Detection of subclinical epileptiform discharges in Alzheimer's disease using long-term outpatient EEG monitoring.

BACKGROUND: In patients with Alzheimer's disease (AD) without clinical seizures, up to half have epileptiform discharges on long-term in-patient electroencephalography (EEG) recordings. Long-term in-patient monitoring is obtrusive, and expensive as compared to outpatient monitoring. No studies have so far investigated if long-term outpatient EEG monitoring is able to identify epileptiform discharges in AD. Our aim is to investigate if epileptiform discharges as measured with ear-EEG are more common in patients with AD compared to healthy elderly controls (HC). METHODS: In this longitudinal observational study, 24 patients with mild to moderate AD and 15 age-matched HC were included in the analysis. Patients with AD underwent up to three ear-EEG recordings, each lasting up to two days, within 6 months. RESULTS: The first recording was defined as the baseline recording. At baseline, epileptiform discharges were detected in 75.0% of patients with AD and in 46.7% of HC (p-value = 0.073). The spike frequency (spikes or sharp waves/24 h) was significantly higher in patients with AD as compared to HC with a risk ratio of 2.90 (CI: 1.77-5.01, p < 0.001). Most patients with AD (91.7%) showed epileptiform discharges when combining all ear-EEG recordings. CONCLUSIONS: Long-term ear-EEG monitoring detects epileptiform discharges in most patients with AD with a three-fold increased spike frequency compared to HC, which most likely originates from the temporal lobes. Since most patients showed epileptiform discharges with multiple recordings, elevated spike frequency should be considered a marker of hyperexcitability in AD.

Subclinical Epileptiform Activity in Dementia with Lewy Bodies.

BACKGROUND: Patients with dementia with Lewy bodies (DLB) have a higher probability of seizures than in normal aging and in other types of neurodegenerative disorders. Depositions of α-synuclein, a pathological hallmark of DLB, can induce network excitability, which can escalate into seizure activity. Indicator of seizures are epileptiform discharges as observed using electroencephalography (EEG). However, no studies have so far investigated the occurrence of interictal epileptiform discharges (IED) in patients with DLB. OBJECTIVES: To investigate if IED as measured with ear-EEG occurs with a higher frequency in patients with DLB compared to healthy controls (HC). METHODS: In this longitudinal observational exploratory study, 10 patients with DLB and 15 HC were included in the analysis. Patients with DLB underwent up to three ear-EEG recordings, each lasting up to 2 days, over a period of 6 months. RESULTS: At baseline, IED were detected in 80% of patients with DLB and in 46.7% of HC. The spike frequency (spikes or sharp waves/24 hours) was significantly higher in patients with DLB as compared to HC with a risk ratio of 2.52 (CI, 1.42-4.61; P-value = 0.001). Most IED occurred at night. CONCLUSIONS: Long-term outpatient ear-EEG monitoring detects IED in most patients with DLB with an increased spike frequency compared to HC. This study extends the spectrum of neurodegenerative disorders in which epileptiform discharges occurs at an elevated frequency. It is possible that epileptiform discharges are, therefore, a consequence of neurodegeneration. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Long-term ear-EEG monitoring of sleep - A case study during shift work.

The interest in sleep as a potential clinical biomarker is growing, but the standard method of sleep assessment, polysomnography, is expensive, time consuming, and requires a lot of expert assistance for both set-up and interpretation. To make sleep analysis more available both in research and in the clinic, there is a need for a reliable wearable device for sleep staging. In this case study, we test ear-electroencephalography. A wearable, where electrodes are placed in the outer ear, as a platform for longitudinal at-home recording of sleep. We explore the usability of the ear-electroencephalography in a shift work case with alternating sleep conditions. We find the ear-electroencephalography platform to be reliable both in terms of showing substantial agreement to polysomnography after long-time use (with an overall agreement, using Cohen's kappa, of 0.72) and by being unobtrusive enough to wear during night shift conditions. We find that fractions of non-rapid eye movement sleep and transition probability between sleep stages show great potential as sleep metrics when exploring quantitative differences in sleep architecture between shifting sleep conditions. This study shows that the ear-electroencephalography platform holds great potential as a reliable wearable for quantifying sleep "in the wild", pushing this technology further towards clinical adaptation.

