Cerebellum and Cognition CEREBELLUM AND COGNITION Elena Cano and Ismael Loinaz Abstract: The scientific literature

has traditionally defended only the involvem ent of the cerebellum in motor functions. The traditional belief that the cerebe llum is only a motor control device seems to have been overcome and a growing nu mber of studies have shown that the cerebellum acts as diverse due to its struct ural complexity and its multiple connections with different brain regions. This review is intended to be an update of existing critical data on the involvement of the cerebellum in different cognitive functions in diverse psychopathology and how the neuroimaging studies and cerebellar lesions contribute to better understanding the complex world cerebell um. INTRODUCTION Traditionally the cerebellum has been associated exclusively with m otor functions and scientific literature available on the subject is extensive. A growing number of empirical studies have begun to highlight the involvement of the cerebellum in emotional and cognitive functions (Schmahmann, 2004). Underst anding the human cerebellum has improved in recent decades thanks to the availab ility of detailed anatomical images 1 Cerebellum and Cognition provided by neuroimaging studies with MRI, and cerebellar activation with PET an d fMRI studies of motor functions, sensory and cognitive / emotional (Fliessbach , Trautner, Quesada, Elger and Weber, 2007). The three-dimensional atlas of the human cerebellum by MRI were introduced almost a decade ago (Schmahmann et al., 1999). The atlas of Schmahmann and colleagues has become a reference tool in ide ntifying the cerebellar lobes and fissures in functional imaging studies. Howeve r, deep cerebellar nuclei are difficult to access, so the study of the different interfaces has been complicated. A recently published an atlas of MRI on human cerebellar nuclei (Dimitrova et al., 2002) in a study designed especially for st udying the anatomy of the deep cerebellar nuclei. We could not understand the co mplexity of the cerebellum without regard to their anatomy, so dedicate a small section cereblares connections. Anatomical studies on the cerebellum and its fun ctions, especially those relating to motor connections have often been carried o ut on primates (Ramnani, 2006) has recently increased the number of empirical st udies that demonstrate the involvement of the cerebellum in cognitive and emotio nal functions (Schmahmann and Caplan, 2006). The studies that have been investig ated in patients with cerebellar damage have demonstrated the involvement of it in executive functions, language (Chen and Desmond, 2005) and emotional regulati on ("cerebellar cognitive-affective syndrome," SCAC) (Schmahmann and Sherman, 19 98). As outlined below, many studies have analyzed the involvement of the cerebe llum in determinded psychopathology. Psychopathology in which most comprehensive ly studied the involvement of cerebellar abnormalities in the etiology of schizo phrenia has been (Paradiso, Andreasen et al., 2003), but also discuss their invo lvement in trichotillomania (Keuthen et al., 2006, Swedo et al., 1991), Williams Syndrome (Eckert et al., 2006, Jones et al., 2002) or autism (Townsend et al., 2001). 2 Cerebellum and Cognition Analyze the involvement of the cerebellum in cognitive functions such as languag

e, memory, attention, temporal perception and empathy. ANATOMY OF THE CEREBELLUM AND ITS CONNECTIONS To better understand the involveme nt of the cerebellum in different functions and pathologies, it is necessary to understand some anatomical peculiarities of the cerebellum (Makris et al., 2005) and its connections, which are precisely the cause of their functional diversit y . In a recent review of the cerebellum in nonhuman primates (Ramnani, 2006) st ates that despite the various trials that support the theory that the primate ce rebellum contributes not only to motor control, but also to higher cognitive fun ctions, there is still no consensus among professionals on how the cerebellum pr ocesses such connections. The answer lies in the nature of the connections of th e cerebellum with areas of the cortex, especially the prefrontal cortex and the uniformity of their cellular organization. Understanding this cellular organizat ion, you can extend the model of information processing of motor cortex to proce ss information from the prefrontal cortex. The main processing unit of informati on in the cerebellar cortex is the Purkinje cell,€which integrates information from two major relay stations precerebelares: pontine nucleus and inferior olive . The diverse information processed by the cerebellum does not stem from differe nces in local circuits, but the diverse nature of inputs, especially those from the cerebral cortex. The cerebellum appears to be composed of multiple independe nt anatomical modules, each forming a component of a closed anatomical loop that sends and receives projections from a specific area of the cerebral cortex (Ram nani, 2006). In addition to morphological or structural abnormalities of the cer ebellum, other studies attempt to show the connections of the cerebellum to cere bral cortical areas, especially with first-order cortical areas. The evidence in this regard are becoming more extensive, having 3 Cerebellum and Cognition demonstrated powerful connections of the cerebellum through the cerebellar nucle i, with the primary motor cortex or the prefrontal cortex, the Purkinje cells of the cerebellar nuclei exert an inhibitory effect mediated by the GABA system (O liveri, Koch, Torriero and Caltagirone , 2005). The cerebellar nuclei receive af ferents mainly from the cerebellar cortex, but the main source of efferents from the cerebellum, are precisely the cerebellar nuclei (Schoch, Dimitrova, Gizewsk i and Timmann, 2006). At the same time is described as afferents to the cerebell um are much higher than the efferents from the cerebellum, which is interpreted as a sign of the integrative role that has the cerebellum in the overall functio ning of the central nervous system (Gottwald, Wilde, Mihajlovic and Mehdorn, 200 4 .) One of the ways in which they have demonstrated connections of the cerebell um (and the type of modulation exerted) to the contralateral primary motor areas has been using transcranial magnetic stimulation (TMS), measuring the response using motor evoked potentials (in controls healthy). It has been observed that i nhibition of the cerebellum following stimulation results in facilitation of evo ked potentials in the contralateral primary motor cortex. This result shows that the connections between cerebellum and primary motor areas are cross-connection s, connections that exert inhibitory control over these areas (Oliveri et al., 2 005). In the same vein, a study conducted with healthy controls shows how, befor e the development of a verbal fluency task (which takes place in silence), a rig ht-handed person there is a significant activation in the right cerebellar hemis phere, and activation frontoparietal cortex contralateral (left), while left-han ded, activates the left cerebellar hemisphere with the right frontoparietal cort ex (Hubrich-Ungureanu, Kaemmerer, Henn and Braus, 2002). It demonstrates both the existence of connections with cortical areas directly invo lved in cognitive processing, such as the fact that these connections take place on a crusade. The demonstration of the connections with the first-order cortica l areas consistent with the fact that, phylogenetically, the brain areas of asso ciation and the neocerebellum have been developed in parallel.

