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Abstract

Background: Although depressive symptoms are often reported to be comorbid with degenerative cerebellar diseases, the role of the cerebellum in depressive disorder needs to be elucidated. To address this aim, we investigated self-perception of the negative mood state in patients with cerebellar pathology and depressive symptoms. Methods: Thirty-eight patients with cerebellar damage (10 with depressive symptoms – CB-DP and 28 with no depressive symptoms – CB-nDP), 11 subjects with depressive disorders without cerebellar damage (DP) and 29 healthy controls (CTs) were enrolled. A device for self-monitoring of the mood state (MoMo) and validated scales such as the Profile of Mood States questionnaire (POMS), the Self-Report Symptom Inventory-Revised (SCL-90-R) and the Hamilton Depression Rating Scale (HDRS) were used to evaluate depressive symptoms. Results: Both CB-DP and DP patients showed higher scores than CTs on the POMS and SCL-90-R for depressive factors and on the HDRS. DP patients showed a lower frequency of ‘good’ mood and a higher frequency of ‘bad’ mood than CTs when using the MoMo device. However, although the two depressed populations showed comparable scores on these validated scales, CB-DP patients showed impaired self-awareness of the mood experience in ‘the here and now’ as evidenced by the absence of significant differences, compared with CTs, in the subjective mood evaluation performed with the MoMo device. Limitations: The number of CB patients and inhomogeneity across MRI scans were study limitations. Conclusion: Cerebellar dysfunction might slow the data integration necessary for mood state awareness, resulting in difficulty of depressed CB patients in explicitly recognizing their mood “in the here and now”.

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... The DN alteration is of particular interest, given the cerebellar anatomy. Indeed, the DN is the major cerebellar output channel connecting to the cerebral cortex (8), and modifications in functional connectivity (FC) within specific cerebello-cortical networks have already been described in patients affected by other forms of cerebellar atrophy (9)(10)(11)(12) and linked to motor, cognitive, and behavioral symptoms (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). ...
... Additionally, the in-depth investigation of social skills indicated specific difficulties in the attribution of the "embarrassed" emotion, in the automatic attribution of relevant mental states regardless of the context (RME), and in theory of mind. Interestingly, a recent study by Clausi et al. (9) described a similar impairment in patients affected by cerebellar atrophy. Indeed, they were characterized by a lack of ability to "tune in" to the mental state of another person both at an unconscious and an automatic level, as assessed by RME, and at a more complex and conscious level, as assessed by ToM. ...
... The left DN showed an increased FC with the ipsilateral occipital cortex, the left supramarginal gyrus, and the left superior parietal lobule. In particular, the supramarginal gyrus is involved not only in retrieval and episodic memory but also in social interaction, similar to the left superior parietal lobe (61)(62)(63)(64)(65), confirming the cerebello-cortical dysregulation in different networks involved in social functioning (9,12,61,64). ...
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Spastic paraplegia type 7 (SPG7), which represents one of the most common forms of autosomal recessive spastic paraplegia (MIM#607259), often manifests with a complicated phenotype, characterized by progressive spastic ataxia with evidence of cerebellar atrophy on brain MRI. Recent studies have documented the presence of peculiar dentate nucleus hyperintensities on T2-weighted images and frontal executive dysfunction in neuropsychological tests in SPG7 patients. Therefore, we decided to assess whether any particular MRI pattern might be specifically associated with SPG7 mutations and possibly correlated with patients' cognitive profiles. For this purpose, we evaluated six SPG7 patients, studying the cerebello-cortical network by MRI voxel-based morphometry and functional connectivity techniques, compared to 30 healthy control subjects. In parallel, we investigated the cognitive and social functioning of the SPG7 patients. Our results document specific cognitive alterations in language, verbal memory, and executive function in addition to an impairment of social task and emotional functions. The MRI scans showed a diffuse symmetric reduction in the cerebellar gray matter of the right lobule V, right Crus I, and bilateral lobule VI, together with a cerebral gray matter reduction in the lingual gyrus, precuneus, thalamus, and superior frontal gyrus. The evidence of an over-connectivity pattern between both the right and left cerebellar dentate nuclei and specific cerebral regions (the lateral occipital cortex, precuneus, left supramarginal gyrus, and left superior parietal lobule) confirms the presence of cerebello-cortical dysregulation in different networks involved in cognition and social functioning in SPG7 patients.
... The experience of feeling is fundamentally influenced by one's conscious awareness and interpretation of one's mood[129], requiring interdependence between emotion and cognition that is sustained by the extensive interconnections between the limbic system and the cortical association areas[130]to which the cerebellum is strongly connected. Cerebellar recruitment in the conscious component of emotional behavior, related to the awareness of one's affective state and the interpretation of one's mood, has been observed as a loss in self-perception of emotions in the presence of cerebellar pathology[70,71,131]. In recent studies, we found that patients with cerebellar damage were unable to feel conscious emotions of regret as a consequence of their disadvantageous choices in a gambling task[71]or to explicitly recognize their bad mood in the presence of clinically relevant depressive disorder[70,131](seeTable 1for details on reported studies). ...
... Cerebellar recruitment in the conscious component of emotional behavior, related to the awareness of one's affective state and the interpretation of one's mood, has been observed as a loss in self-perception of emotions in the presence of cerebellar pathology[70,71,131]. In recent studies, we found that patients with cerebellar damage were unable to feel conscious emotions of regret as a consequence of their disadvantageous choices in a gambling task[71]or to explicitly recognize their bad mood in the presence of clinically relevant depressive disorder[70,131](seeTable 1for details on reported studies). ...
... In this framework, we have demonstrated that in estimating regret, a subject with cerebellar damage fails to compare the basic emotional state (internal state) that follows his decision and the state that is determined by the external event, based on a gambling result[71]. Similarly, in estimating mood state by a mood monitoring (MoMo) device[150], a subject who is affected by cerebellar damage is unable to recognize his bad mood state (internal state), which shows his inability to compare the internal state with the external negative or positive event[70,131]. These observations are consistent with the cerebellar involvement in optimizing internal and external responses according to the environment, akin to a master regulatory structure for integrating motor, emotional, and sensory information that affects " mind–world synchronization "[151]. ...
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Studies from the past three decades have demonstrated that there is cerebellar involvement in the emotional domain. Emotional processing in humans requires both unconscious and conscious mechanisms. A significant amount of evidence indicates that the cerebellum is one of the cerebral structures that subserve emotional processing, although conflicting data has been reported on its function in unconscious and conscious mechanisms. This review discusses the available clinical, neuroimaging, and neurophysiological data on this issue. We also propose a model in which the cerebellum acts as a mediator between the internal state and external environment for the unconscious and conscious levels of emotional processing.
... Indeed, neuroimaging studies have described cerebellar alterations in patients with bipolar disorder [24][25][26][27] over the last twenty years and researchers have focused on this structure [28][29][30][31][32] in light of the cerebellar connections with cortical areas involved in the pathophysiology of bipolar disorder [13,28,31,33,34] and the cerebellar role in emotion [35][36][37][38][39], social cognition [16,40,41] and cognitive functions [42][43][44][45]. Moreover, it is worth noting that very recently the onset of mood disorders (manic and depressive symptoms) has been demonstrated in the presence of isolated cerebellar lesions and neurodegenerative cerebellar pathologies [46][47][48][49]. These data confirm that cerebellar alterations are associated with mood symptoms, as reported in cerebellar-cognitive affective syndrome (CCAS) [50]. ...
... The comparison between cerebellar-related neurodegenerative syndromes (such as SCA) and BD mainly arises from the growing evidence of a cerebellar involvement in manic symptoms of BD [49] and the presence of mood disturbance in cerebellar diseases [46]. As largely demonstrated, the posterior cerebellum is involved in the processing of cognitive and emotional information and takes part in the network involved in mentalizing and social interactions [16,40,41,49,[52][53][54][55][56]. ...
... In line with the presence of typical cerebellar motor syndrome [19,55,69], an extensive pattern of GM loss involved motor anterior (i.e., I−IV, V) and posterior cerebellar regions (i.e., VIIIA and VIIIB). On the other hand, a pattern of GM loss was also found to extensively affect cognitive posterior cerebellar lobules, specifically crus I, crus II and lobe VI, in line with the presence of cognitive and emotional alterations as reported in CCAS [46,54,55,[69][70][71][72]. Finally, when directly comparing BD and CD patients, significantly reduced cerebellar GM was found in the CD compared to the BD patients, only involving motor anterior cerebellar regions. ...
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The aim of this study was to compare the patterns of cerebellar alterations associated with bipolar disease with those induced by the presence of cerebellar neurodegenerative pathologies to clarify the potential cerebellar contribution to bipolar affective disturbance. Twenty-nine patients affected by bipolar disorder, 32 subjects affected by cerebellar neurodegenerative pathologies, and 37 age-matched healthy subjects underwent a 3T MRI protocol. A voxel-based morphometry analysis was used to show similarities and differences in cerebellar grey matter (GM) loss between the groups. We found a pattern of GM cerebellar alterations in both bipolar and cerebellar groups that involved the anterior and posterior cerebellar regions (p = 0.05). The direct comparison between bipolar and cerebellar patients demonstrated a significant difference in GM loss in cerebellar neurodegenerative patients in the bilateral anterior and posterior motor cerebellar regions, such as lobules I−IV, V, VI, VIIIa, VIIIb, IX, VIIb and vermis VI, while a pattern of overlapping GM loss was evident in right lobule V, right crus I and bilateral crus II. Our findings showed, for the first time, common and different alteration patterns of specific cerebellar lobules in bipolar and neurodegenerative cerebellar patients, which allowed us to hypothesize a cerebellar role in the cognitive and mood dysregulation symptoms that characterize bipolar disorder.
... In the context of mood disorders, the cerebellum has recently gained a great attention in line with its role in emotion and affective processing [9][10][11]. The hypothesis of cerebellar involvement in mood symptoms of BD is supported by an extensive body of anatomical and clinical research that has widely demonstrated the presence of anatomical connections between cerebellar regions and cerebral associative and subcortical limbic regions implicated in emotional processing and affective behavior [12]. ...