Real-Time Decoding of Attentional States Using Closed-Loop EEG Neurofeedback.

Sustained attention is a cognitive ability to maintain task focus over extended periods of time (Mackworth, 1948; Chun, Golomb, & Turk-Browne, 2011). In this study, scalp electroencephalography (EEG) signals were processed in real time using a 32 dry-electrode system during a sustained visual attention task. An attention training paradigm was implemented, as designed in DeBettencourt, Cohen, Lee, Norman, and Turk-Browne (2015) in which the composition of a sequence of blended images is updated based on the participant's decoded attentional level to a primed image category. It was hypothesized that a single neurofeedback training session would improve sustained attention abilities. Twenty-two participants were trained on a single neurofeedback session with behavioral pretraining and posttraining sessions within three consecutive days. Half of the participants functioned as controls in a double-blinded design and received sham neurofeedback. During the neurofeedback session, attentional states to primed categories were decoded in real time and used to provide a continuous feedback signal customized to each participant in a closed-loop approach. We report a mean classifier decoding error rate of 34.3% (chance = 50%). Within the neurofeedback group, there was a greater level of task-relevant attentional information decoded in the participant's brain before making a correct behavioral response than before an incorrect response. This effect was not visible in the control group (interaction p=7.23e-4), which strongly indicates that we were able to achieve a meaningful measure of subjective attentional state in real time and control participants' behavior during the neurofeedback session. We do not provide conclusive evidence whether the single neurofeedback session per se provided lasting effects in sustained attention abilities. We developed a portable EEG neurofeedback system capable of decoding attentional states and predicting behavioral choices in the attention task at hand. The neurofeedback code framework is Python based and open source, and it allows users to actively engage in the development of neurofeedback tools for scientific and translational use.

Wearables in real life: A qualitative study of experiences of people with epilepsy who use home seizure monitoring devices.

OBJECTIVE: To explore the experiences of people with epilepsy using wearables for home seizure monitoring. METHODS: Nine people with epilepsy participated in eighteen semistructured individual interviews before and after home monitoring with wearable seizure monitoring equipment. An open-ended interview guide was used to encourage the participants to elaborate on their thoughts and experiences. Interviews were analyzed using a three-level process inspired by the philosopher Max van Manen. RESULTS: The overall findings illustrate that patients experienced being placed in the spotlight when wearing wearables. The meaning of being in this spotlight is reflected in three themes: Becoming vulnerable through exposure, Standing alone while being with others, and Having a renewed life situation. The analysis and interpretation showed that although the participants expressed readiness to use the wearables, they were less willing to do so after a few days of monitoring. The visibility of the devices influenced how they experienced themselves and were perceived by others. CONCLUSION: For people with epilepsy, wearables are more than just technical tools; they have a significant existential impact on everyday life. Wearables spotlight the epilepsy condition, and this causes people with epilepsy to experience an existential disruption, as they experience being exposed and vulnerable. This results in a renewed way of perceiving oneself. Nevertheless, wearables also validate epilepsy symptoms, thereby reducing the uncertainty related to epilepsy.

EEG Headset Evaluation for Detection of Single-Trial Movement Intention for Brain-Computer Interfaces.

Brain-computer interfaces (BCIs) can be used in neurorehabilitation; however, the literature about transferring the technology to rehabilitation clinics is limited. A key component of a BCI is the headset, for which several options are available. The aim of this study was to test four commercially available headsets' ability to record and classify movement intentions (movement-related cortical potentials-MRCPs). Twelve healthy participants performed 100 movements, while continuous EEG was recorded from the headsets on two different days to establish the reliability of the measures: classification accuracies of single-trials, number of rejected epochs, and signal-to-noise ratio. MRCPs could be recorded with the headsets covering the motor cortex, and they obtained the best classification accuracies (73%-77%). The reliability was moderate to good for the best headset (a gel-based headset covering the motor cortex). The results demonstrate that, among the evaluated headsets, reliable recordings of MRCPs require channels located close to the motor cortex and potentially a gel-based headset.

EEG discrimination of perceptually similar tastes.

