Lack of normal association between cerebellar volume and neuropsychological functions in first-episode schizophrenia

OBJECTIVE: Functional neuroimaging studies have identified a role for the cerebellum in the neuropsychology of schizophrenia. Few studies, however, have examined the relationship between cerebellar size and neuropsychological functioning in schizophrenia. The authors' goal was to examine this relationship in patients and healthy comparison subjects. METHOD: Total cerebellar volume was computed from magnetic resonance images in 48 male and 33 female patients experiencing a first episode of schizophrenia and in 14 male and nine female healthy comparison subjects. Patients and comparison subjects completed a comprehensive neuropsychological assessment encompassing six domains of functioning: executive, motor, language, visuospatial, memory, and attention. A global domain of functioning was computed as the mean of these six domains. RESULTS: Larger cerebellar volume correlated significantly with better global functioning in healthy subjects but not among patients with schizophrenia; this relationship was significantly stronger in healthy subjects than in patients. Additional analyses revealed significant associations between cerebellar volume and visuospatial, executive, and memory functions in healthy volunteers but not among patients. CONCLUSIONS: The cerebellum plays a role in higher cognitive functions in healthy individuals, and normal associations between cerebellar size and function are absent in patients experiencing a first episode of schizophrenia. These findings are consistent with neurobiological models implicating the cerebellum in the pathogenesis of schizophrenia.     

Reduced Cerebellar Inhibition in Migraine with Aura: A TMS Study

Subtle clinical cerebellar alterations have been found in migraine. Moreover, abnormalities in visual and motor cortex excitability consistent with a lack of inhibitory efficiency have been described in migraine, and it is known that cerebellum exerts an inhibitory control on cerebral cortex. Here, we investigated if impairment of cerebellar activity on motor cortex, i.e. reduced inhibitory control, can be found in migraine. Ten migraineurs with aura and seven healthy controls underwent a transcranial magnetic stimulation (TMS) protocol to investigate the cerebellar inhibitory drive on motor cortex: a conditioning pulse on right cerebellar cortex was delivered 5, 7, 10, 15 ms before a test stimulus (TS) on contralateral motor cortex. The cerebellar conditioning stimulus inhibits the size of the motor-evoked potential (MEP) produced by the TS alone by approximately 30–50%. Amplitude of MEP to TS alone showed no significant difference between patients and controls. Cerebellar conditioning TMS showed a significant deficit of cerebellar inhibition in migraine patients as compared to controls at all interstimulus intervals (5–15 ms) tested. Cerebellar inhibition is reduced in migraineurs. This could account, at least in part, for the reduced inhibitory efficiency previously showed in cerebral cortex of these patients.     

Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation

BACKGROUND: Cortical inhibition (CI) deficits have been proposed as a pathophysiologic mechanism in schizophrenia. This study employed 3 transcranial magnetic stimulation (TMS) paradigms to assess CI in patients with schizophrenia. Paired-pulse TMS involves stimulating with a lower-intensity pulse a few milliseconds before a higher-intensity pulse, thereby inhibiting the size of the motor evoked potential produced by the higher-intensity pulse. In the cortical silent period paradigm, inhibition is reflected by the silent period duration (ie, the duration of electromyographic activity cessation following a TMS-induced motor evoked potential). Transcallosal inhibition involves stimulation of the contralateral motor cortex several milliseconds prior to stimulation of the ipsilateral motor cortex, inhibiting the size of the motor evoked potential produced by ipsilateral stimulation. METHODS: We measured CI using these 3 paradigms in 15 unmedicated patients with schizophrenia (14 medication-naive and 1 medication-free for longer than 1 year) (13 were in the transcallosal inhibition paradigm), 15 medicated patients with schizophrenia (11 taking olanzapine, 1 risperidone, 1 quetiapine, 1 methotrimeprazine + perphenazine, 1 quetiapine + loxapine), and 15 healthy controls. RESULTS: Unmedicated patients demonstrated significant CI deficits compared with healthy controls across all inhibitory paradigms whereas medicated patients did not (at all inhibitory intervals, paired-pulse TMS: controls = 59.9%, medicated = 44.3%, unmedicated = 28.7%; cortical silent period: controls = 55.0 milliseconds, medicated = 60.4 milliseconds, unmedicated = 39.7 milliseconds; transcallosal inhibition: controls = 33.6%, medicated = 23.7%, unmedicated = 10.4%; P<.05). CONCLUSIONS: These results suggest that schizophrenia is associated with deficits in CI and that antipsychotic medications may increase CI.     

