Non-invasive brain stimulation techniques, including transcranial direct current stimulation (t-DCS) have been used in the rehabilitation of cognitive function in a spectrum of neurological disorders. The present review outlines methodological communalities and differences of t-DCS procedures in neurocognitive rehabilitation. We consider the efficacy of tDCS for the management of specific cognitive deficits in four main neurological disorders by providing a critical analysis of recent studies that have used t-DCS to improve cognition in patients with Parkinson's Disease, Alzheimer's Disease, Hemi-spatial Neglect, and Aphasia. The evidence from this innovative approach to cognitive rehabilitation suggests that tDCS can influence cognition. However, the results show a high variability between studies both in terms of the methodological approach adopted and the cognitive functions targeted. The review also focuses both on methodological issues such as technical aspects of the stimulation (electrode position and dimension; current intensity; duration of protocol) and on the inclusion of appropriate assessment tools for cognition. A further aspect considered is the optimal timing for administration of tDCS: before, during or after cognitive rehabilitation. We conclude that more studies using common methodology are needed to gain a better understanding of the efficacy of tDCS as a new tool for rehabilitation of cognitive disorders in a range of neurological disorders.

BACKGROUND:Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for selected Parkinson's disease (PD) patients, but therapy is often limited by side effects. Previous studies indicate an inverse relationship of the therapeutic window (TW) to pulse width (PW) settings down to 60µs, but there is limited data available on the effect of shorter PWs.

Background Alzheimer’s disease (AD) is associated with alterations in cortical perfusion that correlate with cognitive impairment. Recently, neural activity in the gamma band has been identified as a driver of arteriolar vasomotion while, on the other hand, gamma activity induction on preclinical models of AD has been shown to promote protein clearance and cognitive protection. Methods In two open-label studies, we assessed the possibility to modulate cerebral perfusion in 15 mild to moderate AD participants via 40Hz (gamma) transcranial alternating current stimulation (tACS) administered 1 h daily for 2 or 4 weeks, primarily targeting the temporal lobe. Perfusion-sensitive MRI scans were acquired at baseline and right after the intervention, along with electrophysiological recording and cognitive assessments. Results No serious adverse effects were reported by any of the participants. Arterial spin labeling MRI revealed a significant increase in blood perfusion in the bilateral temporal lobes after the tACS treatment. Moreover, perfusion changes displayed a positive correlation with changes in episodic memory and spectral power changes in the gamma band. Conclusions Results suggest 40Hz tACS should be further investigated in larger placebo-controlled trials as a safe, non-invasive countermeasure to increase fast brain oscillatory activity and increase perfusion in critical brain areas in AD patients. Trial registration Studies were registered separately on ClinicalTrials.gov (NCT03290326, registered on September 21, 2017; NCT03412604, registered on January 26, 2018).

Major depressive disorder (MDD) is a worldwide cause of disability in older age, especially during the covid pandemic. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that has shown encouraging efficacy for treatment of depression. Here, we investigate the feasibility of an innovative protocol where tDCS is administered within the homes of older adults with MDD (patient participants) with the help of a study companion (i.e. caregiver). We further analyze the feasibility of a remotely-hosted training program that provides the knowledge and skills to administer tDCS at home, without requiring them to visit the lab. We also employed a newly developed multi-channel tDCS system with real-time monitoring designed to guarantee the safety and efficacy of home-based tDCS. Patient participants underwent a total of 37 home-based tDCS sessions distributed over 12 weeks. The protocol consisted of three phases each lasting four weeks: an acute phase, containing 28 home-based tDCS sessions, a taper phase containing nine home-based tDCS sessions, and a follow up phase, with no stimulation sessions. We found that the home-based, remotely-supervised, study companion administered, multi-channel tDCS protocol for older adults with MDD was feasible and safe. Further, the study introduces a novel training program for remote instruction of study companions in the administration of tDCS. Future research is required to determine the translatability of these findings to a larger sample.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT04799405?term=NCT04799405&draw=2&rank=1, identifier NCT04799405.

