Electroencephalographic functional connectivity is altered in persons with Down syndrome and Alzheimer's disease.

BACKGROUND: Persons with Down syndrome (DS) are at increased risk of developing Alzheimer's dementia (DS-AD). Due to heterogeneity in the functioning in persons with DS, it is difficult to use cognitive testing to assess whether a person with DS has developed dementia due to AD. Electroencephalography (EEG) functional connectivity has shown promising results as a diagnostic tool for AD in persons without DS. In the current exploratory study, we investigated whether EEG functional connectivity could be used as a diagnostic marker of AD in persons with DS and the association with symptoms. METHODS: Electroencephalography from 12 persons with DS and 16 persons with DS-AD were analysed, and both coherence and weighted phase lag index were calculated. In addition, we calculated the average coherence for fronto-parietal and temporo-parietal connections. Lastly, we investigated the correlation between the informant-based Dementia Screening Questionnaire in Intellectual Disability (DSQIID) and total alpha coherence. RESULTS: Decreased alpha and increased delta coherence and weighted phase lag index were observed in DS-AD as compared with DS. The decrease in alpha coherence was more marked in the fronto-parietal connections as compared with the temporo-parietal connections. No significant correlation was found between DSQIID and total alpha coherence (P value = 0.095, rho = -0.335). CONCLUSION: The decreased alpha coherence and weighted phase lag index have previously been found in AD. The increased delta coherence and weighted phase lag index may indicate a different initial neurophysiological presentation as compared with patients with AD or may be a sign of more advanced disease. Larger studies are needed to confirm the current findings.

Associations between electroencephalography power and Alzheimer's disease in persons with Down syndrome.

BACKGROUND: It is complicated to diagnose dementia in persons with Down syndrome (DS). Older studies have, however, demonstrated low-frequency activity in electroencephalography (EEG) in persons with concurrent DS and Alzheimer's disease (DS-AD). The aim of this study was to examine whether it was possible to identify AD-associated changes (increased high-frequency power and decreased low-frequency power) in persons with DS-AD compared with DS. METHODS: We included 21 persons with DS-AD and 16 with DS without cognitive deterioration assessed by the informant-based Dementia Screening Questionnaire in Intellectual Disability. EEG was recorded for all participants. Absolute power for each electrode and global power were calculated for all frequency bands for both eyes open and eyes closed. RESULTS: For global power in the eyes closed condition, we found an increased global slow-frequency activity and a decreased global high-frequency activity in DS-AD compared with DS. In addition, we found a significant difference in the global alpha/delta ratio with the largest difference found for global alpha power in DS-AD compared with DS. CONCLUSIONS: In the current study, we found that changes known to be associated with AD could also be identified when comparing DS-AD with DS using quantitative EEG. In general, these findings suggest that EEG might be a useful tool in diagnosing AD in persons with DS, but larger studies are needed.

Detection of generalized tonic-clonic seizures from ear-EEG based on EMG analysis.

PURPOSE: Sudden unexpected death in epilepsy (SUDEP) is associated with generalized tonic-clonic seizures (GTCS) with most deaths occurring during sleep. Seizure detection devices have been suggested as a SUDEP prevention strategy. EMG-based GTCS detection can take advantage of the GTCS characteristic of sustained high-amplitude, high-frequency activity in the time-domain. METHOD: We present a GTCS-detection method based on median-filtered variance estimates on surface EMG measurements and describe its performance in a small exploratory proof-of-concept setting involving a group of 15 patients with 3 GTCS recorded with ear-EEG and another group of 6 patients with 11 GTCS recorded with scalp-EEG. RESULTS: GTCS intervals were detected within 4.2-12.9 s of onset with 100% sensitivity (CI 29.2-100%) without false positives in 820.7 h of ear-EEG. The same detection method worked for the 11 GTCS from scalp EEG data with 100% sensitivity (CI 71.5-100%) and no false positives. CONCLUSIONS: Ear-EEG contains enough GTCS-specific EMG activity for GTCS detection to be feasible. Ear-EEG could be considered for nocturnal GTCS monitoring as a supplement to SUDEP preventive interventions.

Shorter preschool, leukocyte telomere length is associated with obesity at age 9 in Latino children.

