have rarely been assessed. To address this question we performed voxel-based lesion symptom mapping (VLSM) in patients with chronic focal cerebellar lesions in relation to specific deficits in prehensile movements. Patients with stroke within the posterior inferior cerebellar artery territory (n = 13) or the superior cerebellar artery (SCA) territory (n = 7) and corresponding control subjects were included in the study. Participants reached out, grasped, and lifted an object with either the left or right hand and with fast or normal movement speed. Both kinematic and grip-force parameters were recorded. Magnetic resonance imaging anatomical scans of the cerebellum were acquired, and lesions were marked as regions of interest. For VLSM analysis, a nonparametric test (Brunner-Munzel) was applied. Cerebellar patients showed clear abnormalities in hand transport (impaired movement speed and straightness) and, to a lesser degree, in hand shaping (increased finger touch latencies) while grip function was preserved. Deficits were most prominent in patients with SCA lesions and for ipsilesional, fast movements. Disorders in hand transport may be more difficult to compensate than deficits in hand shaping and grip-force control in chronic focal lesions of the cerebellum because of higher demands on predictive control of interaction torques. Lesions of the superior cerebellar cortex (lobules IV, V, VI) were associated with slower hand transport, whereas lesions of both superior (lobules VI, V, VI) and inferior cerebellar cortex (lobules VII, VIII) were associated with impaired movement straightness. These findings show that both the superior and inferior hand representations within the cerebellum contribute to hand transport during prehensile movements; however, they may have a different functional role.

Cerebellar transcranial direct current stimulation modulates the fMRI signal in the cerebellar nuclei in a simple motor task.

BACKGROUND: In a seminal paper, Galea et al. (Modulation of cerebellar excitability by polarity-specific noninvasive direct current stimulation. 2009. J Neurosci 29, 9115-9122) showed that cerebellar transcranial direct current stimulation (ctDCS) alters cerebellar-M1 connectivity. This effect has been explained by ctDCS-related changes of excitability of the cerebellar cortex with consecutive modulation of its main output, the dentate-thalamo-cortical pathway. OBJECTIVES: The aim of this functional magnetic resonance imaging (fMRI) study was to provide evidence that cathodal ctDCS decreases the activity of the cerebellar cortex, resulting in increased activity of the cerebellar nuclei, whereas anodal ctDCS has the opposite effect. METHODS: A total of 48 participants (female/male: 23/25, age: 23.8 ±â€¯4.1yrs., mean ±â€¯standard deviation) performed a finger tapping task with the right hand in a 3T MRI scanner. Functional MR images were acquired prior, during and after tDCS of the right cerebellum. Participants were assigned randomly to anodal, cathodal or sham ctDCS. RESULTS: No significant difference of cerebellar cortical activation was found after comparing the three modes of stimulation. On the level of the dentate nuclei, however, a significant increase of activation was detected during and after cathodal stimulation. Furthermore, dentate nuclei activation was suppressed on a trend level following anodal stimulation. CONCLUSIONS: The present findings support the hypothesis that cathodal ctDCS leads to a disinhibition of the dentate nucleus, whereas anodal ctDCS may have the opposite effect.

A cerebellar role in performance monitoring - evidence from EEG and voxel-based morphometry in patients with cerebellar degenerative disease.

The cerebellum applies an internal forward-model to predict the sensory consequences of actions. This forward-model is updated based on on-line performance monitoring. A previous study has shown that performance monitoring is altered in patients with focal vascular cerebellar lesions, but altered neural responses are not paralleled by impaired behaviour, and the critical cerebellar sites have yet to be identified. The present study investigated if saccadic performance monitoring is more severely altered in patients with cerebellar degenerative disease relative to the previously examined patients with focal vascular cerebellar lesions, and which cerebellar regions support performance monitoring. 16 patients and 16 healthy controls performed an antisaccade task while an electroencephalogram (EEG) was recorded. Error rates were increased, and the error-related negativity (ERN), an event-related potential (ERP) component associated with error processing/performance monitoring, was reduced while the error positivity (Pe), a later ERP component related to more conscious aspects of error processing, was preserved in patients. Thus, performance monitoring is altered in patients with cerebellar degeneration, confirming a critical role of the cerebellum for fast classification of saccadic accuracy. In contrast to patients with focal lesions, post-acute functional reorganization and compensation presumably is hampered by disease progression, resulting in altered neural processing and impaired behavioural performance. Voxel-based morphometry (VBM) indicated the strongest effects for behavioural performance, with correlations between gray matter volume reduction in bilateral posterolateral regions (left Crus II and right lobule VI) and increased error rates. Moreover, somewhat smaller correlations were found for volume loss in left lobule VIIb/VIIIa and right lobule V and ERN amplitude, and in right Crus I and Pe amplitude. The present findings are consistent with involvement of posterolateral cerebellar regions in motor and cognitive functions.

Evaluation of a new approach for semi-automatic segmentation of the cerebellum in patients with multiple sclerosis.

Cerebellar dysfunction is an important contributor to disability in patients with multiple sclerosis (MS), however, few in vivo studies focused on cerebellar volume loss so far. This relates to technical challenges regarding the segmentation of the cerebellum. In this study, we evaluated the semi-automatic ECCET software for performing cerebellar volumetry using high-resolution 3D T1-MR scans in patients with MS and healthy volunteers. We performed test-retest as well as inter-observer reliability testing of cerebellar segmentation and compared the ECCET results with a fully automatic cerebellar segmentation using the FreeSurfer software pipeline in 15 MS patients. In a pilot matched-pair analysis with another data set from 15 relapsing-remitting MS patients and 15 age- and sex-matched healthy controls (HC), we assessed the feasibility of the ECCET approach to detect MS-related cerebellar volume differences. For total normalized cerebellar volume as well as grey and white matter volumes, intrarater (intraclass correlation coefficient (ICC) = 0.99, 95 % CI = 0.98-0.99) and interobserver agreement (ICC = 0.98, 95 % CI = 0.74-0.99) were strong. Comparison between ECCET and FreeSurfer results likewise yielded a good intraclass correlation (ICC = 0.86, 95 % CI = 0.58-0.95). Compared to HC, MS patients had significantly reduced normalized total brain, total cerebellar, and grey matter volumes (p ≤ 0.05). ECCET is a suitable tool for cerebellar segmentation showing excellent test-retest and inter-observer reliability. Our matched-pair analysis between MS patients and healthy volunteers suggests that the method is sensitive and reliable in detecting cerebellar atrophy in MS.