The role of the cerebellum in sequencing and predicting social and non-social events in patients with bipolar disorder.

Introduction: Advances in the operational mode of the cerebellum indicate a role in sequencing and predicting non-social and social events, crucial for individuals to optimize high-order functions, such as Theory of Mind (ToM). ToM deficits have been described in patients with remitted bipolar disorders (BD). The literature on BD patients' pathophysiology reports cerebellar alterations; however, sequential abilities have never been investigated and no study has previously focused on prediction abilities, which are needed to properly interpret events and to adapt to changes. Methods: To address this gap, we compared the performance of BD patients in the euthymic phase with healthy controls using two tests that require predictive processing: a ToM test that require implicit sequential processing and a test that explicitly assesses sequential abilities in non-ToM functions. Additionally, patterns of cerebellar gray matter (GM) alterations were compared between BD patients and controls using voxel-based morphometry. Results: Impaired ToM and sequential skills were detected in BD patients, specifically when tasks required a greater predictive load. Behavioral performances might be consistent with patterns of GM reduction in cerebellar lobules Crus I-II, which are involved in advanced human functions. Discussion: These results highlight the importance of deepening the cerebellar role in sequential and prediction abilities in patients with BD.

The Cerebellum Gets Social: Evidence from an Exploratory Study of Cerebellar, Neurodevelopmental, and Psychiatric Disorders.

Social prediction is a key feature of social cognition (SC), a function in which the modulating role of the cerebellum is recognized. Accordingly, cerebellar alterations are reported in cerebellar pathologies, neurodevelopmental disorders, and psychiatric conditions that show SC deficits. Nevertheless, to date, no study has directly compared populations representative of these three conditions with respect to SC and cerebellar alterations. Therefore, the present exploratory study aimed to compare the SC profiles of individuals with cerebellar neurodegenerative disorders (CB), autism (ASD), bipolar disorder type 2 (BD2), or healthy subjects (HS) using a battery of social tests requiring different degrees of prediction processing. The patterns of cerebellar gray matter (GM) alterations were compared among the groups using voxel-based morphometry. Compared to HS, the clinical groups showed common SC deficits in tasks involving a moderate to high level of prediction. The behavioral results of the clinical groups are consistent with the presence of overlapping GM reduction in cerebellar right Crus II, an area notably involved in complex social processing and prediction. Although exploratory and preliminary, these results deepen the cerebellar role in social prediction and highlight the transdiagnostic value of the cerebellum in social functioning and prediction in pathologies of different aetiologies, forecasting novel possibilities for shared interventions.

The Impact of Affective Temperaments on Suicidal Ideation and Behaviors: Results from an Observational Multicentric Study on Patients with Mood Disorders.

Suicide ideation and behaviors are major health issues in the field of mental health. Several psychological and psychosocial factors have been taken into account as possible predictors of suicidality. Only recently affective temperaments have been considered as possible factors linked to suicide. This study aims to investigate the relationship between affective temperaments and suicidality, including the lifetime onset of suicide ideation, lifetime presence of suicide attempts and the total number of lifetime suicide attempts. This is a naturalistic multicentric observational study, involving outpatient units of seven University sites in Italy. Patients were administered with the short version of TEMPS-M and the Columbia Suicide Severity Rating Scale. A total of 653 participants were recruited, with a diagnosis of bipolar (55.7%), unipolar (35.8%) and cyclothymic disorder (8.4%). Regression models showed that the presence of lifetime suicide behaviors was increased in patients presenting trait related impulsivity (p < 0.0001), poor free-interval functioning (p < 0.05), higher number of affective episodes (p < 0.01), higher number of hospitalizations (p < 0.0001), cyclothymic and irritable affective temperaments (p < 0.05 and p < 0.05, respectively). Conversely, the presence of hyperthymic affective disposition reduced the likelihood of having suicidal behaviors (p < 0.01). Lifetime suicidal ideation was associated with trait-related impulsivity (p < 0.001), poor free-interval functioning (p < 0.05), higher number of affective episodes (p < 0.001) and of hospitalizations (p < 0.001). Depressive temperaments increased the likelihood of presenting suicidal ideation (p < 0.05), along with irritable temperaments (p < 0.01), contrary to hyperthymic affective (p < 0.05). Results of the present study confirm that affective disposition has a significant impact on the onset of suicidal ideation and behaviors, and that affective dispositions should be assessed in clinical settings to identify people at risk of suicide. Moreover, a wider clinical evaluation, including different clinical psychopathological dimensions, should be taken into consideration to develop effective preventive interventions.

