Region-specific changes in brain activity and memory after continuous positive airway pressure therapy in obstructive sleep apnea: a pilot high-density electroencephalography study.

STUDY OBJECTIVES: Limited channel electroencephalography (EEG) investigations in obstructive sleep apnea (OSA) have revealed deficits in slow wave activity (SWA) and spindles during sleep and increased EEG slowing during resting wakefulness. High-density EEG (Hd-EEG) has also detected local parietal deficits in SWA (delta power) during NREM. It is unclear whether effective continuous positive airway pressure (CPAP) treatment reverses regional SWA deficits, and other regional sleep and wake EEG abnormalities, and whether any recovery relates to improved overnight memory consolidation. METHODS: A clinical sample of men with moderate-severe OSA underwent sleep and resting wake recordings with 256-channel Hd-EEG before and after 3 months of CPAP. Declarative and procedural memory tasks were administered pre- and post-sleep. Topographical spectral power maps and differences between baseline and treatment were compared using t-tests and statistical nonparametric mapping (SnPM). RESULTS: In 11 compliant CPAP users (5.2 ±â€…1.1 hours/night), total sleep time did not differ after CPAP but N1 and N2 sleep were lower and N3 was higher. Centro-parietal gamma power during N3 increased and fronto-central slow spindle activity during N2 decreased (SnPM < 0.05). No other significant differences in EEG power were observed. When averaged specifically within the parietal region, N3 delta power increased after CPAP (p = 0.0029) and was correlated with the change in overnight procedural memory consolidation (rho = 0.79, p = 0.03). During resting wakefulness, there were trends for reduced delta and theta power. CONCLUSIONS: Effective CPAP treatment of OSA may correct regional EEG abnormalities, and regional recovery of SWA may relate to procedural memory improvements in the short term.

Insomnia subtypes characterised by objective sleep duration and NREM spectral power and the effect of acute sleep restriction: an exploratory analysis.

Insomnia disorder (ID) is a heterogeneous disorder with proposed subtypes based on objective sleep duration. We speculated that insomnia subtyping with additional power spectral analysis and measurement of response to acute sleep restriction may be informative in overall assessment of ID. To explore alternative classifications of ID subtypes, insomnia patients (n = 99) underwent two consecutive overnight sleep studies: (i) habitual sleep opportunity (polysomnography, PSG) and, (ii) two hours less sleep opportunity (electroencephalography, EEG), with the first night compared to healthy controls (n = 25). ID subtypes were derived from data-driven classification of PSG, EEG spectral power and interhemispheric EEG asymmetry index. Three insomnia subtypes with different sleep duration and NREM spectral power were identified. One subtype (n = 26) had shorter sleep duration and lower NREM delta power than healthy controls (short-sleep delta-deficient; SSDD), the second subtype (n = 51) had normal sleep duration but lower NREM delta power than healthy controls (normal-sleep delta-deficient; NSDD) and a third subtype showed (n = 22) no difference in sleep duration or delta power from healthy controls (normal neurophysiological sleep; NNS). Acute sleep restriction improved multiple objective sleep measures across all insomnia subtypes including increased delta power in SSDD and NSDD, and improvements in subjective sleep quality for SSDD (p = 0.03), with a trend observed for NSDD (p = 0.057). These exploratory results suggest evidence of novel neurophysiological insomnia subtypes that may inform sleep state misperception in ID and with further research, may provide pathways for personalised care.

Assessing the role of nocturnal core body temperature dysregulation as a biomarker of neurodegeneration.