Perceptually similar stimuli, despite not being consciously distinguishable, may result in distinct cortical brain activations. Hypothesizing that perceptually similar tastes are discriminable by electroencephalography (EEG), we recorded 22 human participants' response to equally intense sweet-tasting stimuli: caloric sucrose, low-caloric aspartame, and a low-caloric mixture of aspartame and acesulfame K. Time-resolved multivariate pattern analysis of the 128-channel EEG was used to discriminate the taste responses at single-trial level. Supplementing the EEG study, we also performed a behavioral study to assess the participants' perceptual ability to discriminate the taste stimuli by a triangle test of all three taste pair combinations. The three taste stimuli were found to be perceptually similar or identical in the behavioral study, yet discriminable from 0.08 to 0.18 s by EEG analysis. Comparing the participants' responses in the EEG and behavioral study, we found that brain responses to perceptually similar tastes are discriminable, and we also found evidence suggesting that perceptually identical tastes are discriminable by the brain. Moreover, discriminability of brain responses was related to individual participants' perceptual ability to discriminate the tastes. We did not observe a relation between brain response discriminability and calorie content of the taste stimuli. Thus, besides demonstrating discriminability of perceptually similar and identical tastes with EEG, we also provide the first proof of a functional relation between brain response and perception of taste stimuli at individual level.

Bruch's membrane allows unhindered passage of up to 2 µm latex beads in an in vivo porcine model.

PURPOSE: It has been proposed that changes in the permeability of Bruch's membrane play a role in the pathogenesis of age-related macular degeneration (AMD). This paper investigates, in an in vivo porcine model, the migration of fluorescent latex beads across the Bruch's membrane after subretinal injection. METHODS: Forty-one healthy eyes of 33 three-month-old domestic pigs received a subretinal injection of 0.5, 1.0, 2.0, or 4.0 µm fluorescent latex beads. Between three hours and five weeks after injection evaluations were performed with fundus photographs and histology. Fluorescent beads were identified in unstained histologic sections using the rhodamine filter with the light microscope. RESULTS: The fluorescent latex beads relocated from the subretinal space. Intact beads up to 2.0 µm were found in the choroid, sclera, and extrascleral space. The smaller beads were also found inside choroidal and extrascleral blood vessels. In contrast, the larger beads of 4.0 µm did not pass the Bruch's membrane. CONCLUSION: Subretinally implanted beads up to 2.0 µm pass the Bruch's membrane intact and cross the blood-ocular barrier. The intact beads are found in the choroid, sclera and inside blood vessels. The results give reason to consider the role of subretinal clearance and passage of Bruch's membrane in the development of AMD.

Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease: effect of l-DOPA treatment and changes in levodopa-induced dyskinesia.

Levodopa (l-DOPA, l-3,4-dihydroxyphenylalanine) is the most effective drug in the symptomatic treatment of Parkinson's disease (PD), but chronic use initiates a maladaptive process leading to l-DOPA-induced dyskinesia (LID). Risk factors for early onset LID include younger age, more severe disease at baseline and higher daily l-DOPA dose, but biomarkers to predict the risk of motor complications are not yet available. Here, we investigated whether CSF levels of catecholamines and its metabolites are altered in PD patients with LID [PD-LID, n = 8)] as compared to non-dyskinetic PD patients receiving l-DOPA (PD-L, n = 6), or not receiving l-DOPA (PD-N, n = 7) as well as non-PD controls (n = 16). PD patients were clinically assessed using the Unified Parkinson's Disease Rating Scale and Unified Dyskinesia Rating Scale and CSF was collected after overnight fasting and 1-2 h after oral intake of l-DOPA or other anti-Parkinson medication. CSF catecholamines and its metabolites were analyzed by HPLC with electrochemical detection. We observed (i) decreased levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid in PD patients not receiving l-DOPA (ii) higher dopamine (DA) levels in PD-LID as compared to controls (iii) higher DA/l-DOPA and lower DOPAC/DA ratio's in PD-LID as compared to PD-L and (iv) an age-dependent increase of DA and decrease of DOPAC/DA ratio in controls. These results suggest increased DA release from non-DA cells and deficient DA re-uptake in PD-LID. Monitoring DA and DOPAC in CSF of l-DOPA-treated PD patients may help identify patients at risk of developing LID.

Repeated subretinal surgery and removal of subretinal decalin is well tolerated - evidence from a porcine model.