4 Cerebellum and Cognition In line with the connections between the cerebellum and the brain areas related to language, to the evidence of dysfunction of cerebellar activity following the injury of the brain areas related to language, it is proposed that the frontal lesion may in a lower cerebral blood flow and a decreased metabolism in the cont ralateral cerebellum. Given this scenario raises a job, measuring precisely the blood oxygen level in these areas, while performing a verbal task in silence. Th is study shows that in patients with aphasia, despite the absence of injury to t he right cerebellar hemisphere, this is not working properly, proposing could be due to lack of inputs from the frontal cortex affected. When, in the same study , the task is repeated (and, therefore, verbal learning) changes were observed i n oxygen consumption in the cerebellum both left and right frontooccipitales are as, changes that correspond to the improvement in the performance of the task. G iven these results, the authors propose two hypotheses to justify the role of th e cerebellum in language: the cerebellum stores phonological information while p erforming the task, and, second, that the cerebellum is involved in the detectio n of errors in production tasks verbal (Connor et al., 2006). Following research on the connections of the cerebellum,€proposed that it participates in the lea rning of procedures through a network that interconnects with the prefrontal are as via the thalamus, a network composed of both excitatory connections as inhibi tory connections, and it presents the hypothesis that injury to any node that ma ke up this network, would upset the balance of excitatory-inhibitory connections , which would be the deterioration in the performance of the function. Following this theory, conducting a study in which performance is measured against the le arning of a motor task, performed with one hand, in patients with cerebellar les ion located in the cerebellar hemisphere contralateral to the hand, after applyi ng transcranial magnetic stimulation low frequency (Torriero et. al., 2007). Thr ough this study shows that cerebellar injury is accompanied by a decline in acti vity in the contralateral prefrontal cortex (specifically the dorsolateral prefr ontal cortex). 5 Cerebellum and Cognition When stimulated by rTMS on prefrontal cortex contralateral to the lesion, the ta sk performance suffers the most damage (about the deterioration of departure), i n contrast, when stimulated the prefrontal cortex ipsilateral to the cerebellar lesion and contralateral to the affected limb , learning of the task improvement , which suggests that compensation is due to excess stimulation of the cortex re ceives from the cerebellum intact, compared with less stimulation to the contral ateral prefrontal area receives from the cerebellum injury. For the aforemention ed reasons, we conclude that the cerebellum has connections with primary motor a reas, as areas of language (specifically the frontoparietal cortex) and prefront al cortical areas (particularly the dorsolateral cortex) in the case of cross co nnections, to contralateral cerebral hemisphere. In line with the establishment of the cerebellar connections with other brain areas, has made a study of functi onal localization in this case from the motor component in the cerebellum. In th is study proves the existence of somatotopic representation in the superior cere bellar cortex, a finding that coincides with the result set from other studies. (Schoch, 2006). According to this representation, lobules III and IV (vermis and paravermis) are associated with ataxia in the lower extremities, while IV and V I lobes (vermis, and hemispheres paravermis) are linked to upper limb ataxia, dy sarthria is linked to the lobes V and VI (paravermis and hemispheres), the lobes II and III (superior vermis) are associated with ataxic gait, while the postura l ataxia is linked to the lobe III. These findings are consistent with the resul ts obtained through functional neuroimaging. A second finding of this study is t he demonstration that the prognosis for recovery of motor functions depends on w

here the injury settles, resulting in worse prognosis those functions which were created in the cerebellar nuclei. 6 Cerebellum and Cognition PSYCHOPATHOLOGY AND CEREBELLUM Several studies have shown the existence of struc tural alterations in the cerebellum in various disorders such as schizophrenia, autism, attention deficit hyperactivity disorder or trichotillomania, conditions that, in turn, share some symptoms with those listed by cerebellar lesions. Sch izophrenia: In the group of schizophrenic subjects Paradiso (Paradiso et al., 2003) observed by PET imaging study, these patients did not tr igger the NL phylogenetic fear-danger while viewing unpleasant pictures. Similar ly, the cerebellum of these patients, and the prefrontal cortex showed a reduced activity during the evaluation of pleasant images, being unable to recog nize them as such. A recent study conducted with a relatively large sample of pe ople with first episode schizophrenia, and so far had not made the same drug treatment showed a lower vo lume of gray matter in various parts of the central nervous system, including th e cerebellum is apparently significantly lower compared to previous studies (Chu a et al., 2007). SÍndorme Williams: The Williams Syndrome (SW), the visuo-spati al ability is particularly affected. SW neurobiological studies show an unusual structure and activity in posterior regions of parietal, thalamic and cerebellar , which are important to implement actions based on space (Eckert et al., 2006). Individuals with Williams syndrome have a disproportionately large cerebellum, particularly the cerebellar vermis, a component of visual-spatial system (Jones et al., 2002). Trichotillomania: A gro up of Keuthen (2006) explored the cerebellar volume in 14 patients diagnosed wit h trichotillomania (TTM) according to DSM-IV. Was the first structural investiga tion of the involvement of cerebellum in the TTM. The sensory and affective