... Although the abnormal FC in BD patients has been consistently reported during acute mood episodes [18], a persistent FC vulnerability has been hypothesized also during euthymia when bipolar patients exhibit minimal symptoms by definition [19]. This is probably the result of over-reactive emotional brain networks (i.e., anterior limbic network) that would always leave patients at risk for mood and cognitive disturbances [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. ...
Article
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Bipolar disorder (BD) is a major mental illness characterized by periods of (hypo) mania and depression with inter-episode remission periods. Functional studies in BD have consistently implicated a set of linked cortical and subcortical limbic regions in the pathophysiology of the disorder, also including the cerebellum. However, the cerebellar role in the neurobiology of BD still needs to be clarified. Seventeen euthymic patients with BD type1 (BD1) (mean age/SD, 38.64/13.48; M/F, 9/8) and 13 euthymic patients with BD type 2 (BD2) (mean age/SD, 41.42/14.38; M/F, 6/7) were compared with 37 sex- and age-matched healthy subjects (HS) (mean age/SD, 45.65/14.15; M/F, 15/22). T1 weighted and resting-state functional connectivity (FC) scans were acquired. The left and right dentate nucleus were used as seed regions for the seed based analysis. FC between each seed and the rest of the brain was compared between patients and HS. Correlations between altered cerebello-cerebral connectivity and clinical scores were then investigated. Different patterns of altered dentate-cerebral connectivity were found in BD1 and BD2. Overall, impaired dentate-cerebral connectivity involved regions of the anterior limbic network specifically related to the (hypo)manic states of BD. Cerebello-cerebral connectivity is altered in BD1 and BD2. Interestingly, the fact that these altered FC patterns persist during euthymia, supports the hypothesis that cerebello-cerebral FC changes reflect the neural correlate of subthreshold symptoms, as trait-based pathophysiology and/or compensatory mechanism to maintain a state of euthymia.
... Moreover, dysregulation between the limbic cerebellum and the well-known limbic cerebral networks consequent to a cerebellar lesion is at the root of BD, at least the manic state, and provides a new framework for interpreting cerebellar modulation in the regulation of mood in specific psychiatric conditions 63 . Cerebellar dysfunction might slow the data integration necessary for mood state awareness, resulting in difficulty of depressed cerebellar damage patients in explicitly recognizing their mood 64 . Therefore, our findings provide additional evidence for the involvement of cerebellar dysfunction in the pathophysiology of affective disorders. ...
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Identification of intrinsic brain activity differences and similarities between major depression (MDD) and bipolar disorder (BD) is necessary. However, results have not yet yielded consistent conclusions. A meta-analysis of whole-brain resting-state functional MRI (rs-fMRI) studies that explored differences in the amplitude of low-frequency fluctuation (ALFF) between patients (including MDD and BD) and healthy controls (HCs) was conducted using seed-based d mapping software. Systematic literature search identified 50 studies comparing 1399 MDD patients and 1332 HCs, and 15 studies comparing 494 BD patients and 593 HCs. MDD patients displayed increased ALFF in the right superior frontal gyrus (SFG) (including the medial orbitofrontal cortex, medial prefrontal cortex [mPFC], anterior cingulate cortex [ACC]), bilateral insula extending into the striatum and left supramarginal gyrus and decreased ALFF in the bilateral cerebellum, bilateral precuneus, and left occipital cortex compared with HCs. BD showed increased ALFF in the bilateral inferior frontal gyrus, bilateral insula extending into the striatum, right SFG, and right superior temporal gyrus (STG) and decreased ALFF in the bilateral precuneus, left cerebellum (extending to the occipital cortex), left ACC, and left STG. In addition, MDD displayed increased ALFF in the left lingual gyrus, left ACC, bilateral precuneus/posterior cingulate gyrus, and left STG and decreased ALFF in the right insula, right mPFC, right fusiform gyrus, and bilateral striatum relative to BD patients. Conjunction analysis showed increased ALFF in the bilateral insula, mPFC, and decreased ALFF in the left cerebellum in both disorders. Our comprehensive meta-analysis suggests that MDD and BD show a common pattern of aberrant regional intrinsic brain activity which predominantly includes the insula, mPFC, and cerebellum, while the limbic system and occipital cortex may be associated with spatially distinct patterns of brain function, which provide useful insights for understanding the underlying pathophysiology of brain dysfunction in affective disorders, and developing more targeted and efficacious treatment and intervention strategies.
... Specifically, current theories of the pathophysiology of mood disorders mainly focus on three cortical-striatal-limbic circuits: (1) the orbital-frontal network, (2) the ventromedial emotion network and (3) the dorsal cognitive network (which includes dorsolateral and dorsomedial frontal cortices) (Shakiba, 2014). It is worth noting that within the emotional network, the cerebellar vermis, or "limbic cerebellum", has to be considered (Clausi et al., 2019(Clausi et al., , 2017Schmahmann, 2000;Heath et al., 1978). ...
Article
Background: Several studies have shown cerebellar abnormalities during depressive and manic states, although the specific cerebellar role in mood fluctuations remains poorly defined. Therefore, the study of pathologies characterized by frequent mood swings, such as bipolar disorder, is of great interest to investigate the relationship between the cerebellum and mood alterations. Methods: A systematic literature search on the occurrence of mood disorders in patients with cerebellar pathologies (1st research strategy) and on the presence of cerebellar alterations in mood disorders (2nd research strategy) was conducted using the PubMed electronic Internet database. For this systematic review all information was written based on the PRISMA-P statement. Results: The results of the 1st research strategy generated 9 articles, and in one of these, a direct correlation between cerebellar damage and the onset of mood disorder was reported. The 2nd research strategy generated 14 articles that were grouped according to the patient's mood phase (manic or depressive) or diagnosis (bipolar I or bipolar II). Conclusions: The present review suggests that the cerebellum should be considered a key structure involved in the regulation of mood.
... As proposed by Braitenberg et al. (1997), we applied a "sequence detection model" to highlight the cerebellar operational mode in several domains, including the processing of emotions Lupo et al., 2015;Adamaszek et al., 2017;Clausi et al., 2018). ...
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Optimal control mechanisms require prediction capabilities. If one cannot predict the consequences of a motor act or behavior, one will continually collide with walls or become a social pariah. “Looking into the future” is thus one of the most important prerequisites for smooth movements and social interactions. To achieve this goal, the brain must constantly predict future events. This principle applies to all domains of information processing, including motor and cognitive control, as well as the development of decision-making skills, theory of mind, and virtually all cognitive processes. Sequencing is suggested to support the predictive capacity of the brain. To recognize that events are related, the brain must discover links among them in the spatiotemporal domain. To achieve this, the brain must often hold one event in working memory and compare it to a second one, and the characteristics of the two must be compared and correctly placed in space and time. Among the different brain structures involved in sequencing, the cerebellum has been proposed to have a central function. We have suggested that the operational mode of the cerebellum is based on “sequence detection” and that this process is crucial for prediction. Patterns of temporally or spatially structured events are conveyed to the cerebellum via the pontine nuclei and compared with actual ones conveyed through the climbing fibers olivary inputs. Through this interaction, data on previously encountered sequences can be obtained and used to generate internal models from which predictions can be made. This mechanism would allow the cerebellum not only to recognize sequences but also to detect sequence violations. Cerebellar pattern detection and prediction would thus be a means to allow feedforward control based on anticipation. We will argue that cerebellar sequencing allows implementation of prediction by setting the correct excitatory levels in defined brain areas to implement the adaptive response for a given pattern of stimuli that embeds sufficient information to be recognized as a previously encountered template. Here, we will discuss results from human and animal studies and correlate them with the present understanding of cerebellar function in cognition and behavior.
... In recent years, an increasing body of studies focused on the cerebellar role in cognitive functions and emotional regulation also including social cognition abilities [1][2][3][4][5][6][7][8][9][10]. From an anatomical point of view, research documented the existence of reciprocal connections between specific cerebellar regions and associative and paralimbic cerebral structures related to emotional and social processing such as the temporo-parietal junction (TPJ), the lateral temporal cortex, the posterior cingulate cortex, the inferior frontal gyrus [11], the amygdala [12], and the insula [13]. ...
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In recent years, increasing evidence of the cerebellar role in social cognition has emerged. The cerebellum has been shown to modulate cortical activity of social brain regions serving as a regulator of function-specific mentalizing and mirroring processes. In particular, a mentalizing area in the posterior cerebellum, specifically Crus II, is preferentially recruited for more complex and abstract forms of social processing, together with mentalizing cerebral areas including the dorsal medial prefrontal cortex (dmPFC), the temporo-parietal junction (TPJ), and the precuneus. In the present study, the network-based statistics approach was used to assess functional connectivity (FC) differences within this mentalizing cerebello-cerebral network associated with a specific cerebellar damage. To this aim, patients affected by spinocerebellar ataxia type 2 (SCA2), a neurodegenerative disease specifically affecting regions of the cerebellar cortex, and age-matched healthy subjects have been enrolled. The dmPFC, left and right TPJ, the precuneus, and the cerebellar Crus II were used as regions of interest to construct the mentalizing network to be analyzed and evaluate pairwise functional relations between them. When compared with controls, SCA2 patients showed altered internodal connectivity between dmPFC, left (L-) and right (R-) TPJ, and right posterior cerebellar Crus II. The present results indicate that FC changes affect a function-specific mentalizing network in patients affected by cerebellar damage. In particular, they allow to better clarify functional alteration mechanisms driven by the cerebellar damage associated with SCA2 suggesting that selective cortico-cerebellar functional disconnections may underlie patients’ social impairment in domain-specific complex and abstract forms of social functioning.
... Over the years, many scientific studies have recognized the cerebellum as being part of these brain networks (Stoodley and Schmahmann, 2010;Baumann and Mattingley, 2012;Leggio and Olivito, 2018;Clausi et al., 2019a;Van Overwalle et al., 2019a) and have evidenced its role in affective and emotional functioning (Adamaszek et al., 2015;Clausi et al., 2015Clausi et al., , 2019bLupo et al., 2015Lupo et al., , 2018. Accordingly, functional and anatomical connections have been found between the cerebellum and the cortical and subcortical structures involved in both implicit and explicit emotional processing (Critchley et al., 2000;Singer et al., 2004;Schutter et al., 2009;Stoodley and Schmahmann, 2010;Schraa-Tam et al., 2012). ...
