Brain white matter damage and its association with neuronal synchrony during sleep.

The restorative function of sleep partly relies on its ability to deeply synchronize cerebral networks to create large slow oscillations observable with EEG. However, whether a brain can properly synchronize and produce a restorative sleep when it undergoes massive and widespread white matter damage is unknown. Here, we answer this question by testing 23 patients with various levels of white matter damage secondary to moderate to severe traumatic brain injuries (ages 18-56; 17 males, six females, 11-39 months post-injury) and compared them to 27 healthy subjects of similar age and sex. We used MRI and diffusion tensor imaging metrics (e.g. fractional anisotropy as well as mean, axial and radial diffusivities) to characterize voxel-wise white matter damage. We measured the following slow wave characteristics for all slow waves detected in N2 and N3 sleep stages: peak-to-peak amplitude, negative-to-positive slope, negative and positive phase durations, oscillation frequency, and slow wave density. Correlation analyses were performed in traumatic brain injury and control participants separately, with age as a covariate. Contrary to our hypotheses, we found that greater white matter damage mainly over the frontal and temporal brain regions was strongly correlated with a pattern of higher neuronal synchrony characterized by slow waves of larger amplitudes and steeper negative-to-positive slopes during non-rapid eye movement sleep. The same pattern of associations with white matter damage was also observed with markers of high homeostatic sleep pressure. More specifically, higher white matter damage was associated with higher slow-wave activity power, as well as with more severe complaints of cognitive fatigue. These associations between white matter damage and sleep were found only in our traumatic brain injured participants, with no such correlation in controls. Our results suggest that, contrary to previous observations in healthy controls, white matter damage does not prevent the expected high cerebral synchrony during sleep. Moreover, our observations challenge the current line of hypotheses that white matter microstructure deterioration reduces cerebral synchrony during sleep. Our results showed that the relationship between white matter and the brain's ability to synchronize during sleep is neither linear nor simple.

Sleep from acute to chronic traumatic brain injury and cognitive outcomes.

STUDY OBJECTIVES: Traumatic brain injuries (TBIs) cause persistent cerebral damage and cognitive deficits. Because sleep may be a critical factor for brain recovery, we characterized the sleep of patients with TBI from early hospitalization to years post-injury and explored the hypothesis that better sleep during hospitalization predicts more favorable long-term cognitive outcomes. METHODS: We tested patients with moderate-to-severe TBI in the hospitalized (n = 11) and chronic (n = 43) stages using full-night polysomnography, with 82% of the hospitalized group being retested years post-injury. Hospitalized patients with severe orthopedic and/or spinal cord injury (n = 14) and healthy participants (n = 36) were tested as controls for the hospitalized and chronic TBI groups, respectively. Groups had similar age and sex and were compared for sleep characteristics, including slow waves and spindles. For patients with TBI, associations between sleep during hospitalization and long-term memory and executive function were assessed. RESULTS: Hospitalized patients with TBI or orthopedic injuries had lower sleep efficiency, higher wake after sleep onset, and lower spindle density than the chronic TBI and healthy control groups, but only hospitalized patients with brain injury had an increased proportion of slow-wave sleep. During hospitalization for TBI, less fragmented sleep, more slow-wave sleep, and higher spindle density were associated to more favorable cognitive outcomes years post-injury, while injury severity markers were not associated with these outcomes. CONCLUSION: These findings highlight the importance of sleep following TBI, as it could be a strong predictor of neurological recovery, either as a promoter or an early marker of cognitive outcomes.

Slow wave activity moderates the association between new learning and traumatic brain injury severity.

STUDY OBJECTIVES: Sleep-wake complaints and difficulties in making new learning are among the most persistent and challenging long-term sequelea following moderate to severe traumatic brain injury (TBI). Yet, it is unclear whether, and to what extent, sleep characteristics during the chronic stage of TBI contribute to sleep-wake and cognitive complaints. We aimed to characterize sleep architecture in chronic moderate to severe TBI adults and assess whether non-rapid eye movement slow wave activity (SWA) is associated to next day performance in episodic memory tasks according to TBI severity. METHODS: Forty-two moderate to severe TBI participants, 12-47 months post-injury, and 38 healthy controls were tested with one night of in-laboratory polysomnography, followed the next morning by questionnaires (sleep quality, fatigue, and sleepiness) and neuropsychological assessment. We used multiple regression analyses to assess the moderator effect of SWA power on TBI severity and next-day memory performance. RESULTS: We found that TBI participants reported worse sleep quality and fatigue, and had worse cognitive performance than controls. No between group differences were found on macro- and micro-architecture of sleep. However, SWA significantly interacted with TBI severity to explain next-day memory performance: higher SWA was more strongly associated to better memory performance in more severe TBI compared to milder TBI. CONCLUSIONS: This study provides evidence that the injured brain is able to produce macro- and micro-architecture of sleep comparable to what is seen in healthy controls. However, with increasing TBI severity, lower non-rapid eye movement SWA power is associated with reduced ability to learn and memorise new information the following day.