The aim of this study was to determine the potential role of leukocyte telomere length as a biomarker for development of childhood obesity in a low-income Latino population. A birth cohort of Latino children (N = 201) in San Francisco (recruited May 2006-May 2007) was followed until age 9 and assessed annually for obesity and dietary intake. Leukocyte telomere length was measured at 4 and 5 years (n = 102) and assessed as a predictor for obesity at age 9, adjusting for known risk factors. Furthermore, leukocyte telomere length at age 4 and 5 was evaluated as a possible mediator of the relationship between excessive sugar-sweetened beverage consumption and obesity at age 9. Shorter leukocyte telomere length in preschoolers was associated with obesity at age 9 (adjusted odds ratio 0.35, 95% confidence interval 0.13-0.94) after adjustment for known risk factors. Telomere length mediated 11% of the relationship between excessive sugar-sweetened beverage consumption and obesity. Shorter leukocyte telomere length may be an indicator of future obesity risk in high-risk populations as it is particularly sensitive to damage from oxidative stress exposure, including those from sugar-sweetened beverages.

Ear-EEG detects ictal and interictal abnormalities in focal and generalized epilepsy - A comparison with scalp EEG monitoring.

OBJECTIVE: Ear-EEG is recording of electroencephalography from a small device in the ear. This is the first study to compare ictal and interictal abnormalities recorded with ear-EEG and simultaneous scalp-EEG in an epilepsy monitoring unit. METHODS: We recorded and compared simultaneous ear-EEG and scalp-EEG from 15 patients with suspected temporal lobe epilepsy. EEGs were compared visually by independent neurophysiologists. Correlation and time-frequency analysis was used to quantify the similarity between ear and scalp electrodes. Spike-averages were used to assess similarity of interictal spikes. RESULTS: There were no differences in sensitivity or specificity for seizure detection. Mean correlation coefficient between ear-EEG and nearest scalp electrode was above 0.6 with a statistically significant decreasing trend with increasing distance away from the ear. Ictal morphology and frequency dynamics can be observed from visual inspection and time-frequency analysis. Spike averages derived from ear-EEG electrodes yield a recognizable spike appearance. CONCLUSIONS: Our results suggest that ear-EEG can reliably detect electroencephalographic patterns associated with focal temporal lobe seizures. Interictal spike morphology from sufficiently large temporal spike sources can be sampled using ear-EEG. SIGNIFICANCE: Ear-EEG is likely to become an important tool in clinical epilepsy monitoring and diagnosis.

Drug taper during long-term video-EEG monitoring: efficiency and safety.

OBJECTIVES: Anti-epileptic drugs (AED) are often tapered to reduce the time needed to record a sufficient number of seizure during long-term video-EEG monitoring (LTM). Fast AED reduction is considered less safe, but few studies have examined this. Our goal is to examine whether the rate of AED reduction affects efficiency and safety. MATERIALS & METHODS: We performed a retrospective observational study of patients referred for presurgical evaluation. Each patient was categorized by two dichotomous parameters of AED tapering: (i) fast vs slow AED reduction the first 24 h of LTM and (ii) complete vs partial AED discontinuation during LTM. RESULTS: Of 79 patients, 51% underwent a fast AED reduction and 58% ended up with AEDs completely discontinued. Complete AED discontinuation was associated with three times increased likelihood of receiving rescue therapy during LTM and double risk of having secondary generalized tonic-clonic seizures (sGTCS) compared to the group partially discontinued. Fast vs slow AED reduction had no effect on the safety of LTM. The fast AED reduction group and the complete AED discontinuation group had a significantly longer time to first seizure and total recording time compared to the slow AED reduction and partial discontinuation groups, respectively. CONCLUSIONS: Fast AED reduction was found safe in patients undergoing presurgical video-EEG monitoring. Patients completely discontinued from AEDs had more sGTCS than patients partially discontinued. Further studies are suggested to confirm this finding and to evaluate whether fast reduction is safe and efficient in other subgroups of patients referred for LTM.

Case comparison of sleep features from ear-EEG and scalp-EEG.

BACKGROUND: We investigate the potential usability of a novel in-the-ear electroencephalography recording device for sleep staging. METHODS: In one healthy subject we compare simultaneous earelectroencephalography to standard scalp EEG visually and using power spectrograms. Hypnograms independently derived from the records are compared. RESULTS: We find that alpha activity, K complexes, sleep spindles and slow wave sleep can be visually distinguished using earelectroencephalography. Spectral peaks are shared between the two records. Hypnograms are 90.9% similar. CONCLUSION: The results indicate that ear-electroencephalography can be used for sleep staging.

