Comparative coherence studies in healthy volunteers and Down's syndrome patients from childhood to adult age

Within the scope of the Munich Pediatric Longitudinal Study, EEG coherence was studied in 212 Down's syndrome patients and 342 healthy controls aged from 6 months up to 30 years. The digitalized EEG records were subjected to spectral analysis. Frequency band-related coherences were calculated to reveal age-specific differences in the functional relationship between two brain areas in Down's syndrome patients and controls.The results show that in the “eyes-open” state the intra-hemispheric coherence in the alpha band was significantly lower (P < 0.05) in the Down's syndrome patients than in the controls whereas that in the delta bands it was generally higher. The intra-hemispheric coherence in the “eyes-closed” state was generally higher in the Down's syndrome groups than in the controls; however, significant differences could be detected only in some age groups. The age-specific development of coherence in the inter-hemispheric parieto-occipital region was almost identical in Down's syndrome children as in controls, both with open and closed eyes. The most distinct differences were found in the fronto-central inter-hemispheric coherence (P < 0.01), while the coherence deficiencies in the Down's syndrome group became more prominent with increasing age from school age onwards.These electrophysiological results are compared with the results of neuropathological and neurophysiological studies of other authors. It can be suggested that there are correlations with a significantly small number of dendritic spines in Down's syndrome patients, which was determined in neuropathological examinations. A neuronal model of interpretation is presented which explains the increasing developmental deficit with age in Down's syndrome children.     

Age and gender effects in EEG coherence: II. Boys with attention deficit/hyperactivity disorder.

OBJECTIVE: This study investigated intra-hemispheric and inter-hemispheric EEG coherences as a function of age in boys with different subtypes of Attention Deficit/Hyperactivity Disorder (AD/HD), in comparison with a control group of normal boys. METHODS: Three groups of 40 children (AD/HD combined type, AD/HD inattentive type, and normal controls) participated. Each group contained 8 males in each 1 year band from 8 to 12 years. EEG was recorded from 21 sites during an eyes-closed resting condition. Wave-shape coherence was calculated for 8 intra-hemispheric electrode pairs (4 in each hemisphere), and 8 inter-hemispheric electrode pairs, within each of the delta, theta, alpha and beta bands. RESULTS: Developmental effects in intra-hemispheric coherences at shorter and longer inter-electrode distances generally supported Thatcher's two-compartment model. Control boys showed evidence of development in longer-range inter-hemispheric coherences which was not apparent in AD/HD boys. Boys with AD/HD of the combined type showed qualitatively different anomalies than boys with AD/HD of the inattentive type. CONCLUSIONS: EEG coherences in normal boys of this age range develop systematically with age in a non-linear fashion. Boys with AD/HD do not show this development. They display coherence anomalies which differ in nature between DSM-IV subtypes, suggesting differences which are not relatable to simple symptom severity. SIGNIFICANCE: The data reported here indicate differences in the development of EEG coherences in boys with AD/HD, and point to differences between the AD/HD subtypes which may help understanding of the disorder.     

Age and gender effects in EEG coherence: I. Developmental trends in normal children.

OBJECTIVE: This study investigated intra-hemispheric and inter-hemispheric EEG coherences as a function of age and gender in normal children. METHODS: Two groups of 40 boys and 40 girls, each containing 8 normal children in each 1-year band from 8 to 12 years, participated. EEG was recorded from 21 sites during an eyes-closed resting condition. Wave-shape coherence was calculated for 8 intra-hemispheric electrode pairs (4 in each hemisphere), and 8 inter-hemispheric electrode pairs, within each of the delta, theta, alpha and beta bands. RESULTS: There was consistent evidence of coherences developing across this age range, particularly in long-range intra- and inter-hemispheric electrode pairs. Coherences were larger in the left hemisphere than the right. Coherences also appeared to develop further in males than females, across several regions and frequency bands, suggesting that females lag males in this aspect of brain development. CONCLUSIONS: EEG coherences in normal children of this age range develop systematically with age. These developmental effects vary substantially with gender, brain region and frequency bands. SIGNIFICANCE: The data reported here provide basic norms for coherence development in different brain regions in normal children.     

