Transcranial electrical stimulation (tES) has garnered significant attention as a non-invasive neuromodulation technique with promising therapeutic potential for various neurological and neuropsychiatric conditions. However, considerable variability in response to tES both between and within-individuals is a prevailing issue. This review explored recent advancements in optimising tES through individualised protocols that consider individual head anatomy, neural oscillatory activities and dynamic changes in the neurophysiology of the stimulated brain. Real-time monitoring and closed-loop systems allow adaptive adjustments of stimulation parameters in response to ongoing brain activity, which holds promise for enhancing tES effectiveness and overcoming the challenge of inter-session response variability. Overall, the reviewed literature highlights the emerging trend towards individualised tES protocols as a means to unlock the full potential of tES in research and clinical use. While promising, further research is warranted to establish standardised methodologies and validate the efficacy of individually tailored tES protocols to realise its full potential. 

Recent advancements in optimising transcranial electrical stimulation: reducing response variability through individualised stimulation

Abstract Purpose of Review Pioneering work in rodents has shown that the reactivation of recently acquired memories during sleep is a key mechanism underlying the beneficial effect of sleep on memory consolidation. In this review, we consider recent evidence of memory reactivation processes in human sleep. Recent Findings The precise temporal coupling of sleep spindles to slow oscillations during non-rapid eye movement sleep plays a central role in sleep-associated memory consolidation. Both correlational studies and studies directly manipulating oscillatory activity in the sleeping brain have confirmed that spindles coupled to slow oscillations are better predictors of memory than uncoupled spindles and that the greatest memory benefit comes when spindles are tightly coupled to the up-state of the slow oscillation. Recent evidence suggests that memory content is reactivated during sleep, with a functional benefit for memory performance after sleep. Reactivation events are time-locked around slow oscillation-spindle coupling events, as well as sharp-wave ripples in hippocampus. Summary Memory reactivation, which is facilitated by slow oscillation-spindle coupling events, can be observed during human sleep and shows promise as a prime mechanism underlying sleep’s beneficial effects on memory. 

Electrophysiological Mechanisms of Memory Consolidation in Human Non-rapid Eye Movement Sleep

We aimed to build a tool which facilitates manual labeling of sleep slow oscillations (SOs) and evaluate the performance of traditional sleep SO detection algorithms on such a manually labeled data set. We sought to develop improved methods for SO detection.SOs in polysomnographic recordings acquired during nap time from ten older adults were manually labeled using a custom built graphical user interface tool. Three automatic SO detection algorithms previously used in the literature were evaluated on this data set. Additional machine learning and deep learning algorithms were trained on the manually labeled data set.Our custom built tool significantly decreased the time needed for manual labeling, allowing us to manually inspect 96,277 potential SO events. The three automatic SO detection algorithms showed relatively low accuracy (max. 61.08%), but results were qualitatively similar, with SO density and amplitude increasing with sleep depth. The machine learning and deep learning algorithms showed higher accuracy (best: 99.20%) while maintaining a low prediction time.Accurate detection of SO events is important for investigating their role in memory consolidation. In this context, our tool and proposed methods can provide significant help in identifying these events.

Improving the detection of sleep slow oscillations in electroencephalographic data

Certain neurophysiological characteristics of sleep, in particular slow oscillations (SOs), sleep spindles, and their temporal coupling, have been well characterised and associated with human memory abilities. Delta waves, which are somewhat higher in frequency and lower in amplitude compared to SOs, and their interaction with spindles have only recently been found to play a critical role in memory processing of rodents, through a competitive interaction between SO–spindle and delta–spindle coupling. However, human studies that comprehensively address delta wave interactions with spindles and SOs, as well as their functional role for memory are still lacking. Electroencephalographic data were acquired across three naps of 33 healthy older human participants (17 female) to investigate delta–spindle coupling and the interplay between delta‐ and SO‐related activity. Additionally, we determined intra‐individual stability of coupling measures and their potential link to the ability to form novel memories in a verbal memory task. Our results revealed weaker delta–spindle compared to SO–spindle coupling. Contrary to our initial hypothesis, we found no evidence for an opposing dependency between SO‐ and delta‐related activities during non‐rapid eye movement sleep. Moreover, the ratio between SO‐ and delta‐nested spindles rather than SO–spindle and delta–spindle coupling measures by themselves predicted the ability to form novel memories best. In conclusion, our results do not confirm previous findings in rodents on competitive interactions between delta activity and SO–spindle coupling in older adults. However, they support the hypothesis that SO, delta wave, and spindle activity should be jointly considered when aiming to link sleep physiology and memory formation.