variables play a role in the ac tivation and maintenance of symptoms in this pathology. Studies carried out with PET had demonstrated hypermetabolism 7 Cerebellum and Cognition in left and right cerebellar areas in patients with TMD (Swedo et al., 1991). Th e TMD is a disorder considered as belonging to the spectrum of obsessive-compuls ive disorder are identified motor routines, stereotyped behaviors, behaviors whi ch lead to the study of the cerebellum as the site of coordinated control of mot or sequences. The results of this study show that patients diagnosed with tricho tillomania have a cerebellar cortical volume lower than healthy individuals, thi s remains lower cerebellar volume in both hemispheres, and cerebellum when exami ned by subterritories (Keuthen et al., 2006 .) In this study, there was a compar tmentalization of the cerebellum in 10 functional groupings: group related to po sture and balance, emocionalautonómico cluster, clusters sensorimotor, oculomot or groups (right and left) or cognitive clusters. Cortical volume was observed s ignificantly low in emotional-autonomic group, a finding that is interpreted as related to anxiety that patients have with pre-form trichotillomania pull hair, or if they resist it, or at the pleasure generated by the tug. There was also a significantly lower in the cognitive cluster, which is interpreted in the contex t of the present deterioration in patients with trichotillomania executive-type cognitive functions and planning, allocating a significant contribution to these

functions of the cerebellum. Lower volumes also been identified in the oculomot or groups, which the authors propose in relation to the presence of visual stimu li that trigger the behavior of the hair growth spurt or the display of colors a nd textures identifying motivating the choice of either strand hair. The results obtained in the study of Keuthen and collaborators confirmed the hypothesis: th ere were significant differences between patients and controls in the total volu me of the cerebellum, this being lower in those affected. Autism: Another exampl e is that of autism, which also appear in stereotyped and repetitive motor behav iors. It has been reported that approximately 95% of autopsies performed in pati ents with 8 Cerebellum and Cognition autism, have structural abnormalities in the objectified (Gottwald et al, 2003). In connection with this disorder have been several structural studies, one of t he most recent studies show that the cerebellum of patients with autism having a smaller volume of gray matter, while there is an increase volume of gray matter in areas as the right and left medial gyrus or prefrontal gyrus (Rojas et al., 2006). COGNITIVE FUNCTIONS Language: Recent studies have shown how patients with cerebe llar damage present in language disorders (Ravizza et al., 2006, Chen and Desmon d, 2005; Akil, Statham, Götz., Bramley and Whittle, 2005). Often in neuroimagin g research, the cerebellum has appeared active in processes of verbal working me mory (verbal working memory, MTV). Ravizza et al, recently designed a study to d etermine whether damage to the cerebellum were associated with damage affecting the range of tasks MTV. They studied 15 patients with cerebellar damage, focusin g on those with unilateral lesions. During his several experiments found that pa tients appeared modest but consistently affected in immediate verbal retrieval t asks (Experiments 1 and 3) and that their deficits were aggravated when introduc ing the delay before recall (Experiment 2). These results are consistent with re sults from neuroimaging studies, and mild illness in MTV standardized test is co nsistent with clinical observations that suggest that the cerebellar damage appe ars not typically associated with deficits in short-term memory (Ravizza et al. 2006). In Akil et al. (2005) described cerebellar mutism. This is a rare, often tends to occur in children after surgery of the posterior fossa. In his brief re port, discussed the unusual case of a preoperative cerebellar mutism in an adult in the context of a 9 Cerebellum and Cognition cognitive affective syndrome caused by cystic hemangioblastoma. Cerebellar musti smo The term refers to a anarthria resulting in severe damage of fluency, articu lation and modulation of speech. The exact mechanism underlying the silence is u nknown, but they have mentioned the dentate nucleus lesions of the middle pedunc le (brachium pontis) of dento-thalamic tracts and ruptures of the inferior vermi s to cause (Janssen et al., 1998; Mewasingh, Khadim, Christophe, and Dan Christiaens, 2003; Ozgur, Berberian, Aryan, Meltzer and Levy, 2006). Chen and Desmond (2005) condu cted a study using fMRI to demonstrate the involvement of the cerebellum on MTV, finding areas of common activation in verbal working tasks and tasks of articul atory control, as well as regions that are activated only for the memory of work . We found activation in Broca's area (BA 44 / 6) and the superior cerebellar he misphere for both the working memory to the test motor. But only during MTV acti vation found in the inferior parietal lobe and right inferior cerebellum. Their findings provide evidence to postulate the existence of two networks of cerebrocerebellar working for MTV. On one hand the network of frontal-superior cerebell