Intra-hemispheric alpha coherence decreases with increasing cognitive impairment in HIV patients

Inter-hemispheric and intra-hemispheric canonical coherences in the alpha range between EEG signals collected from frontal and posterior groups of electrodes were estimated for 38 HIV positive subjects and 23 uninfected controls. Neuropsychological testing was used to categorize the degree of cognitive impairment evident in each of the subjects. A linear regression analysis provided evidence that intra-hemispheric coherence decreased with increasing cognitive impairment in impaired HIV⁺ subjects, as measured by a Global Impairment Score (GIS). There was no evidence that cognitively unimpaired HIV⁺ subjects differed in coherence when compared to uninfected control subjects. Severely impaired HIV⁺ subjects showed significantly decreased coherence compared to uninfected controls. These data contradict previous work demonstrating increased intra-hemispheric and inter-hemispheric alpha coherence in impaired HIV subjects. In addition, they provide evidence that intra-hemispheric (and possibly inter-hemispheric) disconnection is associated with cognitive impairment in HIV.     

EEG power, frequency, asymmetry and coherence in male depression

Quantitative electroencephalographic (EEG) power topography has served as a useful tool for investigating brain regional mechanisms underlying affective disorders. In an attempt to examine the role of gender and widen the scope of the measurement probes used in these investigations, the traditional power and inter-hemispheric power ratio indices were supplemented with intra-hemispheric power ratios, mean frequency and both inter and intra-hemispheric coherence indices, in the comparison of depressed male patients and healthy controls. Resting (eyes closed), vigilance controlled EEG recordings from 21 scalp sites were collected from 70 male, unmedicated, unipolar major depressive disorder outpatients and 23 normal control male subjects. Absolute and relative power, frequency, asymmetry and coherence measures derived from spectrally analyzed EEGs were subjected to univariate analyses for group comparisons as well as to discriminant function analysis to examine their utility as classification indices. Compared with controls, patients evidenced greater overall relative beta power and, at bilateral anterior regions, greater absolute beta power and faster mean total spectrum frequency. Inter-hemispheric alpha power asymmetry index differences were noted, with controls exhibiting relatively reduced left hemisphere activation, and widespread reduced delta, theta, alpha and beta coherence indices. Whereas intra-hemispheric theta power asymmetry reduction was exhibited in patients bilaterally at all regions, group differences with intra-hemispheric beta power asymmetry were unilateral, being restricted to the right hemisphere. Discriminant analysis correctly classified 91.3% of the patients and controls. Quantitative EEG measurements in male depression appear to describe a pattern of aberrant inter-hemispheric synchrony/asymmetry and a profile of frontal activation.     

Resting state EEG power and coherence abnormalities in bipolar disorder and schizophrenia

Resting state electroencephalogram (EEG) abnormalities in schizophrenia and bipolar disorder patients suggest alterations in neural oscillatory activity. However, few studies directly compare these anomalies between patient groups, and none have examined EEG coherence. Therefore, this study investigated whether these electrophysiological characteristics differentiate clinical populations from one another, and from non-psychiatric controls. To address this question, resting EEG power and coherence were assessed in 76 bipolar patients (BP), 132 schizophrenia patients (SZ), and 136 non-psychiatric controls (NC). We conducted separate repeated-measures ANOVAs to examine group differences within seven frequency bands across several brain regions. BP showed significantly greater power relative to SZ at higher frequencies including Beta and Gamma across all regions. In terms of intra-hemispheric coherence, while SZ generally exhibited higher coherence at Delta compared to NC and BP, both SZ and BP showed higher coherence at Alpha1 and Alpha2. In contrast, BP and HC showed higher coherence within hemispheres compared to SZ at Beta 1. In terms of inter-hemispheric coherence, SZ displayed higher coherence compared to NC at temporal sites at both Alpha1 and Alpha2. Taken together, BP exhibited increased high frequency power with few disruptions in neural synchronization. In contrast, SZ generally exhibited enhanced synchronization within and across hemispheres. These findings suggest that resting EEG can be a sensitive measure for differentiating between clinical disorders.     

Pathological theta oscillations in idiopathic generalised epilepsy.