Cerebellar functional abnormalities in schizophrenia are suggested by classical eyeblink conditioning.

BACKGROUND: Previous research suggests that schizophrenia may result from disruptions in a cortico-cerebellar-thalamic-cortical circuit (CCTCC) producing a mental incoordination or "cognitive dysmetria." To further evaluate the cerebellar contribution to this disrupted circuitry, medication-free patients with schizophrenia completed classical eyeblink conditioning, a cerebellar-mediated learning task. METHODS: For classical eyeblink conditioning, 70 trials with a tone conditioned stimulus (CS) and air puff unconditioned stimulus (US) were presented to 15 patients with schizophrenia and 15 healthy control subjects. Acquisition rate for the conditioned response (CR) and response timing were compared between the two groups. RESULTS: Patients with schizophrenia displayed facilitated conditioning compared to control subjects based on a greater number of CRs during the session and a faster acquisition of the learned response. CONCLUSIONS: Facilitated conditioning suggests that an enhanced excitability in the cerebellum occurs as part of a disrupted CCTCC in schizophrenia. The enhanced cerebellar-mediated associative learning may be maladaptive in the context of normal cerebro-cerebellar interactions, leading to the characteristic motor and mental incoordination of the disorder. Classical eyeblink conditioning may provide a useful model system for studying cerebellar involvement in the pathogenesis and treatment of schizophrenia.     

Further evidence for altered cerebellar neuronal integrity in schizophrenia

OBJECTIVE: The authors' goal was to investigate the distribution of metabolites and voxel composition in the pons and three cerebellar subregions and compare metabolite integral values and differences in voxel composition between patients with schizophrenia and healthy subjects. METHOD: Proton magnetic resonance spectroscopic imaging was used to study the cerebellum and pons of 14 patients with schizophrenia and 14 healthy comparison subjects. RESULTS: The voxel composition was not significantly different between the groups, but the patients with schizophrenia had significantly lower N-acetylaspartate levels in the cerebellar cortex and vermis. CONCLUSIONS: The lower integral value of N-acetylaspartate in the cerebellar cortex and the vermis of patients with schizophrenia supports the theory of a dysfunctional corticocerebellar-thalamic-cortical circuit in schizophrenia.     

The effects of cerebellar stimulation on the motor cortical excitability in neurological disorders: A review

The cerebellum regulates execution of skilled movements through neural connections with the primary motor cortex. A main projection from the cerebellum to the primary motor cortex is a disynaptic excitatory pathway relayed at the ventral thalamus. This dentatothalamocortical pathway receives inhibitory inputs from Purkinje cells of the cerebellar cortex. These pathways (cerebellothalamocortical pathways) have been characterized extensively using cellular approaches in animals. Advances in non-invasive transcranial activation of neural structures using electrical and magnetic stimulation have allowed us to investigate these neural connections in humans. This review summarizes various studies of the cerebellothalamocortical pathway in humans using current transcranial electrical and magnetic stimulation techniques. We studied effects on motor cortical excitability elicited by electrical or magnetic stimulation over the cerebellum by recording surface electromyographic (EMG) responses from the first dorsal interosseous (FDI) muscle. Magnetic stimuli were given with a round or figure eight coil (test stimulation) for primary motor cortical activation. For cerebellar stimulation, we gave high-voltage electrical stimuli or magnetic stimuli through a cone-shaped coil ipsilateral to the surface EMG recording (conditioning stimulation). We examined effects of interstimulus intervals (ISIs) with randomized condition-test paradigm, using a test stimulus given preceded by a conditioning stimulus by ISIs of several milliseconds. We demonstrated significant gain of EMG responses at an ISI of 3 ms (facilitatory effect) and reduced responses starting at 5 ms, which lasted 3-7 ms (inhibitory effect). We applied this method to patients with ataxia and showed that the inhibitory effect was only absent in patients with a lesion at cerebellar efferent pathways or dentatothalamocortical pathway. These results imply that this method activates the unilateral cerebellar structures. We confirmed facilitatory and inhibitory natures of cerebellothalamocortical pathways in humans. We can differentiate ataxia attributable to somewhere in the cerebello-thalamo-cortical pathways from that caused by other pathways.     