... Hence, it seems likely that patients in the current study with a diminished fear recognition, suggesting a diminished experience of fear, were not able to use fear to avoid making a risky decision in the AST, a task that highly resembles decision-making behavior in possibly dangerous, everyday life traffic situations. This idea is furthermore supported by findings of Clausi et al. [38], who showed that patients with cerebellar damage have a decreased awareness of their emotional state. This study is subject to some limitations. ...
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An increasing amount of research has shown a cerebellar involvement in higher order cognitive functions, including emotional processing and decision-making. However, it has not been investigated whether impairments in facial emotion recognition, which could be a marker of impaired emotional experiences, are related to risky decision-making in these patients. Therefore, we aimed to investigate facial emotion recognition and risky decision-making in these patients as well as to investigate a relationship between these constructs. Thirteen patients with a discrete, isolated, cerebellar lesion as a consequence of a stroke were included in the study. Emotion recognition was assessed with the Facial Expressions of Emotions—Stimuli and Test (FEEST). Risk-taking behavior was assessed with the Action Selection Test (AST). Furthermore, 106 matched healthy controls performed the FEEST and 20 matched healthy controls performed the AST. Compared with healthy controls, patients were significantly worse in the recognition of emotional expressions and they took significantly more risks. In addition, a worse ability to recognize fearful facial expressions was strongly related to an increase in risky decisions in the AST. Therefore, we suggest that tests of emotion recognition should be incorporated into the neuropsychological assessment after cerebellar stroke to boost detection and treatment of these impairments in these patients.
... Beyond neuroimaging studies of healthy cerebellar function, studies of cerebellar lesion patients have elucidated the role of this structure in affective processes by identifying specific behavioral difficulties that occur in patients (Schmahmann, 2019). Reports have described problems with emotion recognition and expression in patients, as well as alterations in mood control and the experience of emotional states, with cerebellar patients exhibiting a variety of behavioral and mood disturbances (Schmahmann et al., 2007;Lupo et al., 2015;Clausi et al., 2019a). Problems with social cognition and understanding of others' emotions have been reported in patients with cerebellar degeneration, including spinocerebellar ataxia, potentially related to disrupted formation of internal models that predict others' behavior using theory of mind processes (Sokolovsky et al., 2010;Leggio and Olivito, 2018;Clausi et al., 2019b). ...
Article
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The basal ganglia and the cerebellum historically have been relegated to a functional role in producing or modulating motor output. Recent research, however, has emphasized the importance of these subcortical structures in multiple functional domains, including affective processes such as emotion recognition, subjective feeling elicitation, and reward valuation. Pathways through the thalamus that connect the basal ganglia and cerebellum directly to each other and with extensive regions of cortex provide a structural basis for their combined influence on limbic function. By regulating cortical oscillations to guide learning and strengthening rewarded behavior or thought patterns to achieve a desired goal state, these regions can shape the way an individual processes emotional stimuli. This review will discuss the basic structure and function of the basal ganglia and cerebellum and propose an updated view of their functional role in human affective processing.
... Moreover, it is possible that CA may not manifest in a psychiatrically predictive manner (i.e., may not follow DSM criteria) given that localization of pathology is concentrated in the cerebellum. When studies evaluated symptoms using rating scales, which would allow detection of sub-clinical symptoms, typically only one class of symptoms was measured, such as depression, thereby overlooking the full spectrum of impairments [12][13][14][15]. Therefore, it is important to understand the nature and prevalence of neuropsychiatric changes associated with CA so that patients, caregivers, and clinicians can be prepared to address this class of symptoms as part of clinical care. ...
Article
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While cerebellar ataxia (CA) is a neurodegenerative disease known for motor impairment, changes in mood have also been reported. A full account of neuropsychiatric symptomology in CA may guide improvements in treatment regimes, measure the presence and severity of sub-clinical neuropsychiatric disturbance symptomology in CA, and compare patient versus informant symptom recognition. Neuropsychiatric phenomena were gathered from CA patients with genetic and unknown etiologies and their informants (e.g., spouse or parent). Information was obtained from in-person interviews and the Center for Epidemiologic Studies Depression Scale. Responses were converted to the Neuropsychiatric Inventory-Questionnaire (NPI-Q) scores by consensus ratings. Patient NPI-Q scores were evaluated for symptom prevalence and severity relative to those obtained from healthy controls. Patient-informant NPI-Q score disagreements were evaluated. In this cohort, 95% of patients presented with at least one neuropsychiatric symptom and 51% of patients with three or more symptoms. The most common symptoms were anxiety, depression, nighttime behaviors (e.g., interrupted sleep), irritability, disinhibition, abnormal appetite, and agitation. The prevalence of these neuropsychiatric symptoms was uniform across patients with genetic versus unknown etiologies. Patient and informant symptom report disagreements reflected that patients noted sleep impairment and depression, while informants noted irritability and agitation. Neuropsychiatric disturbance is highly prevalent in patients with CA and contributes to the phenomenology of CA, regardless of etiology. Clinicians should monitor psychiatric health in their CA patients, considering that supplemental information from informants can help gauge the impact on family members and caregivers.
... A la fecha, el empleo de versiones breves de la escala POMS y el uso de sus subescalas continúan siendo empleadas en una diversidad de poblaciones clínicas diferentes a las abordadas tradicionalmente en la validación de la escala (Clausi et al., 2019;Haenen, Nyklíček, van Son, Pop, & Pouwer, 2016;Muise, Bergeron, Impett, Delise, & Rosen, 2018). En la mayoría de dichos estudios, un problema común es que no existe información sobre la validez de constructo (e.g. ...
Article
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The structural validity of the Mexican adaptation to Spanish of the Profile of Mood States Scale (POMS) was examined in samples of healthy and chronically ill adults. Through a non-probabilistic and intentional sampling, 530 adults participated (mean age 35.71, SD= 17); 210 were patients with chronic diseases (cancer and kidney disease) and the rest were healthy adults. An exploratory factor analysis revealed a model of 38 items and 6 factors with acceptable internal consistency indices. A confirmatory factor analysis (CFA) showed adequate goodness-of-fit indices. Subsequent multi-group CFA comparing the samples of healthy adults and patients reveal the non-equivalence of the structure in both samples, merging the negative mood factors for the sample of patients and a better distribution in the sample of healthy adults. Different alternative versions are proposed for healthy adult and patient samples.
... Upon her re-admission 1 month later, the patient's major complaint was worsening of the ataxia and an increased cognitive-emotional deficit. In recent years, increasing evidence for a role for the cerebellum in emotion and cognition has emerged [8][9][10][11][12] and the patient was identified as having cerebellar cognitive affective syndrome [13]. The default mode network (DMN) has become the primary and most popular target of resting state networks and is thought to be involved in advanced cognitive functions and emotion [14][15][16]. ...
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Background Brain magnetic resonance imaging (MRI) rarely reveals structural changes in patients with suspected anti-Tr/DNER encephalitis and thus provides very limited information. Here, we combined structural MRI, functional MRI, and positron emission tomography-computed tomography (PET-CT) findings to characterize this rare disorder in a patient. Case presentation A 43-year-old woman presented with progressive cerebellar ataxia, memory impairment, anxiety, and depression. Anti-Tr antibodies were detected in both her serum (1:10) and cerebrospinal fluid (1:10). A diagnosis of anti-Tr-positive autoimmune cerebellar ataxia was established. The patient’s symptoms were worse, but her brain MRI was normal. Meanwhile, voxel-based morphometry analysis showed bilateral reduced cerebellar volume, especially in the posterior lobe and uvula of the cerebellum and the middle of the left temporal lobe compared with 6 sex- and age-matched healthy subjects (6 females, 43 ± 2 years; p < 0.05). Using seed-based functional connectivity analysis, decreased connectivity between the posterior cingulate cortex/precuneus and left frontal lobe compared to the control group ( p < 0.05) was detected. PET-CT revealed bilateral hypometabolism in the cerebellum and relative hypermetabolism in the cerebellar vermis and bilateral frontal lobe, but no malignant changes. Conclusions A combination of structural MRI, functional MRI, and brain PET-CT has higher diagnostic and prognostic value than conventional MRI in patients with suspected anti-Tr/DNER encephalitis.
... However, as shown in Supplementary Table 1, none of the patients scored 1 point at stance, only one patient scored 1 point at speech, and discrepancies in these items were also found with scores of 2 or even 3 points. A third, intriguing possibility, extrapolated from studies investigating mood state awareness in cerebellar patients, could be that the aforementioned discrepancies arise from a general alteration of self-perception and disturbed conscious awareness of physical complaints [14]. ...
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Background The Scale for the Assessment and Rating of Ataxia (SARA) is commonly used as the primary outcome measure in therapeutic trials. Driven by spontaneous comments from ataxia patients participating in a trial, we aimed to examine the clinical meaningfulness of the SARA from their perspective. Methods Twenty mildly to moderately affected individuals with spinocerebellar ataxia type 3 (SARA score 11.3 ± 4.1) completed a custom-designed survey. SARA item scores were compared with self-reported complaints in everyday life. Discrepancies between SARA ratings and patients’ daily life experiences were reported as “overestimation” (SARA item score more than 0, but no corresponding complaints) or “underestimation” (SARA item score 0, yet accompanying complaints). Results Patient-physician discrepancies were present in essentially all SARA items except for gait. The mean number of overestimated SARA points per patient was 3.1 ± 2.1. Underestimation occurred less frequently, but was relatively common in stance and fast alternating hand movements. Three quarters of patients marked gait as the most valuable SARA item, while the remaining 25% selected stance. Conclusion On average, a quarter of total SARA score does not reflect meaningful impairments from a patient’s perspective. Our data suggest that it is doubtful whether potential improvements at some of the items will be perceived as comparably important by ataxia patients. These observations question the utility of delta SARA score as the most appropriate primary endpoint in clinical trials and call for the addition of outcome measures, such as the Patient Global Impression of Change scale and ataxia-specific patient-reported outcome measures.
... The effectiveness of depression therapy in the form of climbing can be explained by stimulation and changes in the cerebellum. This is indicated by the latest research on the role of the cerebellum in depressive disorders [10][11][12]. A review by Depping et al. notes features characterizing depression in the form of cerebellar neuroanatomic correlates that communicate with cortical networks supporting cognitive and autoreferential processing [11]. ...