OBJECTIVE: To investigate spectral power, inter- and intra-hemispheric coherence in the interictal scalp electroencephalography (EEG) of 41 patients with idiopathic generalised epilepsy. METHODS: Two minutes of eyes-closed waking interictal EEG activity was analysed. Fast Fourier transformation was performed. Raw and age-regressed, Z-transformed values were computed for 19 electrodes and 4 frequency bands: absolute power (AP, ZAP), percent power (RP, ZRP), band mean frequency (MF, ZMF), inter-hemispheric (CO, ZCO) and intra-hemispheric (IC, ZIC) coherence. Compressed values (scalp averages) were computed for each parameter and 4 frequency bands. Compressed data of the patients (GE group) and the healthy controls (C group) were compared. RESULTS: ZAP across the entire 1.5-25.0 Hz range was greater in the GE than in the C group. Delta and theta ZRP was greater, alpha ZRP was less in GE than in C. ZMF and ZIC was about the same in the GE and C groups. The crucial, band-specific finding was significantly greater theta-ZCO in the GE group, in contrast to normal or decreased ZCO in the other bands. In addition, within-group correlation between ZAP of the frequency bands, correlation of ZAP and ZCO, correlation of ZIC and ZCO were different for the two groups. CONCLUSIONS: The pattern of enhanced ZAP, ZRP, ZCO, together with normal ZIC and ZMF in the theta range was a peculiar, novel finding in GE. It was incompatible with any of the known patterns of altered power and coherence due to lesional or metabolic aetiology. This pattern presumably indicates the presence of a powerful, diffuse, hypersynchronous, hypercoherent theta oscillation at the thalamo-cortical level of the brain. The role of inter-hemispheric connections in maintaining this oscillation was suggested. The other findings suggest disturbed central regulation of EEG power and coherence in the interictal state.     

EEG coherence analysis in never-medicated patients with panic disorder.

To investigate the functional abnormalities in the central nervous system (CNS) of patients with panic disorder (PD), we compared the electroencephalography (EEG) coherence values in 18 never-medicated PD patients with those in age-matched normal control subjects, and examined the relationships between EEG coherence values and both the duration of disease and the severity of panic attacks. EEG data were recorded in the resting state. The PD patients had lower coherence values with significant differences in F3-F4, C3-C4, P3-P4, F7-T5, and F8-T6. There were positive correlations for the higher alpha band between coherence values and both the duration of disease and the severity of panic attacks. These findings provide further evidence that PD patients have a lower degree of inter-hemispheric functional connectivity in the frontal region and intra-hemispheric functional connectivity in the bilateral temporal region, and that chronic condition or frequent panic attacks in PD patients may be related to the pathophysiological CNS changes.     

The topographical features of EEGs in patients with affective disorders.

EEG data were obtained in the basic state from 16 scalp sites of 44 patients with affective disorder, diagnosed by DSM-III criteria, and 44 normal controls. The EEG power spectra were computed and the t statistic significance probability mapping (SPM) was applied to visualize regions where the patient group showed differences in the EEG topogram from the controls. The results show: (1) left occipital predominance (P3, O1) of alpha activities in the patients with affective disorders, (2) decreased alpha activities in Fp2 and F8 areas in patients with major depression without melancholia, (3) decreased alpha activities in F7 area in patients with bipolar disorder, manic, and (4) increased beta 2 activity in F4 and C4 areas in patients with major depression with melancholia. These results suggest that inter-hemispheric and intra-hemispheric relationships may be disturbed in patients with affective disorder.     

EEG reactivity correlates with neuropsychological test scores in Down's syndrome

Introduction – Down's syndrome patients express a neurodegenerative disorder and mental retardation. We studied the reactivity of EEG and its correlation with neuropsychological test score in Down's syndrome. Material and methods – We studied 32 patients with Down's syndrome and 31 controls for blocking of occipital EEG activity. The temporo-occipital EEG with eyes open (EO) was compared with resting EEG with eyes closed (EC), (EC/EO ratio). Results – Both Down patients and controls showed significant diminution of alpha, beta and theta activity and decrease of EEG frequency with EO. However, there was a significant impairment in Down patients in the EC/EO ratio in alpha band, compared to controls. The controls had no correlation of the alpha EC/EO ratio with age or gender. The Down patients showed a significant correlation of this variable with age which is in accordance with a gradually progressing disease. They had also significant correlations of the alpha EC/EO ratio and neuropsychological test scores which indicates that this ratio may be a more general measure of cerebral or hemispherical dysfunction than a mere impairment of visual activation. Down patients also showed significant differences in resting EEG variables, compared to the controls, even if the conventional EEG showed normal or mildly slowed dominant occipital rhythm in most of the patients. The correlation analysis between resting EEG and EC/EO ratio variables pointed out that they are relatively independent, representing different factors in the regulation of EEG. Conclusions – We believe that the alpha EC/EO ratio of EEG add a new domain in the assessment of cerebral dysfunction in Down's syndrome.     