Differential effects of developmental cerebellar abnormality on cognitive and motor functions in the cerebellum: an fMRI study of autism

OBJECTIVE: Recent years have seen a revolution in views regarding cerebellar function. New findings suggest that the cerebellum plays a role in multiple functional domains: cognitive, affective, and sensory as well as motor. These findings imply that developmental cerebellar pathology could play a role in certain nonmotor functional deficits, thereby calling for a broader investigation of the functional consequences of cerebellar pathology. Autism provides a useful model, since over 90% of autistic cerebella examined at autopsy have shown well-defined cerebellar anatomic abnormalities. The aim of the present study was to examine how such pathology ultimately impacts cognitive and motor function within the cerebellum. METHOD: Patterns of functional magnetic resonance imaging (fMRI) activation within anatomically defined cerebellar regions of interest were examined in eight autistic patients (ages 14-38 years) and eight matched healthy comparison subjects performing motor and attention tasks. For the motor task, subjects pressed a button at a comfortable pace, and activation was compared with a rest condition. For the attention task, visual stimuli were presented one at a time at fixation, and subjects pressed a button to every target. Activation was compared with passive visual stimulation. RESULTS: While performing these tasks, autistic individuals showed significantly greater cerebellar motor activation and significantly less cerebellar attention activation. CONCLUSIONS: These findings shed new light on the cerebellar role in attention deficits in autism and suggest that developmental cerebellar abnormality has differential functional implications for cognitive and motor systems.     

Enhanced intracortical inhibition in cerebellar patients

OBJECTIVE: The aim of the study was to examine intracortical excitability in cerebellar patients. METHODS: Short-latency intracortical inhibition (SICI), long-latency intracortical inhibition (LICI) and intracortical facilitation (ICF) to paired transcranial magnetic stimulation (TMS) were investigated in 8 patients with 'pure' cerebellar syndromes and in 14 age-matched normal controls. The conditioning stimulus for short-latency intracortical inhibition and intracortical facilitation was set at 70% of the resting motor threshold (RMT) and preceded the test stimulus (110-120% of the resting motor threshold) by interstimulus intervals (ISIs) of 1-30 ms. For the long-latency intracortical inhibition determinations, the conditioning stimulus was set at 120% of the resting motor threshold and preceded the test stimulus (also 120% of the resting motor threshold) by interstimulus intervals of 30-500 ms. RESULTS: No statistically significant differences were found between patients and controls as regards either short-latency intracortical inhibition or intracortical facilitation. A significant prevalence of long-latency intracortical inhibition was present in cerebellar patients at interstimulus intervals of 200-500 ms (conditioned MEP amplitude=29-41% of test MEP) as compared to controls (71-96% of test MEP). The amplitude of conditioned MEPs was persistently less than 45% of the test MEP in six patients, who were studied at interstimulus intervals up to 1000 ms. CONCLUSIONS: Long-latency intracortical inhibition was prevalent and abnormally longer-lasting in patients. Tonic hyperactivation of a subpopulation of GABAergic interneurons in the motor cortex of patients may be the mechanism responsible for this abnormality. Our findings seem to be specific to cerebellar diseases and are the opposite of those found in movement disorders such as dystonia and Parkinson's disease. These data suggest that the cerebellum and the basal ganglia may have opposite influences in tuning the excitability of the motor cortex.     