Trait-Related Impulsivity, Affective Temperaments and Mood Disorders: Results from a Real-World Multicentric Study.

Trait-related impulsiveness is highly prevalent in patients with mood disorders, being associated with negative outcomes. The predictive role of affective temperaments on trait-related impulsivity is still understudied. The aim of the present study is to investigate the relationship between impulsivity and affective temperaments in a sample of euthymic patients with mood disorders. This is a real-world multicentric observational study, carried out at the outpatient units of seven university sites in Italy. All patients filled in the short version of Munster Temperament Evaluation of the Memphis, Pisa, Paris and San Diego and the Barratt Impulsiveness Scale. The study sample included 653 participants, mainly female (58.2%), with a mean age of 46.9 (±14.1). Regression analyses showed that higher levels of trait-related impulsivity were associated to suicide attempts (p < 0.000), the presence of psychotic symptoms during acute phases (p < 0.05), a seasonal pattern (p < 0.05), a lower age at onset of the disorder (p < 0.05), cyclothymic (p < 0.01) and irritable temperaments (p < 0.01). The results of our study highlight the importance to screen patients with mood disorders for impulsivity and affective temperaments in order to identify patients who are more likely to present a worse outcome and to develop personalized and integrated early pharmacological and psychosocial treatment plans. Novelties of the present paper include the recruitment of patients in a stable phase, which reduced possible bias in patients' self-reports, and the multicentric nature of the study, resulting in the recruitment of a large sample of patients with mood disorders, geographically distributed across Italy, thus improving the generalizability of study results.

Theory of mind profile and cerebellar alterations in remitted bipolar disorder 1 and 2: a comparison study.

The literature on social cognition abilities in bipolar disorder (BD) is controversial about the occurrence of theory of mind (ToM) alterations. In addition to other cerebral structures, such as the frontal and limbic areas, the processing of socially relevant stimuli has also been attributed to the cerebellum, which has been demonstrated to be involved in the above-mentioned disorder. Nevertheless, the cerebellar contribution to ToM deficits in bipolar patients needs to be elucidated further. To this aim, two tests assessing different components of ToM were used to evaluate the ability to appreciate affective and mental states of others in 17 individuals with a diagnosis of BD type 1 (BD1) and 13 with BD type 2 (BD2), both in the euthymic phase, compared to healthy matched controls. Cerebellar gray matter (GM) volumes were extracted and compared between BD1 and controls and BD2 and controls by using voxel-based morphometry. The results showed that BD1 patients were compromised in the cognitive and advanced components of ToM, while the BD2 ToM profile resulted in a more widespread compromise, also involving affective and automatic components. Both overlapping and differing areas of cerebellar GM reduction were found. The two groups of patients presented a pattern of GM reduction in cerebellar portions that are known to be involved in the affective and social domains, such as the vermis and Crus I and Crus II. Interestingly, in both BD1 and BD2, positive correlations were detected between lower ToM scores and decreased volumes in the cerebellum. Overall, BD2 patients showed a more compromised ToM profile and greater cerebellar impairment than BD1 patients. The different patterns of structural abnormalities may account for the different ToM performances evidenced, thus leading to divergent profiles between BD1 and BD2.

Chronic Migraine Preventive Treatment by Prefrontal-Occipital Transcranial Direct Current Stimulation (tDCS): A Proof-of-Concept Study on the Effect of Psychiatric Comorbidities.

