Network Disruption and Cerebrospinal Fluid Amyloid-Beta and Phospho-Tau Levels in Mild Cognitive Impairment.

Synaptic dysfunction is a core deficit in Alzheimer's disease, preceding hallmark pathological abnormalities. Resting-state magnetoencephalography (MEG) was used to assess whether functional connectivity patterns, as an index of synaptic dysfunction, are associated with CSF biomarkers [i.e., phospho-tau (p-tau) and amyloid beta (Aß42) levels]. We studied 12 human subjects diagnosed with mild cognitive impairment due to Alzheimer's disease, comparing those with normal and abnormal CSF levels of the biomarkers. We also evaluated the association between aberrant functional connections and structural connectivity abnormalities, measured with diffusion tensor imaging, as well as the convergent impact of cognitive deficits and CSF variables on network disorganization. One-third of the patients converted to Alzheimer's disease during a follow-up period of 2.5 years. Patients with abnomal CSF p-tau and Aß42 levels exhibited both reduced and increased functional connectivity affecting limbic structures such as the anterior/posterior cingulate cortex, orbitofrontal cortex, and medial temporal areas in different frequency bands. A reduction in posterior cingulate functional connectivity mediated by p-tau was associated with impaired axonal integrity of the hippocampal cingulum. We noted that several connectivity abnormalities were predicted by CSF biomarkers and cognitive scores. These preliminary results indicate that CSF markers of amyloid deposition and neuronal injury in early Alzheimer's disease associate with a dual pattern of cortical network disruption, affecting key regions of the default mode network and the temporal cortex. MEG is useful to detect early synaptic dysfunction associated with Alzheimer's disease brain pathology in terms of functional network organization. SIGNIFICANCE STATEMENT: In this preliminary study, we used magnetoencephalography and an integrative approach to explore the impact of CSF biomarkers, neuropsychological scores, and white matter structural abnormalities on neural function in mild cognitive impairment. Disruption in functional connectivity between several pairs of cortical regions associated with abnormal levels of biomarkers, cognitive deficits, or with impaired axonal integrity of hippocampal tracts. Amyloid deposition and tau protein-related neuronal injury in early Alzheimer's disease are associated with synaptic dysfunction and a dual pattern of cortical network disorganization (i.e., desynchronization and hypersynchronization) that affects key regions of the default mode network and temporal areas.

Short-Term Effects of Binaural Beats on EEG Power, Functional Connectivity, Cognition, Gait and Anxiety in Parkinson's Disease.

We applied rhythmic binaural sound to Parkinson's Disease (PD) patients to investigate its influence on several symptoms of this disease and on Electrophysiology (Electrocardiography and Electroencephalography (EEG)). We conducted a double-blind, randomized controlled study in which rhythmic binaural beats and control were administered over two randomized and counterbalanced sessions (within-subjects repeated-measures design). Patients ([Formula: see text], age [Formula: see text], stage I-III Hoehn & Yahr scale) participated in two sessions of sound stimulation for 10[Formula: see text]min separated by a minimum of 7 days. Data were collected immediately before and after both stimulations with the following results: (1) a decrease in theta activity, (2) a general decrease in Functional Connectivity (FC), and (3) an improvement in working memory performance. However, no significant changes were identified in the gait performance, heart rate or anxiety level of the patients. With regard to the control stimulation, we did not identify significant changes in the variables analyzed. The use of binaural-rhythm stimulation for PD, as designed in this study, seems to be an effective, portable, inexpensive and noninvasive method to modulate brain activity. This influence on brain activity did not induce changes in anxiety or gait parameters; however, it resulted in a normalization of EEG power (altered in PD), normalization of brain FC (also altered in PD) and working memory improvement (a normalizing effect). In summary, we consider that sound, particularly binaural-rhythmic sound, may be a co-assistant tool in the treatment of PD, however more research is needed to consider the use of this type of stimulation as an effective therapy.