ar control and articulatory network of phonological storage parietalinferior. Fu rther studies to confirm the existence of this modulatory influences between the cerebellum and brain cortical areas related to phonological processing, recipro cal influences between the two areas, cortical areas related to language (with p honological processing) have noted that the the fusiform gyrus which has a more powerful connections with the cerebellum. Given this evidence, the authors propo se that the cerebellum acts in a process of amplification and refinement of the patterns of activation of cortical areas, through loops established by the recip rocal connections between areas. It also justifies the greater connection to the fusiform gyrus, suggesting that the cerebellum exerts a role in the processing of orthographic representations (Booth, Wood, Lu, Houk, and Bitan, 2007). 10 Cerebellum and Cognition This evidence and the demonstration by functional magnetic resonance imaging stu dies that the cerebellum in children with dyslexia has a smaller size (anterior right lobe) have the approach that the cerebellum is related to language process ing, and reading processing (Booth et al., 2007). Memory: It has been described, for example, a deterioration in the memory of patients with cerebellar lesion i n the case of a general memory impairment, and deterioration in visual memory an d the evocation in this deterioration has noted that this is more marked when th e task requires a greater effort by the patient (Gottwaldet al., 2004). Note: Se veral studies have shown the involvement of care in patients with cerebellar les ions (Gottwald et al., 2004). In fact, we have demonstrated the existence of str uctural alterations in the cerebellum in patients diagnosed with Attention Hyper activity Disorder. In this sense, both demonstrated a clear impairment of divide d attention and working memory, this term as an executive system of organization of the new incoming information, both intimately connected with selective atten tion as divided attention. However there is no evidence of selective attention i mpairment in patients with cerebellar injury. That is, cognitive performance is affected when the processing of stimuli requires a parallel processing system, o r when an exchange is required between modes of processing, a finding that suppo rts the theory of the dysmetria of thought (Schmahmann, 2004) . Assessing the co gnitive performance of patients with cerebellar lesions, several studies have sh own that the deterioration was more marked when the lesion was located in the ri ght hemisphere, in contrast, patients whose lesion involved the left cerebellar hemisphere showed no involvement of any verbal functions . This is explained by the 11 Cerebellum and Cognition connection of the right cerebellar hemisphere with the left cerebral hemisphere, the dominant language (Gottwald, Mihajlovic, Wilde and Mehdorn, 2003). Dysmetri a of thought: The theory of the dysmetria of thought is to objectify both altera tions of motor functions, but most of the cognitive functions in patients with c erebellar lesions€suggesting that the cerebellar lesion does not eliminate the cognitive function but disrupts the normal development of the same. This suggest s, in turn, an integrative role of the cerebellum in brain function, in which th e cerebellum would prepare the way before any stimuli, optimizing processing (Sc hmahmann, 2004). Perception and temporal processing in recent years there have b een several studies to elucidate the possible involvement of the cerebellum in t he perception or representation of time. This line of research began to identify behaviors that depend on temporal processing, which are affected in patients su ffering from lesions in the cerebellum, as conditioned learning or control over agonist and antagonist muscles to develop a movement. Regarding this fact, sever al authors propose the metaphor of the clock as time control system by the accum ulation of pulses, a system that would depend on the attention to make represent

ation, which would then stored in working memory. Based on this information, and for the purpose of identifying whether cerebelol injury damages the "timer" (Ha rrington, Lee, Boyd, Rapcsak, and Knight, 2004), designed a study in which they intend to observe the impact of injury cerebellar temporal production tasks and time perception tasks. Their findings concluded that cerebellar damage did not a ffect significantly the performance of any of the two tasks, also noted that, wh en there were deficits in the performance of the tests, these were associated wi th damage to the upper and middle cerebellar lobes and it was only deficits in t asks of production. 12 Cerebellum and Cognition These results lead the authors to conclude that deficits in temporal processing in case of injury of the cerebellum should be related to alterations in other co gnitive processes required by the temporal processing tasks. Then we have develo ped new work addressing this issue, with results opposite to those described by Hamilton et al. In order to evaluate the processing time have developed four ran ges or time scales, based on functional aspects, namely, microseconds, milliseco nds, seconds, and rhythm circardiano. For example, motor control and development of motor behavior or control of the language would be processed in the range of milliseconds, while the reasoning would be processed in the range of seconds (K och et al., 2006). Following this line of work, there seems to be consensus at t he time of linking the cerebellum to the mechanism of "internal clock" with the basal ganglia (Lee et al., 2007). Based on this classification and on the assump tion that the cerebellum is involved in temporal processing in the range of mill iseconds for a study using transcranial magnetic stimulation over the cerebellum (Koch et al., 2006). The results indicate that the cerebellum is necessary for processing in the range of milliseconds, while not involved in processing in sec onds, proving more important the role of the left lateral cerebellum. Also get a link right dorsolateral prefrontal cortex in processing at intervals over the s econd, suggesting the existence of a network for conscious perception of time wi th a dissociation within the range of processing. He had previously developed a model whereby there is an automatic processing system and a cognitive system, th e first intervene in temporal processing in milliseconds, and could be related w ith the movements, while the second part in the extent intervals within seconds. The first system would allow the completion of the task in a more automatic, in contrast, the second system would undertake the task with greater cognitive req uirement. 