"Moldofsky and his colleagues described the presence of an EEG sleep anomaly, a wave form known as alpha-delta sleep, that corresponds with the nonrestorative sleep experienced by fibromyalgia patients [44].
Alpha-delta sleep is thought to intrude upon NREM sleep and cause the patient to awaken feeling unrefreshed and tired. Alpha intrusion has also been reported in other pain disorders, most notably rheumatoid arthritis [22,45]. However, study samples are small and the phenomenon has not been widely replicated in other studies. Several theories regarding the relation between the alpha-delta EEG sleep anomaly and chronic pain syndromes will be discussed later in the paper.
Fibromyalgia shares several clinical symptoms with chronic fatigue syndrome, including non-restorative sleep, musculoskeltal pain, and fatigue. EEG abnormalities have been shown for patients with chronic fatigue syndrome, most notably delayed sleep onset, decreased REM sleep and increased alpha activity during NREM sleep.
Alpha-delta sleep is characterized by 5% to 20% delta waves mixed with large amplitude alpha waves. Alpha-delta sleep was described as occurring early in the evening, and opposite REM sleep in the 90-minute sleep cycle when delta sleep is normally expected. The pattern correlated with reports of “a general feeling of chronic somatic malaise and fatigue. Moldofsky and colleagues proposed that fibromyalgia patients experience a cycle of nonrestorative sleep, in which alpha waves intrude upon NREM sleep. In their initial study, 7 out of 10 fibromyalgia patients showed the alpha-delta pattern of sleep disturbance. The remaining 3, who did not show this disturbance, had negligible delta sleep.
Six healthy individuals were then subjected to an auditory arousal stimulus during NREM sleep that caused the alpha-delta pattern. These healthy individuals subsequently reported musculoskeletal pain and mood disturbance similar to the symptoms reported by patients with fibromyalgia [44]. The mean percent of alpha frequency (intrusions) during NREM and REM sleep was associated with increased pain and decreased energy and mood.
Although alpha-delta sleep may be an indicator of fibromyalgia, and may affect symptoms such as pain and tenderness, it does not seem to be exclusive to this disease. Both morning stiffness [45] and fatigue [22] have been proposed as consequences of the presence of alpha-delta sleep for individuals with RA.
The alpha-delta anomaly has been found to occur in healthy individuals as well. Scheuler et al. reported this anomaly in 6 of 44 healthy people and individuals taking benzodiazepines
Exercise has also been hypothesized to improve sleep quality for individuals with chronic pain conditions. In a small pilot study in 1976, Moldofsky and Scarisbrick were unable to induce musculoskeletal symptoms in long-distance runners using selective stage 4 sleep disruption. In contrast, sedentary individuals developed musculoskeletal symptoms which mimicked fibrositis [73] Individuals who are physically fit have been shown to have more slow wave sleep than unfit individuals [132].
An electroencephalographic pattern of alpha wave intrusion in delta wave sleep (alpha-delta sleep) is observed in some subjects with major depressive disorder. The treatment-resistant symptoms in major depressive disorder, nonrestorative sleep and fatigue, are associated with alpha-delta sleep.
One hundred and fifty subjects were included in this study, of which 75 (50%) were subjects with MDD and the other 75 (50%) were subjects without MDD.
Subjects with major depressive disorder compared to nondepressed subjects had a higher sleep efficiency (83.0±9.6; 78.1±8.2%), shorter rapid eye movement latency (85.0±44.5; 189.9±25.6 min), less slow wave sleep (8.3±3.0; 13.5±6.2%), and greater rapid eye movement (24.7±7.0; 19.2±8.2%), and all of these findings were statistically significant.
Patients with major depressive disorder had higher alpha-delta sleep (23.4±14.2%; 2.3±6.7%, p<0.01) !
Patients with major depressive disorder were categorized into high and low alpha-delta sleep based on percentage of alpha-delta sleep present in slow wave sleep (alpha-delta sleep was present ≥15% or ≤15% of slow wave sleep, respectively). Patients with major depressive disorder with high alpha-delta sleep were at 3.15 greater odds (1.22–8.14; p=0.018) to have excessive daytime sleepiness. !
Ware et al 34 were one of the first to describe alpha intrusions in sleep of patients with depression. They found that alpha intrusion during NREM sleep in depressed patients was “common.” They did not specifically look at alpha intrusion in slow wave or delta sleep, but rather they studied any alpha intrusion in NREM sleep. In addition, they graded the severity of alpha intrusion in NREM sleep on a four point scale: 1=0 to 25 percent of NREM sleep has alpha intrusion; 2=26 to 50 percent alpha intrusion; 3=51 to 75 percent; and 4=76 to 100 percent intrusion. Five out of 12 depressed patients had a rating of 3 or 4 (i.e., alpha intrusion occurred in more than 50% of the NREM sleep).