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According to the World Health Organization (WHO), 4.3% of the global population exhibits symptoms of depression. In Poland, 1.5 million people suffer from this illness. Treatment of depression generates significant costs calculated in billions of zlotys. According to the International Statistical Classification of Diseases and Health Problems, depression is characterized by: reduced mood, reduced psychomotor drive, loss of interest (axial symptoms), as well as low self-esteem, pessimistic attitude, weakness of concentration, sleep disorders, and loss of appetite (additional symptoms). The aim of this research was to review and evaluate studies on the impact of sport climbing as a complementary form of treatment on reducing depressive symptoms. This is the first literature review undertaking a collective assessment of studies on this subject. The appropriate studies were selected in a three-stage process. PubMed, Re-searchGate, and Google Scholar databases were searched. Finally, 4 studies were qualified for the review and then assessed using the QUADAS-2 tool developed by Bristol Medical School: Population Health Sciences. Analysis of the research gives grounds to consider introducing an additional form of treatment for depression in the form of boulder climbing. The evaluation according to the QUADAS-2 questionnaire indicates a low possibility of making mistakes in all assessed works.
... In our study we found that the fALFF value of the left superior frontal lobe of MOG-lgG ON patients was positively correlated with HADS score, highlighting the functional consequences of MOG-lgG ON. The difference in fALFF value of the right cerebellum between MOG-lgG ON patients and HCs suggests abnormalities in the processing of nerve impulses from head proprioceptors and external receptors, but recent studies have also showed that there is a link between cerebellar disorders and depression [27]. Thus, changes in fALFF in specific brain regions associated with MOG-lgG ON can not only cause visual im-pairment, but can also have behavioral consequences such as anxiety and depression (Fig. 4). ...
Article
Optic neuritis (ON) is a general term for inflammation of any part of the optic nerve resulting from demyelination or infection. The number of patients with MOG-lgG antibody-related optic neuritis is increasing recently. Our study uses the fractional amplitude of low-frequency fluctuation (fALFF) method to compare the activity of specific brain regions in MOG-lgG ON patients and healthy controls (HCs). We selected a total of 21 MOG-lgG ON patients and 21 HCs were included in the study. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI). The independent-samples t-test was used to compare demographic data and average fALFF values between groups. The specificity and sensitivity of fALFF values for distinguishing between MOG-lgG ON patients and HCs were evaluated by receiver operating characteristic (ROC) curve analysis. Pearson's correlation analysis was used to analyze the relationship between fALFF values and clinical characteristics in MOG-lgG ON patients. Our results showed that fALFF values of the right cerebellum and left middle cingulum were lower whereas those of bilateral inferior temporal lobes, right gyrus rectus, and the left superior and right middle frontal lobes of MOG-lgG ON patients were higher than those of HCs (P < 0.05). The average fALFF value of the left superior frontal lobe in MOG-lgG ON patients was positively correlated with Hospital Anxiety and Depression Scale score (HADS) (r = 0.6004; P < 0.05) and duration of MOG-lgG ON (r = 6487; P < 0.05). Thus, patients with MOG-lgG ON have abnormal activity in the brain regions related to vision. Changes in fALFF value can reflect functional sequelae of MOG-lgG ON, including abnormal anxiety or depressive emotional changes.
... These brain structures are known to be important in equilibrium and coordination. Of note, patients with cerebellar dysfunction show higher scores on depression inventories when compared to controls (21). Interestingly, in some genetic conditions characterized by ataxia, depression appears to be an important feature. ...
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Neuropsychiatry mainly deals with processes of the mind related to neurological diseases. Only secondarily, it deal with depressive and anxiety syndromes, as reactions to the presence of an acute, chronic, or degenerative neurological disease. This review illustrate the most frequent neuropsychiatric disorders in the context of the main neurological diseases, focusing on secondary psychic reactions to the development of neurological diseases. The main purpose of this paper is therefore to amplify the sensitivity of psychiatric colleagues towards these clinical conditions in order to create a communication channel with fellow neurologists and neuroradiologists that is not limited to simple counseling.
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Background: The overall satisfaction of patients after total knee arthroplasty (TKA) is approximately 80%, and current studies have demonstrated that patients with depression may have lower patient satisfaction. The purpose of this study was to determine whether perioperative psychological intervention in patients with depression improves the clinical outcomes and patient satisfaction in patients undergoing TKA. Methods: Six hundred patients who underwent primary TKA from May 2016 to January 2018 were prospectively screened for eligibility. A preoperative psychological evaluation was conducted by a psychiatrist to evaluate each patient's psychological status. Patients who were diagnosed with depression were randomly divided into 2 groups: the intervention group (patients received psychological interventions that were administered by a psychiatrist at the first visit before surgery and from then on) and the control group (patients received routine TKA care without psychological interventions). The primary outcome was patient satisfaction at 6 months postoperatively. The secondary outcomes were patient satisfaction at 2 years postoperatively as well as the Hospital for Special Surgery (HSS) scores, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, and range of motion at 6 months and 2 years postoperatively. Results: Fifty-three patients with depression were identified. Fifty-one patients were enrolled in the randomized controlled trial. Two patients were lost to follow-up at 6 months after surgery. Therefore, 49 patients (25 in the intervention group and 24 in the control group) remained in the final analysis. At 6 months postoperatively, statistical differences in patient satisfaction were identified between the 2 groups (88.0% in the intervention group compared with 62.5% in the control group; odds ratio = 4.40; 95% confidence interval, 1.02 to 18.99). There was a significant improvement in the Self-Rating Depression Scale (SDS) score (the reduction rate was 51.97% in the intervention group compared with 17.35% in the control group) and the Symptom Checklist 90 Revised (SCL-90-R) subscore for depression (the reduction rate was 44.66% in the intervention group compared with 15.73% in the control group). The clinical outcomes, including the WOMAC scores, the HSS scores, and maximal range of motion, in the intervention group had improved significantly more compared with those in the. Conclusions: Psychological interventions during the perioperative period can improve patient satisfaction in patients with depression who undergo TKA. Therefore, psychological intervention and management may be beneficial for patients with depression who are planning to undergo TKA. Level of evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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In recent years, structural and functional alterations in the cerebellum have been reported in autism spectrum disorder (ASD). Intriguingly, recent studies demonstrated that the social behavioral profile of individuals with cerebellar pathologies is characterized by a theory of mind (ToM) impairment, one of the main behavioral hallmarks of ASD. The aim of the present study was to compare ToM abilities and underlying cerebello-cortical structural patterns between ASD individuals and individuals with cerebellar atrophy to further specify the cerebellar role in mentalizing alterations in ASD. Twenty-one adults with ASD without language and intellectual impairments (based on DSM-5), 36 individuals affected by degenerative cerebellar damage (CB), and 67 healthy participants were enrolled in the study. ToM abilities were assessed using the reading the mind in the eyes test and the faux pas test. One-way ANCOVA was conducted to compare the performances between the two cohorts. Three-dimensional T1-weighted magnetic resonance scans were collected, and a voxel-based morphometry analysis was performed to characterize the brain structural alterations in the two cohorts. ASD and CB participants had comparable ToM performance with similar difficulties in both the tests. CB and ASD participants showed an overlapping pattern of gray matter (GM) reduction in a specific cerebellar portion (Crus-II). Our study provides the first direct comparison of ToM abilities between ASD and CB individuals, boosting the idea that specific cerebellar structural alterations impact the mentalizing process. The present findings open a new perspective for considering the cerebellum as a potential target for treatment implementation. The present work will critically advance current knowledge about the cerebellar role in ToM alterations of ASD, in particular, elucidating the presence of common cerebellar structural abnormalities in ASD and cerebellar individuals that may underlie specific mentalizing alterations. These findings may pave the way for alternative therapeutic indications, such as cerebellar neuromodulation, with a strong clinical impact. Lay Summary The present work will critically advance current knowledge about the cerebellar role in theory of mind alterations of autism spectrum disorder (ASD), in particular, elucidating the presence of common cerebellar structural abnormalities in ASD and cerebellar individuals that may underlie specific mentalizing alterations. These findings may pave the way for alternative therapeutic indications, such as cerebellar neuromodulation, with a strong clinical impact.
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Background Cumulative evidence indicated the cerebellum is involved in the pathophysiology of bipolar disorder (BD). It was reported that the apparent diffusion coefficient from ultra-high b-values (ADCuh) could reflect the function of aquaporin-4 (AQP4) which was involved in neurological disorders. However, no studies have reported the AQP4 alteration in the cerebellum in BD. Therefore, this study aimed to investigate the ADCuh and AQP4 in the cerebellum in BD-II. Methods Fifty patients with BD-II as well as 43 healthy controls underwent enhance diffusion weighted imaging (eDWI) with ultra-high b-values. The eDWI parameters including ADCuh , pure water diffusion (D) and pseudodiffusion (D*) was measured using regions-of-interest analysis in the superior cerebellar peduncles (SCP), middle cerebellar peduncles (MCP) , cerebellar hemisphere, dentate nuclei, tonsil and vermis of the cerebellum. Results BD-II exhibited increased ADCuh values in the bilateral SCP, cerebellar hemisphere, tonsil and right dentate nuclei, and increased D* and D in the bilateral SCP, and decreased D* in the tonsil. Additionally, there were positive correlations between Hamilton Rating Scale for Depression-24 scores and bilateral ADCuh values in the SCP and cerebellar hemisphere. Conclusions The alteration of the ADCuh values in the cerebellum may reflect the changes of the AQP4, especially the abnormality of eDWI parameters in the SCP may be a key neurobiological feature of BD-II. The current results provide a novel insight to look into the pathophysiology mechanisms underlying BD-II.
