Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia

Neurofeedback training builds upon the simple concept of instrumental conditioning, i.e. behaviour that is rewarded is more likely to reoccur, an effect Thorndike referred to as the ‘law of effect. In the case of neurofeedback, information about specific electroencephalographic activity is fed back to the participant who is rewarded whenever the desired electroencephalography pattern is generated. If some kind of hyperarousal needs to be addressed, the neurofeedback community considers sensorimotor rhythm neurofeedback as the gold standard. Earlier treatment approaches using sensorimotor-rhythm neurofeedback indicated that training to increase 1215 Hz sensorimotor rhythm over the sensorimotor cortex during wakefulness could reduce attention-deficit/hyperactivity disorder and epilepsy symptoms and even improve sleep quality by enhancing sleep spindle activity (lying in the same frequency range). In the present study we sought to critically test whether earlier findings on the positive effect of sensorimotor rhythm neurofeedback on sleep quality and memory could also be replicated in a double-blind placebo-controlled study on 25 patients with insomnia. Patients spent nine polysomnography nights and 12 sessions of neurofeedback and 12 sessions of placebo-feedback training (sham) in our laboratory. Crucially, we found both neurofeedback and placebo feedback to be equally effective as reflected in subjective measures of sleep complaints suggesting that the observed improvements were due to unspecific factors such as experiencing trust and receiving care and empathy from experimenters. In addition, these improvements were not reflected in objective electroencephalographic-derived measures of sleep quality. Furthermore, objective electroencephalographic measures that potentially reflected mechanisms underlying the efficacy of neurofeedback such as spectral electroencephalographic measures and sleep spindle parameters remained unchanged following 12 training sessions. A stratification into ‘true insomnia patients and ‘insomnia misperceivers (subjective, but no objective sleep problems) did not alter the results. Based on this comprehensive and well-controlled study, we conclude that for the treatment of primary insomnia, neurofeedback does not have a specific efficacy beyond unspecific placebo effects. Importantly, we do not find an advantage of neurofeedback over placebo feedback, therefore it cannot be recommended as an alternative to cognitive behavioural therapy for insomnia, the current (non-pharmacological) standard-of-care treatment. In addition, our study may foster a critical discussion that generally questions the effectiveness of neurofeedback, and emphasizes the importance of demonstrating neurofeedback efficacy in other study samples and disorders using truly placebo and double-blind controlled trials.(VLID)192045

Sleep Spindles & Cortical Up States / Individual baseline memory performance and its significance for sleep-dependent memory consolidation

Today, there is little doubt concerning the significance of sleep for memory consolidation. Some studies have suggested, however, that overnight memory consolidation as well as their underpinning neural mechanisms might be modulated by general cognitive abilities. In this paper, we used a more specific trait measure of declarative word-pair encoding efficiency, namely “baseline memory performance (BMP).” We explored its relation to consolidation and stabilization of declarative memories overnight as well as its relationship to sleep mechanisms. We included healthy subjects and insomnia patients from two studies with slightly differing demands on declarative memory. In the first study, an insomnia sample (N=21) performed a declarative word-pair association task with pre- and post-sleep retrieval sessions and recorded 8 hr of nocturnal sleep following learning. In the second study, insomnia (N=24) as well as sex-and-age-matched control (N=29) subjects underwent a similar task but with an additional interference and time delay manipulation. Based on their encoding efficiency in the evening, all three study samples were split into good (BMP+) and moderate (BMP) learners. Although not each subsample reached statistical significance, we observed across all three samples a pattern of only BMP forgetting overnight and BMP+ showing enhanced activity and density of sleep spindles. Our findings suggest that independent of the exact study design and subjective sleep complaint exclusively participants with high BMP seem to be able to eliminate forgetting over sleep which may be related to stronger “offline” replay.(VLID)192048

Susceptibility to Declarative Memory Interference is Pronounced in Primary Insomnia

<div><p>Sleep has been shown to stabilize memory traces and to protect against competing interference in both the procedural and declarative memory domain. Here, we focused on an interference learning paradigm by testing patients with primary insomnia (N = 27) and healthy control subjects (N = 21). In two separate experimental nights with full polysomnography it was revealed that after morning interference procedural memory performance (using a finger tapping task) was not impaired in insomnia patients while declarative memory (word pair association) was decreased following interference. More specifically, we demonstrate robust associations of central sleep spindles (in N3) with motor memory susceptibility to interference as well as (cortically more widespread) fast spindle associations with declarative memory susceptibility. In general the results suggest that insufficient sleep quality does not necessarily show up in worse overnight consolidation in insomnia but may only become evident (in the declarative memory domain) when interference is imposed.</p> </div

Overnight memory change (procedural learning) and sleep spindles.

