P300 component in euthymic patients with bipolar disorder type I, bipolar disorder type II and healthy controls: a preliminary event-related potential study

The aim of the present study was to investigate P300 event-related potential components in euthymic bipolar disorder type I (BDI) and bipolar disorder type II (BDII) patients and matched controls. A total of 10 BDI patients, 10 BDII patients and 10 healthy individuals were enrolled in the study. Event-related potential data were collected according to a standard auditory 'oddball' paradigm. A significant groups effect in both the peak amplitude (P<0.001) and the mean amplitude (P<0.001) was observed; post-hoc comparisons showed that the peak and mean amplitudes of BDI and BDII patients were significantly lower than the peak and mean amplitudes of the healthy controls. The neurophysiological patterns found in the present study might at least partially reflect the presence of a mild selective cognitive impairment in euthymic BDI and BDII patients. From a clinical point of view, these evidences support the potential role of cognitive interventions in the treatment of BD

Cross-correlations between motifs in the 5′-UTR of DAT1 gene. Findings from Parkinson’s disease

Parkinson’s disease (PD) is a neuro-degenerative disorder affecting the striatal motor system, caused by the loss of neuronal cells in the mid-brain, where reduced amounts of dopamine do cause involuntary movements and others symptoms. Alterations of methylome have been reported in PD epigenomic studies, and also human dopamine transporter gene (DAT1, SLC6A3) is considered as a candidate risk factor for PD. Since the DNA methylation on DAT promoter may well have a role in the development of this disease, we aimed to further assess the epigenetic control, by focusing on specific CpG sites located in the 5′ -untranslated region (5′ -UTR) of the DAT1 gene. Significant changes in DAT 5′ -UTR methylation were already found in peripheral blood mononuclear cells (PBMCs) of PD subjects (Rubino et al., 2020). Of note, methylation values at the CpG 5 were increased. We run on same data a novel statistical approach: crosscorrelation between pairs of loci. CpG 5 was the only always-differing variable but, alternatively, CpGs 2 and 6 or CpGs 1 and 3 were also significantly correlated with CpG 5. Interestingly, this picture emerged for those patients whose M2xM6 index was above-median; loci were rather independent for below-median patients. Present data may shed light into dynamics occurring at 5′ -UTR of DAT1, a gene involved in PD but also in many psycho-physiological pathologies

A dataset of Visible – Short Wave InfraRed reflectance spectra collected in–vivo on the dorsal and ventral aspect of arms

Advancement of technology and device miniaturization have made near infrared spectroscopy (NIRS) techniques cost–effective, small–sized, simple, and ready to use. We applied NIRS to analyze healthy human muscles in vivo, and we found that this technique produces reliable and reproducible spectral “fingerprints” of individual muscles, that can be successfully discriminated by chemometric predictive models. The dataset presented in this descriptor contains the reflectance spectra acquired in vivo from the ventral and dorsal aspects of the arm using an ASD FieldSpec® 4 Standard–Res field portable spectroradiometer (350–2500 nm), the values of the anthropometric variables measured in each subject, and the codes to assist access to the spectral data. The dataset can be used as a reference set of spectral signatures of “biceps” and “triceps” and for the development of automated methods of muscle detection

Prefronto-cerebellar transcranial direct current stimulation increases amplituded 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

Visual electrophysiological responses in subjects with cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Objectives: To evaluate visual electrophysiological responses in subjects with cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods: Three subjects tone male and two females, mean age 55.3 +/- 2.9 years) belonging to an Italian family already diagnosed with CADASIL through clinicopathological and genetic studies and 14 control subjects (6 males and 8 females, mean age 52.7 +/- 3.6 years) were enrolled in the study. Flash electroretinogram (ERG), oscillatory potentials (OPs) and simultaneous recordings of pattern electroretinogram (PERG) and visual evoked potentials (VEPs) were assessed in all 3 subjects with CADASIL and age-matched controls. Results: Subjects with CADASIL showed: reduced ERG, OP and PERG (N35-P50, P50-N95) amplitudes with respect to our normal limits; delayed PERG (N35, P50) and VEP (P100) implicit times when compared with our normal limits; and VEP (N75-P100) amplitudes and retinocortical times within our normal limits. Conclusions: Subjects with CADASIL present a dysfunction in the outer, middle and innermost retinal layers when the index of neural conduction in the postretinal visual pathways is normal. The delay in visual cortical responses observed in subjects with CADASIL may be ascribable to retinal impairment with a possible functional sparing of the postretinal visual structures. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved

The Ventricular System Enlarges Abnormally in the Seventies, Earlier in Men, and First in the Frontal Horn: A Study Based on More Than 3,000 Scans

Objectives: To detect on computed tomography (CT) brain scans the trajectories of normal and abnormal ventricular enlargement during aging. Methods: For each 1-year age cohort, we assessed in 3,193 axial CT scans the Evans' index (EI) in the anterior frontal horns and the parieto-occipital (POR) and temporal ratio (TR) in the posterior and inferior horns. Cut-off values for abnormal enlargement were based on previous clinical studies. Results: The mean age associated with normal linear measures was 71 years. Values for all three measures increased with age, showing a linear relationship below-but not above-each cut-off value. The mean age of participants with abnormal enlargement on CT progressed from 79 years for EI to 83 years for POR to 87 years for TR. These results suggested that ventricular dilatation progresses in an age-location relationship. First comes enlargement of the frontal horns (13.8% of scans), followed by the parieto-occipital horns (15.1% of scans) and then temporal horn enlargement (6.8% of scans). Scans from men displayed abnormal values earlier than scans from women (on average 6 years). Risk increased 5.1% annually for abnormal EI, 9.0% for abnormal POR, and 11% for abnormal TR (all p &lt; 0.001). The most frequent agreement between categories (normal-abnormal) for values of neuroimaging measures was identified for POR-TR. Conclusion: The results of this large radiological study suggest that the ventricular system enlarges progressively during aging, and in a subset of patients follows an abnormal consecutive geometric dilatation, influenced by age and sex