Abnormalities of inhibitory neuronal mechanisms in the motor cortex of patients with schizophrenia

BACKGROUND: Focal transcranial magnetic stimulation (TMS) of the motor cortex was used to study two cortically activated inhibitory neuronal mechanisms that suppress ongoing tonic voluntary electromyographic activity in contralateral (postexcitatory inhibition [PI]) and ipsilateral (transcallosal inhibition [TI]) hand muscles. The PI follows the corticospinally mediated excitatory motor response (MEP) and is influenced by dopaminergic neurotransmission. TI reflects transcallosally mediated inhibition of the contralateral motor cortex, leading to motor inhibition in muscles ipsilateral to stimulation. PI and TI were studied to explore whether dopaminergic neurotransmission or interhemispheric transfers are altered in schizophrenia. METHODS: TMS was performed in 16 patients with this disease and in 16 healthy control subjects. Surface electromyographic activity was recorded bilaterally from the first dorsal interosseous muscle during a sustained strong isometric contraction. RESULTS: When compared with the findings in healthy subjects, patients with schizophrenia had a significantly longer PI and TI. The changes of the PI support the notion of an overactivity of the central dopaminergic system in schizophrenia. CONCLUSION: The prolonged TI suggests an abnormal activation of interhemispheric connections between the motor cortices and may be related to previously reported pathology of the corpus callosum in schizophrenic patients.     

Emotion and Theory of Mind in Schizophrenia—Investigating the Role of the Cerebellum

Social cognitive dysfunction, including deficits in facial emotion recognition and theory of mind, is a core feature of schizophrenia and more strongly predicts functional outcome than neurocognition alone. Although traditionally considered to play an important role in motor coordination, the cerebellum has been suggested to play a role in emotion processing and theory of mind, and also shows structural and functional abnormalities in schizophrenia. The aim of this systematic review was to investigate the specific role of the cerebellum in emotion and theory of mind deficits in schizophrenia using previously published functional neuroimaging studies. PubMed and PsycINFO were used to search for all functional neuroimaging studies reporting altered cerebellum activity in schizophrenia patients during emotion processing or theory of mind tasks, published until December 2014. Overall, 14 functional neuroimaging studies were retrieved. Most emotion studies reported lower cerebellum activity in schizophrenia patients relative to healthy controls. In contrast, the theory of mind studies reported mixed findings. Altered activity was observed across several posterior cerebellar regions involved in emotion and cognition. Weaker cerebellum activity in schizophrenia patients relative to healthy controls during emotion processing may contribute to blunted affect and reduced ability to recognise emotion in others. This research could be expanded by examining the relationship between cerebellum function, symptomatology and behaviour, and examining cerebellum functional connectivity in patients during emotion and theory of mind tasks.     

Smaller cerebellar vermis but not hemisphere volumes in patients with chronic schizophrenia

OBJECTIVE: The authors previously reported that men with chronic schizophrenia had a smaller vermian subregion than did healthy men. In this study, they tested whether posterior superior vermis reduction would be seen in a larger group of schizophrenia patients, both male and female. METHOD: Brain volumetric analyses were performed with magnetic resonance imaging (MRI) in 59 male and female patients with chronic schizophrenia and 57 male and female healthy comparison subjects. RESULTS: The men as well as the women with schizophrenia had significantly smaller total vermis volume and smaller vermian subregions than did the healthy subjects. Total intracranial volume and cerebellar hemisphere volumes did not differ between schizophrenic and healthy subjects. CONCLUSIONS: The findings support the previous finding that in patients with chronic schizophrenia, there is a selective volume reduction of the cerebellar vermis within the cerebellum.     