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The notion that the cerebellum is devoted exclusively to motor control has been replaced by a more sophisticated understanding of its role in neurological function, one that includes cognition and emotion. Early clinical reports, as well as physiological and behavioral studies in animal models, raised the possibility of a nonmotor role for the cerebellum. Anatomical studies demonstrate cerebellar connectivity with the distributed neural circuits linked with autonomic, sensorimotor, vestibular, associative, and limbic/paralimbic brain areas. Identification of the cerebellar cognitive affective syndrome in adults and children underscored the clinical relevance of the role of the cerebellum in cognition and emotion. It opened new avenues of investigation into higher-order deficits that accompany the ataxias and other cerebellar diseases, as well as the contribution of cerebellar dysfunction to neuropsychiatric and neurocognitive disorders. Brain imaging studies have demonstrated the complexity of cerebellar functional topography, revealing a double representation of the sensorimotor cerebellum in the anterior lobe and lobule VIII and a triple cognitive representation in the cerebellar posterior lobe, as well as representation in the cerebellum of the intrinsic connectivity networks identified in the cerebral hemispheres. This paradigm shift in thinking about the cerebellum has been advanced by the theories of dysmetria of thought and the universal cerebellar transform, harmonizing the dual anatomic realities of homogeneously repeating cerebellar cortical microcircuitry set against the heterogeneous and topographically arranged cerebellar connections with extracerebellar structures. This new appreciation of cerebellar incorporation into circuits that subserve cognition and emotion mandates a deeper understanding of the cerebellum by practitioners in behavioral neurology and neuropsychiatry because it impacts the understanding and diagnosis of disorders of emotion and intellect and has potential for novel cerebellar-based approaches to therapy.
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Background : Negative bias—a mood-congruent bias in emotion processing—is an important aspect of major depressive disorder (MDD), and such a bias in facial expression recognition has a significant effect on patients’ social lives. Neuroscience research shows abnormal activity in emotion-processing systems regarding facial expressions in MDD. However, the neural basis of negative bias in facial expression processing has not been explored directly. Methods : Sixteen patients with MDD and twenty-three healthy controls (HC) who underwent an fMRI scan during an explicit facial emotion task with happy to sad faces were selected. We identified brain areas in which the MDD and HC groups showed different correlations between the behavioral negative bias scores and functional activities. Results : Behavioral data confirmed the existence of a higher negative bias in the MDD group. Regarding the relationship with neural activity, higher activity of happy faces in the posterior cerebellum was related to a higher negative bias in the MDD group, but lower negative bias in the HC group. Limitations : The sample size was small, and the possible effects of medication were not controlled for in this study. Conclusions : We confirmed a negative bias in the recognition of facial expressions in patients with MDD. fMRI data suggest the cerebellum as a moderator of facial emotion processing, which biases the recognition of facial expressions toward their own mood.
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Studies from the past three decades have demonstrated that there is cerebellar involvement in the emotional domain. Emotional processing in humans requires both unconscious and conscious mechanisms. A significant amount of evidence indicates that the cerebellum is one of the cerebral structures that subserve emotional processing, although conflicting data has been reported on its function in unconscious and conscious mechanisms. This review discusses the available clinical, neuroimaging, and neurophysiological data on this issue. We also propose a model in which the cerebellum acts as a mediator between the internal state and external environment for the unconscious and conscious levels of emotional processing.
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Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease characterized by a progressive cerebellar syndrome, which can be isolated or associated with extracerebellar signs. It has been shown that patients affected by SCA2 present also cognitive impairments and psychiatric symptoms. The cerebellum is known to modulate cortical activity and to contribute to distinct functional networks related to higher-level functions beyond motor control. It is therefore conceivable that one or more networks, rather than isolated regions, may be dysfunctional in cerebellar degenerative diseases and that an abnormal connectivity within specific cerebello-cortical regions might explain the widespread deficits typically observed in patients. In the present study, the network-based statistics (NBS) approach was used to assess differences in functional connectivity between specific cerebellar and cerebral “nodes” in SCA2 patients. Altered inter-nodal connectivity was found between more posterior regions in the cerebellum and regions in the cerebral cortex clearly related to cognition and emotion. Furthermore, more anterior cerebellar lobules showed altered inter-nodal connectivity with motor and somatosensory cerebral regions. The present data suggest that in SCA2 a cerebellar dysfunction affects long-distance cerebral regions and that the clinical symptoms may be specifically related with connectivity changes between motor and non-motor cerebello-cortical nodes.
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The notion that the cerebellum is a central regulator of motor function is undisputed. There exists, however, considerable literature to document a similarly vital role for the cerebellum in the regulation of various non-motor domains, including emotion. Research from numerous avenues of investigation (i.e., neurophysiological, behavioural, electrophysiological, imagining, lesion, and clinical studies) have documented the importance of the cerebellum, in particular, the vermis, in affective processing that appears preserved across species. The cerebellum possesses a distinct laminar arrangement and highly organized neuronal circuitry. Moreover, the cerebellum forms reciprocal connections with several brain regions implicated in diverse functional domains, including motor, sensory, and emotional processing. It has been argued that these unique neuroanatomical features afford the cerebellum with the capacity to integrate information about an organism, its environment, and its place within the environment such that it can respond in an appropriate, coordinated fashion, with such theories extending to the regulation of emotion. This review puts our current understanding of the cerebellum and its role in behaviour in historical perspective, presents an overview of the neuroanatomical and functional organization of the cerebellum, and reviews the literature describing the involvement of the cerebellum in emotional regulation in both humans and non-human animals. In summary, this review discusses the importance of the functional connectivity of the cerebellum with various brain regions in the ability of the cerebellum to effectively regulate emotional behaviour.
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Over the past three decades, insights into the role of the cerebellum in emotional processing have substantially increased. Indeed, methodological refinements in cerebellar lesion studies and major technological advancements in the field of neuroscience are in particular responsible to an exponential growth of knowledge on the topic. It is timely to review the available data and to critically evaluate the current status of the role of the cerebellum in emotion and related domains. The main aim of this article is to present an overview of current facts and ongoing debates relating to clinical, neuroimaging, and neurophysiological findings on the role of the cerebellum in key aspects of emotion. Experts in the field of cerebellar research discuss the range of cerebellar contributions to emotion in nine topics. Topics include the role of the cerebellum in perception and recognition, forwarding and encoding of emotional information, and the experience and regulation of emotional states in relation to motor, cognitive, and social behaviors. In addition, perspectives including cerebellar involvement in emotional learning, pain, emotional aspects of speech, and neuropsychiatric aspects of the cerebellum in mood disorders are briefly discussed. Results of this consensus paper illustrate how theory and empirical research have converged to produce a composite picture of brain topography, physiology, and function that establishes the role of the cerebellum in many aspects of emotional processing.
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Patients with spinocerebellar ataxia type 3 (SCA3) have exhibited cerebral cortical involvement and various mental deficits in previous studies. Clinically, conventional measurements, such as the Mini-Mental State Examination (MMSE) and electroencephalography (EEG), are insensitive to cerebral cortical involvement and mental deficits associated with SCA3, particularly at the early stage of the disease. We applied a three-dimensional fractal dimension (3D-FD) method, which can be used to quantify the shape complexity of cortical folding, in assessing cortical degeneration. We evaluated 48 genetically confirmed SCA3 patients by employing clinical scales and magnetic resonance imaging and using 50 healthy participants as a control group. According to the Scale for the Assessment and Rating of Ataxia (SARA), the SCA3 patients were diagnosed with cortical dysfunction in the cerebellar cortex; however, no significant difference in the cerebral cortex was observed according to the patients' MMSE ratings. Using the 3D-FD method, we determined that cortical involvement was more extensive than involvement of traditional olivopontocerebellar regions and the corticocerebellar system. Moreover, the significant correlation between decreased 3D-FD values and disease duration may indicate atrophy of the cerebellar cortex and cerebral cortex in SCA3 patients. The change of the cerebral complexity in the SCA3 patients can be detected throughout the disease duration, especially it becomes substantial at the late stage of the disease. Furthermore, we determined that atrophy of the cerebral cortex may occur earlier than changes in MMSE scores and EEG signals.
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Recent studies have implicated the cerebellum as part of a circuitry that is necessary to modulate higher order and behaviorally relevant information in emotional domains. However, little is known about the relationship between the cerebellum and emotional processing. This study examined cerebellar function specifically in the processing of negative emotions. Transcranial Doppler ultrasonography was performed to detect selective changes in middle cerebral artery flow velocity during emotional stimulation in patients affected by focal or degenerative cerebellar lesions and in matched healthy subjects. Changes in flow velocity during non-emotional (motor and cognitive tasks) and emotional (relaxing and negative stimuli) conditions were recorded. In the present study, we found that during negative emotional task, the hemodynamic pattern of the cerebellar patients was significantly different to that of controls. Indeed, whereas relaxing stimuli did not elicit an increase in mean flow velocity in any group, negative stimuli increased the mean flow velocity in the right compared with left middle cerebral artery only in the control group. The patterns by which mean flow velocity increased during the motor and cognitive tasks were similar within patients and controls. These findings support that the cerebellum is part of a network that gives meaning to external stimuli, and this particular involvement in processing negative emotional stimuli corroborates earlier phylogenetic hypotheses, for which the cerebellum is part of an older circuit in which negative emotions are crucial for survival and prepare the organism for rapid defense.
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Various lines of evidence accumulated over the past 30 years indicate that the cerebellum, long recognized as essential for motor control, also has considerable influence on perceptual processes. In this paper, we bring together experts from psychology and neuroscience, with the aim of providing a succinct but comprehensive overview of key findings related to the involvement of the cerebellum in sensory perception. The contributions cover such topics as anatomical and functional connectivity, evolutionary and comparative perspectives, visual and auditory processing, biological motion perception, nociception, self-motion, timing, predictive processing, and perceptual sequencing. While no single explanation has yet emerged concerning the role of the cerebellum in perceptual processes, this consensus paper summarizes the impressive empirical evidence on this problem and highlights diversities as well as commonalities between existing hypotheses. In addition to work with healthy individuals and patients with cerebellar disorders, it is also apparent that several neurological conditions in which perceptual disturbances occur, including autism and schizophrenia, are associated with cerebellar pathology. A better understanding of the involvement of the cerebellum in perceptual processes will thus likely be important for identifying and treating perceptual deficits that may at present go unnoticed and untreated. This paper provides a useful framework for further debate and empirical investigations into the influence of the cerebellum on sensory perception.
