Highlights: Polyimide-based flexible microneedle array (PI-MNA) electrodes realize high electrical/mechanical performance and are compatible with wearable wireless recording systems. The normalized electrode–skin interface impedance (EII) of the PI-MNA electrodes reaches 0.98 kΩ cm² at 1 kHz and 1.50 kΩ cm² at 10 Hz, approximately 1/250 of clinical standard electrodes. This is the first report on the clinical study of microneedle electrodes. The PI-MNA electrodes are applied to clinical long-term continuous monitoring for polysomnography. Microneedle array (MNA) electrodes are an effective solution to achieve high-quality surface biopotential recording without the coordination of conductive gel and are thus very suitable for long-term wearable applications. Existing schemes are limited by flexibility, biosafety, and manufacturing costs, which create large barriers for wider applications. Here, we present a novel flexible MNA electrode that can simultaneously achieve flexibility of the substrate to fit a curved body surface, robustness of microneedles to penetrate the skin without fracture, and a simplified process to allow mass production. The compatibility with wearable wireless systems and the short preparation time of the electrodes significantly improves the comfort and convenience of electrophysiological recording. The normalized electrode–skin contact impedance reaches 0.98 kΩ cm² at 1 kHz and 1.50 kΩ cm² at 10 Hz, a record low value compared to previous reports and approximately 1/250 of the standard electrodes. The morphology, biosafety, and electrical/mechanical properties are fully characterized, and wearable recordings with a high signal-to-noise ratio and low motion artifacts are realized. The first reported clinical study of microneedle electrodes for surface electrophysiological monitoring was conducted in tens of healthy and sleep-disordered subjects with 44 nights of recording (over 8 h per night), providing substantial evidence that the electrodes can be leveraged to substitute for clinical standard electrodes.

Insomnia disorder is the most common sleep disorder and has drawn increasing attention. Many studies have shown that hyperarousal plays a key role in the pathophysiology of insomnia disorder. However, the specific brain mechanisms underlying insomnia disorder remain unclear. To elucidate the neuropathophysiology of insomnia disorder, we investigated the brain functional networks of patients with insomnia disorder and healthy controls across the sleep–wake cycle. EEG‐fMRI data from 33 patients with insomnia disorder and 31 well‐matched healthy controls during wakefulness and nonrapid eye movement sleep, including N1, N2 and N3 stages, were analyzed. A medial and anterior thalamic region was selected as the seed considering its role in sleep–wake regulation. The functional connectivity between the thalamic seed and voxels across the brain was calculated. ANOVA with factors “group” and “stage” was performed on thalamus‐based functional connectivity. Correlations between the misperception index and altered functional connectivity were explored. A group‐by‐stage interaction was observed at widespread cortical regions. Regarding the main effect of group, patients with insomnia disorder demonstrated decreased thalamic connectivity with the left amygdala, parahippocampal gyrus, putamen, pallidum and hippocampus across wakefulness and all three nonrapid eye movement sleep stages. The thalamic connectivity in the subcortical cluster and the right temporal cluster in N1 was significantly correlated with the misperception index. This study demonstrated the brain functional basis in insomnia disorder and illustrated its relationship with sleep misperception, shedding new light on the brain mechanisms of insomnia disorder and indicating potential therapeutic targets for its treatment.

Previous studies have documented that heightened impulsivity likely contributes to the development and maintenance of alcohol use disorders. However, there is still a lack of studies that comprehensively detected the brain changes associated with abnormal impulsivity in alcohol addicts. This study was designed to investigate the alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. Brain structural and functional magnetic resonance imaging data as well as impulsive behavior data were collected from 20 alcohol dependent patients and 20 age- and sex-matched healthy controls respectively. Voxel-based morphometry was used to investigate the differences of grey matter volume, and tract-based spatial statistics was used to detect abnormal white matter regions between alcohol dependent patients and healthy controls. The alterations in resting-state functional connectivity in alcohol dependent patients were examined using selected brain areas with gray matter deficits as seed regions. Compared with healthy controls, alcohol dependent patients had significantly reduced gray matter volume in the mesocorticolimbic system including the dorsal posterior cingulate cortex, the dorsal anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex and the putamen, decreased fractional anisotropy in the regions connecting the damaged grey matter areas driven by higher radial diffusivity value in the same areas and decreased resting-state functional connectivity within the reward network. Moreover, the gray matter volume of the left medial prefrontal cortex exhibited negative correlations with various impulse indices. These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity.

Objective sleep duration has been linked to insomnia severity. However, cognitive functions of insomniacs with different sleep duration have been seldom addressed. Brain-derived neurotrophic factor (BDNF) has an important role in cognitive function and has been linked to clinical insomnia recently. The present study aimed to evaluate the comprehensive cognitive functions in primary insomniacs with different objective sleep durations, and further examine the involvement of peripheral BDNF. Fifty-seven insomniacs were subdivided into short sleep duration (SSD, sleep time < 6h) group and normal sleep duration (NSD, sleep time ≥ 6h) group based on polysomnography data. Twenty-nine healthy controls (HC) were matched on age, gender and education. Cognitive function was assessed using a comprehensive and sensitive neuropsychological test battery. Both objective and subjective insomnia status were estimated. Serum BDNF level was measured using enzyme-linked immune sorbent assay. Compared to HC, the SSD group showed impaired neuropsychological performances in spatial span, brief visuospatial memory test, fluency, managing emotions and continuous performance tests. In contrast, NSD had bad performance only in brief visuospatial memory test and continuous performance tests, and relatively better than SSD group in the latter test. SSD insomniacs but not NSD had decreased BDNF levels compared to HC, and neuropsychological performance was positively correlated with BDNF levels only in SSD group. Primary insomnia was associated with impaired neuropsychological performance, and the impairment might be related to decreased objective sleep duration. In addition, decreased peripheral BDNF might mediate the impaired cognitive functions of insomniacs with SSD.

Positron emission tomography – computed tomography (PET-CT) research has shown that sleep discrepancy recorded by self-report and polysomnography (PSG) may be related to the altered metabolic rate of the anterior insula (aINS) during non-rapid eye movement (NREM) sleep in patients with insomnia disorder. We aim to explore the functional connectivity of aINS across wake and NREM sleep in the patients and to reveal the association between aINS connectivity and sleep discrepancy. Patients with insomnia disorder (n = 33) and healthy controls (n = 31) underwent simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) during nighttime sleep, and aINS-based connectivity was calculated across wake and NREM sleep. A linear mixed-effects model was used to assess the main effect of group and group-by-stage (wake, NREM stages 1–3) interaction effect on aINS connectivity. Similar mixed models were used to assess the potential correlation between aINS connectivity and the sleep misperception index (MI). A significant group-by-stage interaction effect on aINS-based connectivity was observed in the bilateral frontal gyrus, right inferior temporal gyrus, bilateral middle occipital gyrus and right postcentral gyrus (p < 0.05, corrected). There was also a significant group-by-MI interaction effect on aINS connectivity with the putamen and thalamus during wakefulness (p < 0.05 corrected); MI was significantly associated with aINS–putamen/thalamus connectivity in the control group, whereas the association was weak or even nonsignificant in the patient group. There was no significant main effect of group. The waking activity of a neural pathway containing the aINS, putamen, and thalamus may underlie sleep perception, potentially providing important perspectives to reveal complex mechanisms of sleep discrepancy between self-report and PSG.