Genetic architecture of MAPT gene region in Parkinson disease subtypes

The microtubule-associated protein tau (MAPT) region has been conceptualized as a model of the interaction between genetics and functional disease outcomes in neurodegenerative disorders, such as Parkinson disease (PD). Indeed, haplotype-specific differences in expression and alternative splicing of MAPT transcripts affect cellular functions at different levels, increasing susceptibility to a range of neurodegenerative processes. In order to evaluate a possible link between MAPT variants, PD risk and PD motor phenotype, we analyzed the genetic architecture of MAPT in a cohort of PD patients. We observed a statistically significant association between the H1 haplotype and PD risk (79.5 vs 69.5%; χ(2) = 9.9; OR, 1.7; 95% CI, 1.2-2.4; p = 0.002). The effect was more evident in non tremor dominant (TD) PD subjects (NTD-PD) (82 vs 69.5%; χ(2) = 13.6; OR, 2.03; 95% CI, 1.4-3; p = 0.0003), while no difference emerged between PD subgroup of tremor dominant patients (TD-PD) and control subjects. Examination of specific intra-H1 variations showed that the H1h subhaplotype was overrepresented in NTD-PD patients compared with controls (p = 0.007; OR, 2.9; 95% CI, 1.3-6.3). Although we cannot exclude that MAPT variation may be associated with ethnicity, our results may support the hypothesis that MAPT H1 clade and a specific H1 subhaplotype influence the risk of PD and modulate the clinical expression of the disease, including motor phenotype

DNA methylation of the 5'-UTR DAT 1 gene in Parkinson's disease patients

The involvement of epigenetics mechanisms in the transcriptional regulation of key genes has been investigated in the initiation and progression of neurodegenerative disorders, including Parkinson's disease (PD). Among others, we, here, focused the attention on the dopamine transporter (DAT) gene playing a critical role in maintaining the integrity of dopaminergic neurons

Near-Infrared Transflectance Spectroscopy Discriminates Solutions Containing Two Commercial Formulations of Botulinum Toxin Type A Diluted at Recommended Volumes for Clinical Reconstitution

: Botulinum neurotoxin type A (BoNT-A) is the active substance in pharmaceutical preparations widely used worldwide for the highly effective treatment of various disorders. Among the three commercial formulations of BoNT-A currently available in Italy for neurological indications, abobotulinum A toxin (Dysport\uae, Ipsen SpA, Milano, Italy) and incobotulinum A toxin (Xeomin\uae, Merz Pharma Italia srl, Milano, Italy) differ in the content of neurotoxin, non-toxic protein, and excipients. Clinical applications of BoNT-A adopt extremely diluted solutions (10-6 mg/mL) for injection in the target body district. Near-infrared spectroscopy (NIRS) and chemometrics allow rapid, non-invasive, and non-destructive methods for qualitative and quantitative analysis. No data are available to date on the chemometric analysis of the spectral fingerprints acquired from the diluted commercial formulations of BoNT-A. In this proof-of-concept study, we tested whether NIRS can categorize solutions of incobotulinum A toxin (lacking non-toxic proteins) and abobotulinum A toxin (containing non-toxic proteins). Distinct excipients in the two formulations were also analyzed. We acquired transmittance spectra in the visible and short-wave infrared regions (350-2500 nm) by an ASD FieldSpec 4\u2122 Standard-Res Spectrophotoradiometer, using a submerged dip probe designed to read spectra in transflectance mode from liquid samples. After preliminary spectra pre-processing, principal component analysis was applied to characterize the spectral features of the two BoNT-A solutions and those of the various excipients diluted according to clinical standards. Partial least squares-discriminant analysis was used to implement a classification model able to discriminate the BoNT-A solutions and excipients. NIRS distinguished solutions containing distinct BoNT-A commercial formulations (abobotulinum A toxin vs. incobotulinum A toxin) diluted at recommended volumes for clinical reconstitution, distinct proteins (HSA vs. incobotulinum A toxin), very diluted solutions of simple sugars (lactose vs. sucrose), and saline or water. Predictive models of botulinum toxin formulations were also performed with the highest precision and accuracy

Do flexible inter-injection intervals improve the effects of botulinum toxin A treatment in reducing impairment and disability in patients with spasticity?

In patients treated with botulinum toxin-A (BoNT-A), toxin-directed antibody formation was related to the dosage and frequency of injections, leading to the empirical adoption of minimum time intervals between injections of 3&nbsp;months or longer. However, recent data suggest that low immunogenicity of current BoNT-A preparations could allow more frequent injections. Our hypothesis is that a short time interval between injections may be safe and effective in reducing upper limb spasticity and related disability. IncobotulinumtoxinA was injected under ultrasound guidance in spastic muscles of 11 subjects, who were evaluated just before BoNT-A injection (T0), and 1&nbsp;month (T1), 2&nbsp;months (T2) and 4&nbsp;months (T3) after injecting. At T1, in the case of persistent disability related to spasticity interfering with normal activities, patients received an additional toxin dose. Seven subjects received the additional dose at T1 because of persistent disability; 4 of them had a decrease of disability 1&nbsp;month later (T2). Rethinking the injection scheme for BoNT-A treatment may have a major impact in the management of spasticity and related disability. Future studies with larger sample sizes are warranted to confirm that injection schedules with short time intervals should no longer be discouraged in clinical practice