Sleep spindles are resilient to extensive white matter deterioration.

Sleep spindles are an essential part of non-rapid eye movement sleep, notably involved in sleep consolidation, cognition, learning and memory. These oscillatory waves depend on an interaction loop between the thalamus and the cortex, which relies on a structural backbone of thalamo-cortical white matter tracts. It is still largely unknown if the brain can properly produce sleep spindles when it underwent extensive white matter deterioration in these tracts, and we hypothesized that it would affect sleep spindle generation and morphology. We tested this hypothesis with chronic moderate to severe traumatic brain injury (n = 23; 30.5 ± 11.1 years old; 17 m/6f), a unique human model of extensive white matter deterioration, and a healthy control group (n = 27; 30.3 ± 13.4 years old; 21m/6f). Sleep spindles were analysed on a full night of polysomnography over the frontal, central and parietal brain regions, and we measured their density, morphology and sigma-band power. White matter deterioration was quantified using diffusion-weighted MRI, with which we performed both whole-brain voxel-wise analysis (Tract-Based Spatial Statistics) and probabilistic tractography (with High Angular Resolution Diffusion Imaging) to target the thalamo-cortical tracts. Group differences were assessed for all variables and correlations were performed separately in each group, corrected for age and multiple comparisons. Surprisingly, although extensive white matter damage across the brain including all thalamo-cortical tracts was evident in the brain-injured group, sleep spindles remained completely undisrupted when compared to a healthy control group. In addition, almost all sleep spindle characteristics were not associated with the degree of white matter deterioration in the brain-injured group, except that more white matter deterioration correlated with lower spindle frequency over the frontal regions. This study highlights the resilience of sleep spindles to the deterioration of all white matter tracts critical to their existence, as they conserve normal density during non-rapid eye movement sleep with mostly unaltered morphology. We show that even with such a severe traumatic event, the brain has the ability to adapt or to withstand alterations in order to conserve normal sleep spindles.

Towards a better understanding of increased sleep duration in the chronic phase of moderate to severe traumatic brain injury: an actigraphy study.

INTRODUCTION: Most adults with moderate to severe traumatic brain injury (TBI) report persistent sleep-wake disturbances. Whether these complaints are either associated with abnormal sleep-wake patterns or can be explained by TBI-related characteristics is unclear. The present study aimed at characterising the subjective and objective sleep-wake patterns in TBI adults by taking into consideration the influence of TBI severity, common comorbidities and psychoactive medication. METHODS: Overall, 34 adults with moderate-severe TBI (one to four years post-injury) were compared to 34 controls. Sleepiness, fatigue, sleep quality, mood, and pain were assessed with questionnaires. A seven day sleep diary and actigraphy was used to document sleep and wake patterns. RESULTS: Compared to controls, TBI participants reported more sleepiness and fatigue, as well as poorer sleep quality. On actigraphy, they had earlier bedtime and longer time spent in bed, but equivalent sleep efficiency during the nighttime episode compared to controls. TBI participants also took more naps and accumulated more time asleep over the 24 h period than controls. These group differences were accentuated when only TBI adults using psychoactive medication were included. More comorbidities, more severe injuries and longer hospital stay were positively correlated with fatigue, sleepiness and sleep duration. CONCLUSIONS: Our results showed that despite complaints regarding sleep and diurnal functioning, TBI survivors have very marginal changes in their objective sleep-wake schedules. Prolonged time spent in bed may reflect an attempt to increase their sleep duration in response to fatigue and sleepiness. TBI adults who use psychoactive medication are those with more evident changes in their sleep-wake schedules.

Reprint of: Efficacy, tolerability, and safety of non-pharmacological therapies for chronic pain: An umbrella review on various CAM approaches.