The vast majority of patients with idiopathic rapid eye movement sleep behaviour disorder will develop a neurodegenerative α-synuclein-related condition, such as Parkinson's disease or dementia with Lewy bodies. The pathology underlying dream enactment overlaps anatomically with the brainstem regions that regulate circadian core body temperature. Previously, nocturnal core body temperature regulation has been shown to be impaired in Parkinson's disease. However, no study to date has investigated nocturnal core body temperature changes in patients with idiopathic rapid eye movement sleep behaviour disorder, which may prove to be an early objective biomarker for α-synucleinopathies. Ten healthy controls, 15 patients with idiopathic rapid eye movement sleep behaviour disorder, 31 patients with Parkinson's disease and six patients with dementia with Lewy bodies underwent clinical assessment and nocturnal polysomnography with core body temperature monitoring. A validated cosinor method was utilised for core body temperature analysis. No differences in mesor, nadir or time of nadir were observed between groups. However, when compared with healthy controls, the amplitude of the nocturnal core body temperature (mesor minus nadir) was significantly reduced in patients with idiopathic rapid eye movement sleep behaviour disorder, Parkinson's disease with concurrent rapid eye movement sleep behaviour disorder and dementia with Lewy bodies (p < 0.001, p = 0.043 and p = 0.017, respectively). Importantly, this relationship was not seen in those patients with Parkinson's disease without rapid eye movement sleep behaviour disorder. In addition, there was a significant negative correlation between amplitude of the core body temperature and self-reported rapid eye movement sleep behaviour disorder symptoms. Changes in thermoregulatory circadian rhythm may be specifically associated with the pathology underlying rapid eye movement sleep behaviour disorder rather than simply that of α-synucleinopathy. These findings implicate thermoregulatory dysfunction as a potential early biomarker for development of rapid eye movement sleep behaviour disorder-associated neurodegeneration, and suggest that subpopulations with differing pathological underpinnings might exist in Parkinson's disease.

Structural brain correlates of obstructive sleep apnoea in older adults at risk for dementia.

This study aimed to investigate associations between obstructive sleep apnoea (OSA) and cortical thickness in older adults with subjective and objective cognitive difficulties, who are considered "at-risk" for dementia.83 middle-aged to older adults (51-88 years) underwent neuropsychological testing, polysomnography assessment of OSA and a structural magnetic resonance imaging brain scan. A principal components analysis was performed on OSA measures. Cortical thickness and subcortical volumes were compared to extracted components of "oxygen desaturation" and "sleep disturbance".Oxygen desaturation was significantly related to reduced cortical thickness in the bilateral temporal lobes (left: r=-0.44, p<0.001; right: r=-0.39, p=0.003). Conversely, sleep disturbance was associated with increased thickness in the right postcentral gyrus (r=0.48, p<0.001), pericalcarine (r=0.50, p=0.005) and pars opercularis (r=0.46, p=0.009) and increased volume of the hippocampus and amygdala. Decreased thickness in the bilateral temporal regions was associated with reduced verbal encoding (r=0.28, p=0.010).Given the clinical significance of this sample in terms of dementia prevention, these changes in grey matter reveal how OSA might contribute to neurodegenerative processes in older adults.

Neural activity during affect labeling predicts expressive writing effects on well-being: GLM and SVM approaches.

Affect labeling (putting feelings into words) is a form of incidental emotion regulation that could underpin some benefits of expressive writing (i.e. writing about negative experiences). Here, we show that neural responses during affect labeling predicted changes in psychological and physical well-being outcome measures 3 months later. Furthermore, neural activity of specific frontal regions and amygdala predicted those outcomes as a function of expressive writing. Using supervised learning (support vector machines regression), improvements in four measures of psychological and physical health (physical symptoms, depression, anxiety and life satisfaction) after an expressive writing intervention were predicted with an average of 0.85% prediction error [root mean square error (RMSE) %]. The predictions were significantly more accurate with machine learning than with the conventional generalized linear model method (average RMSE: 1.3%). Consistent with affect labeling research, right ventrolateral prefrontal cortex (RVLPFC) and amygdalae were top predictors of improvement in the four outcomes. Moreover, RVLPFC and left amygdala predicted benefits due to expressive writing in satisfaction with life and depression outcome measures, respectively. This study demonstrates the substantial merit of supervised machine learning for real-world outcome prediction in social and affective neuroscience.