PURPOSE: Subretinal perfluorocarbon liquid (PFCL) is a serious complication that can occur after retinal detachment repair. It is possible to remove the PFCL surgically, but retinal damage related to the procedure is unknown. Also, increasing interest in subretinal treatment makes it relevant to examine the functional and morphological consequences of repeated subretinal manipulation. We hypothesized that PFCL in a porcine model can be injected in the subretinal space and removed with minimal effect on retinal structure and function. METHODS: The left eyes of ten healthy three-month-old female domestic pigs were included. Multifocal electroretinograms (mfERG) were recorded before surgery. Following vitrectomy, a PFCL bleb (decalin) was injected subretinally using a 41G cannula. After 14 days the decalin was removed through a 41G cannula in combination with a 2 ml syringe and an intermediate flexible tube. Two weeks after removal, a control mfERG was recorded, the pigs were enucleated and sacrificed and eyes were examined histologically. All statistics were carried out with a paired t-test in SAS Enterprise Guide 7.1® (SAS Institute Inc., Cary, NC, USA). RESULTS: There was no significant difference in mfERG amplitude ratio (left/right eye) between baseline and recordings two weeks after removal of decalin (P1 (M = 0.26, SD = 0.80, p = 0.39), second order kernel (M = -0.18, SD = 0.86, p = 0.57), Direct Response (M = 0.39, SD = 0.61, p = 0.12) or Induced Component (M = -0.03, SD = 0.40, p = 0.80)). Histologically, the photoreceptor outer segments were minimally affected. Otherwise the retina was normal 14 days after removal of decalin. In four pigs the subretinal decalin displaced inferiorly and was no longer accessible for removal. CONCLUSION: Subretinal decalin can be removed within 14 days without lasting retinal damage. Decalin is a heavy liquid where the risk of displacement is high. Future studies using PFCLs to control duration of an experimental retinal separation should focus on PFCLs that are isodense to the vitreus body.

Can DMCO Detect Visual Field Loss in Neurological Patients? A Secondary Validation Study.

Unrecognized visual field loss is caused by a range of blinding eye conditions as well as serious brain diseases. The commonest cause of asymptomatic visual field loss is glaucoma. No screening tools have been proven cost-effective. Damato Multifixation Campimetry Online (DMCO), an inexpensive online test, has been evaluated as a future cost-beneficial tool to detect glaucoma. To further validate DMCO, this study aimed to test DMCO in a preselected population with neurological visual field loss. METHODS: The study design was an evaluation of a diagnostic test. Patients were included if they had undergone surgery for epilepsy during 2011-2014, resulting in visual field loss. They were examined with DMCO and results were compared with those obtained with the Humphrey Field Analyzer (30:2 SITA-Fast). DMCO sensitivity and specificity were estimated with 95% confidence intervals. RESULTS: The cohort comprised 40 patients (25 female and 15 male) with a mean age of 39 years (range 17-60 years). The mean visual acuity was >1.0 and all eyes had an intraocular pressure <21 mm Hg. Sensitivity and specificity of DMCO compared to the reference standard were 72.7 and 96.3%, respectively. CONCLUSIONS: DMCO detects moderate-to-severe homonymous quadrantanopia; it can be useful in settings where the current practice is confrontation visual field examination, and where standard conventional perimetry is not available.

Transient impairment of the axolemma following regional anaesthesia by lidocaine in humans.

The local anaesthetic lidocaine is known to block voltage-gated Na(+) channels (VGSCs), although at high concentration it was also reported to block other ion channel currents as well as to alter lipid membranes. The aim of this study was to investigate whether the clinical regional anaesthetic action of lidocaine could be accounted for solely by the block of VGSCs or whether other mechanisms are also relevant. We tested the recovery of motor axon conduction and multiple measures of excitability by 'threshold-tracking' after ultrasound-guided distal median nerve regional anaesthesia in 13 healthy volunteers. Lidocaine caused rapid complete motor axon conduction block localized at the wrist. Within 3 h, the force of the abductor pollicis brevis muscle and median motor nerve conduction studies returned to normal. In contrast, the excitability of the motor axons at the wrist remained markedly impaired as indicated by a 7-fold shift of the stimulus-response curves to higher currents with partial recovery by 6 h and full recovery by 24 h. The strength-duration properties were abnormal with markedly increased rheobase and reduced strength-duration time constant. The changes in threshold during electrotonus, especially during depolarization, were markedly reduced. The recovery cycle showed increased refractoriness and reduced superexcitability. The excitability changes were only partly similar to those previously observed after poisoning with the VGSC blocker tetrodotoxin. Assuming an unaltered ion-channel gating, modelling indicated that, apart from up to a 4-fold reduction in the number of functioning VGSCs, lidocaine also caused a decrease of passive membrane resistance and an increase of capacitance. Our data suggest that the lidocaine effects, even at clinical 'sub-blocking' concentrations, could reflect, at least in part, a reversible structural impairment of the axolemma.