Reduction in gray matter of cerebellum in schizophrenia and its influence on static and dynamic connectivity

Pathophysiological and atrophic changes in the cerebellum have been well‐documented in schizophrenia. Reduction of gray matter (GM) in the cerebellum was confirmed across cognitive and motor cerebellar modules in schizophrenia. Such abnormalities in the cerebellum could potentially have widespread effects on both sensorimotor and cognitive symptoms. In this study, we investigated how reduction change in the cerebellum affects the static and the dynamic functional connectivity (FC) between the cerebellum and cortical/subcortical networks in schizophrenia. Reduction of GM in the cerebellum was confirmed across the cognitive and motor cerebellar modules in schizophrenic subjects. Results from this study demonstrates that the extent of reduction of GM within cerebellum correlated with increased static FCs between the cerebellum and the cortical/subcortical networks, including frontoparietal network (FPN), and thalamus in patients with schizophrenia. Decreased GM in the cerebellum was also associated with a declined dynamic FC between the cerebellum and the FPN in schizophrenic subjects. The severity of patients' positive symptom was related to these structural‐functional coupling score of cerebellum. These findings identified potential cerebellar driven functional changes associated with positive symptom deficits. A post hoc analysis exploring the effect of changed FC within cerebellum, confirmed that a significant positive relationship, between dynamic FCs of cerebellum–thalamus and intracerebellum existed in patients, but not in controls. The reduction of GM within the cerebellum might be associated with modulation of cerebellum–thalamus, and contributes to the dysfunctional cerebellar‐cortical communication in schizophrenia. Our results provide a new insight into the role of cerebellum in understanding the pathophysiological of schizophrenia.     

Cerebellar dysfunction in neuroleptic naive schizophrenia patients: clinical, cognitive, and neuroanatomic correlates of cerebellar neurologic signs.

BACKGROUND: There is increasing evidence that, aside from motor coordination, the cerebellum also plays an important role in cognition and psychiatric disorders. Our previous studies support the hypothesis that cerebellar dysfunction may disrupt the cortico-cerebellar-thalamic-cortical circuit and, in turn, lead to cognitive dysmetria in schizophrenia. The goal of this study was to investigate cerebellar dysfunction in schizophrenia by examining the clinical, cognitive, and neuroanatomic correlates of cerebellar neurologic signs in schizophrenia patients. METHODS: We compared the prevalence of cerebellar neurologic signs in 155 neuroleptic-naive schizophrenia patients against 155 age- and gender-matched healthy control subjects. Differences in clinical characteristics, standardized neuropsychologic performance, and magnetic resonance imaging brain volumes between patients with and without cerebellar signs were also examined. RESULTS: Patients had significantly higher rates of cerebellar signs than control subjects, with coordination of gait and stance being the most common abnormalities. Patients with lifetime alcohol abuse or dependence were no more likely than those without alcoholism to have cerebellar signs. Presence of cerebellar signs in patients was associated with poorer premorbid adjustment, more severe negative symptoms, poorer cognitive performance, and smaller cerebellar tissue volumes. CONCLUSIONS: These findings lend further support for cerebellar dysfunction in schizophrenia.     

Ataxic Hemiparesis: Neurophysiological Analysis by Cerebellar Transcranial Magnetic Stimulation

The aim of this study was to investigate physiological mechanisms underlying ataxia in patients with ataxic hemiparesis. Subjects were three patients with ataxic hemiparesis, whose responsible lesion was located at the posterior limb of internal capsule (case 1), thalamus (case 2), or pre- and post-central gyri (case 3). Paired-pulse transcranial magnetic stimulation (TMS) technique was used to evaluate connectivity between the cerebellum and contralateral motor cortex. The conditioning cerebellar stimulus was given over the cerebellum and the test stimulus over the primary motor cortex. We studied how the conditioning stimulus modulated motor evoked potentials (MEPs) to the cortical test stimulus. In non-ataxic limbs, the cerebellar stimulus normally suppressed cortical MEPs. In ataxic limbs, the cerebellar inhibition was not elicited in patients with a lesion at the posterior limb of internal capsule (case 1) or thalamus (case 2). In contrast, normal cerebellar inhibition was elicited in the ataxic limb in a patient with a lesion at sensori-motor cortex (case 3). Lesions at the internal capsule and thalamus involved the cerebello-thalamo-cortical pathways and reduced the cerebellar suppression effect. On the other hand, a lesion at the pre- and post-central gyri should affect cortico-pontine pathway but not involve the cerebello-thalamo-cortical pathways. This lack of cerebello-talamo-cortical pathway involvement may explain normal suppression in this patient. The cerebellar TMS method can differentiate cerebellar efferent ataxic hemiparesis from cerebellar afferent ataxic hemiparesis.     