Multimodal data and machine learning for surgery outcome prediction in complicated cases of mesial temporal lobe epilepsy.

BACKGROUND: This study sought to predict postsurgical seizure freedom from pre-operative diagnostic test results and clinical information using a rapid automated approach, based on supervised learning methods in patients with drug-resistant focal seizures suspected to begin in temporal lobe. METHOD: We applied machine learning, specifically a combination of mutual information-based feature selection and supervised learning classifiers on multimodal data, to predict surgery outcome retrospectively in 20 presurgical patients (13 female; mean age±SD, in years 33±9.7 for females, and 35.3±9.4 for males) who were diagnosed with mesial temporal lobe epilepsy (MTLE) and subsequently underwent standard anteromesial temporal lobectomy. The main advantage of the present work over previous studies is the inclusion of the extent of ipsilateral neocortical gray matter atrophy and spatiotemporal properties of depth electrode-recorded seizures as training features for individual patient surgery planning. RESULTS: A maximum relevance minimum redundancy (mRMR) feature selector identified the following features as the most informative predictors of postsurgical seizure freedom in this study's sample of patients: family history of epilepsy, ictal EEG onset pattern (positive correlation with seizure freedom), MRI-based gray matter thickness reduction in the hemisphere ipsilateral to seizure onset, proportion of seizures that first appeared in ipsilateral amygdala to total seizures, age, epilepsy duration, delay in the spread of ipsilateral ictal discharges from site of onset, gender, and number of electrode contacts at seizure onset (negative correlation with seizure freedom). Using these features in combination with a least square support vector machine (LS-SVM) classifier compared to other commonly used classifiers resulted in very high surgical outcome prediction accuracy (95%). CONCLUSIONS: Supervised machine learning using multimodal compared to unimodal data accurately predicted postsurgical outcome in patients with atypical MTLE.

Ictal depth EEG and MRI structural evidence for two different epileptogenic networks in mesial temporal lobe epilepsy.

Hypersynchronous (HYP) and low voltage fast (LVF) activity are two separate ictal depth EEG onsets patterns often recorded in presurgical patients with MTLE. Evidence suggests the mechanisms generating HYP and LVF onset seizures are distinct, including differential involvement of hippocampal and extra-hippocampal sites. Yet the extent of extra-hippocampal structural alterations, which could support these two common seizures, is not known. In the current study, preoperative MRI from 24 patients with HYP or LVF onset seizures were analyzed to determine changes in cortical thickness and relate structural changes to spatiotemporal properties of the ictal EEG. Overall, onset and initial ipsilateral spread of HYP onset seizures involved mesial temporal structures, whereas LVF onset seizures involved mesial and lateral temporal as well as orbitofrontal cortex. MRI analysis found reduced cortical thickness correlated with longer duration of epilepsy. However, in patients with HYP onsets, the most affected areas were on the medial surface of each hemisphere, including parahippocampal regions and cingulate gyrus, whereas in patients with LVF onsets, the lateral surface of the anterior temporal lobe and orbitofrontal cortex showed the greatest effect. Most patients with HYP onset seizures were seizure-free after resective surgery, while a higher proportion of patients with LVF onset seizures had only worthwhile improvement. Our findings confirm the view that recurrent seizures cause progressive changes in cortical thickness, and provide information concerning the structural basis of two different epileptogenic networks responsible for MTLE. One, identified by HYP ictal onsets, chiefly involves hippocampus and is associated with excellent outcome after standardized anteromedial temporal resection, while the other also involves lateral temporal and orbitofrontal cortex and a seizure-free surgical outcome occurs less after this procedure. These results suggest that a more extensive tailored resection may be required for patients with the second type of MTLE.

Towards a physiological signal-based access solution for a non-verbal adolescent with severe and multiple disabilities.