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Following the fundamental recognition of its involvement in sensory-motor coordination and learning, the cerebellum is now also believed to take part in the processing of cognition and emotion. This hypothesis is recurrent in numerous papers reporting anatomical and functional observations, and it requires an explanation. We argue that a similar circuit structure in all cerebellar areas may carry out various operations using a common computational scheme. On the basis of a broad review of anatomical data, it is conceivable that the different roles of the cerebellum lie in the specific connectivity of the cerebellar modules, with motor, cognitive, and emotional functions (at least partially) segregated into different cerebro-cerebellar loops. We here develop a conceptual and operational framework based on multiple interconnected levels (a meta-levels hypothesis): from cellular/molecular to network mechanisms leading to generation of computational primitives, thence to high-level cognitive/emotional processing, and finally to the sphere of mental function and dysfunction. The main concept explored is that of intimate interplay between timing and learning (reminiscent of the "timing and learning machine" capabilities long attributed to the cerebellum), which reverberates from cellular to circuit mechanisms. Subsequently, integration within large-scale brain loops could generate the disparate cognitive/emotional and mental functions in which the cerebellum has been implicated. We propose, therefore, that the cerebellum operates as a general-purpose co-processor, whose effects depend on the specific brain centers to which individual modules are connected. Abnormal functioning in these loops could eventually contribute to the pathogenesis of major brain pathologies including not just ataxia but also dyslexia, autism, schizophrenia, and depression.
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Numerous studies have demonstrated the higher-order functions of the cerebellum, including emotion regulation and cognitive processing, and have indicated that the cerebellum should therefore be included in the pathophysiological models of major depressive disorder. The aim of this study was to compare the resting-state functional connectivity of the cerebellum in adults with major depression and healthy controls. Twenty adults with major depression and 20 gender-, age-, and education-matched controls were investigated using seed-based resting-state functional connectivity magnetic resonance imaging. Compared with the controls, depressed patients showed significantly increased functional connectivity between the cerebellum and the temporal poles. However, significantly reduced cerebellar functional connectivity was observed in the patient group in relation to both the default-mode network, mainly including the ventromedial prefrontal cortex and the posterior cingulate cortex/precuneus, and the executive control network, mainly including the superior frontal cortex and orbitofrontal cortex. Moreover, the Hamilton Depression Rating Scale score was negatively correlated with the functional connectivity between the bilateral Lobule VIIb and the right superior frontal gyrus in depressed patients. This study demonstrated increased cerebellar coupling with the temporal poles and reduced coupling with the regions in the default-mode and executive control networks in adults with major depression. These differences between patients and controls could be associated with the emotional disturbances and cognitive control function deficits that accompany major depression. Aberrant cerebellar connectivity during major depression may also imply a substantial role for the cerebellum in the pathophysiological models of depression.
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"Mental time travel" refers to conscious experience of remembering the personal past and imagining the personal future. Little is known about its neural correlates. Here, using functional magnetic resonance imaging, we explored the hypothesis that mental time travel into "nonpresent" times (past and future) is enabled by a special conscious state (chronesthesia). Well-trained subjects repeatedly imagined taking one and the same short walk in a familiar environment, doing so either in the imagined past, present, or future. In an additional condition, they recollected an instance in which they actually performed the same short walk in the same familiar setting. This design allowed us to measure brain activity correlated with "pure" conscious states of different moments of subjective time. The results showed that the left lateral parietal cortex was differentially activated by nonpresent subjective times compared with the present (past and future > present). A similar pattern was observed in the left frontal cortex, cerebellum, and thalamus. There was no evidence that the hippocampal region is involved in subjective time travel. These findings provide support for theoretical ideas concerning chronesthesia and mental time travel.
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Since the discoveries of Camillo Golgi and Ramón y Cajal, the precise cellular organization of the cerebellum has inspired major computational theories, which have then influenced the scientific thought not only on the cerebellar function but also on the brain as a whole. However, six major issues revealing a discrepancy between morphologically inspired hypothesis and function have emerged. (1) The cerebellar granular layer does not simply operate a simple combinatorial decorrelation of the inputs but performs more complex non-linear spatio-temporal transformations and is endowed with synaptic plasticity. (2) Transmission along the ascending axon and parallel fibers does not lead to beam formation but rather to vertical columns of activation. (3) The olivo-cerebellar loop could perform complex timing operations rather than error detection and teaching. (4) Purkinje cell firing dynamics are much more complex than for a linear integrator and include pacemaking, burst-pause discharges, and bistable states in response to mossy and climbing fiber synaptic inputs. (5) Long-term synaptic plasticity is far more complex than traditional parallel fiber LTD and involves also other cerebellar synapses. (6) Oscillation and resonance could set up coherent cycles of activity designing a functional geometry that goes far beyond pre-wired anatomical circuits. These observations clearly show that structure is not sufficient to explain function and that a precise knowledge on dynamics is critical to understand how the cerebellar circuit operates.
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Here, we propose that global brain function is geared towards the implementation of intelligent motricity. Motricity is the only possible external manifestation of nervous system function (other than endocrine and exocrine secretion and the control of vascular tone). The intelligence component of motricity requires, for its successful wheeling, a prediction imperative to approximate the consequences of the impending motion. We address how such predictive function may originate from the dynamic properties of neuronal networks.
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Anatomical, physiological and functional neuroimaging studies suggest that the cerebellum participates in the organization of higher order function, but there are very few descriptions of clinically relevant cases that address this possibility. We performed neurological examinations, bedside mental state tests, neuropsychological studies and anatomical neuroimaging on 20 patients with diseases confined to the cerebellum, and evaluated the nature and severity of the changes in neurological and mental function. Behavioural changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis, and in some cases they were the most noticeable aspects of the presentation. These changes were characterized by: impairment of executive functions such as planning, set-shifting, verbal fluency, abstract reasoning and working memory; difficulties with spatial cognition including visual-spatial organization and memory; personality change with blunting of affect or disinhibited and inappropriate behaviour; and language deficits including agrammatism and dysprosodia. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. We have called this newly defined clinical entity the 'cerebellar cognitive affective syndrome'. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits that link prefrontal, posterior parietal, superior temporal and limbic cortices with the cerebellum.
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A Symptom Checklist (SCL-90-R) is a potentially useful measure of psychological distress; it is frequently used in psychotherapy research and clinical practice. The purpose of this study was to illustrate the use of the SCL-90-R for determining statistically reliable change and clinical significance outlined by Jacobson and Truax in 1991. This paper describes the concepts of statistical and clinical significance of change. A proposal for obtaining and characterizing samples is made. Then a clinician's perspective is taken. Reliable change estimates and cut-off scores are chosen based on outcome data. Selected data from a single psychotherapeutic process and outcome study then were used to test the estimates of change and cut-off scores.
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Transient feelings of depression are a universal experience, and depressed mood is easy to recognize. The outward expression or affect of depression is on a continuum with normal experience, and even when a depressive state has a known organic precipitant (e.g., reserpine toxicity), the observable change in affect is usually one more of degree than of quality.
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Major depressive disorder (MDD) is the most prevalent psychiatric comorbidity among patients with treatment-resistant seizures. The Beck Depression Inventory-II (BDI-II) is often used to measure the severity of self-reported depressive symptoms among patients with seizure disorders. In contrast, researchers often use the Profile of Mood States (POMS) Depression (D) scale to assess depressed mood among other medical patient groups. The clinical significance of POMS-D scores among seizure disorder patients is not clear. In this study, we computed the correlation of POMS-D and BDI-II scores, determined a formula for converting POMS-D scores to BDI-II scores, and computed the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the POMS-D among seizure disorder patients. Two BDI-II cutoffs (BDI-II >=, 16 and 20) were used as criteria for significant reported depressive symptoms. We found a strong correlation between POMS-D and BDI-II scores. Analyses indicated that POMS-D scores strongly predict BDI-II scores. In addition, the sensitivity, specificity, PPV, and NPV values obtained demonstrated that POMS-D scores accurately classify seizure disorder patients who endorse significant depressive symptoms. These results suggest that the POMS-D may be effective in measuring reported depressive symptoms among seizure disorder patients. (c) 2005 Elsevier Inc. All rights reserved.
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Depressive disorders are a frequent psychiatric comorbidity in patients with neurologic disease with prevalence rates ranging between 30% and 50%. Yet, despite their relative high prevalence, they remain underrecognized and undertreated. Depressive disorders can have a negative impact on the course and response to treatment of several neurologic disorders, including stroke, migraine, epilepsy, Parkinson's disease, and Alzheimer's dementia. This chapter reviews some of the evidence and tries to make the case of why neurologists should care to recognize early the presence of a comorbid depressive disorder and facilitate its treatment.
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We aimed to investigate the integrity of the Resting State Networks in spinocerebellar ataxia type 2 (SCA2) and the correlations between the modification of these networks and clinical variables. Resting-state functional magnetic resonance imaging (RS-fMRI) data from 19 SCA2 patients and 29 healthy controls were analyzed using an independent component analysis and dual regression, controlling at voxel level for the effect of atrophy by co-varying for gray matter volume. Correlations between the resting state networks alterations and disease duration, age at onset, number of triplets, and clinical score were assessed by Spearman's coefficient, for each cluster which was significantly different in SCA2 patients compared with healthy controls. In SCA2 patients, disruption of the cerebellar components of all major resting state networks was present, with supratentorial involvement only for the default mode network. When controlling at voxel level for gray matter volume, the reduction in functional connectivity in supratentorial regions of the default mode network, and in cerebellar regions within the default mode, executive and right fronto-parietal networks, was still significant. No correlations with clinical variables were found for any of the investigated resting state networks. The SCA2 patients show significant alterations of the resting state networks, only partly explained by the atrophy. The default mode network is the only resting state network that shows also supratentorial changes, which appear unrelated to the cortical gray matter volume. Further studies are needed to assess the clinical significance of these changes. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
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Anatomical, clinical, and neuroimaging evidence implicates the cerebellum in processing emotions and feelings. Moreover recent studies showed a cerebellar involvement in pathologies such as autism, schizophrenia and alexithymia, in which emotional processing have been found altered. However, cerebellar function in the modulation of emotional responses remains debated. In this study, emotions that are involved directly in decision-making were examined in 15 patients (six males; age range 17-60 years) affected by cerebellar damage and 15 well matched healthy controls. We used a gambling task, in which subjects' choices and evaluation of outcomes with regard to their anticipated and actual emotional impact were analyzed. Emotions, such as regret and relief, were elicited, based on the outcome of the unselected gamble. Interestingly, despite their ability to avoid regret in subsequent choices, patients affected by cerebellar lesions were significantly impaired in evaluating the feeling of regret subjectively. These results demonstrate that the cerebellum is involved in conscious recognizing of negative feelings caused by the sense of self-responsibility for an incorrect decision.
