A method for detection of Alzheimer's disease using ICA-enhanced EEG measurements

OBJECTIVE: Many researchers have studied automatic EEG classification and recently a lot of work has been done on artefact-removal from EEG data using independent component analyses (ICA). However, demonstrating that a ICA-processed multichannel EEG measurement becomes more interpretable compared to the raw data (as is usually done in work on ICA-processing of EEG data) does not yet prove that detection of (incipient) anomalies is also better possible after ICA-processing. The objective of this study is to show that ICA-preprocessing is useful when constructing a detection system for Alzheimer's disease. METHODS AND MATERIAL: The paper describes a method for detection of EEG patterns indicative of Alzheimer's disease using automatic pattern recognition techniques. Our method incorporates an artefact removal stage based on ICA prior to automatic classification. The method is evaluated on measurements of a length of 8s from two groups of patients, where one group is in an initial stage of the disease (28 patients), whereas the other group is in a more progressed stage (15 patients). Both setups include a control group that should be classified as normal (10 and 21, respectively). RESULTS: Our final classification results for the group with severe Alzheimer's disease are comparable to the best results from literature. We show that ICA-based reduction of artefacts improves classification results for patients in an initial stage. CONCLUSION: We conclude that a more robust detection of Alzheimer's disease related EEG patterns may be obtained by employing ICA as ICA based pre-processing of EEG data can improve classification results for patients in an initial stage of Alzheimer's disease.     

Genetic components of functional connectivity in the brain: the heritability of synchronization likelihood

Cognitive functions require the integrated activity of multiple specialized, distributed brain areas. Such functional coupling depends on the existence of anatomical connections between the various brain areas as well as physiological processes whereby the activity in one area influences the activity in another area. Recently, the Synchronization Likelihood (SL) method was developed as a general method to study both linear and nonlinear aspects of coupling. In the present study the genetic architecture of the SL in different frequency bands was investigated. Using a large genetically informative sample of 569 subjects from 282 extended twin families we found that the SL is moderately to highly heritable (41-67%) especially in the alpha frequency (8-13 Hz) range. This index of functional connectivity of the brain has been associated with a number of pathological states of the brain. The significant heritability found here suggests that SL can be used to examine the genetic susceptibility to these conditions.     

Periodic limb movement disorder and restless legs syndrome in dialysis patients

BACKGROUND: Sleep disturbances, in particular restless legs or limb movements, during the night are often reported by uremic patients. However, polysomnography (PSG) studies have never been carried out to confirm the actual occurrence of these disorders and the association with other objective and self-reported sleep-wake data. METHODS: Forty-eight participants were subjected to a 2-day PSG. These data on sleep including periodic limb movements, which are associated with restless legs, were correlated with clinical observations, quality of sleep-wake and life questionnaires, and with biochemical and neurographical measures. RESULTS: Restless legs syndrome (RLS) was observed in 58.3% of the patients and periodic limb movement disorder (PLMD) occurred in 70.8% of the patients. PLMD was revealed polysomnographically in almost 90% of the RLS patients. Patients with both PLMD and RLS had significantly poorer sleep quality than those with neither disorder or with PLMD alone, both in terms of self-reported data and the PSG. Quality of life was significantly worse in patients with RLS and PLMD compared to those patients with neither disorder. PLMD patients also tended to have a lower quality of life. All other metabolic measures and the results of a nerve conduction test were not correlated with RLS and/or PLMD. CONCLUSION: There was a high prevalence of severe RLS and PLMD in the present sample of uraemia patients. Nearly all RLS patients had severe PLMD. RLS (in combination with PLMD) in dialysis is associated with poor sleep quality, insomnia complaints, depression and emotional distress. Our results suggest that PLMD per se is also clinically relevant.     

Physiological and behavioural responses to duodenal pain in freely moving rats

Luminal distention of the intestine can be aversive in humans and laboratory animals, and hypersensitivity to distention is found in functional gastrointestinal disorders. Current animal models either require anaesthesia or acute balloon intubation or use implanted balloons of irritant materials, for which the aversive quality of distention and physiological responses have not been well characterised. We report here that silicone balloon catheters implanted in the duodenum via the stomach have long patency without obvious tissue damage. Balloon inflation in freely moving rats caused passive avoidance learning and classic 'pain' postures, as well as graded cardiovascular responses which can be recorded telemetrically. The method should make long-lasting studies of pharmacological and environmental effects on visceral sensitivity more feasible.     