OBJECTIVE: To find physiologically arousing stimuli and labile physiological channels in a non-verbal adolescent with severe and multiple congenital disabilities, who did not have a reliable means of communication. METHODS: The client was repeatedly presented with visual and audiovisual stimuli, representing variations of six contextual factors over three sessions in a one month period. For each stimulus, reactions were detected in the client's four peripheral autonomic nervous system signals using a rule-based classification algorithm. RESULTS: During the presentation of audiovisual stimuli, the number of physiological reactions significantly differed from that observed in baseline (χ(2) = 3.93, p = 0.0476). Aural stimuli articulated in an unfamiliar voice, and aural stimuli containing anticipatory patterns were also physiologically arousing. Fingertip temperature was the client's most labile physiological signal. CONCLUSIONS: The results of this case study suggest that physiological data may complement caregiver acumen in deciphering the reactions of non-verbal clients with severe and multiple disabilities.

Quantitative analysis of structural neuroimaging of mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (MTLE) is the most common of the surgically remediable drug-resistant epilepsies. MRI is the primary diagnostic tool to detect anatomical abnormalities and, when combined with EEG, can more accurately identify an epileptogenic lesion, which is often hippocampal sclerosis in cases of MTLE. As structural imaging technology has advanced the surgical treatment of MTLE and other lesional epilepsies, so too have the analysis techniques that are used to measure different structural attributes of the brain. These techniques, which are reviewed here and have been used chiefly in basic research of epilepsy and in studies of MTLE, have identified different types and the extent of anatomical abnormalities that can extend beyond the affected hippocampus. These results suggest that structural imaging and sophisticated imaging analysis could provide important information to identify networks capable of generating spontaneous seizures and ultimately help guide surgical therapy that improves postsurgical seizure-freedom outcomes.

Cortical activity during speech and non-speech oromotor tasks: a magnetoencephalography (MEG) study.

We used whole-head magnetoencephalography to investigate cortical activity during two oromotor activities foundational to speech production. 13 adults performed mouth opening and phoneme (/pa/) production tasks to a visual cue. Jaw movements were tracked with an ultrasound-emitting device. Trials were time-locked to both stimulus onset and peak of jaw displacement. An event-related beamformer source reconstruction algorithm was used to detect areas of cortical activity for each condition. Beamformer output was submitted to iterative K-means clustering analyses. The time course of neural activity at each cluster centroid was computed for each individual and condition. Peaks were identified and latencies submitted for statistical analysis to reveal the relative timing of activity in each brain region. Stimulus locked activations for the mouth open task included a progression from left cuneus to left frontal and then right pre-central gyrus. Phoneme generation revealed the same sequence but with bilateral frontal activation. When time locked to jaw displacement, the mouth open condition showed left frontal followed by right frontal-temporal areas. Phoneme generation showed a complicated sequence of bilateral temporal and frontal areas. This study used three unique approaches (beamforming, clustering and jaw tracking) to demonstrate the temporal progression of neural activations that underlie the motor control of two simple oromotor tasks. These findings have implications for understanding clinical conditions with deficits in articulatory control or motor speech planning.

Client-centred development of an infrared thermal access switch for a young adult with severe spastic quadriplegic cerebral palsy.

PURPOSE: This study reports a client-centred development of a non-contact access switch based on an infrared thermal imaging of mouth opening-closing activity of an individual with severe spastic quadriplegic cerebral palsy. METHOD: Over a 6-month period, the client participated in five test sessions to inform the development of an infrared thermal switch. The client completed eight stimulus-response trials (switch test) and eight word-matching trials (scan test) using the infrared thermal switch and provided subjective feedback throughout. RESULTS: For the switch test, the client achieved an average correct activation rate of 90% and average response time of 2.4 s. His mean correct activation rate on the scan test improved from 65 to 80% over the course of system development, with an average response time of 11.7 s. CONCLUSIONS: An infrared thermography switch tuned to a client's extant orofacial gestures is a practical non-invasive access solution and warrants further research in clients with severe physical disability.