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Background: Alzheimer’s disease (AD) is characterized by diffuse amyloid-β (Aβ) and phosphorylated Tau (p-Tau) aggregates as well as neuroinflammation. Exogenously-induced 40 Hz gamma oscillations have been showing to reduce Aβ and p-Tau deposition presumably via microglia activation in AD mouse models. Objective: We aimed to translate preclinical data on gamma-induction in AD patients by means of transcranial alternating current stimulation (tACS). Methods: Four participants with mild-to-moderate AD received 1 h of daily 40 Hz (gamma) tACS for 4 weeks (Monday to Friday) targeting the bitemporal lobes (20 h treatment duration). Participant underwent Aβ, p-Tau, and microglia PET imaging with [11C]-PiB, [18F]-FTP, and [11C]-PBR28 respectively, before and after the intervention along with electrophysiological assessment. Results: No adverse events were reported, and an increase in gamma spectral power on EEG was observed after the treatment. [18F]-FTP PET revealed a significant decrease over 2% of p-Tau burden in 3/4 patients following the tACS treatment, primarily involving the temporal lobe regions targeted by tACS and especially mesial regions (e.g., entorhinal cortex). The amount of intracerebral Aβ as measured by [11C]-PiB was not significantly influenced by tACS, whereas 1/4 reported a significant decrease of microglia activation as measured by [11C]-PBR28. Conclusion: tACS seems to represent a safe and feasible option for gamma induction in AD patients, with preliminary evidence of a possible effect on protein clearance partially mimicking what is observed in animal models. Longer interventions and placebo control conditions are needed to fully evaluate the potential for tACS to slow disease progression.

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Background Deep brain stimulation in the ventral tegmental area (VTA-DBS) has provided remarkable therapeutic benefits in decreasing headache frequency and severity in patients with medically refractory chronic cluster headache (CH). However, to date the effects of VTA-DBS on cognition, mood and quality of life have not been examined in detail. Methods The aim of the present study was to do so in a case series of 18 consecutive patients with cluster headache who underwent implantation of deep brain stimulation electrodes in the ventral tegmental area. The patients were evaluated preoperatively and after a mean of 14 months of VTA-DBS on tests of global cognition (Mini Mental State Examination), intelligence (Wechsler Abbreviated Scale of Intelligence), verbal memory (California Verbal Learning Test-II), executive function (Delis–Kaplan Executive Function System), and attention (Paced Auditory Serial Addition Test). Depression (Beck Depression Inventory and Hospital Anxiety and Depression Rating Scale-D), anxiety (Hospital Anxiety and Depression Rating Scale-A), apathy (Starkstein Apathy Scale), and hopelessness (Beck Hopelessness Scale) were also assessed. Subjective pain experience (McGill Pain Questionnaire), behaviour (Pain Behaviour Checklist) and quality of life (Short Form-36) were also evaluated at the same time points. Results VTA-DBS resulted in significant improvement of headache frequency (from a mean of five to two attacks daily, p < .001) and severity (from mean Verbal Rating Scale [VRS] of 10 to 7, p < .001) which was associated with significant reduction of anxiety (from mean HADS-A of 11.94 to 8.00, p < .001) and help-seeking behaviours (from mean PBC of 4.00 to 2.61, p < .001). VTA-DBS did not produce any significant change to any tests of cognitive function and any other outcome measures (BDI, HADS-D, SAS, BHS, McGill Pain Questionnaire, Short Form-36). Conclusion We confirm the efficacy of VTA-DBS in the treatment of medically refractory chronic cluster headache. The reduction of headache frequency and severity was associated with a significant reduction of anxiety. Furthermore, the result suggests that VTA-DBS for chronic cluster headache improves pain-related help-seeking behaviours and does not produce any change in cognition.