Effect of Closed-Loop Direct Electrical Stimulation during Sleep Spindles in Humans

Abstract

Sleep spindles are transient oscillations in the brain related to sleep consolidation and memory. We investigated if brief, localized electrical pulses could perturb spindles on five human patients with intracerebral electrodes implanted for clinical purpose. We used a closed-loop setup to specifically detect spindles and stimulate in real-time during these events. Stimulation latency was 200-400 ms following spindle onset. Analyzing the intracranial electroencephalographic (iEEG) data both locally and globally, we found, in two of the patients, that single pulse stimulation could stop the spindles locally. Spindles were shorter than those without stimulation and a decrease in power at the same frequency as spindles was observed following stimulation. Clinical Relevance-This study shows that brief and precise electrical stimulation may be used to modulate oscillatory behavior of the human brain. Applied to sleep spindles, further studies may establish that single pulses applied in a closed-loop manner could be used to modulate memory and could help understand effect of neuromodulation in sleep disruption.

Modular pipeline for reconstruction and localization of implanted intracranial ECoG and sEEG electrodes

“…This allows us to algorithmically determine the locations of electrode contacts in the brain. This brain region localization alone has been useful for following seizure activity, planning stimulation, and localizing neural activity relative to cognitive processes [5,6,[11][12][13][14][30][31][32][33][34][35][36][37][38]. Finally, this output data is easily converted into a universal format so that we can share our data with the greater scientific community (iEEG BIDS; [43]).…”

“…The visualization is used to validate whether electrodes are implanted in the desired brain regions and to map neural epileptiform activity and the seizure onset zone (SOZ) to specified brain regions. This pipeline has been shared with clinical teams at Massachusetts General Hospital and Brigham and Women's Hospital for nearly 15 years, which accounts for over 260 patients as of publication [5,6,[11][12][13][14][30][31][32][33][34][35][36][37][38]. The end product is a shareable.pdf file (Adobe Acrobat; S1 File) that provides clinical and research teams with the appropriate electrode locations and labels, the three MRI views, a re-sliced coronal view along the length of a depth electrode shaft, and the electrode locations in the 3D brain per page of the.pdf.…”

“…In addition to its clinical uses, this pipeline is also valuable for researchers. For example, this pipeline has been used in understanding how stimulation alters brain activity as well as probe activity in different states such as during sleep and under general anesthesia (N = 82, [11,13,14,[33][34][35][36]38]), where the reconstructed localizations were used to inform selecting stimulation sites. Localizing stimulation sites is important because a key facet of stimulation is understanding the distance between stimulation sites and the brain areas that are targets for stimulation [13,14].…”

“…In addition, some co-registration pipelines require the pre-operative and post-operative scans to first be transformed into a standardized brain space (e.g., Montreal Neurological Institute (MNI) space) before identifying electrode locations [28,29]. There are various methods for a user to achieve their goal when attempting to localize implanted electrodes, but here we lay out a protocol involving multiple software packages that we have used in a large data set (>260 patients) and which we have used to address many neuroscientific and clinically-relevant goals [5,6,[11][12][13][14][30][31][32][33][34][35][36][37][38].…”

CLoSES: A platform for closed-loop intracranial stimulation in humans

“…As a research tool, CLoSES streamlines the testing of a wide variety of questions in humans. CLoSES-RT has been used to investigate some mechanisms and roles of sleep spindles ( Krempp et al, 2020 ) and epileptic IIDs. CLoSES-SEM has been used to investigate the effect of stimulation during cognitive flexibility and emotion conflict resolution tasks.…”