13 Cerebellum and Cognition A recent study, which is also used transcranial magnetic stimulation (Lee et al. , 2007), was found linking cerebellum perception in the sub-second range, while not objectified in the rang e suprasegundos intervention, according to the results obtained by the authors o f the preceding article. Other authors (Lee et al., 2007) observed (also by tran scranial stimulation magnetic) that stimulation of the dorsolateral prefrontal cortex altered process ing in the range suprasegundo without affecting the processing sub-second range. This is consistent with the approach regarding the temporal processing network in which the cerebellum participates as well as the dorsolateral prefrontal cort ex,€and possibly explain the result, and could explain the reason why patients affected by cerebellar injury with impaired processing in both the sub-second ra nge as the range suprasegundo. Therefore, the authors conclude that the cerebell um does not act as internal clock, but consider the cerebellum as part of a temp

oral processing system that would also include the basal ganglia, thalamus and p refrontal cortex. Another way in which addresses this issue has been studying ce rebellar function in patients suffering from other disorders, which, as describe d at the beginning of the exhibition, there are similarities, in this case with schizophrenia, whereas the study of the cerebellum in this condition may help to elucidate the involvement of the cerebellum in processing time. This approach i s based on the fact that in this disorder are a number of symptoms that can be i nterpreted as symptoms secondary to alterations in the temporal coordination of behavior cognitive, perceptual or motor, or alteration of information processing , such as alterations in the train of thought, and the fact that patients with s chizophrenia also have impaired executive functions and visuospatial problems (B rown et al., 2005). In addition, it has been observed that the volume of cerebel lum correlates with increased cognitive impairment, supporting the theory of the dysmetria of thought. The findings of the study (comparison of controls and sch izophrenic patients in a conditioning task) 14 Cerebellum and Cognition showed that schizophrenia patients showed a deterioration in the learning of the conditioned response, suggesting a deficit in the circuit responsible for the a cquisition of this response, which is thought that the cerebellum is a core elem ent. Also found a high variability for each subject to perform the task, which i s consistent with the hypothesis of deterioration in temporal processing. Was ru led out in this paper that the results were skewed by changes in attentional or memory. In addition to what is the involvement of the cerebellum in executive fu nctions, are yielding evidence of their involvement in other types of cognitive functions. Through a study which intends to healthy patients to imagine themselv es in a future situation, it was observed that among the various areas of the ce ntral nervous system that showed increased activation, premotor cortex and the l ateral or posterior medial parietal cortex also were activated specific areas of the cerebellum, mainly the back, areas that are activated when it is necessary to imagine or simulate the movements of the body, and, also related to spatial m emory and attention. We therefore propose that one of the keys to imagine the fu ture is the simulation of representations (the body) in storage, which suggests that the image of oneself in the future is based on the reactivation of represen tations of the past (Szpunar , Watson, and McDermott, 2007). Empathy: In a study of empathy, in which the task was passive viewing of faces and hands, in imitat ion active in the development of a specific motor behavior it was observed that, over the task of imitation (both faces and hands) activation occurred cerebella r areas. This is consistent with the hypothesis above, on the question of repres entation. (Leslie, Johnson-Frey and Grafton, 2004). 15 Cerebellum and Cognition INJURY cerebellar cerebellar lesions do not always manifest as ataxia. Schmahman n and colleagues conducted a study with 20 patients with cerebellar lesions (Schmahmann and Sherman, 1998). They concluded the existence of a pattern of clinically significant behavioral changes they cal led Cerebellar cognitive-affective syndrome. (SCAC), characterized by: a) disturbance of executive function, including defici ts in planning, abstract reasoning, working memory and reduced verbal fluency, 2 ) damage in spatial cognition, including visual-spatial disorganization, memory impairment visual-spatial, 3) changes in personality, uninhibited or inappropria te behavior, 4) language difficulties, including disprosodia, agrammatism, mild anomia. The net effect of these disorders in cognitive function is a general dec

line in global intellectual function. The damage includes SCAC executive skills, visual-spatial and linguistic minorities, including affective disorders from em otional weakness and depression, to disinhibition and psychotic features. The co gnitive and psychiatric components SCAC€with disability cerebellar ataxia disorder are conceptualized within the dysmetria of thought hy pothesis (Schmahmann, 2004). Cerebellar damage is manifests as ataxia when the sensorimotor cerebellum is involved and as SCAC, wh en the pathology is located in the posterior cerebellar hemisphere side (involve d in cognitive processing) or in the vermis. Schmahmann at work also reviews non -motor aspects of cerebellar function. Has recently been shown that patients wit h cerebellar damage have also intellectual and mood changes (Konarski, McIntyre, Grupp and Kennedy, 2005). Clinical studies identify the relationship between ce rebellum and personality, aggression and emotion, and link psychosis (especially schizophrenia) with a growth in the fourth ventricle, a smaller cerebellar verm is and cerebellar atrophy, found up to 40% of schizophrenic subjects (Suppriam e t al., 2000). Hokkanen, kauranes, Roine, Salonen, and Kotila (2006) investigated the neuropsychological functioning of patients with cerebellar infarction and 16 Cerebellum