Somatosensory inputs modulate the excitability of cerebellar-cortical interaction

ObjectiveTranscranial magnetic stimulation (TMS) delivered over the cerebellum 5–7 ms prior to a stimulus over the contralateral primary motor cortex (M1) reduces the excitability of M1 output, a phenomenon termed cerebellar brain inhibition (CBI). The cerebellum receives sensory information for adaptive motor coordination and motor planning. Here, we explored through TMS whether a peripheral electrical stimulus modulates CBI.MethodsWe studied the effect of right median nerve electrical stimulation (ES) on CBI from right cerebellum (conditioning stimulus, CS) to left M1 (test stimulus, TS) in 12 healthy subjects. The following ES-CS inter-stimulus intervals (ISIs) were tested: 25, 30 and 35 ms. CS-TS ISI was set at 5 ms.ResultsWe found significantly weaker CBI when the ES was delivered 25 ms (p < 0.001) and 35 ms (p < 0.001) earlier the CS over the ipsilateral cerebellum and a trend for 30 ms ES-CS ISI (p = 0.07).ConclusionsWe hypothesize that the activation of cerebellar interneurons together with intrinsic properties of Purkinje cells may be responsible of the decreased CBI when the peripheral stimulation preceded the cerebellar stimulation of 25 and 35 ms.SignificanceTo test the interaction between somatosensory inputs and cerebello-cortical pathway may be important in a variety of motor tasks and neuropsychiatric disorders.     

Suppression of motor cortical excitability by electrical stimulation over the cerebellum in ataxia

We studied the effect of electrical stimulation over the cerebellum on electromyographic responses evoked by magnetic stimulation over the cerebral motor cortex in 14 normal volunteers and 32 patients with ataxia due to various disorders. In all the normal subjects, stimulation over the cerebellum significantly reduced the size of electromyographic response in the first dorsal interosseous muscle evoked by magnetic cortical stimulation, when the cerebellar stimulus preceded the cortical stimulus by 5, 6, and 7 msec. This suppression was absent or reduced in ataxic patients who had atrophy of the cerebellar hemispheres as demonstrated by magnetic resonance imaging and in patients with dysfunction of the cerebellothalamocortical pathway who had lesions in the superior cerebellar peduncle or in the motor thalamus. In contrast, suppression was normal in ataxic patients who had pontine lesions that affected the pontocerebellar afferent pathway to the cerebellum. Results were also normal in patients without cerebellar ataxia, such as those with Parkinson's disease, sensory ataxia, and cerebrovascular disease without ataxia. We conclude that electrical stimulation activates cerebellar structures that suppress motor cortical excitability through a cerebellothalamocortical pathway and that the afferent systems to the cerebellum make no or little contribution to the effect. The technique described here would be useful for distinguishing ataxia due to lesions of cerebellar afferent pathway from other types of cerebellar ataxia.     

A transcranial magnetic stimulation study of abnormal cortical inhibition in schizophrenia

Previous research suggests that patients with schizophrenia demonstrate deficits in a range of parameters of motor cortical and cognitive inhibition. I-wave facilitation and long-interval cortical inhibition (LICI) are two paired pulse transcranial magnetic stimulation paradigms that appear to assess aspects of cortical inhibitory function that have not previously been assessed in this patient group. Eighteen patients with schizophrenia (nine medication-free) were compared with eight control subjects. We assessed resting motor threshold (RMT) levels, LICI and I-wave facilitation. RMT levels did not differ between the three groups. There was a significant overall difference in I-wave facilitation levels. Both patient groups as compared with the control group showed increased facilitation. There were no differences between the groups in the measure of LICI. Patients with schizophrenia appear to have increased I-wave facilitation. Increased I-wave facilitation suggests deficient function of cortical inhibitory GABAergic activity. This is consistent with previous research that has found deficient cortical inhibition in patients with schizophrenia.     