Chronic migraine (CM) is often complicated by medication overuse headache (MOH) and psychiatric comorbidities that may influence the clinical outcome. This study aimed to investigate the relationship between psychiatric comorbidities and the effect of transcranial direct current stimulation (tDCS) in patients with CM with or without MOH. We recruited 16 consecutive CM patients who had an unsatisfactory response to at least three pharmacological preventive therapies. They were treated with anodal right-prefrontal and cathodal occipital tDCS (intensity: 2 mA, time: 20 min) three times per week for 4 weeks. All patients underwent a psychopathological assessment before and after treatment, and five of them were diagnosed with bipolar disorder (BD). After treatment, all the patients showed a significant decrease of severe and overall headache days per month. Despite having a higher migraine burden at baseline, patients with CM and BD showed a significantly greater reduction of severe headaches and psychiatric symptoms. Overall, tDCS seems to be effective in the treatment of CM patients with a poor response to different classes of pharmacological therapies, whereas BD status positively influences the response of migraineurs to tDCS.

Comparison of Cerebellar Grey Matter Alterations in Bipolar and Cerebellar Patients: Evidence from Voxel-Based Analysis.

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.

Effects of Cerebellar tDCS on Inhibitory Control: Evidence from a Go/NoGo Task.

Response inhibition as an executive function refers to the ability to suppress inappropriate but prepotent responses. Several brain regions have been implicated in the process underlying inhibitory control, including the cerebellum. The aim of the present study was to explore the role of the cerebellum in executive functioning, particularly in response inhibition. For this purpose, we transitorily inhibited cerebellar activity by means of cathodal tDCS and studied the effects of this inhibition on ERP components elicited during a Go/NoGo task in healthy subjects. Sixteen healthy subjects underwent a Go/NoGo task prior to and after cathodal and sham cerebellar tDCS in separate sessions. A reduction in N2-NoGo amplitude and a prolongation in N2-NoGo latency emerged after cathodal tDCS whereas no differences were detected after sham stimulation. Moreover, commission errors in NoGo trials were significantly higher after cathodal tDCS than at the basal evaluation. No differences emerged between performances in Go trials and those after sham stimulation. These data indicate that cerebellar inhibition following cathodal stimulation alters the ability to allocate attentional resources to stimuli containing conflict information and the inhibitory control. The cerebellum may regulate the attentional mechanisms of stimulus orientation and inhibitory control both directly, by making predictions of errors or behaviors related to errors, and indirectly, by controlling the functioning of the cerebral cortical areas involved in the perception of conflict signals and of the basal ganglia involved in the inhibitory control of movement.

Cognitive remediation for the treatment of neuropsychological disturbances in subjects with euthymic bipolar disorder: findings from a controlled study.

INTRODUCTION: Individuals with euthymic Bipolar Disorder (BD) can experience deteriorated cognitive functioning, with such deterioration being associated with functional impairment. Cognitive remediation (CR) is considered an effective add-on intervention for neuropsychological impairments, but relatively few CR controlled studies have been performed on BD. In the present study the efficacy of a CR intervention designed for the improvement of cognition and functioning in patients with euthymic BD was tested. METHODS: Patients (n = 54) with euthymic BD were assigned to receive active (n = 27) or control (n = 27) intervention. The active intervention (i.e. the Cognitive Remediation in Integrated Treatment - CRIIT - protocol) was made of 20 individual sessions focused on the treatment of attention, memory and executive functioning through the COGPACK software; each session was integrated with psychoeducation and rehabilitation interventions implemented through a metacognitive approach aimed at ameliorating personal agency. RESULTS: A significant (p ≤ 0.015) time x group interaction at repeated measures MANOVA was observed on Rey Auditory Verbal Learning Test, Rey Complex Figure Test, Wisconsin Card Sorting Test, Trail Making Test, Visual Search, Life Skills Profile, and Barratt Impulsiveness Scale. LIMITATIONS: A single-blind approach was used. DISCUSSION: The results showed that patients undergoing active intervention improved in domains related to executive functions, attention, memory, functioning and impulsivity more significantly than patients undergoing control interventions. This study adds to the evidence that CR improves neurocognition in BD, and suggests that CRIIT protocol represents an add-on intervention of potential relevance to increase cognition and functioning in BD euthymic patients.