and Cognition assessed the laterality of cognitive symptoms. They analyzed 26 patients with ce rebellar lesions exclusively in the acute phase and three months, and compared w ith 14 controls. They focused on four domains: 1) visuospatial functions / motor , 2) episodic memory, 3) working memory and 4) execution / attentional shift. St atistical differences in visuospatial function, as well as episodic memory and w orking. They concluded that patients with left cerebellar lesion were slower in visuospatial tasks, whereas those who suffered injury right, had difficulties in verbal memory compared with controls. Cerebellar infarcts subtle cognitive dama ge occasioned, perhaps initially associated with deficits in working memory. The se symptoms appear to be mediated by the contralateral cortical hemisphere, cere bellar infarcts left hemispheric dysfunction producing right, and right cerebellar infarct produ cing left cerebellar dysfunction. CEREBELLUM AND EMOTIONAL EXPERIENCE Two lines of research have demonstrated the association cerebeloemoción in humans: studies of lesions and functional neuroi maging studies. Lesions of the posterior lobe and cerebellar vermis are associat ed with emotional weakness, as well as damages in a variety of cognitive domains including executive function, spatial cognition and language (Schmahmann and Sh erman, 1998). Neuroimaging studies have shown cerebellar activation during emoti onal processing (Paradiso et al., 2003). But lesion studies alone can not fully explain the basic mechanisms of emotional disruption in patients with cerebellar damage. Collaborate and Turner have recently published the first study that has used functional neuroimaging (PET) in combination with lesions to determine the involvement of the cerebellum in processing emotional material. (Turner et al., 2007). Stop It examined six patients with cerebellar infarction, while reacting to visual stimuli evoking pleasant and unpleasant emotions. They discovered a p henomenon 17 Cerebellum and Cognition interesting lesions of the cerebellum does not seem to affect the normal ability to experience negative emotions, but are associated with a reduced ability to e xperience positive emotions. While patients with cerebellar lesions may experien ce unpleasant feelings in response to frightening stimuli, fail to recruit struc

tures of normal brain would be involved in this task (eg amygdala) instead activated a lternate limbic circuit which includes ventromedial prefrontal cortex, insula an d cingulate gyrus. Still remains unclear why despite an adaptation of new circui ts when the cerebellum is damaged, positive emotional responses were reduced whi le the negatives were preserved. There is evidence that lesions in the posterior lobe of the cerebellum and vermis are associated with blunted affect, in fact, have been observed in patients with cerebellar lesion in which the affective sym ptoms is checked, the vermis was systematically affected. (Turner et al., 2007). An example of the relationship between the cerebellum and the excitement is tha t depression is one of the main problems in patients suffering from spinocerebel lar ataxia. Another example is the youngest of the vermis volume in patients, be ing diagnosed with bipolar disorder, have had multiple depressive episodes (Schm ahmann, 2004). Subsequently raised the possibility that this alteration in the volume of the ve rmis may be an artifact secondary to a neurotoxic effect of antidepressants on t he cerebellar region. (Mills, Delbello, Adler and Strakowski, 2005). All this, t ogether with identification of connections between areas of the midline of the c erebellum with regions of the limbic system, the description of manic episodes i n patients with cerebellar injury or structural abnormalities of the cerebellum in bipolar disorder patients suggests that the cerebellar vermis plays an import ant role in mood regulation. In the above line in a functional neuroimaging stud y has described the existence of structural alterations in 18 Cerebellum and Cognition patients diagnosed with bipolar disorder in those regions of the vermis which ha ve connections with the limbic system areas, such as the anterior cingulate cort ex, amygdala, hippocampus, and even with the hypothalamus (Mills et al., 2005). Before this evidence and to the findings of neuroimaging studies in which it det ects an increase in the activity of the cerebellum with emotional demands, studi es have emerged that seek to examine the role of the cerebellum in emotion. One study this aspect in patients affected by cerebellar injury. It was noted that p atients are able to identify the emotional significance of the stimulus, but hav e an impaired ability to experience, so subjective, the emotional charge of it, mainly when it comes to pleasant stimuli, evoking joy, on the contrary there is no deterioration in the ability to perceive stimuli that evoke fear. In addition , this study shows that, although patients respond emotionally unpleasant stimul i, they do not activate the brain areas that are generally activated in this sit uation, but that activate brain areas "alternatives." These findings lead the au thors to propose that the cerebellum plays a role as coordinator of the activity , so that, before his injury, alternate nodes are activated to develop an adapti ve response, which is in agreement with the results of other studies (Turner et al., 2007). Using a functional neuroimaging study which sought to demonstrate ho w the music enhances the emotional intensity of feeling to an image (image compa red to no music), it was noted that precisely in this situation of empowerment o f the stimulus, the cerebellum was among the activated areas. The authors interp ret this activation on the basis of connections that the cerebellum receives fro m the coming of the pons and anterior cingulate cortex, an area whose involvemen t in emotional processing is demonstrated. With respect to these connections is hypothesized that these projections to the cerebellum as guide or guide you in c oordinating the various action programs in response to emotional stimuli (Baumga rtner, Lutz, Schmidt, and Jancke, 2006). 19 Cerebellum and Cognition