Impairments and activity limitations in subjects with chronic upper-limb complex regional pain syndrome type I

OBJECTIVE: To determine the degree of impairments and activity limitations and their interrelationship in complex regional pain syndrome type I (CRPS type I). DESIGN: Cross-sectional study interrelating impairments and objectively measured activity limitations. SETTING: Ambulatory and home environment. PARTICIPANTS: Thirty nonacute upper-limb CRPS type I subjects. INTERVENTIONS: Not applicable.Main outcome measures Sensory, motor, and autonomic impairments, as well as activity-limitation outcome measures. The latter were objectively measured with a novel upper-limb activity monitor (based on ambulatory accelerometry). RESULTS: All subjects were impaired to some degree but with a large variability with respect to magnitude. Regarding activity limitations, the involved upper limb was clearly less active (lower intensity and percentage of activity) than the noninvolved side. Impaired active range of motion (adjusted R(2) range, 18%-39%) and grip strength (adjusted R(2) range, 12%-45%) were the most important factors explaining variance in activity limitations. CONCLUSIONS: All subjects were still impaired nearly 3 years after the causative event. The involved upper limb was also clearly less active than the noninvolved side, especially when the subjects were sitting and when the dominant side was involved. The more impairments a subject had, especially motor impairments, the more activity limitations were present.     

Physical training and fatigue, fitness, and quality of life in Guillain-Barré syndrome and CIDP

Many patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) experience excessive fatigue, which may persist for years and reduce quality of life. The authors performed a 12-week study of bicycle exercise training in 20 patients with severe fatigue, 16 with relatively good recovery from GBS, and 4 with stable CIDP. Training seemed well tolerated, and self-reported fatigue scores decreased 20% (p = 0.001). Physical fitness, functional outcome, and quality of life were improved.     

Very low levels of the glucocorticoid receptor beta isoform in the human hippocampus as shown by Taqman RT-PCR and immunocytochemistry

The hippocampus is an important target for glucocorticoid hormones. Glucocorticoid receptor (GR) mediated feedback in this area is important for control of behavioural adaptation. An alternative splice variant, the GRbeta (GRbeta) isoform, does not bind ligand and has been proposed to inhibit classic GRalpha-mediated transactivation of target genes. Hence, an increased ratio of GRbeta to GRalpha may induce relative corticosteroid-resistance, as e.g. presumed to occur in major depression. To investigate whether GRbeta is involved in the human hippocampus, we studied GRalpha and GRbeta expression levels in postmortem hippocampal tissue of control subjects by quantitative PCR (Taqman RT-PCR) and immunocytochemistry. Taqman RT-PCR demonstrated a very low relative abundance of GRbeta in the human hippocampus (GRalpha:GRbeta ratio approximately 14,500:1). Immunohistochemical analysis confirmed the occurrence of isolated profiles indeed displaying nuclear staining in the main hippocampal subregions. Subsequent double immunofluorescent analysis revealed that >98% of these GRbeta positive cells were double positive for leucocyte common antigen, that identifies exclusively blood-derived cells of haematopoietic origin, including microglia. We conclude that GRbeta is present in very low amounts in the control human hippocampus, and that of these low numbers of cells, notably, almost all are derived from blood which is inevitably present in postmortem tissue. A functionally relevant role for the GRbeta in control of the human hippocampus is therefore not very likely. Whether this is altered in disease conditions awaits further research.     

The influence of brain tumor treatment on pathological delta activity in MEG

The goal of the MEG study was to investigate the influence of tumor treatment on pathological delta activity (1-4 Hz). The treatment consisted of neurosurgery, and in some of the patients, additional radiotherapy. MEG and MR recordings were made both before and after the treatment in 17 patients. The signal power in the delta frequency band was determined for each recording. The malignant tumors were associated with large tumor volumes. Furthermore, both malignant tumors and tumor volume were associated with high signal powers in the delta band, indicating a correlation of delta power with the severity of the lesions. In all patients with high grade tumors, the delta power was lower after the treatment. The sources underlying the delta signals were estimated with an automatic single dipole analysis method. Estimated sources were projected onto MR scans. Preoperatively 14 clusters of equivalent sources describing focal activity were found in 12 out of 17 patients. Thirteen of these clusters were located near the tumor, and one cluster near an edema border. The locations near tumors are plausible and suggest that in general the source estimation was reliable. After the operation, 13 such clusters were found in 12 patients. Eleven clusters were located near the lesion border and one cluster near the edema border. Furthermore a cluster contralateral to the lesion in the other hemisphere indicated that brain lesions can affect the functioning of more distant brain areas than just the peritumoral brain tissue. Of the 12 patients who had preoperatively peritumoral clusters, 11 patients had postoperatively perilesional sources. In these cases the shift in source locations was in general considerably smaller than the dimension of the preoperative tumors. This finding indicates that similar areas generate the pre- and postoperative delta activity. Furthermore, focal delta sources were found in a case without tumor recurrence, and also in cases that most tumor tissue was removed. These findings suggest that the pathology underlying the slow waves is not the presence of the tumor bulk but the structural damage done by the tumors on the surrounding white/gray matter.