[Effects of Group Psychoeducation on stress reactivity neuroendocrine profile in stabilized bipolar patients. A controlled study]. / Effetti della psicoeducazione di gruppo sul profilo neuroendocrino di reattività allo stress in pazienti bipolari stabilizzati. Uno studio controllato.

INTRODUCTION: Patients with bipolar disorder show a high relapse rate generally related to their poor adherence to the prescribed medications and to their high stress vulnerability, linked to genetic, neuroendocrine and cognitive factors. AIMS: The first aim of this study was to verify if for a group of pharmacologically stabilized bipolar patients, the attendance to a Group Psychoeducation program according to the Barcelona model would result in an improvement of their stress resilience, as measurable by evaluating their morning cortisol secretory profile. The second aim of the study has been to verify if these effects would maintain stable over time, organizing follow-up evaluations, after one year and after two years form the end of the group psychoeducation program. MATERIALS AND METHODS: 96 patients who had been euthymic for at least 6 months and were under stabilized pharmacologic maintenance treatment, were randomized in two groups: pharmacological treatment as usual (TAU) or pharmacological treatment plus group Psychoeducation (PE). Patients in both groups underwent a psychological assessment (HAMD, YMRS e ARMS), and to a functional assessment of the HPA axis activity, obtained evaluating cortisol levels from salivary samples collected in 5 different moments of the day: at baseline, at the end of the group psychoeducation program, and after 1 year and 2 years from the end of the last PE session. RESULTS: At the end of the study, both groups (PE and TAU) did not show any significant intergroup difference with regard to all the clinical variables and the patients' adherence to the prescribed medications. On the contrary, significative intergroup differences were observed with regard to morning cortisol secretory profile, that was found normalized at the endpoint only among patients of the PE group, but not among those of the TAU group. This normalization of the morning cortisol secretory profile observed among patients of the PE group, proved to maintain stably overtime, since it was observed also in the two follow-up assessments, organized after 1 year and after 2 year from the end the treatment. DISCUSSION: Data collected in this study may indicate that the efficacy of the psychoeducation programs for bipolar patients may activate an improvement of the functional activation of the HPA axis, and so obtaining a reduction of their stress vulnerability.

The Cerebellum Modulates Attention Network Functioning: Evidence from a Cerebellar Transcranial Direct Current Stimulation and Attention Network Test Study.

The functional domain of the cerebellum extends beyond its traditional role in motor control. In recent years, this structure has increasingly been considered to play a crucial role even in cognitive performance and attentional processes. Attention is defined as the ability to appropriately allocate processing resources to relevant stimuli. According to the Posnerian model, three interacting networks modulate attentive processes: the alerting, orienting, and executive networks. The aim of this study was to investigate the role played by the cerebellum in the functioning of the attentive networks using the Attention Network Test (ANT). We studied the effects of transcranial direct current stimulation (tDCS), delivered over the cerebellum in cathodal, anodal, and sham sessions, on ANT parameters in healthy subjects. After anodal and sham tDCS, the efficiency of the three attention networks remained stable, and a significant reduction in reaction time (RT) following the task repetition was observed for both congruent and incongruent targets, indicating a learning effect. After cathodal stimulation, instead, while the efficiency of the alerting and orienting networks remained stable, the efficiency of the executive network was significantly reduced. Moreover, a significant reduction in RT was observed for the congruent target alone, with no difference being detected for the incongruent target, indicating that cerebellar inhibition caused an attentive executive dysfunction specifically related to the ability to process complex stimuli in which conflict signals or errors are present. These results point to a role of the cerebellum, a subcortical structure that is thought to affect error processing both directly, by making predictions of errors or behaviors related to errors, and indirectly, by managing the functioning of brain cortical areas involved in the perception of conflicting signals, in the functioning of the attentional networks, particularly the executive network.

Investigating gaze processing in euthymic bipolar disorder: Impaired ability to infer mental state and intention, but preservation of social attentional orienting.