Electroencephalography (EEG) for neurological prognostication after cardiac arrest and targeted temperature management; rationale and study design.

BACKGROUND: Electroencephalography (EEG) is widely used to assess neurological prognosis in patients who are comatose after cardiac arrest, but its value is limited by varying definitions of pathological patterns and by inter-rater variability. The American Clinical Neurophysiology Society (ACNS) has recently proposed a standardized EEG-terminology for critical care to address these limitations. METHODS/DESIGN: In the TTM-trial, 399 post cardiac arrest patients who remained comatose after rewarming underwent a routine EEG. The presence of clinical seizures, use of sedatives and antiepileptic drugs during the EEG-registration were prospectively documented. DISCUSSION: A well-defined terminology for interpreting post cardiac arrest EEGs is critical for the use of EEG as a prognostic tool. TRIAL REGISTRATION: The TTM-trial is registered at ClinicalTrials.gov (NCT01020916).

Subclinical epileptiform discharges in Alzheimer's disease are associated with increased hippocampal blood flow.

BACKGROUND: In epilepsy, the ictal phase leads to cerebral hyperperfusion while hypoperfusion is present in the interictal phases. Patients with Alzheimer's disease (AD) have an increased prevalence of epileptiform discharges and a study using intracranial electrodes have shown that these are very frequent in the hippocampus. However, it is not known whether there is an association between hippocampal hyperexcitability and regional cerebral blood flow (rCBF). The objective of the study was to investigate the association between rCBF in hippocampus and epileptiform discharges as measured with ear-EEG in patients with Alzheimer's disease. Our hypothesis was that increased spike frequency may be associated with increased rCBF in hippocampus. METHODS: A total of 24 patients with AD, and 15 HC were included in the analysis. Using linear regression, we investigated the association between rCBF as measured with arterial spin-labelling MRI (ASL-MRI) in the hippocampus and the number of spikes/sharp waves per 24 h as assessed by ear-EEG. RESULTS: No significant difference in hippocampal rCBF was found between AD and HC (p-value = 0.367). A significant linear association between spike frequency and normalized rCBF in the hippocampus was found for patients with AD (estimate: 0.109, t-value = 4.03, p-value < 0.001). Changes in areas that typically show group differences (temporal-parietal cortex) were found in patients with AD, compared to HC. CONCLUSIONS: Increased spike frequency was accompanied by a hemodynamic response of increased blood flow in the hippocampus in patients with AD. This phenomenon has also been shown in patients with epilepsy and supports the hypothesis of hyperexcitability in patients with AD. The lack of a significant difference in hippocampal rCBF may be due to an increased frequency of epileptiform discharges in patients with AD. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov (NCT04436341).

Protocol for a prospective, longitudinal study of cognitive impairment in young patients with cancer: a multidisciplinary neuroscience approach (MyBrain).

