Local and Transient Changes of Sleep Spindle Density During Series of Prefrontal Repetitive Transcranial Magnetic Stimulation in Patients With a Major Depressive Episode

The neuromodulatory effects of brain stimulation therapies notably involving repetitive transcranial magnetic stimulation (rTMS) on nocturnal sleep, which is critically disturbed in major depression and other neuropsychiatric disorders, remain largely undetermined. We have previously reported in major depression patients that prefrontal rTMS sessions enhanced their slow wave activity (SWA) power, but not their sigma power which is related to sleep spindle activity, for electrodes located nearby the stimulation site. In the present study, we focused on measuring the spindle density to investigate cumulative effects of prefrontal rTMS sessions on the sleep spindle activity. Fourteen male inpatients diagnosed with medication-resistant unipolar or bipolar depression were recruited and subjected to 10 daily rTMS sessions targeting the left dorsolateral prefrontal cortex (DLPFC). All-night polysomnography (PSG) data was acquired at four time points: Adaptation, Baseline, Post-1 (follow-up after the fifth rTMS session), and Post-2 (follow-up after the tenth rTMS session). Clinical and cognitive evaluations were longitudinally performed at Baseline, Post-1, and Post-2 time points to explore associations with the spindle density changes. The PSG data from 12 of 14 patients was analyzed to identify sleep spindles across the sleep stages II–IV at four electrode sites: F3 (frontal spindle near the stimulation site), F4 (contralateral homologous frontal region), P3 (parietal spindle in the hemisphere ipsilateral to the stimulation site), and P4 (contralateral parietal region). Statistical analysis by two-way ANOVA revealed that spindle density at F3 increased at Post-1 but decreased at Post-2 time points. Moreover, the local and transient increase of spindle density at F3 was associated with the previously reported SWA power increase at F3, possibly reflecting a shared mechanism of thalamocortical synchronization locally enhanced by diurnal prefrontal rTMS sessions. Clinical and cognitive correlations were not observed in this dataset. These findings suggest that diurnal rTMS sessions transiently modulate nocturnal sleep spindle activity at the stimulation site, although clinical and cognitive effects of the local changes warrant further investigation.

The adolescent pattern of sleep spindle development revealed by HD-EEG polisomnography

Sleep spindles are developmentally relevant cortical oscillatory patterns; however, they have mostly been studied by considering the entire spindle frequency range (11 to 15 Hz) without a distinction between the functionally and topographically different slow and fast spindles, using relatively few electrodes and analysing wide age-ranges. Here, we employ HD-EEG polysomnography in three age-groups between 12 to 20 years of age, with an equal distribution between the two genders, and analyse the adolescent developmental pattern of the four major parameters of slow and fast sleep spindles. Most of our findings corroborate those very few previous studies that also make a distinction between slow and fast spindles in their developmental analysis. We find spindle frequency increasing with age, although spindle density change is not obvious in our study. We confirm the declining tendencies for amplitude and duration, although within narrower, more specific age-windows than previously. Spindle frequency seems to be higher in females in the oldest age-group. Based on the pattern of our findings, we suggest that HD-EEG, specifically targeting slow and fast spindle ranges and relatively narrow age-ranges would advance the understanding of both adolescent development and the functional relevance of sleep spindles in general.

Theta activity during encoding interacts with NREM sleep oscillations to predict memory generalization

Relatively little is known regarding the interaction between encoding-related neural activity and sleep-based memory consolidation. One suggestion is that a function of encoding-related theta power may be to 'tag' memories for subsequent processing during sleep. This study aimed to extend previous work on the relationships between sleep spindles, slow oscillation-spindle coupling and task-related theta activity with a combined Deese-Roediger-McDermott (DRM) and nap paradigm. This allowed us to examine the influence of task- and sleep-related oscillatory activity on the recognition of both encoded list words and associative theme words. Thirty-three participants (29 females, mean age = 23.2 years) learned and recognised DRM lists separated by either a 2hr wake or sleep period. Mixed-effects modelling revealed the sleep condition endorsed more associative theme words and fewer list words in comparison to the wake group. Encoding related theta power was also found to influence sleep spindle density, and this interaction was predictive of memory outcomes. The influence of encoding-related theta was specific to sleep spindle density, and did not appear to influence the strength of slow oscillation-spindle coupling as it relates to memory outcomes. The finding of interactions between wakeful and sleep oscillatory-related activity in promoting memory and learning has important implications for theoretical models of sleep-based memory consolidation.