Euthymic bipolar disorder (BD) has been associated with subtle impairment in face processing. However, it is not known whether their difficulties extend to the processing of gaze. In the present study, two tasks, both of which rely on the ability to make use of the eye region of a pictured face, were used: the Reading the Mind in the Eyes test and the Eye-gaze cueing task. Compared to healthy controls, BD patients were impaired at judging mental state from images of the face but showed normal susceptibility to the direction of gaze as an attentional cue. These findings suggest that BD patients present selective gaze processing impairment, limited to the sensitivity to intention and emotion. This impairment could account at least partially for the higher levels of interpersonal problems generally observed in BD.

A preliminary study on hot and cool executive functions in bipolar disorder and on their association with emotion regulation strategies.

OBJECTIVE: Individuals with bipolar disorder (BD) experience difficulties in cognitive and emotional regulation in different phases of illness. In the present study, we aimed at exploring differences on hot and cool executive functioning (EF) between BD patients in euthymia (BDe) and mania (BDm), and associations of hot and cool EF with emotion regulation strategies. METHODS: Thirty-seven BD patients (among which 18 with a current manic episode and 19 in euthymia) and 15 healthy controls completed a battery of tests assessing hot and cool EF and emotion regulation strategies. RESULTS: Between group comparisons showed that in all the explored hot dimensions BDm subjects had significantly worse performances than BDe subjects, while in all the explored cool dimensions BDm subjects had significantly worse performances than HC subjects, with BDe patients having an intermediate profile. Results from bivariate correlations among BDe subjects (but not among BDm subjects) showed significant positive correlations (i) between elements of hot EF and elements of cool EF, and (ii) between cognitive reappraisal emotional regulation strategy and planning (i.e., a measure of cool EF), as well as a significant negative correlation between expressive suppression emotional regulation strategy and emotional intelligence. CONCLUSIONS: The results confirm previous findings on a role of impaired EF in BD, and suggest (i) that hot EF is more closely related to mood (i.e., state-dependant) than cool EF, and (ii) that BD patients can more effectively use emotion regulation strategies in association with EF during euthymia than during mania.

[Disturbo dissociativo d'identità, auto-ipnosi e sintomi simil-psicotici: da un caso clinico a un problema di diagnosi differenziale].

We report a case of a forty-nine-year-old patient suffering from his first psychiatric episode, who required hospitalization in a psychiatric unit. The presence of mood alterations with Schneiderian first-rank symptoms could have suggested an initial diagnosis of bipolar disorder (BD) with psychotic symptoms, directing the patient towards a definite therapeutic process. However, we hypothesized that the presence of a clear dissociative state similar to the hypnotic trance preceded by an uncontrolled self-hypnosis process, the presence of 'inner voices' and a high vulnerability to dissociation, were all elements that may reasonably lead to a diagnosis of Dissociative Identity Disorder (DID). Several authors have reported the presence of psychotic-like symptoms in patients with DID. However, in clinical practice there is a tendency not to acknowledge the possibility of dissociative disorders diagnoses, in favor of others more frequent psychiatric disorders. This paper aims to highlight some etiopathogenetic and psychopathological features that might help clinicians in identifying a DID.

Investigating the link between drug-naive first episode psychoses (FEPs), weight gain abnormalities and brain structural damages: Relevance and implications for therapy.

Evidence suggests that obesity and overweight may be associated with severe brain structural abnormalities and poor cognitive and functional outcomes in the general population. Despite these observations and the high prevalence of weight gain abnormalities in patients with psychosis spectrum disorders (PSDs), no studies have investigated the impact that these metabolic disturbances may have on brain structures and development in the earliest stages of PSDs. In the present review we shed light on the association between weight gain and brain structural abnormalities that may affect the course of illness in drug-naïve FEPs. Given the lack of studies directly investigating this issue, we firstly identified and critically evaluated the literature assessing weight gain abnormalities and gray or white matter (GM, WM) volumes (either globally or in specific regions of interest) in otherwise healthy obese/overweight adolescents and young adults. We then compared the results of this systematic review with those of two recent meta-analysis investigating GM and WM abnormalities in drug-naïve FEPs. Weight gain in otherwise healthy subjects was consistently associated with frontal and temporal GM atrophy and with reduced integrity of WM in the corpus callosum. Of relevance, all these brain regions are affected in drug-naïve FEPs, and their integrity is associated with clinical, cognitive and functional outcomes. The underlying mechanisms that may explain the association between weight gain, adiposity, and brain damage in both healthy subjects and drug-naïve FEPs are widely discussed. On the basis of this knowledge, we tried: a) to deduce an integrative model for the development of obesity in psychosis spectrum disorders; b) to identify the key vulnerability factors underlying the association between weight gain and psychosis; c) to provide information on new potential targets of intervention.

