Cerebellar Neurostimulation for Boosting Social and Affective Functions: Implications for the Rehabilitation of Hereditary Ataxia Patients

Beyond motor deficits, spinocerebellar ataxia (SCA) patients also suffer cognitive decline and show socio-affective difficulties, negatively impacting on their social functioning. The possibility to modulate cerebello-cerebral networks involved in social cognition through cerebellar neurostimulation has opened up potential therapeutic applications for ameliorating social and affective difficulties. The present review offers an overview of the research on cerebellar neurostimulation for the modulation of socio-affective functions in both healthy individuals and different clinical populations, published in the time period 2000–2022. A total of 25 records reporting either transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) studies were found. The investigated clinical populations comprised different pathological conditions, including but not limited to SCA syndromes. The reviewed evidence supports that cerebellar neurostimulation is effective in improving social abilities in healthy individuals and reducing social and affective symptoms in different neurological and psychiatric populations associated with cerebellar damage or with impairments in functions that involve the cerebellum. These findings encourage to further explore the rehabilitative effects of cerebellar neurostimulation on socio-affective deficits experienced by patients with cerebellar abnormalities, as SCA patients. Nevertheless, conclusions remain tentative at this stage due to the heterogeneity characterizing stimulation protocols, study methodologies and patients’ samples

Incidence and predictors of heart failure hospitalization and death in permanent pacemaker patients: a single-centre experience over medium-term follow-up

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Microstructural MRI basis of the cognitive functions in patients with Spinocerebellar ataxia type 2

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease involving the cerebellum. The particular atrophy pattern results in some typical clinical features mainly including motor deficits. In addition, the presence of cognitive impairments, involving language, visuospatial and executive functions, has been also shown in SCA2 patients and it is now widely accepted as a feature of the disease. The aim of the study is to investigate the microstructural patterns and the anatomo-functional substrate that could account for the cognitive symptomatology observed in SCA2 patients. In the present study, diffusion tensor imaging (DTI) based-tractography was performed to map the main cerebellar white matter (WM) bundles, such as Middle and Superior Cerebellar Peduncles, connecting cerebellum with higher order cerebral regions. Damage-related diffusivity measures were used to determine the pattern of pathological changes of cerebellar WM microstructure in patients affected by SCA2 and correlated with the patients' cognitive scores. Our results provide the first evidence that WM diffusivity is altered in the presence of the cerebellar cortical degeneration associated with SCA2 thus resulting in a cerebello-cerebral dysregulation that may account for the specificity of cognitive symptomatology observed in patients

Alginate bioconjugate and graphene oxide in multifunctional hydrogels for versatile biomedical applications

In this work, we combined electrically-conductive graphene oxide and a sodium alginatecaffeic acid conjugate, acting as a functional element, in an acrylate hydrogel network to obtain multifunctional materials designed to perform multiple tasks in biomedical research. The hybrid material was found to be well tolerated by human fibroblast lung cells (MRC-5) (viability higher than 94%) and able to modify its swelling properties upon application of an external electric field. Release experiments performed using lysozyme as the model drug, showed a pH and electro-responsive behavior, with higher release amounts and rated in physiological vs. acidic pH. Finally, the retainment of the antioxidant properties of caffeic acid upon conjugation and polymerization processes (Trolox equivalent antioxidant capacity values of 1.77 and 1.48, respectively) was used to quench the effect of hydrogen peroxide in a hydrogel-assisted lysozyme crystallization procedure

Neural substrates of motor and cognitive dysfunctions in SCA2 patients: a network based statistics analysis

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease characterized by a progressive cerebellar syndrome, which can be isolated or associated with extracerebellar signs. It has been shown that patients affected by SCA2 present also cognitive impairments and psychiatric symptoms. The cerebellum is known to modulate cortical activity and to contribute to distinct functional networks related to higher-level functions beyond motor control. It is therefore conceivable that one or more networks, rather than isolated regions, may be dysfunctional in cerebellar degenerative diseases and that an abnormal connectivity within specific cerebello-cortical regions might explain the widespread deficits typically observed in patients. In the present study, the network-based statistics (NBS) approach was used to assess differences in functional connectivity between specific cerebellar and erebral “nodes” in SCA2 patients. Altered inter-nodal connectivity was found between more posterior regions in the cerebellum and regions in the cerebral cortex clearly related to cognition and emotion. Furthermore, more anterior cerebellar lobules showed altered inter-nodal connectivity with motor and somatosensory cerebral regions. The present data suggest that in SCA2 a cerebellar dysfunction affects long-distance cerebral regions and that the clinical symptoms may be specifically related with connectivity changes between motor and non-motor cerebello-cortical nodes

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 allows us to hypothesize a cerebellar role in cognitive and mood dysregulation symptoms that characterize bipolar disorde

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 abovementioned 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 grey 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 pattern of structural abnormalities may account for the different ToM performances evidenced, thus leading to divergent profiles between BD1 and BD2

Penicillamine-related lichenoid dermatitis and utility of zinc acetate in a wilson disease patient with hepatic presentation, anxiety and spect abnormalities

Wilson disease is an autosomal recessive disorder of hepatic copper metabolism with consequent copper accumulation and toxicity in many tissues and consequent hepatic, neurologic and psychiatric disorders. We report a case of Wilson disease with chronic liver disease; moreover, in our patient, presenting also with high levels of state anxiety without depression, 99mTc-ECD- SPECT showed cortical hypoperfusion in frontal lobes, more marked on the left frontal lobe. During the follow-up of our patient, penicillamine was interrupted after the appearance of a lichenoid dermatitis, and zinc acetate permitted to continue the successful treatment of the patient without side-effects. In our case the therapy with zinc acetate represented an effective treatment for a Wilson disease patient in which penicillamine-related side effects appeared. The safety of the zinc acetate allowed us to avoid other potentially toxic chelating drugs; this observation is in line with the growing evidence on the efficacy of the drug in the treatment of Wilson disease. Since most of Wilson disease penicillamine-treated patients do not seem to develop this skin lesion, it could be conceivable that a specific genetic factor is involved in drug response. Further studies are needed for a better clarification of Wilson disease therapy, and in particular to differentiate specific therapies for different Wilson disease phenotypes

Cutaneous manifestations in celiac disease

Celiac disease (CD) is an autoimmune gluten-dependent enteropathy characterized by atrophy of intestinal villi that improves after gluten-free diet (GFD). CD is often associated with extra-intestinal manifestations; among them, several skin diseases are described in CD patients. The present review reports all CD-associated skin manifestations described in the literature and tries to analyze the possible mechanisms involved in this association. The opportunity to evaluate the possible presence of CD in patients affected by skin disorders is discussed

On the merit of a Central Limit Theorem-based approximation in statistical physics

The applicability conditions of a recently reported Central Limit Theorem-based approximation method in statistical physics are investigated and rigorously determined. The failure of this method at low and intermediate temperature is proved as well as its inadequacy to disclose quantum criticalities at fixed temperatures. Its high temperature predictions are in addition shown to coincide with those stemming from straightforward appropriate expansions up to (k_B T)^(-2). Our results are clearly illustrated by comparing the exact and approximate temperature dependence of the free energy of some exemplary physical systems.Comment: 12 pages, 1 figur