P110 The association between sleep spindles and cognitive function in middle-aged and older men: A community-based study

Introduction The association between sleep spindles and cognitive function and the potential confounding influence of obstructive sleep apnea (OSA) remains uncertain. This study examined cross-sectional associations between sleep spindle metrics and cognitive function outcomes in community-dwelling men. Methods Men, Androgen, Inflammation, Lifestyle, Environment, and Stress (MAILES) study participants (n=477) underwent home-based polysomnography between 2010–2011 and completed the inspection time task, trail-making test A (TMT-A) and B (TMT-B), and Fuld object memory evaluation. Frontal spindle metrics derived from sleep electroencephalography included occurrence (total no. of sleep spindle events) and slow (11–13 Hz) and fast (13–16 Hz) spindle density (no./min) during N2 and N3 sleep. Results Men with OSA (any OSA and severe OSA) had significantly impaired sleep spindles (reduced occurrence and densities). In the complete study sample, higher spindle occurrence during N2 sleep was independently associated with faster inspection time (B= -0.44, 95% CI [-0.87, -0.02], p=0.041), whereas higher fast spindle density during N3 sleep was independently associated with worse TMT-B performance (B=20.7, 95% CI [0.55, 40.9], p=0.044). Furthermore, in men with severe OSA (apnea-hypopnea index ≥30/h), higher slow spindle density during N2 sleep was independently associated with worse TMT-A and TMT-B performance, whereas only higher spindle occurrence during N2 sleep was independently associated with worse TMT-A performance (all p<0.05). Discussion Specific spindle metrics during N2 and N3 sleep are independently associated with cognitive function in an unselected population of men and men with undiagnosed severe OSA. The utility of sleep spindles for predicting cognitive dysfunction and decline requires further investigation.

P018 The effects of zopiclone on sleep spindles in obstructive sleep apnea: A randomized placebo-controlled trial

Purpose This study aimed to determine the effects of a standard dose of zopiclone (7.5mg) on sleep spindle activity and to assess if potential changes in sleep spindles correlate with improvements in next-day measures of sleepiness and simulated driving performance in people with obstructive sleep apnoea (OSA). Methods Thirty-one people with OSA completed polysomnography (PSG) at baseline followed by 1-month nightly treatment with 7.5mg zopiclone or placebo according to a double-blind, parallel design (ANZCTRN12613001106729). Participants completed two further PSGs on the first (night1) and final (night30) night of treatment. A 30-min AusEd driving simulator task and a subjective sleepiness questionnaire (Karolinska sleepiness scale, KSS) on each visit were also performed in the morning. Sleep spindle events and spindle frequency activity (SFA, sigma EEG power) were quantified during N2 sleep from all-night EEG recordings. Results Sleep spindle events were consistently higher in both frontal and central EEG sites on night1 and night30 treatment nights in the zopiclone group compared to placebo (e.g. F4 night30 = 346[SEM±28] vs. 239[SEM±27] total # of sleep spindles respectively, p=0.009). Additionally, greater sleep spindle density in the zopiclone group correlated with better next-day simulated driving performance on night1 and night30. No correlations were observed between sleep spindle activity and the KSS. Conclusions Zopiclone is associated with greater sleep spindle activity in OSA compared to placebo, and sleep spindle increases are associated with better driving simulator performance. Thus, hypnotic-induced increases in sleep spindles may help alleviate certain cognitive performance decrements in people with OSA.

Diazepam induced sleep spindle increase correlates with cognitive recovery in a child with epileptic encephalopathy

Background Continuous spike and wave of sleep with encephalopathy (CSWS) is a rare and severe developmental electroclinical epileptic encephalopathy characterized by seizures, abundant sleep activated interictal epileptiform discharges, and cognitive regression or deceleration of expected cognitive growth. The cause of the cognitive symptoms is unknown, and efforts to link epileptiform activity to cognitive function have been unrevealing. Converging lines of evidence implicate thalamocortical circuits in these disorders. Sleep spindles are generated and propagated by the same thalamocortical circuits that can generate spikes and, in healthy sleep, support memory consolidation. As such, sleep spindle deficits may provide a physiologically relevant mechanistic biomarker for cognitive dysfunction in epileptic encephalopathies. Case presentation We describe the longitudinal course of a child with CSWS with initial cognitive regression followed by dramatic cognitive improvement after treatment. Using validated automated detection algorithms, we analyzed electroencephalograms for epileptiform discharges and sleep spindles alongside contemporaneous neuropsychological evaluations over the course of the patient’s disease. We found that sleep spindles increased dramatically with high-dose diazepam treatment, corresponding with marked improvements in cognitive performance. We also found that the sleep spindle rate was anticorrelated to spike rate, consistent with a competitively shared underlying thalamocortical circuitry. Conclusions Epileptic encephalopathies are challenging electroclinical syndromes characterized by combined seizures and a deceleration or regression in cognitive skills over childhood. This report identifies thalamocortical circuit dysfunction in a case of epileptic encephalopathy and motivates future investigations of sleep spindles as a biomarker of cognitive function and a potential therapeutic target in this challenging disease.