Virtual neural network-guided optimization of non-invasive brain stimulation in Alzheimer's disease.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique with potential for counteracting disrupted brain network activity in Alzheimer's disease (AD) to improve cognition. However, the results of tDCS studies in AD have been variable due to different methodological choices such as electrode placement. To address this, a virtual brain network model of AD was used to explore tDCS optimization. We compared a large, representative set of virtual tDCS intervention setups, to identify the theoretically optimized tDCS electrode positions for restoring functional network features disrupted in AD. We simulated 20 tDCS setups using a computational dynamic network model of 78 neural masses coupled according to human structural topology. AD network damage was simulated using an activity-dependent degeneration algorithm. Current flow modeling was used to estimate tDCS-targeted cortical regions for different electrode positions, and excitability of the pyramidal neurons of the corresponding neural masses was modulated to simulate tDCS. Outcome measures were relative power spectral density (alpha bands, 8-10 Hz and 10-13 Hz), total spectral power, posterior alpha peak frequency, and connectivity measures phase lag index (PLI) and amplitude envelope correlation (AEC). Virtual tDCS performance varied, with optimized strategies improving all outcome measures, while others caused further deterioration. The best performing setup involved right parietal anodal stimulation, with a contralateral supraorbital cathode. A clear correlation between the network role of stimulated regions and tDCS success was not observed. This modeling-informed approach can guide and perhaps accelerate tDCS therapy development and enhance our understanding of tDCS effects. Follow-up studies will compare the general predictions to personalized virtual models and validate them with tDCS-magnetoencephalography (MEG) in a clinical AD patient cohort.

Oscillatory Activity of the Hippocampus in Prodromal Alzheimer's Disease: A Source-Space Magnetoencephalography Study.

BACKGROUND: In Alzheimer's disease (AD), oscillatory activity of the human brain slows down. However, oscillatory slowing varies between individuals, particularly in prodromal AD. Cortical oscillatory changes have shown suboptimal accuracy as diagnostic markers. We speculated that focusing on the hippocampus might prove more successful, particularly using magnetoencephalography (MEG) for capturing subcortical oscillatory activity. OBJECTIVE: We explored MEG-based detection of hippocampal oscillatory abnormalities in prodromal AD patients. METHODS: We acquired resting-state MEG data of 18 AD dementia patients, 18 amyloid-ß-positive amnestic mild cognitive impairment (MCI, prodromal AD) patients, and 18 amyloid-ß-negative persons with subjective cognitive decline (SCD). Oscillatory activity in 78 cortical regions and both hippocampi was reconstructed using beamforming. Between-group and hippocampal-cortical differences in spectral power were assessed. Classification accuracy was explored using ROC curves. RESULTS: The MCI group showed intermediate power values between SCD and AD, except for the alpha range, where it was higher than both (p < 0.05 and p < 0.001). The largest differences between MCI and SCD were in the theta band, with higher power in MCI (p < 0.01). The hippocampi showed several unique group differences, such as higher power in the higher alpha band in MCI compared to SCD (p < 0.05). Classification accuracy (MCI versus SCD) was best for absolute theta band power in the right hippocampus (AUC = 0.87). CONCLUSION: In this MEG study, we detected oscillatory abnormalities of the hippocampi in prodromal AD patients. Moreover, hippocampus-based classification performed better than cortex-based classification. We conclude that a focus on hippocampal MEG may improve early detection of AD-related neuronal dysfunction.