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Thirty patients with cerebellar ataxia and 40 healthy volunteers underwent 7 days of mood monitoring using a new device requiring a low motor load. Its convergent validity and compliance were tested. The measurements resulted consistent with validated scale scores. Patients׳ motor impairment did not affect the compliance.
Article
Anatomical, clinical, and functional imaging studies suggest that the cerebellum is an essential component of the distributed neural circuitry subserving cognition. This paper addresses the experimental and clinical data pointing to the role of the cerebellum in the modulation of affect and emotion as well as of thought. There are cerebellar connections with the reticular system (arousal), hypothalamus (autonomic function and emotional expression), limbic system (experience and expression of emotion), and paralimbic and neocortical association areas (cognitive dimensions of affect). Clinical studies point to cerebellar modulation of aggression and mood, including the cerebellar cognitive affective syndrome in adults and children, the posterior fossa syndrome of transient mutism and behavioral change following surgery that involves the vermis, and behavioral modification by cerebellar neurosurgical manipulation. Functional imaging studies reveal cerebellar involvement in nociception, in autonomic behaviors such as hunger and thirst, and in affective experiences. These observations provide support for the hypothesis that the cerebellum is an essential node in the distributed neural circuitry subserving cognitive and affective functions, and that there is a topographic organization of behaviors in the cerebellum. The hypothesis that the phylogenetically older fastigial nucleus, vermis and flocculonodular lobe constitute the “limbic cerebellum” is further developed to suggest that these cerebellar structures should be considered an extension of the Papez circuit. The concept is proposed that there is a universal cerebellar transform (UCT), possibly error detection, prevention, and correction utilizing an internal model, the disruption of which leads to dysmetria, the universal cerebellar impairment (UCI). Dysmetria of movement, or ataxia, is matched by dysmetria of thought, including the cerebellar cognitive affective syndrome, abnormalities of affect, and psychotic thinking.
Article
This review will focus on the possibility that the cerebellum contains an internal model or models of the motor apparatus. Inverse internal models can provide the neural command necessary to achieve some desired trajectory. First, we review the necessity of such a model and the evidence, based on the ocular following response, that inverse models are found within the cerebellar circuitry. Forward internal models predict the consequences of actions and can be used to overcome time delays associated with feedback control. Secondly, we review the evidence that the cerebellum generates predictions using such a forward model. Finally, we review a computational model that includes multiple paired forward and inverse models and show how such an arrangement can be advantageous for motor learning and control.
Article
Spinocerebellar ataxia type 7 (SCA7) is a progressive neurodegenerative disorder characterized by cerebellar ataxia and visual loss. It is caused by a CAG repeat expansion in the gene encoding the ataxin 7 protein. Visual loss is due to a progressive atrophy of photoreceptor cells that results in macular degeneration in more advanced stages. Initial semiautomatic measures in magnetic resonance imaging (MRI) studies on the brain stem have shown a diminished volume mainly in the cerebellum and pons, while T2 images have shown hyperintensities in transverse fibers at the pons. Neuropathological research, however, has shown more widespread brain damage including loss of myelinated fibers. In this study we decided to take advantage of recent MRI methodological advances to further explore the gray and white matter changes that occur in SCA7 patients. We studied nine genetically confirmed SCA7 patients and their matched controls using voxel based morphometry and tract-based spatial statistics. As expected, we found significant bilateral gray matter volume reductions (p<0.05, corrected for multiple comparisons) in patients' cerebellar cortex. However, we also found significant bilateral gray matter reductions in pre and postcentral gyrus, inferior and medial frontal, parietal inferior, parahippocampal and occipital cortices. The analysis also showed a decrement in fractional anisotropy (p<0.05, corrected) of SCA7 patients in the cerebellum's white matter, brainstem, cerebellar and cerebral peduncles, midbrain, anterior and posterior internal capsule, external/extreme capsule, corpus callosum, corona radiata, optical radiations, and the occipital, temporal and frontal lobe's white matter. These results confirm previous evidence of widespread damage beyond the cerebellum and the pons in SCA7 patients. They also confirmed previous results that had been only detectable through neuropathological analyses and, more importantly, identified new regions affected by the disease that previous methods could not detect. These new results could help explain the symptom's spectrum that affects these patients.
Article
To investigate cerebral and cerebellar gray matter abnormalities in patients with first-episode major depressive disorder (MDD). We examined the structural difference in regional gray matter density (GMD) between 22 first-episode MDD patients and 30 age-, gender- and education-matched healthy controls by optimized voxel-based morphometry (VBM) based on magnetic resonance imaging. Compared with healthy controls, MDD patients showed decreased GMD in the right medial and left lateral orbitofrontal cortex, right dorsolateral prefrontal cortex (DLPFC), bilateral temporal pole, right superior temporal gyrus, bilateral anterior insular cortex, left parahippocampal gyrus, and left cerebellum. In addition, in MDD patients, there was a negative correlation between GMD values of the right DLPFC and the score of the depression rating scale. Our findings provided additional support for the involvement of limbic-cortical circuits in the pathophysiology of MDD and preliminary evidence that a defect involving the cerebellum may also be implicated.
Article
Patients with cerebellar damage often present with the cerebellar motor syndrome of dysmetria, dysarthria and ataxia, yet cerebellar lesions can also result in the cerebellar cognitive affective syndrome (CCAS), including executive, visual spatial, and linguistic impairments, and affective dysregulation. We have hypothesized that there is topographic organization in the human cerebellum such that the anterior lobe and lobule VIII contain the representation of the sensorimotor cerebellum; lobules VI and VII of the posterior lobe comprise the cognitive cerebellum; and the posterior vermis is the anatomical substrate of the limbic cerebellum. Here we analyze anatomical, functional neuroimaging, and clinical data to test this hypothesis. We find converging lines of evidence supporting regional organization of motor, cognitive, and limbic behaviors in the cerebellum. The cerebellar motor syndrome results when lesions involve the anterior lobe and parts of lobule VI, interrupting cerebellar communication with cerebral and spinal motor systems. Cognitive impairments occur when posterior lobe lesions affect lobules VI and VII (including Crus I, Crus II, and lobule VIIB), disrupting cerebellar modulation of cognitive loops with cerebral association cortices. Neuropsychiatric disorders manifest when vermis lesions deprive cerebro-cerebellar-limbic loops of cerebellar input. We consider this functional topography to be a consequence of the differential arrangement of connections of the cerebellum with the spinal cord, brainstem, and cerebral hemispheres, reflecting cerebellar incorporation into the distributed neural circuits subserving movement, cognition, and emotion. These observations provide testable hypotheses for future investigations.
Article
Anatomical, experimental, functional neuroimaging, and clinical data implicate the importance of corticocerebellar interactions in many nonmotor domains, such as sensory, cognitive, emotional, and affective processing. The modular organization and multifarious domains of activity suggest that cerebellar functional specificity has to be searched in a processing modality that is applicable to various contexts. One theory, among many, proposes that "sequence in" of sensory information is critical to understand cerebellar functioning. Here, we aimed at reinterpreting previous findings according to the cerebellar "sequence detection" theory. Spatial function, language, verbal memory, and sequence processing all are domains that are reported impaired after cerebellar damage. Reviewing data that have focused on sequential information processing highlighted the importance of the cerebellum in detecting patterns of incoming stimuli or in central circuit activities. Cerebellar sequence processing should be considered within the known organization of cerebellocortical connections. Within this framework, depending on the involved loop, cerebellar damage can provoke different functional impairments such as defective processing of sensorial stimuli sequences; defective sequential detection error-based learning; defective comparison between incoming sensory patterns and internal modules, and so on.
Article
The functional organization of the cerebellum is reflected in large part by the unique afferent and efferent connectivity of the individual cerebellar lobules. This functional diversity on a relatively small spatial scale makes accurate localization methods for human functional imaging and anatomical patient-based research indispensable. Here we present a probabilistic atlas of the cerebellar lobules in the anatomical space defined by the MNI152 template. We separately masked the lobules on T1-weighted MRI scans (1 mm isotropic resolution) of 20 healthy young participants (10 male, 10 female, average age 23.7 yrs). These cerebella were then aligned to the standard or non-linear version of the whole-brain MNI152 template using a number of commonly used normalization algorithms, or to a previously published cerebellum-only template (Diedrichsen, J., 2006. A spatially unbiased atlas template of the human cerebellum. NeuroImage 33, 127-138.). The resulting average overlap was higher for the cerebellum-only template than for any of the whole-brain normalization methods. The probabilistic maps allow for the valid assignment of functional activations to specific cerebellar lobules, while providing a quantitative measure of the uncertainty of such assignments. Furthermore, maximum probability maps derived from these atlases can be used to define regions of interest (ROIs) in functional neuroimaging and neuroanatomical research. The atlas, made freely available online, is compatible with a number of widely used analysis packages.
Article
Depression is the most frequent psychiatric disorder in Parkinson's disease (PD). Although evidence suggests that depression in PD is related to the degenerative process that underlies the disease, further studies are necessary to better understand the neural basis of depression in this population of patients. In order to investigate neuronal alterations underlying the depression in PD, we studied thirty-six patients with idiopathic PD. Twenty of these patients had the diagnosis of major depression disorder and sixteen did not. The two groups were matched for PD motor severity according to Unified Parkinson Disease Rating Scale (UPDRS). First we conducted a functional magnetic resonance imaging (fMRI) using an event-related parametric emotional perception paradigm with test retest design. Our results showed decreased activation in the left mediodorsal (MD) thalamus and in medial prefrontal cortex in PD patients with depression compared to those without depression. Based upon these results and the increased neuron count in MD thalamus found in previous studies, we conducted a region of interest (ROI) guided voxel-based morphometry (VBM) study comparing the thalamic volume. Our results showed an increased volume in mediodorsal thalamic nuclei bilaterally. Converging morphological changes and functional emotional processing in mediodorsal thalamus highlight the importance of limbic thalamus in PD depression. In addition this data supports the link between neurodegenerative alterations and mood regulation.