Conclusion. Patients with major depressive disorder have a higher prevalence of alpha-delta sleep. Alpha-delta sleep is associated with daytime sleepiness in patients with major depressive disorder. Study limitations include the retrospective nature of the project and the fact that the principle investigator, who scored and interpreted alpha intrusion, was not blind to group membership.
alpha-delta sleep, has been found to be related to a complaint of nonrestorative sleep in patients with musculoskeletal pain or fibrositis and nondepressed patients with chronic fatigue
Since alpha-delta sleep is also associated with similar symptoms (i.e., non-restorative sleep and fatigue), treatment aimed at normalizing the alpha intrusion in slow-wave sleep could potentially benefit MDD patients. Sodium oxybate has demonstrated normalization of alpha-delta sleep in patients with fibromyalgia, and this is associated with a significant improvement of pain, fatigue, and subjective sleep. Therefore, elucidating the nature, severity, and correlates of alpha-delta sleep in patients with MDD can have significant diagnostic and therapeutic implications.
A history of SSRI medication use was associated with decreased alpha-delta sleep. This relationship is probably attributable to the effects of SSRIs on MDD disease activity or on the sleep architecture itself. . Knott et al41 demonstrated that acute paroxetine (an SSRI) did not alter the EEG in MDD patients but chronic treatment was associated with significant alterations as shown by diffuse decrease in alpha power and increases in slow (delta and theta) and anterior fast (beta) wave power.
Kluge et al42 found that duloxetine (an SNRI) increases N3 sleep and suppresses REM sleep in patients with major depression.
McClelland et al43,44 studied the acute effects of paroxetine (6 hours after taking it) on EEG in normal subjects, which revealed a reduction in alpha waves and an increase in delta waves.
However, data on the chronic effects of SSRIs/SNRIs on EEG in otherwise healthy subjects is lacking. Therefore, in addition to an affect on disease severity, SSRIs/SNRIs may have an affect on EEG power itself, and thus this may play an important role in decreasing alpha-delta sleep in the subjects with MDD found in our study.
As mentioned above, alpha-delta sleep is thought to be associated with nonrestorative sleep, which, in turn, may result in daytime sleepiness or fatigue. The post-hoc analysis offers some insight if the severity of alpha-delta sleep has any influence on the symptoms of excessive daytime sleepiness. subjects with MDD with high alpha-delta sleep (as defined as ≥15% of delta waves with superimposed alpha) were at 3.15 greater odds to have excessive daytime sleepiness (ESS≥10) compared to those with low alpha-delta sleep.
A possible mechanism (not sure how useful this can be in finding stuff that works) -> https://www.ncbi.nlm...es/PMC4575971/ " Our model shows how alterations in GABAB currents and two thalamic currents, Ih (a hyperpolarization-activated current) and a potassium leak current, transform a circuit that normally produces delta oscillations into one that produces alpha-delta activity.
Sodium oxybate, which reduces alpha-delta sleep in fibromyalgia patients (Moldofsky et al. 2010; Scharf et al. 2003), potentiates GABAB conductances, reduces Ih conductances, and increases potassium conductances" "Our findings suggest that drugs that reduce Ih conductances and/or increase potassium conductances, without necessarily increasing GABAB conductances, might be sufficient to restore delta sleep.
Furthermore, they suggest that delta sleep might be restored by drugs that preferentially target these currents in the thalamus" "Simultaneously increasing GABAB conductances, decreasing Ih conductances, and increasing IKL conductances can restore delta sleep from alpha-delta sleep. In addition, in our model, alpha-delta sleep is abolished when only Ih conductances are reduced or only IKL conductances are increased in HTC cells to the levels used during delta activity. "
"Thus drugs that target only Ih or only IKL in HTC cells, which generate the alpha activity in all our model alpha-delta conditions, might be sufficient to prevent alpha-delta sleep and its deleterious effects" "One approach in the development of drugs for fibromyalgia would be to use an animal model to look for drugs that preferentially alter the conductances of HTC cells." "In addition, Lőrincz et al. (2009) show that applying a muscarinic acetylcholine receptor (mAChR) antagonist directly to the thalamus reduces HTC bursting and firing rate in a dose-dependent manner, and that this not only reduces alpha power in the thalamus in a dose-dependent manner but also reduces alpha power in the cortical EEG."
things that inhibit thalamic neurons? better if by increasing potassium conductivity?
increasing prefrontal cortex activity / gray matter as a mechanism for reducing alpha interference during SWS https://www.frontier...00020/full#B68 "An Underactive Prefrontal Cortex may Permit Ventral Limbic Over-activation, Resulting in Alpha-Delta Sleep"
If there's accessible compounds that can reduce alpha wave activity acutely for the first few hours of sleep that could be a good target, to reduce delta interruption, restore slow wave stage 3/4 sleep, & restore sleep quality / ease fatigue. alongside things that give higher NREM 3/4 duration too (longer duration & less fragmented/interrupted by alpha waves).
Edited by CarlSagan, 16 March 2022 - 03:05 PM.