It has also raised a possible role of cerebellum in behaviors related to substan ce abuse, specifically cocaine use to the description, by neuroimaging of cerebe llar activation when viewing or imagining experiences related to consumption, an d before the activation of the cerebellum in "craving." In particular, cerebella r vermis appears to be the most relevant in this regard. Thus, activation of the vermis has been found in cocaine-related stimuli to the substance, the areas ac tivated in the vermis, although it is related to oculomotor activity, only indiv iduals were activated in cocaine users. These findings are consistent with the f inding of an enrichment in dopamine transporter protein in the activated areas, precisely because of this fact the authors suggest that the cerebellar vermis ma y be one of the sites of action of substances that interact with the dopamine tr ansporter (Anderson et al., 2006). CONCLUSION: After the collection of scientific literature that have had the oppo rtunity to analyze, has been proved the involvement of the cerebellum in higher cognitive functions, resulting in alterations of the same as the SCAC when there are injuries or developmental abnormalities, being associated with certain psyc hopathologies such as schizophrenia or ADHD, and emotional reactions mediating d eterminded.€The application of new technologies in the study of the human brain has opened the door to endless knowledge so far limited to some extent the unde rstanding of human behavior. A detailed understanding of brain structures allows a specific and effective clinical application, and in the future we will have t o recycle many of the theories that today direct knowledge. 20 Cerebellum and Cognition REFERENCES Afifi, A. K. and Bergman, R. A. (2006). Functional Neuroanatomy (2nd ed.). Mexico: McGraw-Hill Interamericana. Akil, H., P. Statham F. X., M. Götz, P. Bramley and I. Whittle R. (2005). Adult cerebellar mutism and cognitive-affec tive syndrome Caused by cystic hemangioblastoma. Acta Neurochirurgica, 148, 597598. Anderson, C. M., Maas, L. C. Frederick, B., Bendor, J. T., Spencer, T. J., Livni, E., Lukas, S. E., Fischman, A. J., Madras, B. K., Renshaw, P. F. and Kauf man, M. J. (2006). Involvement in cerebellar vermis cocainerelated Behaviors. Ne uropsychopharmacology, 31, 1318-1326. Baumgartner, T., Lutz, K., Schmidt, C. F. and Jancke, L. (2006). The emotional power of music: how music Enhances the feel ing of affective pictures. Brain Research, 1075 (1), 151-164. Booth, J. R., Wood , L., Lu, D., Houk, J. C. and Bitan, T. (2007). The role of the basal ganglia an d Cerebellum in language processing. Brain Research, 1133 (1), 136-144. Brown, S . M., Kieffaber, P. D., Carroll, C. A., Vohs, J. L., Tracy, J. A., Shekhar, A., O'Donnell, B. F., Steinmetz, J. E., and Hetrick, W. P. (2005). Indi cate timing eyeblink conditioning and cerebellar deficits in schizophrenia Abnor malities. Brain and Cognition, 58, 94-108. Chen, S. H. and Desmond, J. E. (2005) . During networks Cerebrocerebellar articulatory rehearsal and verbal working memory task. NeuroImage, 24, 332-338. Chua, S. E., Cheung, C., Cheung, V., Tsang, J. T. K., Chen, E. Y. H., Wong, J. C . H., Cheung, J. P. Y., Yip, L., Tai, K., Suckling, J. and McAlonan, G. M. (2007 ). Cerebral gray, white matter and csf in never-medicate, firstepisode schizophr enia. Schizophrenia Research, 89, 12-21. Connor, L. T., DeShazo Braby, T., Snyde r, A. Z., Lewis, C., Blasi, V. and Corbetta, M. (2006). Hemispheres switches cerebellar activity with cerebral reco very in aphasia. Neuropsychologia, 44, 171-177. Corben, L. A., Georgiou-Karistia nis, N., Fahey, M. C.,. Storey, E., Churchyard, A., Horne, M., Bradshaw, J. L. D elatycki and M. B. (2006). Towards an 21

Cerebellum and Cognition Understanding of cognitive function in Friedreich ataxia. Brain Research Bulleti n, 70, 197-202. Diedrichs, J. (2006). A Spatially unbiased atlas template of the Human Cerebellum. Neuroimage 33, 127-138. Dimitrova, A., Weber, J., Redi, C., K indsvater, K., Maschke, M., Kolb, F. P., Forstinger, M., Diener, H. C. and Timma nn, D. (2001). MRI Atlas of the human cerebellar nuclei. NeuroImage, 17, 240-255 . Eckert, M. A., Galaburda, A. M., Mills, D. L., Bellugi, U., Korenberg, J. R. a nd Reiss, A. L. (2006). The neurobiology of Williams syndrome: Cascading Influen ce of visual system impairment? Cellular and Molecular Life Sciences, 63, 1867-1 875. Fliessbach, K., Trautner, P., Quesada, C. M., Elger, C. E. and Weber, B. (2 007). Cerebellar Contributions to Episodic memory encoding as Revealed by fMRI. NeuroImage, in press. Gottwald, B., Mihajlovic, Z., Wilde, B. and Mehdorn, H. M. (2003). Does the Contribute to specific Cerebellum Aspects of Attention? Neuropsychologia, 41, 14 52-1460. Gottwald, B. Wilde, B., Mihajlovic, Z. and Mehdorn, H. M. (2004). Evide nce for distinct cognitive deficits after-focal cerebellar lesions. Journal of N eurology, Neurosurgery and Psychiatry, 75, 1524-1531. Gross-Tsur, V., Ben-Bashat , D., Shalev, R. S., Levav, M. and Ben Sira, L. (2006). Developmental Evidence o f a cerebellar-cerebral disorder. Neuropsychologia, 44, 2569-2572. Harrington, D. L., Lee, R. R., Boyd, L. A., Rap csak, S. Z. and Knight, R. T. (2004). Does the representation of time depend on the Cerebellum? Effect of cerebellar stroke. Brain, 127, 561-574. Hokkanen, L. S . K., kauranes, V., Roine, R. O., Salonen, O. and Kotila, M. (2006). Subtle cognitive deficits after-cerebellar infarcts. European Journal of Neurology, 13, 161-170. Hubrich-Ungureanu, P., Kaemmerer, N., Henn, F. A. and B raus, D. F. (2002). Lateralized organization of the Cerebellum in a silent verba l Fluency task: a functional magnetic resonance imaging study in healthy volunte ers. Neuroscience Letters, 319, 1991-1994. 