Prediction of functional outcome in young patients with a recent-onset psychiatric disorder: Beyond the traditional diagnostic classification system.

A critical research goal is to identify modifiable risk factors leading to functional disabilities in young psychiatric patients. The authors developed a multidimensional trans-diagnostic predictive model of functional outcome in patients with the recent-onset of a psychiatric illness. Baseline clinical, psychosis-risk status, cognitive, neurological-soft-signs measures, and dopamine-related-gene polymorphisms (DRD1-rs4532, COMT-rs165599, and DRD4-rs1800955) were collected in 138 young non-psychotic outpatients. 116 individuals underwent follow-up (mean=2.2years, SD=0.9) examination. A binary logistic model was used to predict low-functioning status at follow-up as defined by a score lower than 65 in the social occupational functioning assessment scale. A total of 54% of patients experiences low functioning at follow-up. Attention, Avolition, and Motor-Coordination subscale were significant predictors of low-functioning with an accuracy of 79.7%. A non-significant trend was found for a dopamine-related-gene polymorphism (DRD1-rs4532). The model was independent of psychotic-risk status, DSM-diagnosis, and psychotic conversion. A trans-diagnostic approach taking into account specific neurocognitive, clinical, and neurological information has the potential to identify those individuals with low-functioning independent of DSM diagnosis or the level of psychosis-risk. Specific early interventions targeting modifiable risk factors and emphasize functional recovery in young psychiatric samples, independent of DSM-diagnosis and psychosis-risk, are essential.

Prefronto-cerebellar tDCS enhances neurocognition in euthymic bipolar patients. Findings from a placebo-controlled neuropsychological and psychophysiological investigation.

OBJECTIVES: The present double blind placebo-controlled study aimed at investigating the efficacy of 3-weeks prefronto-cerebellar transcranial direct current stimulation (tDCS) on neurocognitive functioning in euthymic BD patients. METHODS: Forty-two outpatients with BD were randomly assigned to receive either active (n=21) or sham (n=21) prefronto-cerebellar tDCS for 3 consecutive weeks. Neurocognitive abilities were assessed with both neuropsychological testing and psychophysiological evaluation with a P300 novelty task. RESULTS: Our results showed that (i) Trail Making Test-B, a measure of executive functioning, decreased significantly in the active but not in the sham group, (ii) Rey Complex Figure Test Delay Recall, a measure of visuospatial memory, increased significantly in both groups with a greater increase in the active compared to the sham group, and (iii) P3b latency, a measure of brain information processing stream, decreased significantly in the active but not in the sham group. No significant changes were observed in the other explored neuropsychological and psychophysiological measures. CONCLUSIONS: The study suggests that concomitant prefrontal-excitatory and cerebellar-inhibitory tDCS in euthymic BD patients may lead to better neurocognitive performance, quantified through neuropsychological and psychophysiological measures.

Pain-processing abnormalities in bipolar I disorder, bipolar II disorder, and schizophrenia: A novel trait marker for psychosis proneness and functional outcome?