INTRODUCTION: The aim of this research is to investigate young cancer patients' cognitive functioning and the underlying neurobiological mechanisms when cognitive functions are impaired. The MyBrain protocol is a multidisciplinary study that investigates cancer-related cognitive impairment in children, adolescents and young adults, combining neuropsychology, cognitive neuroscience and cellular neuroscience. The study is exploratory with a wide focus on trajectories of cognitive functions from diagnosis to the end of treatment and into survivorship. METHODS AND ANALYSIS: Prospective longitudinal study including patients diagnosed with non-brain cancers at age 7-29 years. Each patient is paired with a control matched on age and social circle. PRIMARY OBJECTIVE: Evaluation of neurocognitive function over time. SECONDARY OBJECTIVES: Evaluation of self-perceived quality of life and fatigue, P300 in an electroencephalography (EEG) oddball paradigm, power spectrum in resting state EEG, serum and cerebrospinal fluid levels of biomarkers of neuronal damage, neuroplasticity, proinflammatory and anti-inflammatory markers and their association with cognitive function. ETHICS AND DISSEMINATION: The study is approved by the Regional Ethics Committee for the Capital Region of Denmark (no. H-21028495), and the Danish Data Protection Agency (no. P-2021-473). Results are expected to guide future interventions to prevent brain damage and support patients with cognitive difficulties. TRIAL REGISTRATION NUMBER: The article is registered at clinicaltrials.gov NCT05840575 (https://clinicaltrials.gov/ct2/show/NCT05840575).

Out-of-hospital multimodal seizure detection: a pilot study.

Background: Out-of-hospital seizure detection aims to provide clinicians and patients with objective seizure documentation in efforts to improve the clinical management of epilepsy. In-patient studies have found that combining different modalities helps improve the seizure detection accuracy. In this study, the objective was to evaluate the viability of out-of-hospital seizure detection using wearable ECG, accelerometry and behind-the-ear electroencephalography (EEG). Furthermore, we examined the signal quality of out-of-hospital EEG recordings. Methods: Seventeen patients were monitored for up to 5 days. A support vector machine based seizure detection algorithm was applied using both in-patient seizures and out-of-hospital electrographic seizures in one patient. To assess the content of noise in the EEG signal, we compared the root-mean-square (RMS) of the recordings to a reference threshold derived from manually categorised segments of EEG recordings. Results: In total 1427 hours of continuous EEG was recorded. In one patient, we identified 15 electrographic focal impaired awareness seizures with a motor component. After training our algorithm on in-patient data, we found a sensitivity of 91% and a false alarm rate (FAR) of 18/24 hours for the detection of out-of-hospital seizures using a combination of EEG and ECG recordings. We estimated that 30.1% of the recorded EEG signal was physiological EEG, with an RMS value within the reference threshold. Conclusion: We found that detection of out-of-hospital focal impaired awareness seizures with a motor component is possible and that applying multiple modalities improves the diagnostic accuracy compared with unimodal EEG. However, significant challenges remain regarding a high FAR and that only 30.1% of the EEG data represented usable signal.

Safety, Feasibility, and Potential Clinical Efficacy of 40 Hz Invisible Spectral Flicker versus Placebo in Patients with Mild-to-Moderate Alzheimer's Disease: A Randomized, Placebo-Controlled, Double-Blinded, Pilot Study.

BACKGROUND: Recent studies suggested induction of 40 Hz neural activity as a potential treatment for Alzheimer's disease (AD). However, prolonged exposure to flickering light raises adherence and safety concerns, encouraging investigation of tolerable light stimulation protocols. OBJECTIVE: To investigate the safety, feasibility, and exploratory measures of efficacy. METHODS: This two-stage randomized placebo-controlled double-blinded clinical trial, recruited first cognitive healthy participants (n = 3/2 active/placebo), and subsequently patients with mild-to-moderate AD (n = 5/6, active/placebo). Participants were randomized 1:1 to receive either active intervention with 40 Hz Invisible Spectral Flicker (ISF) or placebo intervention with color and intensity matched non-flickering white light. RESULTS: Few and mild adverse events were observed. Adherence was above 86.1% of intended treatment days, with participants remaining in front of the device for >51.3 min (60 max) and directed gaze >34.9 min. Secondary outcomes of cognition indicate a tendency towards improvement in the active group compared to placebo (mean: -2.6/1.5, SD: 6.58/6.53, active/placebo) at week 6. Changes in hippocampal and ventricular volume also showed no tendency of improvement in the active group at week 6 compared to placebo. At week 12, a potential delayed effect of the intervention was seen on the volume of the hippocampus in the active group compared to placebo (mean: 0.34/-2.03, SD: 3.26/1.18, active/placebo), and the ventricular volume active group (mean: -0.36/2.50, SD: 1.89/2.05, active/placebo), compared to placebo. CONCLUSION: Treatment with 40 Hz ISF offers no significant safety or adherence concerns. Potential impact on secondary outcomes must be tested in larger scale clinical trials.