Inhibition of hand muscle motoneurones by peripheral nerve stimulation in the relaxed human subject. Antidromic versus orthodromic input

In active muscle, a supramaximal conditioning stimulus to peripheral nerve produces a classic silent period in the EMG. The present experiments examined the effect of this type of conditioning stimulus on motoneurone excitability in relaxed muscle.EMG responses evoked by transcranial magnetic stimulation of the brain were recorded from the first dorsal interosseus muscle (FDI) in 10 healthy subjects and 5 patients with sensory neuropathy. These responses (motor evoked potentials) were conditioned by supramaximal peripheral nerve stimuli given 0–150 msec beforehand. In the normal subjects, the classic silent period in the FDI lasted about 100 msec. The same conditioning stimulus only abolished motor evoked potentials when the conditioning-test interval was so short that the antidromic peripheral nerve volley collided with the orthodromic volley set up by magnetic brain stimulation. At longer conditioning-test intervals, although remarkably inhibited (65% mean suppression between 10 and 40 msec), the test motor potential was never completely abolished and gradually recovered by 100 msec.Inhibition of cortically evoked motor potentials did not depend upon activity set up by the conditioning stimulus in peripheral nerve sensory fibres. The patients with complete peripheral sensory neuropathy had the same extent and time-course of inhibition as the normal subjects. We conclude that in relaxed subjects the inhibitory effect of peripheral conditioning results almost exclusively from the motoneuronal inhibitory mechanisms consequent to antidromic invasion.     

The Incidence and Nature of Cerebellar Findings in Schizophrenia: A Quantitative Review of fMRI Literature

Clinical evidence and structural neuroimaging studies linked cerebellar deficits to cognitive-related symptoms in schizophrenia. Yet, in functional neuroimaging literature to date, the role of the cerebellum in schizophrenia was not explored in a systematic fashion. Here, we reviewed 234 functional magnetic resonance imaging studies indexed by PubMed and published in 1997–2010 that had at least one group of schizophrenia patients, used blood oxygenation level dependent contrast and the general linear model to assess neuronal activity. We quantified presence/absence of cerebellar findings and the frequency of hypo- and hyperactivations (ie, less or more activity in patients relative to healthy controls). We used peaks of activations reported in these studies to build a topographical representation of group differences on a cerebellar map. Cerebellar activity was reported in patients in 41.02% of the articles, with more than 80% of these dedicated to cognitive, emotional, and executive processes in schizophrenia. Almost two-thirds of group comparisons resulted in cerebellar hypoactivation, with a frequency that presented an inverted U shape across different age categories. The majority of the hypoactivation foci were located in the medial portion of the anterior lobe and the lateral hemispheres (lobules IV–V) of the cerebellum. Even though most experimental manipulations did not target explicitly the cerebellum’s functions in schizophrenia, the cerebellar findings are frequent and cerebellar hypoactivations predominant. Therefore, although the cerebellum seems to play an important functional role in schizophrenia, the lack of reporting and interpretation of these data may hamper the full understanding of the disorder.     

Cerebellar deficits in schizophrenia are associated with executive dysfunction

Cerebellar abnormalities have been documented in schizophrenia in postmortem, functional and volumetric neuroimaging studies. This study aims to establish the relationship between structural changes in the cerebellum and executive dysfunction in patients with schizophrenia using voxel-based morphometry. We compared 28 outpatients with 28 healthy controls. A widely used executive battery and the voxel-based morphometry approach were used to investigate possible structural cerebellum changes on magnetic resonance imaging. Working memory dysfunctions in schizophrenia correlated with grey matter in both cerebellar hemispheres and vermis. Mental flexibility dysfunctions also correlated with reductions in white matter volume in bilateral cerebellum. This evidence supports the contribution of cerebellar grey and white matter deficits to executive dysfunctions observed in schizophrenia.