Title: Spatiotemporal patterns of sleep spindle activity in human anterior thalamus and cortex 16 Hz) during non-rapid eye movement sleep.

Sleep spindles (8 - are transient electrophysiological events While sleep spindles are routinely observed in the cortex using scalp electroencephalography (EEG), recordings of their thalamic counterparts have not been widely studied in humans. Based on a few existing studies, it has been hypothesized that spindles occur as largely local phenomena. To see whether they also facilitate thalamocortical communication, we investigated intra-thalamic and thalamocortical spindle co-occurrence. We obtained scalp EEG and thalamic recordings from 7 patients that received bilateral deep brain stimulation (DBS) electrodes to the anterior thalamus for the treatment of drug resistant focal epilepsy. Spindles were categorized into subtypes based on their main frequency (i.e., slow (10±2 Hz) or fast (14±2 Hz)) and their level of thalamic involvement (spanning one channel, or spreading uni- or bilaterally within the thalamus). For the first time, we contrasted observed spindle patterns with permuted data to estimate random spindle co-occurrence. We found that multichannel spindle patterns were systematically coordinated at the thalamic and thalamocortical level. Importantly, distinct topographical patterns of thalamocortical spindle overlap were associated with slow and fast subtypes of spindles. These observations provide further evidence for coordinated spindle activity in thalamocortical networks. Here, we addressed these issues and took a statistical approach to measure patterns of slow and fast spindle (co-)occurrence in the anterior thalamus and cortex by controlling for random spindle co-occurrence using permutation testing. This approach allowed us to compare temporal spindle coupling observed in the data with distributions of random spindle co-occurrence, thereby informing whether spindles in thalamocortical loops occur in systematically coordinated patterns. We recorded data in 7 individuals with epilepsy who underwent implantation of DBS quadripolar electrodes targeting the anterior nucleus of the thalamus (ANT). The setup of bilateral thalamic depth electrodes allowed us to assess co-occurrences of thalamic spindles within and across hemispheres. Simultaneous 19-channel scalp EEG recordings made it possible to study thalamocortical spindle co-occurrence globally across the cortex. We categorized spindles based on their main frequency as slow (10±2 Hz) or fast (14±2 Hz) spindles, as well as their level of thalamic involvement (spindles restricted to one channel, or spanning more than one channel unilaterally or bilaterally). We found that both slow and fast thalamic and thalamocortical spindles were more likely to co-occur across channels than expected by chance. Additionally, distinct topographical patterns of spindle overlap were associated with the different spindle subtypes. These observations provide support that slow and fast spindle activity are systematically coordinated in thalamocortical circuits. results point towards differences in thalamocortical overlap depending on the spindle type (slow vs. fast) and level of thalamic involvement. As such, we observed that slow spindles tended to co-occur with cortical slow spindles in frontal EEG sites. Co-occurrence of thalamic and cortical fast spindles was distributed more widely across the cortex, which was reflected by a more centralized average of thalamocortical overlap. Additionally, the level of involvement of the thalamus in spindles was related to the cortical lateralization of thalamocortical overlap: During T 1 C spindles and slow unilateral T >1 C spindles, cortical electrodes ipsilateral to the thalamus channel(s) tended to engage in spindles together, whereas bilateral T >1 C spindles showed a higher overlap with bilateral cortical electrodes. p = 0.62), or their interaction (F 2,60 = 0.35; p = 0.71), but a significant intercept (F 1,60 = 1033.5, p < 0.001). When modeling spindle power, there was a significant main effect of spindle type (F 1,60 = 6.80; p = 0.01), but no significant main effect of nucleus (F 2,60 = 0.40, p = 0.67) and no interaction effect of spindle type and nucleus (F 2,60 = 1.63; p = 0.20). Post-hoc comparisons revealed that slow spindles (9.96 ± 5.53 µV) had significantly higher power (t(60) = 2.61; p = 0.01) than fast spindles (7.67 ± 5.85 µV) The intercept was significant (F 1,60 = 36.47, p < 0.001), suggesting inter-individual differences in both spindle duration and power.