Intraoperative hyperventilation vs remifentanil during electrocorticography for epilepsy surgery - a case report.

BACKGROUND: Traditionally, intraoperative intracranial electroen-cephalography-recordings are limited to the detection of the irritative zone defined by interictal spikes. However, seizure patterns revealing the seizure onset zone are thought to give better localizing information, but are impractical due to the waiting time for spontaneous seizures. Therefore, provocation by seizure precipitants may be used with the precaution that spontaneous and provoked seizures may not be identical. OBJECTIVE: We present evidence that hyperventilation induced and drug induced focal seizures may arise from different brain regions in the same patient. METHODS: Hyperventilation and ultra short acting opioid remifentanil were used separately as intraoperative precipitatants of seizure patterns, while recording from subdural and intraventricular electrodes in a patient with temporal lobe epilepsy. Two different ictal onset zones appeared in response to hyperventilation and remifentanil. Both zones were resected and the patient has remained essentially seizure free for 1 year. Furthermore, this is the first description of hyperventilation used as an intraoperative seizure precipitant in human focal epilepsy.

Remifentanil-induced spike activity as a diagnostic tool in epilepsy surgery.

OBJECTIVES: To assess the value of remifentanil in intraoperative evaluation of spike activity in patients undergoing surgery for mesial temporal lobe epilepsy (MTLE). MATERIALS AND METHODS: Twenty-five patients undergoing temporal lobectomy for medically intractable MTLE were enrolled in the study. Electrocorticography (ECoG) recordings were performed on the intraventricular hippocampus and from the anterior inferior temporal and lateral neocortex before and after a 300 microg intravenous bolus of remifentanil. Spike activity was quantified as spike-count per minute. RESULTS: A significant increase (P < 0.005) in spike activity was observed after administration of remifentanil in 23 of 25 patients (92%). Furthermore, two patients who did not have any spike activity on the baseline ECoG developed spikes after administration of remifentanil. CONCLUSIONS: The results suggest that remifentanil can enhance spike activity in the epileptogenic zone and reveal otherwise concealed epileptogenic tissue in patients with MTLE. Thus, remifentanil may prove to be an important diagnostic tool during surgical treatment for intractable focal epilepsy.

Precuneus-prefrontal activity during awareness of visual verbal stimuli.

Awareness is a personal experience, which is only accessible to the rest of world through interpretation. We set out to identify a neural correlate of visual awareness, using brief subliminal and supraliminal verbal stimuli while measuring cerebral blood flow distribution with H(2)(15)O PET. Awareness of visual verbal stimuli differentially activated medial parietal association cortex (precuneus), which is a polymodal sensory cortex, and dorsolateral prefrontal cortex, which is thought to be primarily executive. Our results suggest participation of these higher order perceptual and executive cortical structures in visual verbal awareness.

Neonatal treatment with beta-cell stimulatory agents reduces the incidence of diabetes in BB rats.

The aim of the study was to investigate whether various beta-cell stimulatory drugs, given neonatally, influence the incidence of diabetes in BB rats. Newborn BB rats were treated twice daily for 6 days and diabetes development was observed during the following 200-day study period. Compared to a diabetes incidence of 63.8% in 163 control BB rats which received saline or were untreated, the percentage of experimental BB rats that developed diabetes was as follows in the different subgroups: arginine-glucose: 47% (n = 73, p < 0.02); glucagon: 37% (n = 93, p < 0.0001); tolbutamide-glucose: 36% (n = 58, p < 0.0005); and theophylline-glucose: 39% (n = 41, p < 0.005). A long-term arginine-glucose treatment was not superior to the shorter neonatal treatment. Histological examination revealed a higher degree of insulitis in diabetic than in non-diabetic animals but no difference according to the kind of treatment was observed. Finally, we found that the diabetes incidence in BB rats was higher in the first litter compared to subsequent litters (p = 0.04). Thus, neonatal treatment with various beta-cell stimulatory agents reduces diabetes incidence in BB rats. The theory behind the study, that the treatment accelerates beta-cell maturation leading to increased immunological tolerance towards beta cells, is discussed.

A 15O-H2O PET study of meditation and the resting state of normal consciousness.