Validating an infrared thermal switch as a novel access technology.

BACKGROUND: Recently, a novel single-switch access technology based on infrared thermography was proposed. The technology exploits the temperature differences between the inside and surrounding areas of the mouth as a switch trigger, thereby allowing voluntary switch activation upon mouth opening. However, for this technology to be clinically viable, it must be validated against a gold standard switch, such as a chin switch, that taps into the same voluntary motion. METHODS: In this study, we report an experiment designed to gauge the concurrent validity of the infrared thermal switch. Ten able-bodied adults participated in a series of 3 test sessions where they simultaneously used both an infrared thermal and conventional chin switch to perform multiple trials of a number identification task with visual, auditory and audiovisual stimuli. Participants also provided qualitative feedback about switch use. User performance with the two switches was quantified using an efficiency measure based on mutual information. RESULTS: User performance (p = 0.16) and response time (p = 0.25) with the infrared thermal switch were comparable to those of the gold standard. Users reported preference for the infrared thermal switch given its non-contact nature and robustness to changes in user posture. CONCLUSIONS: Thermal infrared access technology appears to be a valid single switch alternative for individuals with disabilities who retain voluntary mouth opening and closing.

Infrared thermography as an access pathway for individuals with severe motor impairments.

BACKGROUND: People with severe motor impairments often require an alternative access pathway, such as a binary switch, to communicate and to interact with their environment. A wide range of access pathways have been developed from simple mechanical switches to sophisticated physiological ones. In this manuscript we report the inaugural investigation of infrared thermography as a non-invasive and non-contact access pathway by which individuals with disabilities can interact and perhaps eventually communicate. METHODS: Our method exploits the local temperature changes associated with mouth opening/closing to enable a highly sensitive and specific binary switch. Ten participants (two with severe disabilities) provided examples of mouth opening and closing. Thermographic videos of each participant were recorded with an infrared thermal camera and processed using a computerized algorithm. The algorithm detected a mouth open-close pattern using a combination of adaptive thermal intensity filtering, motion tracking and morphological analysis. RESULTS: High detection sensitivity and low error rate were achieved for the majority of the participants (mean sensitivity of all participants: 88.5% +/- 11.3; mean specificity of all participants: 99.4% +/- 0.7). The algorithm performance was robust against participant motion and changes in the background scene. CONCLUSION: Our findings suggest that further research on the infrared thermographic access pathway is warranted. Flexible camera location, convenience of use and robustness to ambient lighting levels, changes in background scene and extraneous body movements make this a potential new access modality that can be used night or day in unconstrained environments.

Colony size measurement of the yeast gene deletion strains for functional genomics.

BACKGROUND: Numerous functional genomics approaches have been developed to study the model organism yeast, Saccharomyces cerevisiae, with the aim of systematically understanding the biology of the cell. Some of these techniques are based on yeast growth differences under different conditions, such as those generated by gene mutations, chemicals or both. Manual inspection of the yeast colonies that are grown under different conditions is often used as a method to detect such growth differences. RESULTS: Here, we developed a computerized image analysis system called Growth Detector (GD), to automatically acquire quantitative and comparative information for yeast colony growth. GD offers great convenience and accuracy over the currently used manual growth measurement method. It distinguishes true yeast colonies in a digital image and provides an accurate coordinate oriented map of the colony areas. Some post-processing calculations are also conducted. Using GD, we successfully detected a genetic linkage between the molecular activity of the plant-derived antifungal compound berberine and gene expression components, among other cellular processes. A novel association for the yeast mek1 gene with DNA damage repair was also identified by GD and confirmed by a plasmid repair assay. The results demonstrate the usefulness of GD for yeast functional genomics research. CONCLUSION: GD offers significant improvement over the manual inspection method to detect relative yeast colony size differences. The speed and accuracy associated with GD makes it an ideal choice for large-scale functional genomics investigations.