<p>Correlation between procedural (FTT) performance change across interference (OMC 2 = overnight memory change 2; MEM-SUSCEPTIBILITY – MEM_ENCODING) and slow spindle activity (over central electrode C4) in N3 sleep separated for controls (solid regression line) and insomnia patients (dashed regression line). Note that all subjects were performing the FTT using the non-dominant (left) hand.</p

Sleep parameters for healthy controls and primary insomnia patients separated for both experimental nights (finger tapping task, FTT; declarative word pair task, WORDS).

<p>Values are means ± standard deviations (SD). R, rapid eye movement; N1, stage N1; N2, stage N2; N3, stage N3;</p>*<p>p<0.05,</p>**<p>p<0.01.</p

Declarative overnight memory change after interference.

<p>(A) Fast spindle activity (N2 sleep) at frontal recording site F3 is positively related to overnight memory change 2, that is from initial learning (MEM-ENCODING) to post-interference testing (MEM-SUSCEPTIBILITY) in insomnia patients (dashed line). <i>(B)</i> Relationship between overnight memory change 2 and number of awakenings. Note that frequent awakening is related to more pronounced forgetting after interference learning in insomnia patients (dashed regression line).</p

Word-pair-task results.

<p>Declarative verbal memory scores from MEM-ENCODING, subsequent morning recall (MEM-CONSOLIDATION), interference learning (INTERFERENCE), morning recall after interference (MEM-SUSCEPTIBILITY) and follow up (FOLLOW-UP; only a subgroup was tested). Bars represent means ± standard errors. Significant results are indicated by asterisks. **p<0.01. Note that only insomnia patients show significant forgetting after interference learning.</p

Experimental design.

<p>All subjects slept three nights in the sleep laboratory. Whereas the first night was only used for screening and adaptation purposes, nights 2 and 3 served as experimental nights (EXPERIMENTAL NIGHT). Preceding each EXPERIMENTAL NIGHT, subjects either learned (MEMORY ENCODING)the finger tapping task (FTT) or the declarative memory task (WORDS). Note that the order of the tasks were counterbalanced within subjects. In the morning (for either task) a cued recall testing for overnight memory consolidation (MEM-CONSOLIDATION) was followed by an interfering learning session (INTERFERENCE). Thereafter, participants were retested for the initial learning material from the previous day (MEM-SUCEPTIBILITY). A Follow up testing session was done in a subgroup of the study population to control for long-term effects (FOLLOW-UP).</p

Correlation coefficients between memory change scores and sleep parameters.

<p>OMC1 = overnight memory change 1 (MEM-CONSOLIDATION – MEM-ENCODING); OMC2 = overnight memory change 2 (MEM-SUSCEPTIBILITY – MEM-ENCODING); SEFF = sleep efficiency; SOL = sleep onset latency; WASO = wake after sleep onset; NOA = number of awakenings; N2 = stage 2 sleep; N3 = slow-wave sleep; R = rapid eye movement sleep; SpA = spindle activity. (*)p<0.1, *p<0.05, **p<0.01. Note that only representative electrodes are provided for SpA (FTT: C4, WORD: F3), for additional details please refer to the supplementary material.</p

Finger-tapping results.

<p>Bars represent the mean number of correct three element chunks (± standard errors) during MEM-ENCODING, pre-interference (MEM-CONSOLIDATION), at INTERFERENCE, at post-interference (MEM-SUSCEPTIBILITY) and at FOLLOW-UP. Significant results are indicated by asterisks. *p<0.01; (*), p<0.1. Note that a subgroup (N = 28) was also tested for long-term retention (FOLLOW-UP) and that there are no performance differences between insomnia patients and the control group.</p