The aim of the present study was to examine whether the neural structures subserving meditation can be reproducibly measured, and, if so, whether they are different from those supporting the resting state of normal consciousness. Cerebral blood flow distribution was investigated with the 15O-H20 PET technique in nine young adults, who were highly experienced yoga teachers, during the relaxation meditation (Yoga Nidra), and during the resting state of normal consciousness. In addition, global CBF was measured in two of the subjects. Spectral EEG analysis was performed throughout the investigations. In meditation, differential activity was seen, with the noticeable exception of V1, in the posterior sensory and associative cortices known to participate in imagery tasks. In the resting state of normal consciousness (compared with meditation as a baseline), differential activity was found in dorso-lateral and orbital frontal cortex, anterior cingulate gyri, left temporal gyri, left inferior parietal lobule, striatal and thalamic regions, pons and cerebellar vermis and hemispheres, structures thought to support an executive attentional network. The mean global flow remained unchanged for both subjects throughout the investigation (39+/-5 and 38+/-4 ml/100 g/min, uncorrected for partial volume effects). It is concluded that the (H2)15O PET method may measure CBF distribution in the meditative state as well as during the resting state of normal consciousness, and that characteristic patterns of neural activity support each state. These findings enhance our understanding of the neural basis of different aspects of consciousness.

Insensitivity of V1 complex cell responses to small shifts in the retinal image of complex patterns.

An important role for neurons in the early visual system is to convey information about the structure of visual stimuli. However, neuronal responses show substantial variation across presentations of the same stimulus. In awake monkeys, it has been assumed that a great deal of this variation is related to the scatter in eye position (inducing scatter in the retinal position of the stimulus). Here we investigate the implied consequence of this assumption, i.e., that the scatter variation in eye position degrades the decodability of the neural response. We recorded from 50 complex cells in primary visual cortex of fixating monkeys while different complex stimuli were presented. Three types of retinal shifts were considered: natural scatter in the fixation, systematic fixation point shift, and systematic stimulus position shift. The stimulus pattern accounts for >50% of the response variance, always six times that accounted for by the scatter in eye position during fixation. The retinal location of a stimulus had to be shifted by 10-12 min of arc, an amount almost two times larger than the smallest picture element, before the responses changed systematically. Nonetheless, changes of the stimulus at the single pixel level often gave rise to discriminable responses. Thus complex cells convey information about the spatial structure of a stimulus, independent of rigid stimulus displacements on the order of the receptive field size or smaller.

Latency: another potential code for feature binding in striate cortex.

1. We recorded the responses of 37 striate cortical complex cells in fixating monkeys while presenting a set of oriented stimuli that varied in contrast. 2. The two response parameters of strength and latency can be interpreted as a code: the strength defines the stimulus form (here the orientation), and the latency is more a function of the stimulus contrast. 3. Synchronization based on latency could make a strong contribution to the process of organizing the neural responses to different objects, i.e., binding.

Adjacent visual cortical complex cells share about 20% of their stimulus-related information.

The responses of adjacent neurons in inferior temporal (IT) cortex carry signals that are to a large degree independent (Gawne and Richmond, 1993). Adjacent primary visual cortical neurons have similar orientation tuning (Hubel and Wiesel, 1962, 1968), suggesting that their responses might be more redundant than those in IT. We recorded the responses of 26 pairs of adjacent complex cells in the primary visual cortex of two awake monkeys while using both a set of 16 bar-like stimuli, and a more complex set of 128 two-dimensional patterns. Linear regression showed that 40% of the signal variance of one neuron was related to that of the other when the responses to the bar-like stimuli were considered. However, when the responses to the two-dimensional stimuli were included in the analysis, only 19% of the signal variance of one neuron was related to that of the adjacent one, almost exactly the same results as found in IT. An information theoretic analysis gave similar results. We hypothesize that this trend toward independence of information processing by adjacent cortical neurons is a general organizational strategy used to maximize the amount of information carried in local groups.

Information flow and temporal coding in primate pattern vision.

We perform time-resolved calculations of the information transmitted about visual patterns by neurons in primary visual and inferior temporal cortices. All measurable information is carried in an effective time-varying firing rate, obtained by averaging the neuronal response with a resolution no finer than about 25 ms in primary visual cortex and around twice that in inferior temporal cortex. We found no better way for a neuron receiving these messages to decode them than simply to count spikes for this long. Most of the information tends to be concentrated in one or, more often, two brief packets, one at the very beginning of the response and the other typically 100 ms later. The first packet is the most informative part of the message, but the second one generally contains new information. A small but significant part of the total information in the message accumulates gradually over the entire course of the response. These findings impose strong constraints on the codes used by these neurons.