22 Cerebellum and Cognition Ito, M. (2006). Cerebellar circuitry as a neuronal machine. Progress in Neurobio logy, 78, 272-303. Janssen G, Messing-Junger, A. M., Engelbrecht, V., Gobel, U., Bock, W. J. and Lenard, H. G. (1998). Cerebellar mutism syndrome. Klinische Pä diatrie, 210 (4), 243-247. Abstract obtained from PubMed. Jones, W., Hesselink, J., Courchesne, E., Duncan, T., Matsuda, K. and Bellugi, U. (2002). Abnormalitie s in cerebellar infants and toddlers with Williams syndrome.€Developmental Medi cine and Child Neurology. 44, 688-694. Keuthen, N. J., Makris, N., Schlerf, J. E ., Martis, B., Savage, C. R., McMullin, K., Seidman, L. J. Schmahmann, J. D., Ke nnedy D. N., Hodge, S. M. and Rauch, S. L. (2006). Evidence for cerebellar Reduc ed Volumes in Trichotillomania. Biologycal Psychiatry, Article in press. Koch, G ., Oliveri, M., Torriero, S. Salerno, S., engineer Gerd, E. L. and in Caltagiron e, C. (2006). Repetitive TMS of Cerebellum interferes with millisecond time proc essing. Experimental Brain Research, Ahead of print. Konarski, J. Z., McIntyre, R. S., Grupp, L. A. and Kennedy, S. H. (2005). Relevant Is the Cerebellum in the circuitry of neuropsychiatric disorders? Journal of Psychiatry & Neuroscience, 30 (3), 178-186. Lee, K. H., Egleston, P. N., Brown, W. H., Gregory, A. N., Bark er, A. T. and Woodruff, P. W. (2007). The role of the Cerebellum in subsecond ti me perception: evidence from repetitive transcranial magnetic stimulation. Journ al of Cognitive Neuroscience, 19 (1), 147-157. Leslie, K. R., Johnson-Frey, S. H . and Grafton, S. T. (2004). Functional imaging of face and hand imitation: towa rds a motor theory of empathy. NeuroImage, 21, 601-607. Makris, N., Schlerf, J. E., Hodge, S. M., Haselgrove, C., Albaugh, M. D., Seidman, L. J., Rauch, S. L.,

Harris, G., Biederman, J., Caviness, V. S. Jr., Kennedy, D. N. and Schmahmann, J . D. (2005). Surfaceassisted MRI-based parcellation of human cerebellar cortex: an anatomically specified method with Estimates of reliability. NeuroImage, 2, 1 146-1160. Mewasingh, L. D., Kadhim, H., Christophe, C., Christiaens, F. J. and D an, B. (2002). Nonsurgical cerebellar mutism (anarthria) in Two Children. Pediat ric Neurology, 28, 59-63. 23 Cerebellum and Cognition Mills, N. P., Delbello, M. P., Adler, C. M. and Strakowski, S. M. (2005). MRI an alysis of cerebellar Vermala Abnormalities in bipolar disorder. The American Jou rnal of Psychiatry, 162, 1530-1532. Oliveri, M., Koch, G., Torriero, S. and Calt agirone, C. (2005). Increaser Facilitation of the primary motor cortex 1 Hz repe titive transcranial Following magnetic stimulation of the contralateral Cerebell um in normal humans. Neuroscience Letters, 376, 188-193. Ozgur, B. M., Berberian , J., Aryan, H. E., Meltzer, H. S. and Levy, M. L. (2006). The pathophysiologic Mechanism of cerebellar mutism. Surgical Neurology, 66, 18-25. Paradiso, S., And reasen, N. C., Crespo-Facorro, B., O'Leary, D. S., Watkins, G. L., Boles-Ponto, L. L., Hichwa, R. (2003). Emotions in unmedicated Patients with schizophrenia Du ring evaluation with positron emission tomography. American Journal of Psychiatr y, 160, 1775-1783. Paradiso, S., Robinson, R. G., Boles-Ponto, L. L., Watkins, G . L. and Hichwa, R. D. (2003). Regional cerebral blood flow changes during Visua lly induced subjective sadness in healthy elderly persons. Journal of Neuropsychiatry and Clinical Neurosciences, 15, 35-44. Ramnani, N. (2006). The p rimate cortico-cerebellar system: anatomy and function. Nature Reviews Neuroscie nce, 7 (7), 511-522. Ravizza, S. M., McCormick, C. A., Schlerf, J. E., Justus, T ., Ivry, R. B. and Fiez, J. A. (2006). Cerebellar damage you produce selective d eficits in verbal working memory. Brain, 129, 306-320. Rojas, D. C., Peterson, E ., Winterrowd, E., Reite, Tregella, M. L., Rogers, S. J. and J. R. (2002). Regional gray matter volumetric changes file in Associated autism with social and repetitive Behavior Symptoms. BMC Psychiatry, 6: 56. Schmahmann, J. D. (2004). Disorders of the Cerebellum: Ataxia, dysmetria of Thought, and the cerebellar cognitive affective syndrome. The Journal of Neur opsychiatry and Clinical Neurosciences, 16, 367-378. Schmahmann, J. D. and Capla n, D. (2006). Cognition, emotion and the Cerebellum. (Scientific Comments). Brai n, 129, 290-292. Schmahmann, J. D. and Sherman, J. C. (1998). The cerebellar cog nitive affective syndrome. Brain, 121, 561-579. 24 Cerebellum and Cognition Schmahmann, J. D., Doyon, J., McDonald, D., Holmes, C., Lavoie, K., Hurwitz, A. S., Kabani, N., Toga, A., Evans, A., and Petrides, M. (1999). Threedimensional M RI atlas of the human Cerebellum in proportional stereotaxic space. NeuroImage, 10, 233-260. Schoch, B., Dimitrova, A., Gizewski, E. R. and Timmann, D. (2006). Functional localization in the human Cerebellum based on voxelwise statistical a nalysis: A study of 90 Patients. NeuroImage, 30, 36-51. Supprian, T., Ulmar, G., Bauer, M., Schuler, M., Puschel, K., Retz-Junginger, P., Schmitt, H. P. and Hei nsen, H. (2000). Cerebellar vermis area in schizophrenic Patients - a post-morte m study. Schizophrenia Research, 42, 19-28. Swedo, S. E., Rapoport, J. L., Leona rd, H. L., Schapiro, M. B., Rapoport, S. I. and Grady, C. L. (1991). Regional ce rebral glucose metabolism of Women With trichotillomania. Archives of General Ps ychiatry, 48, 828-833. Szpunar, K. K., Watson, J. M. and McDermott, K. B. (2007) . Neural substrates of Envisioning the Future. Proceedings of the National Acade my of Sciences of the USA, 104 (2), 642-647.€Torriero, S., Oliveri, M., Koch, G

., engineer Gerd, E. L., Salerno, S., Petrosini, L. and Caltagirone, C. (2007). Cortical networks of procedural learning: Evidence from cerebellar damage. Neuro psychologia, 45, 1208-1214 Townsend, J., Westerfield, M., Leaver, E., Makeig, S. , Jung, T., Pierce, K. and Courchesne, E. (2001). Event-related brain response A bnormalities in autism: evidence for cerebellar-frontal spatial Impaired Attenti on networks. Cognitive Brain Research, 11 (1), 127-145. Turner, B. M., Paradiso, S., Marvel, C. L., Pierson, R., Boles Ponto, L. L., Hichwa, R. D. and Robinson, R. G. (2007). The Cerebellum and emotional experience. Neuropsychologia, 45, 13 31-1341. Voogd, J. (2003). The Human Cerebellum. Journal of Chemical Neuroanatom y, 26, 243-252. 25