BACKGROUND: Complementary and alternative medicine (CAM) therapies may be used as a non-pharmacological approach to chronic pain management. While hundreds of trials about individual CAM modality have been conducted, a comprehensive overview of their results is currently lacking for pain clinicians and researchers. AIM: This umbrella review synthesized the quality of meta-analytic evidence supporting the efficacy, tolerability and safety of CAM therapies for the management of chronic pain. MATERIALS & METHODS: MEDLINE, EMBASE, CINAHL, and CENTRAL were searched from October 1991 to November 2016. Reviews of clinical trials (randomized and non-randomized) with meta-analysis investigating the utility of any CAM modality for chronic pain were eligible. Pain relief post-intervention was the main outcome and secondary outcomes included patients' adherence and incidence of adverse effects during CAM protocol. RESULTS: Twenty-six reviews (207 clinical trials, >12,000 participants) about 18 CAM modalities, falling under natural products, mind and body practices or other complementary health approaches were included. Inhaled cannabis, graded motor imagery, and Compound Kushen injection (a form of Chinese medicine) were found the most efficient (with moderate-to-high effect sizes and low heterogeneity) and tolerable (≥80% of adherence to study protocols) for chronic pain relief. When reported, adverse effects related to these CAM were minor. CONCLUSION: Although several CAM were found effective for chronic pain relief, it remains unclear when these modalities are a reasonable choice against or in conjunction with mainstream treatments. In that sense, future research with a clear emphasis on concurrent evaluation of CAM overall efficacy and patient adherence/tolerance is needed.

Efficacy, tolerability, and safety of non-pharmacological therapies for chronic pain: An umbrella review on various CAM approaches.

BACKGROUND: Complementary and alternative medicine (CAM) therapies may be used as a non-pharmacological approach to chronic pain management. While hundreds of trials about individual CAM modality have been conducted, a comprehensive overview of their results is currently lacking for pain clinicians and researchers. AIM: This umbrella review synthesized the quality of meta-analytic evidence supporting the efficacy, tolerability and safety of CAM therapies for the management of chronic pain. MATERIALS & METHODS: MEDLINE, EMBASE, CINAHL, and CENTRAL were searched from October 1991 to November 2016. Reviews of clinical trials (randomized and non-randomized) with meta-analysis investigating the utility of any CAM modality for chronic pain were eligible. Pain relief post-intervention was the main outcome and secondary outcomes included patients' adherence and incidence of adverse effects during CAM protocol. RESULTS: Twenty-six reviews (207 clinical trials, >12,000 participants) about 18 CAM modalities, falling under natural products, mind and body practices or other complementary health approaches were included. Inhaled cannabis, graded motor imagery, and Compound Kushen injection (a form of Chinese medicine) were found the most efficient (with moderate-to-high effect sizes and low heterogeneity) and tolerable (≥80% of adherence to study protocols) for chronic pain relief. When reported, adverse effects related to these CAM were minor. CONCLUSION: Although several CAM were found effective for chronic pain relief, it remains unclear when these modalities are a reasonable choice against or in conjunction with mainstream treatments. In that sense, future research with a clear emphasis on concurrent evaluation of CAM overall efficacy and patient adherence/tolerance is needed.

Individuals with pain need more sleep in the early stage of mild traumatic brain injury.

OBJECTIVE: Hypersomnia is frequently reported after mild traumatic brain injury (mTBI), but its cause(s) remain elusive. This study examined sleep/wake activity after mTBI and its association with pain, a comorbidity often associated with insomnia. METHODS: Actigraphy recording was performed for 7 ± 2 consecutive days in 56 individuals at one month post-mTBI (64% male; 38 ± 12 years), 24 individuals at one year post-mTBI (58% male; 44 ± 11years), and in 20 controls (50% male; 37 ± 12 years). Pain intensity and its effect on quality of life was assessed with a visual analogue scale and the Short Form Health Survey (SF-36) bodily pain subscale. RESULTS: Overall, few differences in sleep/wake patterns were found between mTBI patients and controls. However, higher percentages of mTBI individuals with moderate-to-severe pain were found to require more than eight hours of sleep per day (37% vs11%; p = 0.04) and to be frequent nappers (defined as those who took three or more naps per week) (42% vs 22%; p = 0.04) compared to those with mild or no pain at one month postinjury. Correcting for age and depression, The SF-36 score was found to be a significant predictor of sleep duration exceeding eight hours per day at one month (odds ratio = 0.95; 95% confidence interval = 0.92-0.99; p = 0.01), but not at one year post-mTBI. Pain and increased sleep need (in terms of hours per day or napping frequency) were found to co-exist in as much as 29% of mTBI patients at one month postinjury. CONCLUSION: Pain could be associated with more pronounced sleep need in about one-third of mTBI patients during early recovery. Unalleviated pain, found in more than 60% of mTBI patients, should therefore be looked for in all mTBI patients reporting new onset of sleep disorder, not only in those with insomnia.