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Recent findings indicate that measures derived from resting-state magnetoencephalography (rsMEG) are sensitive to cortical dysfunction in post-stroke aphasia. Spectral power and multiscale entropy (MSE) measures show that left-hemispheric areas surrounding the stroke lesion (perilesional) exhibit pathological oscillatory slowing and alterations in signal complexity. In the current study, we tested whether individually-targeted high-definition transcranial direct current stimulation (HD-tDCS) can reduce MEG abnormalities and transiently improve language performance. In eleven chronic aphasia survivors, we devised a method to localize perilesional areas exhibiting peak MSE abnormalities, and subsequently targeted these areas with excitatory/anodal-tDCS, or targeted the contralateral homolog areas with inhibitory/cathodal-tDCS, based on prominent theories of stroke recovery. Pathological MEG slowing in these patients was correlated with aphasia severity. Sentence/phrase repetition accuracy was assessed before and after tDCS. A delayed word reading task was administered inside MEG to assess tDCS-induced neurophysiological changes in relative power and MSE computed on the pre-stimulus and delay task time windows. Results indicated increases in repetition accuracy, decreases in contralateral theta (4–7 Hz) and coarse-scale MSE (slow activity), and increases in perilesional low-gamma (25–50 Hz) and fine-scale MSE (fast activity) after anodal-tDCS, indicating reversal of pathological abnormalities. RsMEG may be a sensitive measure for guiding therapeutic tDCS.

α-Synuclein (asyn) is a key pathogenetic factor in a group of neurodegenerative diseases generically known as synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Although the initial triggers of pathology and progression are unclear, multiple lines of evidence support therapeutic targeting of asyn in order to limit its prion-like misfolding. Here, we review recent pre-clinical and clinical work that offers promising treatment strategies to sequester, degrade, or silence asyn expression as a means to reduce the levels of seed or substrate. These diverse approaches include removal of aggregated asyn with passive or active immunization or by expression of vectorized antibodies, modulating kinetics of misfolding with small molecule anti-aggregants, lowering asyn gene expression by antisense oligonucleotides or inhibitory RNA, and pharmacological activation of asyn degradation pathways. We also discuss recent technological advances in combining low intensity focused ultrasound with intravenous microbubbles to transiently increase blood-brain barrier permeability for improved brain delivery and target engagement of these large molecule anti-asyn biologics.

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