Study on the effect of 40 Hz non-invasive light therapy system. A protocol for a randomized, double-blinded, placebo-controlled clinical trial.

Introduction: With no cure or effective treatment, the prevalence of patients with Alzheimer's disease (AD) is expected to intensify, thereby increasing the social and financial burden on society. Light-based 40 Hz brain stimulation is considered a novel treatment strategy for patients with AD that may alleviate some of this burden. The clinical trial ALZLIGHT will utilize a novel Light Therapy System (LTS). The LTS uses Invisible Spectral Flicker for non-invasive induction of 40 Hz neural activity. This protocol describes a trial evaluating the efficacy and safety of a light-based 40 Hz brain stimulation in patients with mild-to-moderate AD. Methods: 62 patients with mild-to-moderate AD will participate in a randomized, double-blinded, placebo-controlled, parallel-group, and single-center trial. The participants will partake in an enrollment period of 1 month, an intervention period of 6 months, and a 1.5-month post-interventional follow-up period. Prior to the baseline measurement (week 0), the patients will be randomized to either active or placebo intervention from baseline (week 0) to post-intervention follow-up (week 26). Discussion: This protocol describes a randomized, double-blinded, placebo-controlled clinical trial that may increase the understanding of the effect of gamma oscillations in the human brain and how it could be utilized as a novel and important tool for the treatment of AD. The effect is measured through a large, multidisciplinary assessment battery.Clinical trial registration:www.ClinicalTrials.gov, (NCT05260177). Registered on March 2, 2022.

Monocular visual deprivation suppresses excitability in adult human visual cortex.

The adult visual cortex maintains a substantial potential for plasticity in response to a change in visual input. For instance, transcranial magnetic stimulation (TMS) studies have shown that binocular deprivation (BD) increases the cortical excitability for inducing phosphenes with TMS. Here, we employed TMS to trace plastic changes in adult visual cortex before, during, and after 48 h of monocular deprivation (MD) of the right dominant eye. In healthy adult volunteers, MD-induced changes in visual cortex excitability were probed with paired-pulse TMS applied to the left and right occipital cortex. Stimulus-response curves were constructed by recording the intensity of the reported phosphenes evoked in the contralateral visual field at range of TMS intensities. Phosphene measurements revealed that MD produced a rapid and robust decrease in cortical excitability relative to a control condition without MD. The cortical excitability returned to preinterventional baseline levels within 3 h after the end of MD. The results show that in contrast to the excitability increase in response to BD, MD acutely triggers a reversible decrease in visual cortical excitability. This shows that the pattern of visual deprivation has a substantial impact on experience-dependent plasticity of the human visual cortex.

A systematic review of impairment focussed technology in neurology.

OBJECTIVE: We provide an overview of some biomedical technologies able to relieve everyday impairments in neurological patients. METHODS: Two literature searches from 2009 to 2020 were conducted using PubMed, Embase, Cinahl and Scopus. The studies meeting the criteria for eligibility constituted 224 of the 6257 identified studies. RESULTS: The first literature search resulted in the identification of 53 different neurological impairments. The following impairments were selected as the most general: six motor (walking/gait abnormality, paralysis/paresis, hypertonia, dystonia, tremor and ataxia), three cognitive (memory, attention/concentration and executive dysfunction), two sensory (visual and hearing impairments) and three uncategorized impairments (communication impairments, sleep abnormalities and seizures/epilepsies). The second literature search resulted in the identification of 22 biomedical technologies able to compensate or rehabilitate the neurological impairments. CONCLUSIONS: This review identified some of the common neurological impairments across diseases and showed that technology can be beneficial for neurological patients by helping them with everyday living. The review also found that different aspects such as personal aspects of the intended users (e.g., impairments) and physical and environmental context of the task play an essential role in the usefulness of the technology.Implications for rehabilitationNeurological diseases are globally the leading cause of disability, whereby there is a great need for rehabilitation of neurological impairments.Assistive technology can compensate for permanent impairments or be used in rehabilitation as an alternative to usual therapy or an adjunct to increase overall therapy time.This study provides an overview of existing assistive technology and how patients with neurological impairments can benefit from technology.