Decoding cortical neuronal signals: network models, information estimation and spatial tuning.

We have studied the encoding of spatial pattern information by complex cells in the primary visual cortex of awake monkeys. Three models for the conditional probabilities of different stimuli, given the neuronal response, were fit and compared using cross-validation. For our data, a feed-forward neural network proved to be the best of these models. The information carried by a cell about a stimulus set can be calculated from the estimated conditional probabilities. We performed a spatial spectroscopy of the encoding, examining how the transmitted information varies with both the average coarseness of the stimulus set and the coarseness differences within it. We find that each neuron encodes information about many features at multiple scales. Our data do not appear to allow a characterization of these variations in terms of the detection of simple single features such as oriented bars.

Ossification sequence of occipital bone and vertebrae in human fetuses.

The aim of this radiographic study of human fetuses was to examine the pattern and sequence of ossification in the occipital bone and the spinal vertebrae. Together with previous studies of ossification of the human fetal basal cranium, this study can serve as a reference for normalcy in future studies of fetuses with neural tube defects and associated pathological development of the axial skeleton. Thirty-nine normal fetuses aborted between 9 and 14 weeks of gestation were examined. Based on the appearance of ossification centers in the bones under study, the fetuses could be grouped in four well-defined developmental stages, which were named occipito-spinal stages I-IV (OS I-IV). The OS stage was closely related to gestational age, crown-rump length, foot length, and degree of ossification in the hands and feet.

Interleukins increase surface ganglioside expression of pancreatic islet cells in vitro.

This experiment was conducted in order to investigate whether expression of gangliosides on islet cell surface in vitro is influenced by cytokines, especially interleukin 1. Islets from adult Lewis rats were incubated with different concentrations of recombinant-derived human cytokines. Following dispase treatment, the single cells were labeled with monoclonal antiganglioside antibodies A2B5 or R2D6, and conjugate. Both are directed against beta cells; A2B5 is recognized to bind specifically to pancreatic islet cells, while R2D6 is shown to bind no other pancreatic cells than beta cells. Surface labeling was evaluated in blind trials using a fluorescence microscope and a fluorescence-activated cell sorter (FACS). A2B5 staining demonstrated a significantly higher number of labeled cells after incubation with interleukin 1 alpha (14.9% +/- 2.8; p less than 0.005), interleukin 1 beta (23.2% +/- 4.2; p less than 0.0005) or TNF alpha (16.1% +/- 4.0; p = 0.005) compared to endotoxin controls (4.1% +/- 1.1). Interleukin 1 beta (9.5% +/- 1.5; p less than 0.005) showed a significantly increased number of R2D6-stained cells (control: 2.3% +/- 1.3). A similar but not significant effect was seen with interleukin 1 alpha and TNF alpha. Interleukin 6 had no effect on the antigen expression. The intensity of labeling was elevated among interleukin 1 beta-incubated cells compared to control samples. Thus, treatment of islets with different cytokines, especially interleukin 1 beta, increases surface antigen expression. We suggest that this mechanism of action in vitro may be of importance for the putative diabetogenic effect of interleukin 1.

Cranial base angulation and prognathism related to cranial and general skeletal maturation in human fetuses.

The purpose of the present study was to describe normal midsagittal craniofacial morphology in second trimester human fetuses. Measurements of the cranial base angle and the prognathism of the maxilla and the mandible were performed on radiographs of cranial midsagittal tissue blocks of 52 fetuses with a gestational age from 13 to 27 weeks. Special procedures were developed for the definitions of the nasion and sella reference points on the radiographs in the early stages of fetal development. Mean data were reported for stages of crown rump length (CRL) and maturation of the fetal cranial base (MSS), usable as reference in assessment of pathological fetal crania in reports and autopsy procedures. Regression equations were determined for the regression of the angular values on CRL, MSS, and general skeletal maturation (TNO). The cranial base angle was found to decrease significantly, and the angles of prognathism to increase significantly with increasing CRL, TNO, and MSS values. It was suggested that these simultaneous and similar changes in the three angles could be accounted for by the upwards movement of the sella point produced by a cranial displacement of the pituitary fossa caused by local cartilagenous growth and bony remodelling during the period of study. The study thus reflects the influence of cranial skeletal maturation on the early development in shape of the craniofacial complex.