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.

Sleep Power Spectral Density and Spindles in PTSD and Their Relationship to Symptom Severity

Sleep disturbances are common in post-traumatic stress disorder (PTSD), although which sleep microarchitectural characteristics reliably classify those with and without PTSD remains equivocal. Here, we investigated sleep microarchitectural differences (i.e., spectral power, spindle activity) in trauma-exposed individuals that met (n = 45) or did not meet (n = 52) criteria for PTSD and how these differences relate to post-traumatic and related psychopathological symptoms. Using ecologically-relevant home sleep polysomnography recordings, we show that individuals with PTSD exhibit decreased beta spectral power during NREM sleep and increased fast sleep spindle peak frequencies. Contrary to prior reports, spectral power in the beta frequency range (20.31–29.88 Hz) was associated with reduced PTSD symptoms, reduced depression, anxiety and stress and greater subjective ability to regulate emotions. Increased fast frequency spindle activity was not associated with individual differences in psychopathology. Our findings may suggest an adaptive role for beta power during sleep in individuals exposed to a trauma, potentially conferring resilience. Further, we add to a growing body of evidence that spindle activity may be an important biomarker for studying PTSD pathophysiology.

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.

Questionnaire measures of adult attachment correlate with frontal hemispheric asymmetry in sleep spindle activity

Introduction: Attachment anxiety and neuroticism were proposed to be associated with relative right frontal neural activity. Since sleep spindles are argued to reflect enhanced offline neuroplasticity, higher spindle activity measured over the right frontal areas relative to the corresponding left frontal ones could index higher attachment anxiety and neuroticism.Methods: 34 healthy subjects (male = 19; Mage = 31.64; SDage = 9.5) were enrolled in our preliminary study. Second night EEG/polysomnography records and questionnaire measures of personality (Zuckermann-Kuhlman Personality Questionnaire) and adult attachment (Relationship Scales Questionnaire) were collected. Frontal slow sleep spindles were measured by the Individual Adjustment Method (IAM), whereas hemispheric asymmetry indexes of spindle occurrence rate, duration and amplitude were derived as normalized left-right differences (electrode pairs: Fp1-Fp2, F3-F4 and F7-F8).Results: Relative right lateralization of frontolateral and frontopolar slow sleep spindle density and mid-frontal slow spindle duration were associated with attachment anxiety, but spindle lateralization was less closely related to neuroticism. The relationships between frontal slow spindle laterality and attachment anxiety remained statistically significant even after controlling for the effect of neuroticism. The attachment “relationship” dimension (need for close relationships) was related to relative left dominance of frontal slow spindle activation, whereas attachment independence was not correlated with frontal slow spindle lateralization.Conclusion: Right frontal lateralization of slow sleep spindle activity can potentially serve as a marker for attachment anxiety.

Influence of Intervertebral Fixation and Segmental Thrust Level on Immediate Post-Spinal Manipulation Trunk Muscle Spindle Response in an Animal Model

Objective: To characterize the effect of unilateral (single and two-level) lumbar facet/zygapophysial joint fixation on paraspinal muscle spindle activity immediately following L4 or L6 high velocity low amplitude spinal manipulation (HVLA-SM) delivered at various thrust durations. Methods: Secondary analysis of immediate (≤2 s) post-HVLA-SM trunk muscle spindle response from two studies involving anesthetized adult cats (n = 39; 2.3–6.0 kg) with either a unilateral single (L5/6) or two-level (L5/6 and L6/7) facet joint fixation. All facet fixations were contralateral to L6 dorsal root recordings. HVLA-SM was delivered to the spinous process in a posterior-to-anterior direction using a feedback motor with a peak thrust magnitude of 55% of average cat body weight and thrust durations of 75, 100, 150, and 250 ms. Time to 1st action potential and spindle activity during 1 and 2 s post-HVLA-SM comparisons were made between facet joint fixation conditions and HVLA-SM segmental thrust levels. Results: Neither two-level facet joint fixation, nor HVLA-SM segmental level significantly altered immediate post-HVLA-SM spindle discharge at tested thrust durations (FDR > 0.05). Conclusions: Two-level facet joint fixation failed to alter immediate (≤2 s) post-HVLA-SM spindle discharge when compared to single-level facet joint fixation at any thrust duration. Segmental thrust level did not alter immediate post-HVLA-SM spindle response in two-level facet joint fixation preparations.

Sleep spindle dynamics suggest over-consolidation in post-traumatic stress disorder

Devastating and persisting traumatic memories are a central symptom of post-traumatic stress disorder (PTSD). Sleep problems are highly co-occurrent with PTSD and intertwined with its etiology. Notably, sleep hosts memory consolidation processes, supported by sleep spindles (11-16 Hz). Here we assess the hypothesis that intrusive memory symptoms in PTSD may arise from excessive memory consolidation, reflected in exaggerated spindling. We use a newly developed spindle detection method, entailing minimal assumptions regarding spindle phenotype, to assess spindle activity in PTSD patients and traumatized controls (n=2x14, matched on gender). Our results show increased spindle activity in PTSD, which positively correlates with daytime intrusive memory symptoms. Together, these findings provide a putative mechanism through which profound sleep disturbance in PTSD may contribute to memory problems. Due to its uniform and unbiased approach, the new, minimal assumption spindle detection method seems a promising tool to detect aberrant spindling in psychiatric disorders.

Ongoing neural oscillations predict the post-stimulus outcome of closed loop auditory stimulation during slow-wave sleep.

The large slow oscillation (SO, 0.5-2Hz) that characterises slow-wave sleep is crucial to memory consolidation and other physiological functions. Manipulating slow oscillations can enhance sleep and memory, as well as benefitting the immune system. Closed-loop auditory stimulation (CLAS) has been demonstrated to increase the SO amplitude and to boost fast sleep spindle activity (11-16Hz). Nevertheless, not all such stimuli are effective in evoking SOs, even if they are precisely phase-locked. Here, we studied whether it is possible to use ongoing activity patterns to determine which oscillations to stimulate in order to effectively enhance SOs or SO-locked spindle activity. To this end, we trained classifiers using the morphological characteristics of the ongoing SO, as measured by electroencephalography (EEG), to predict whether stimulation would lead to a benefit in terms of the resulting SO and spindle amplitude. Separate classifiers were trained using trials from spontaneous control and stimulated datasets, and we evaluated their performance by applying them to held-out data both within and across conditions. We were able to predict both when large SOs will occur spontaneously, and whether a phase-locked auditory click will effectively enlarge them with an accuracy of ~70%. We were also able to predict when stimulation would elicit spindle activity with an accuracy of ~60%. Finally, we evaluate the importance of the various SO features used to make these predictions. Our results offer new insight into SO and spindle dynamics and provide a new method for online optimisation of stimulation.