Article
Recent neuroimaging studies demonstrate that remembering the past and imagining the future rely on the same core brain network. However, findings of common core network activity during remembering and imagining events and increased activity during future event simulation could reflect the recasting of past events as future events. We experimentally recombined event details from participants' own past experiences, thus preventing the recasting of past events as imagined events. Moreover, we instructed participants to imagine both future and past events in order to disambiguate whether future-event-specific activity found in previous studies is related specifically to prospection or a general demand of imagining episodic events. Using spatiotemporal partial-least-squares (PLS), a conjunction contrast confirmed that even when subjects are required to recombine details into imagined events (and prevented from recasting events), significant neural overlap between remembering and imagining events is evident throughout the core network. However, the PLS analysis identified two subsystems within the core network. One extensive subsystem was preferentially associated with imagining both future and past events. This finding suggests that regions previously associated with future events, such as anterior hippocampus, medial prefrontal cortex and inferior frontal gyrus, support processes general to imagining events rather than specific to prospection. This PLS analysis also identified a subsystem, including hippocampus, parahippocampal gyrus and extensive regions of posterior visual cortex that was preferentially engaged when remembering past events rich in contextual and visuospatial detail.
Article
High-field magnetic resonance (MR) images were used to study posterior fossa morphology in 27 patients with major depression and 36 normal control subjects. Depressed patients demonstrated smaller brain stem and cerebellar vermis than controls. These differences were highly significant for the anterior cerebellar vermis and medulla. There was also a striking age-related decline in midbrain size in depressed patients as well as in controls. Our results are consistent with several lines of evidence implicating a role for the cerebellar vermis in affective disorders and, in addition, provide the first MR documentation of the differential effects of aging on posterior fossa morphology in normal subjects compared with patients with major depression.
Article
Although the cerebellum has traditionally been regarded as a motor mechanism, recent behavioral evidence indicates that the human cerebellum is involved in a wider range of functions: in learning, in planning, in judging time, in some emotional and cognitive disorders such as autism, and in some normal mental activities such as the cognitive processing of words. This evidence suggests that the traditional view of cerebellar function now needs to be reassessed and enlarged to include nonmotor as well as motor functions in the human brain. Whereas the cerebellar connections to frontal motor areas enable the cerebellum to improve motor skills, cerebellar connections to adjacent association areas of the prefrontal cortex can enable the cerebellum to improve mental skills, and cerebellar connections to Broca's area can enable the cerebellum to improve language skills.
Article
The structural neuroimaging findings in mood disorders were reviewed, to evaluate evidence for a neuroanatomic model of pathophysiology, involving the prefrontal cortex, the basal ganglia, the amygdala-hippocampus complex, thalamus, and connections among these structures. Global atrophy is not consistently found. The best replicated finding is an increased rate of white matter and periventricular hyperintensities. A smaller frontal lobe, cerebellum, caudate, and putamen appear present in unipolar depression. A larger third ventricle, and smaller cerebellum and perhaps temporal lobe appear present in bipolar disorder. These localized structural changes involve regions that may be critical in the pathogenesis of mood disorders. Generalized and localized anatomic alterations may be related to age or vascular disease. The clinical and biological correlates of these changes need to be investigated to allow development of a more complete model of pathophysiology of mood disorders.
Article
Despite the involvement of cerebellar ataxia in a large variety of conditions and its frequent association with other neurological symptoms, the quantification of the specific core of the cerebellar syndrome is possible and useful in Neurology. Recent studies have shown that cerebellar ataxia might be sensitive to various types of pharmacological agents, but the scales used for assessment were all different. With the long-term goal of double-blind controlled trials-multicentric and international-an ad hoc Committee of the World Federation of Neurology has worked to propose a one-hundred-point semi-quantitative International Cooperative Ataxia Rating Scale (ICARS). The scale proposed involves a compartimentalized quantification of postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders, in order that a subscore concerning these symptoms may be separately studied. The weight of each symptomatologic compartment has been carefully designed. The members of the Committee agreed upon precise definitions of the tests, to minimize interobserver variations. The validation of this scale is in progress.
Article
Patients with pathological laughter and crying (PLC) are subject to relatively uncontrollable episodes of laughter, crying or both. The episodes occur either without an apparent triggering stimulus or following a stimulus that would not have led the subject to laugh or cry prior to the onset of the condition. PLC is a disorder of emotional expression rather than a primary disturbance of feelings, and is thus distinct from mood disorders in which laughter and crying are associated with feelings of happiness or sadness. The traditional and currently accepted view is that PLC is due to the damage of pathways that arise in the motor areas of the cerebral cortex and descend to the brainstem to inhibit a putative centre for laughter and crying. In that view, the lesions 'disinhibit' or 'release' the laughter and crying centre. The neuroanatomical findings in a recently studied patient with PLC, along with new knowledge on the neurobiology of emotion and feeling, gave us an opportunity to revisit the traditional view and propose an alternative. Here we suggest that the critical PLC lesions occur in the cerebro-ponto-cerebellar pathways and that, as a consequence, the cerebellar structures that automatically adjust the execution of laughter or crying to the cognitive and situational context of a potential stimulus, operate on the basis of incomplete information about that context, resulting in inadequate and even chaotic behaviour.
Article
This study estimated the psychiatric morbidity of patients with degenerative cerebellar diseases. The study included a series of 31 patients with degenerative cerebellar diseases, compared with 21 patients with Huntington's disease and 29 neurologically healthy comparison subjects. Comprehensive psychiatric evaluations, including the Structured Clinical Interview for DSM-IV and psychopathology rating scales, were administered. The overall rate of noncognitive psychiatric disorders was 77% in the patients with degenerative cerebellar diseases, nearly identical to that in the patients with Huntington's disease (81%) and about double that seen in the neurologically healthy subjects (41%). There were high rates of all mood disorders in both the degenerative cerebellar diseases group (68%) and the Huntington's disease group (43%); the rate in the degenerative cerebellar diseases group was significantly higher than that in the neurologically healthy subjects (31%). The frequency of personality change in the three groups was striking: change was present in 26% of the degenerative cerebellar diseases patients, 48% of the Huntington's disease patients, and none of the neurologically healthy comparison subjects. A total of 19% of the degenerative cerebellar diseases subjects and 71% of the Huntington's disease subjects met DSM-IV criteria for either cognitive disorder or dementia. The high rate of psychiatric and cognitive disorders in the patients with degenerative cerebellar diseases suggests that many, if not most, patients with degenerative cerebellar diseases may benefit from psychiatric interventions. These results also support previous findings that the cerebellum may have a role in modulating emotion and cognition.
Article
Most instruments used to assess poststroke depression have never been specifically validated in stroke patients. This study evaluated the depression screening abilities of three questionnaires and one observer-rated scale in 202 consecutive patients 1 month after they experienced their first-ever ischemic stroke. At their respective optimum cutoff values, the sensitivity of the self-rated scales varied between 80% and 90%, while the specificity was about 60%. For the observer-rated scale (Hamilton Depression Rating Scale), sensitivity was 78.1%, and specificity was 74.6%. The instruments clearly performed better in men than in women. Despite this difference, it was concluded that all scales were acceptable screening instruments for poststroke depression.
Article
Emotional blunting can be found after cerebellar lesions. However, the mechanism of such a modification is not clear. We present a patient with emotional flattening and increased risk taking after left cerebellar infarct who had an impaired autonomic reactivity to negative as compared with positive reinforcement. This impairment was demonstrated by the patient's undifferentiated skin conductance responses to negative and positive reinforcement, whereas controls produced larger skin conductance responses after negative feedback. The cooccurrence of emotional flattening and undifferentiated autonomic reactions to positively and negatively valenced stimuli strengthens the role of the cerebellum in the modulation of the autonomic responses.
Article
We applied voxel-based morphometry, an indirect volumetric technique, to MRI volumes of patients carrying the spinocerebellar ataxia type 2 mutation to determine patterns of brain atrophy. Nine patients were compared to 27 controls matched for age, sex and handedness. An optimised voxel-based morphometry protocol was used for pre-processing to minimize systematic bias. We observed significant volume loss in the cerebellar hemispheres, vermis, pons, mesencephalon and thalamus. Also affected were several supratentorial areas such as the right orbito-frontal cortex, right temporo-mesial cortex and the primary sensorimotor cortex bilaterally. The volumetric changes of cerebellar hemispheres were inversely correlated to cerebellar symptoms rated by a cerebellar ataxia scale. Two mechanisms could contribute to the observed cortical atrophy. It could be either the result of primary supratentorial degeneration as part of the disease process and/or secondary atrophy due to cerebellar deafferentation.
Article
The aim of the present study was to investigate if clinically relevant affective or behavioral changes as described in adults in the cerebellar affective syndrome by Schmahmann and Sherman [The cerebellar cognitive affective syndrome, Brain 121 (1998) 561-579] are likely to occur as a long-term sequelae of cerebellar vermis lesions in children. Site and extent of the vermal lesion were defined on the basis of individual 3D-MRI scans and lesion data were correlated with behavioral and affective changes. Affect and behavior were assessed in children after cerebellar tumor surgery by means of experimenter ratings based on the description of the cerebellar affective syndrome and free ratings by the patients and their parents. Twelve children and adolescents with a former cerebellar astrocytoma surgery without subsequent radiation or chemotherapy participated. Detailed analysis of individual 3D-MR images revealed that lesions affected the vermis in nine children. Experimenter ratings according to Schmahmann revealed no relevant problems in patients. In five out of nine patients with vermal affection somewhat increased thoughtful, anxious or aggressive behavior was reported by patients and parents. In conclusion, minor behavioral and affective changes were present in a subset of children with chronic vermal lesions.
Article
Four separate metaanalyses of factor analyses were conducted for the Beck Depression Inventory (BDI), the Center for Epidemiological Studies Depression Scale (CES-D), the Hamilton Rating Scale for Depression (HRSD), and the Zung Self-Rating Depression Scale (SDS). The total number of participants (N) and studies (k) included in each of the metaanalyses were the following: BDI (N = 13,643, k = 33), CES-D (N = 22,340, k = 28), HRSD (N = 2,606, k = 17), and SDS (N = 12,621, k = 13). Metaanalysis results suggest that the specific depression symptom factors within each test appear to be relatively robust and well established and match fairly closely previously hypothesized factor structures. A general Depression Severity factor and a small Somatic Symptoms factor are found in all four tests and two tests had a small Positive Affect factor. There were fewer common specific depression symptom factors across tests than expected.
Diagnostic and Statistical Manual of Mental Disorders
American Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. American Psychiatric Publishing, Washington DC Text Revision.