Closing the loop between brain and electrical stimulation: towards precision neuromodulation treatments

Abstract

One of the most critical challenges in using noninvasive brain stimulation (NIBS) techniques for the treatment of psychiatric and neurologic disorders is inter- and intra-individual variability in response to NIBS. Response variations in previous findings suggest that the one-size-fits-all approach does not seem the most appropriate option for enhancing stimulation outcomes. While there is a growing body of evidence for the feasibility and effectiveness of individualized NIBS approaches, the optimal way to achieve this is yet to be determined. Transcranial electrical stimulation (tES) is one of the NIBS techniques showing promising results in modulating treatment outcomes in several psychiatric and neurologic disorders, but it faces the same challenge for individual optimization. With new computational and methodological advances, tES can be integrated with real-time functional magnetic resonance imaging (rtfMRI) to establish closed-loop tES-fMRI for individually optimized neuromodulation. Closed-loop tES-fMRI systems aim to optimize stimulation parameters based on minimizing differences between the model of the current brain state and the desired value to maximize the expected clinical outcome. The methodological space to optimize closed-loop tES fMRI for clinical applications includes (1) stimulation vs. data acquisition timing, (2) fMRI context (task-based or resting-state), (3) inherent brain oscillations, (4) dose-response function, (5) brain target trait and state and (6) optimization algorithm. Closed-loop tES-fMRI technology has several advantages over non-individualized or open-loop systems to reshape the future of neuromodulation with objective optimization in a clinically relevant context such as drug cue reactivity for substance use disorder considering both inter and intra-individual variations. Using multi-level brain and behavior measures as input and desired outcomes to individualize stimulation parameters provides a framework for designing personalized tES protocols in precision psychiatry.

Frequency-dependent membrane polarization across neocortical cell types and subcellular elements by transcranial alternating current stimulation

“…Our study focuses on the membrane polarization at the cellular level, while the parameter optimization of tACS is usually based on measured EEG or functional magnetic resonance imaging signals [49,50]. To optimize the macroscale tACS parameters using the microscale neural mechanisms, we need to relate membrane polarization with spike activity and identify the crucial role of neural spiking in brain oscillations.…”

“…To optimize the macroscale tACS parameters using the microscale neural mechanisms, we need to relate membrane polarization with spike activity and identify the crucial role of neural spiking in brain oscillations. However, it is challenging to record largescale neuronal responses simultaneously [44] and denoise the high-amplitude stimulation artifacts [50,51]. Our model study combined with subject-specific head models and experiments will be an effective method to optimize the tACS parameters to an individual brain, such as the closed-loop framework proposed in the literature [50] for designing personalized transcranial electric stimulation parameters.…”

A scientometric review of the growing trends in transcranial alternating current stimulation (tACS)

“…As technological advances continue to improve the precision and effectiveness of neuromodulation techniques, there is a growing need to understand how tACS interacts with feedback stimuli and how to optimize this interaction to modulate brain activity and cognitive function. In this context, recent work by Soleimani et al (2023) on closing the loop between the brain and electrical stimulation provides valuable insights into the potential of closed-loop tACS in precise neuromodulation therapy. Their study emphasizes the importance of considering individual differences and real-time brain states when designing effective neuromodulation interventions.…”

“…Their study emphasizes the importance of considering individual differences and real-time brain states when designing effective neuromodulation interventions. The ability of closed-loop tES-fMRI systems to continuously monitor brain activity and adjust stimulation parameters in real time offers unprecedented opportunities for personalized neuromodulation therapy ( Soleimani et al, 2023 ). Future studies should aim to deeply explore how closed-loop tACS interacts with feedback stimuli and how this interaction affects brain activity and cognitive function.…”

U-shaped convolutional transformer GAN with multi-resolution consistency loss for restoring brain functional time-series and dementia diagnosis

“…The constructed features in non-Euclidean space can establish relations between distant brain regions, which is superior than the image-based features in Euclidean space (Chen et al, 2023 ; Wan et al, 2023d ). When evaluating the treatment's performance, fMRI allows researchers to monitor and assess changes in brain activity before and after DBS treatment (Boutet et al, 2021 ; Soleimani et al, 2023 ). However, fMRI can sometimes be impacted by the presence of implanted electrodes.…”