The Network Structure of Cognitive Impairment: From Subjective Cognitive Decline to Alzheimer's Disease.

It was proposed that a reorganization of the relationships between cognitive functions occurs in dementia, a vision that surpasses the idea of a mere decline of specific domains. The complexity of cognitive structure, as assessed by neuropsychological tests, can be captured by exploratory graph analysis (EGA). EGA was applied to the neuropsychological assessment of people (humans) with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD; total N = 638). Both sexes were included. In AD, memory scores detach from the other cognitive functions, and memory subdomains reduce their reciprocal relation. SCD showed a pattern of segregated neuropsychological domains, and MCI showed a noisy and less stable pattern. Results suggest that AD drives a reorganization of cognitive functions toward a less-fractionated architecture compared with preclinical conditions. Cognitive functions show a reorganization that goes beyond the performance decline. Results also have clinical implications in test interpretations and usage.

Heat-induced seizures, premature mortality, and hyperactivity in a novel Scn1a nonsense model for Dravet syndrome.

Dravet syndrome (Dravet) is a severe congenital developmental genetic epilepsy caused by de novo mutations in the SCN1A gene. Nonsense mutations are found in ∼20% of the patients, and the R613X mutation was identified in multiple patients. Here we characterized the epileptic and non-epileptic phenotypes of a novel preclinical Dravet mouse model harboring the R613X nonsense Scn1a mutation. Scn1aWT/R613X mice, on a mixed C57BL/6J:129S1/SvImJ background, exhibited spontaneous seizures, susceptibility to heat-induced seizures, and premature mortality, recapitulating the core epileptic phenotypes of Dravet. In addition, these mice, available as an open-access model, demonstrated increased locomotor activity in the open-field test, modeling some non-epileptic Dravet-associated phenotypes. Conversely, Scn1aWT/R613X mice, on the pure 129S1/SvImJ background, had a normal life span and were easy to breed. Homozygous Scn1aR613X/R613X mice (pure 129S1/SvImJ background) died before P16. Our molecular analyses of hippocampal and cortical expression demonstrated that the premature stop codon induced by the R613X mutation reduced Scn1a mRNA and NaV1.1 protein levels to ∼50% in heterozygous Scn1aWT/R613X mice (on either genetic background), with marginal expression in homozygous Scn1aR613X/R613X mice. Together, we introduce a novel Dravet model carrying the R613X Scn1a nonsense mutation that can be used to study the molecular and neuronal basis of Dravet, as well as the development of new therapies associated with SCN1A nonsense mutations in Dravet.

A systematic review on resting state functional connectivity in patients with neurodegenerative disease and hallucinations.

Hallucinations are a complex and multidimensional phenomenon which can differ based on the involved pathology, typology and sensory modality. Hallucinations are common in patients with neurodegenerative diseases. Recent sparse evidence from resting state functional magnetic resonance imaging (rs-fMRI) studies has identified altered functional connectivity in those patients within several brain networks, such as the default mode, attentional and sensory ones, without, however, providing an organized picture of the mechanisms involved. This systematic review, following PRISMA guidelines, aims at critically analyzing the current literature on the brain networks associated with the phenomenon of hallucinations in patients with neurodegenerative diseases. Ten rs-fMRI studies fulfilled our selection criteria. All these studies focused on synucleinopathies, and most of them focused on visual hallucinations and were characterized by a heterogeneous methodology. Thus, instead of offering a definite picture of the mechanisms underlying hallucinations in neurodegeneration, this systematic review encourages further research especially concerning tauopathies. Notwithstanding, the findings overall suggest a disruption in the top-down (associated with memory intrusion and difficulty of inhibition) and in the bottom-up processes (associated with the sensory areas involved in the hallucinations). Further investigations are needed in order to disentangle the brain mechanisms involved in hallucinations and to overcome possible limitations characterizing the current literature.

A Review on Music Interventions for Frontotemporal Aphasia and a Proposal for Alternative Treatments.

Frontotemporal dementia (FTD) is a rare neurodegenerative disease, characterized by behavioral and language impairments. Primary progressive aphasia (PPA) is the linguistic variant of this heterogeneous disorder. To date, there is a lack of consensus about which interventions are effective in these patients. However, several studies show that music-based interventions are beneficial in neurological diseases. This study aims, primarily, to establish the state of the art of music-based interventions designed for PPA due to FTD and, secondarily, to inform the planning of PPA-dedicated future interventions for Italian neurological institutions. The first aim is fulfilled by a review which critically screens the neurological studies examining the effects of music- and/or rhythm-based interventions, especially, on language rehabilitation in aphasic FTD. We found that only two papers fulfilled our criteria and concerned specifically aphasic patients due to FTD. Of those, one paper reported a study conducted in an Italian institution. Most of the reviewed studies focused, instead, on aphasia in post-stroke patients. The results of our review invite further studies to investigate the role of music as a valuable support in the therapy for neurodegenerative patients with language problems and in particular to PPA due to FTD. Moreover, based on this initial work, we can delineate new music-based interventions dedicated to PPA for Italian institutions.

The association of noise sensitivity with music listening, training, and aptitude.

After intensive, long-term musical training, the auditory system of a musician is specifically tuned to perceive musical sounds. We wished to find out whether a musician's auditory system also develops increased sensitivity to any sound of everyday life, experiencing them as noise. For this purpose, an online survey, including questionnaires on noise sensitivity, musical background, and listening tests for assessing musical aptitude, was administered to 197 participants in Finland and Italy. Subjective noise sensitivity (assessed with the Weinstein's Noise Sensitivity Scale) was analyzed for associations with musicianship, musical aptitude, weekly time spent listening to music, and the importance of music in each person's life (or music importance). Subjects were divided into three groups according to their musical expertise: Nonmusicians (N = 103), amateur musicians (N = 44), and professional musicians (N = 50). The results showed that noise sensitivity did not depend on musical expertise or performance on musicality tests or the amount of active (attentive) listening to music. In contrast, it was associated with daily passive listening to music, so that individuals with higher noise sensitivity spent less time in passive (background) listening to music than those with lower sensitivity to noise. Furthermore, noise-sensitive respondents rated music as less important in their life than did individuals with lower sensitivity to noise. The results demonstrate that the special sensitivity of the auditory system derived from musical training does not lead to increased irritability from unwanted sounds. However, the disposition to tolerate contingent musical backgrounds in everyday life depends on the individual's noise sensitivity.