Interrelations and functional roles of key oscillatory activities during daytime sleep in older adults.

Background: Oscillatory rhythms during sleep such as slow oscillations (SO) and spindles, and most importantly their coupling, are thought to underlie processes of memory consolidation. External slow oscillatory transcranial direct current stimulation (so-tDCS) with a frequency of 0.75 Hz has been shown to improve this coupling and memory consolidation, however, effects varied quite markedly between individuals, studies and species. 
Objective: Here, we aimed to determine how precisely the frequency of stimulation has to match the naturally occurring SO frequency in individuals to optimally improve SO-spindle coupling. Moreover, we systematically tested stimulation durations necessary to induce changes.
Methods: We addressed these questions by comparing so-tDCS with individually adapted SO frequency to standardized frequency of 0.75Hz in a cross-over design with 28 healthy older participants during napping while systematically varying stimulation train durations between 30s, 2min and 5min. 
Results: Stimulation trains as short as 30s were sufficient to modulate the coupling between SOs and spindle activity. Contrary to our expectations, so-tDCS with standardized frequency indicated stronger aftereffects with regard to SO-spindle coupling in comparison to individualized frequency. Angle and variance of spindle maxima occurrence during the SO cycle were similarly modulated.
Conclusion: Short stimulation trains were sufficient to induce significant changes in sleep physiology allowing for more trains of stimulation, which provides methodological advantages and possibly even larger effects in future studies. With regard to individualized stimulation frequency, further options of optimization need to be investigated, such as closed-loop stimulation to calibrate stimulation frequency to the SO frequency at time of stimulation onset.

/pdf/towards-optimization-of-oscillatory-stimulation-during-sleep-1ayjm045bx.pdf

Towards optimization of oscillatory stimulation during sleep

Certain neurophysiological characteristics of sleep, in particular slow oscillations (SO), sleep spindles, and their temporal coupling, have been well characterized and associated with human memory formation. Delta waves, which are somewhat higher in frequency and lower in amplitude compared to SO, have only recently been found to play a critical role in memory processing of rodents, through a competitive interplay between SO-spindle and delta-spindle coupling. However, human studies that comprehensively address delta waves, their interactions with spindles and SOs as well as their functional role for memory are still lacking. Electroencephalographic data were acquired across three naps of 33 healthy older human participants (17 female) to investigate delta-spindle coupling and the interplay between delta and SO-related activity. Additionally, we determined intra-individual stability of coupling measures and their potential link to the ability to form novel memories. Our results revealed weaker delta-spindle compared to SO-spindle coupling. Contrary to our initial hypothesis, we found that increased delta activity was accompanied by stronger SO-spindle coupling. Moreover, we identified the ratio between SO- and delta-nested spindles as the sleep parameter that predicted ability to form novel memories best. Our study suggests that SOs, delta waves and sleep spindles should be jointly considered when aiming to link sleep physiology and memory formation in aging.

/pdf/interrelations-between-delta-waves-spindles-and-slow-3ickut90rk.pdf

Interrelations between delta waves, spindles and slow oscillations in human NREM sleep and their functional role in memory

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Towards optimization of oscillatory stimulation during sleep

Interrelations between delta waves, spindles and slow oscillations in human NREM sleep and their functional role in memory