OBJECTIVES: Overlapping neural system dysfunctions, mainly involving the secondary somatosensory cortex (S2), the anterior cingulate cortex (ACC) and the anterior insular cortex (AIC), seem to be related to both pain-perception abnormalities and psychotic symptoms in schizophrenia (SCZ) and bipolar disorder (BD). Laser-evoked potentials (LEPs) were used to investigate pain-perception and central pain-processing abnormalities in SCZ, bipolar I disorder (BD-I), and bipolar II disorder (BD-II), and to evaluate their relationship with history of psychosis, and social-cognitive and functional impairments. METHODS: Twenty patients with SCZ, 17 patients with BD-I, and 21 patients with BD-II who were all under similar pharmacological treatment underwent clinical, functional, and neuro-psychological assessment. LEPs were analyzed in patients and 19 healthy subjects (HS). LEPs elicit responses reflecting the activity of the S2 (N1 wave) and the ACC/AIC cortices (N2/P2 complex). A four-group ANOVA was conducted between patients and HS to compare pain-perceptive thresholds (PThs), N1, and N2/P2-LEP components. RESULTS: Compared to HS: (i) patients with SCZ showed pain-processing and pain-perception abnormalities, as revealed by significantly higher PTh (P<.01), and lower N1 (P<.01) and N2/P2 (P<.01) amplitudes, (ii) patients with BD-I showed only pain-processing abnormalities, as revealed by significantly lower N1 (P<.05) and N2 (P<.01) amplitudes; and patients with BD-II did not differ for any of the LEP variables investigated. N1 and N2 amplitudes negatively correlated to history of psychosis (P<.01), social-cognition (P<.05), and real-world functioning (P<.01) measures in the whole group of patients. CONCLUSIONS: To the best of our knowledge, this is the first study comparing central pain processing in patients with SCZ, BD-I, and BD-II. Our results suggest that pain-processing abnormalities may represent a novel locus of interest for research investigating trait markers of the psychosis spectrum.

Effects of cerebellar transcranial direct current stimulation on attentional processing of the stimulus: Evidence from an event-related potentials study.

Attentional processing consists of a set of processes that manage the flow of information through the nervous system and appropriately allocate attentional resources to relevant stimuli. Specific networks in the frontal and parietal regions appear to be involved in attention. The cerebellum has been identified as a subcortical structure that interacts with cortical brain areas, thereby controlling attentional processes. The aim of this study was to investigate the role of the cerebellum in attentional processing of the stimulus using a P300 Novelty task. We studied the effects of transcranial Direct Current Stimulation (tDCS) delivered over the left cerebellar hemisphere in cathodal, anodal and sham sessions on the P300 components in healthy subjects. Only cathodal cerebellar tDCS significantly reduced the amplitude of the N1, N2 and P3 components for both the target and novel stimuli. Moreover, N1 latency for all the stimuli was shorter after the cathodal tDCS session than after the sham or anodal sessions. These results point to a role of the cerebellum in attentional processing of the stimulus. The cerebellum may act indirectly by regulating and managing the activation and inhibition levels of the cortical areas involved in attentional networks.

Prefrontocerebellar transcranial direct current stimulation increases amplitude and decreases latency of P3b component in patients with euthymic bipolar disorder.

INTRODUCTION: Neurocognitive impairments have been observed in patients with bipolar disorder (BD) even during the euthymic phase of the disease, potentially representing trait-associated rather than state-associated characteristics of the disorder. In the present study, we used transcranial direct current stimulation (tDCS) applied to cerebellar and prefrontal cortices to improve the neurophysiological performances of patients with euthymic BD. METHODS: Twenty-five outpatients with BD underwent open-label prefrontocerebellar tDCS for 3 consecutive weeks. Neurophysiological performances were assessed through the examination of the P3b and P3a subcomponents of P300 event-related potential at baseline and after stimulation. RESULTS: Compared to baseline, P3b component after tDCS showed significantly higher amplitude and shorter latency (latency: Fz P=0.02, Cz P=0.03, and Pz P=0.04; amplitude: Fz P=0.24, Cz P=0.02, and Pz P=0.35). CONCLUSION: In our sample of patients with euthymic BD, concomitant prefrontoexcitatory and cerebellar-inhibitory modulations led to improved brain information processing stream. This improvement may at least partially result from neuroplastic modulation of prefrontocerebellar circuitry activity.