The topographical features of EEGs in patients with affective disorders

EEG data were obtained in the basic state from 16 scalp sites of 44 patients with affective disorder, diagnosed by DSM-III criteria, and 44 normal controls. The EEG power spectra were computed and the t statistic significance probability mapping (SPM) was applied to visualize regions where the patient group showed differences in the EEG topogram from the controls. The results show: (1) left occipital predominance (P3, O1) of alpha activities in the patients with affective disorders, (2) decreased alpha activities in Fp2 and F8 areas in patients with major depression without melancholia, (3) decreased alpha activities in F7 area in patients with bipolar disorder, manic, and (4) increased beta₂ activity in F4 and C4 areas in patients with major depression with melancholia.These results suggest that inter-hemispheric and intra-hemispheric relationships may be disturbed in patients with affective disorder.     

Functional connections among cortical regions: topography of EEG coherence

The covariance among EEG signals can be examined with coherence analysis. Evidence that the right hemisphere has a more diffuse receptotopic organization than the left, together with evidence that it may have a higher proportion of white to gray matter, suggests a high degree of functional connectedness among right hemisphere regions. To determine whether this is reflected in greater EEG coherence among right than left hemisphere locations, we constructed a matrix of cross-spectra among all unique pairs of EEG channels in an 8-channel montage, then statistically de-structured this matrix to examine multiple coherences and both inter- and intra-hemispheric partial multiple coherences. Analyses on data from the resting EEGs of 14 right-handed men examined weekly for several months showed higher coherences for right hemisphere locations. For the inter-hemispheric partial multiple coherences the frontal lobe values were also higher on the right, but the occipital inter-hemispheric coherences were higher on the left. These asymmetries have interesting parallels with anatomical asymmetries of the human cortex and may have functional implications.     

Performance analysis of univariate and multivariate EEG measurements in the diagnosis of ADHD

ObjectiveTo investigate the performance of univariate and multivariate EEG measurements in diagnosing ADHD subjects in a broad age range.MethodsEEG from eight cortical regions were recorded at rest during eyes open and eyes closed in 22 male ADHD subjects of combined type and 21 healthy male controls (age range 4–15 years). Univariate and interdependence measurements calculated from the frequency domain and from the reconstructed state spaces of EEG signals were computed, and their performance in discriminating ADHD from healthy subjects was analyzed.ResultsSignificant between-group differences in univariate measures were age-dependent. However, certain interdependence inter-hemispheric measures during eyes closed showed significant, age-independent between-groups differences. Among them, coherence in the beta band between inter-occipital regions and between left/occipital–right/central regions provided an overall accuracy classification rate of 74.4%. Even greater accuracy (86.7%) was obtained by an interdependence index of generalized synchronization between left/occipital–right/central regions and left/central–right/temporal regions.ConclusionsEEG beta coherence and especially the degree of generalized synchronization between a few inter-hemispheric regions during resting state with eyes closed allow a high accuracy classification rate of ADHD subjects.SignificanceChanges in inter-hemispheric EEG functional brain connectivity at rest are useful for ADHD diagnosis in a broad age range.     

Comparison of quantitative EEG between patients with Alzheimer’s disease and those with Parkinson’s disease dementia

Objective

Dementia frequently occurs in Parkinson’s disease (PD) but its pathophysiological basis is little known. Comparative EEG studies of Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD) are still rare, but could provide knowledge on the different pathophysiological mechanisms involved. The objective of the present study was to comparatively evaluate the absolute power and coherence on the EEG for patients with AD and PDD.

Methods

This study assessed 38 adults with AD, 12 with PDD, 31 with Parkinson’s disease without dementia, and 37 controls (CG) by a neurological evaluation, CERAD neuropsychological battery, executive functions tests and qEEG, calculating global absolute powers for the delta, theta, alpha and beta bands and inter- and intra-hemispheric coherences.

Results

The delta and theta powers were highest in PDD and lowest in CG (p < 0.05). The beta frontal-occipital inter-hemispheric coherence was highest in PDD (p < 0.05). Whereas, alpha and beta frontal inter-hemispheric coherence was highest in PDD and lowest in AD (p < 0.05).

Conclusion

These results suggest that qEEG power and coherence measures are different in AD and PDD.

Significance

These qEEG differences must be related to the distinct mechanisms of cortical neural connections in AD and PDD.     

Use of electroencephalography to detect Alzheimer's disease in Down's syndrome

We studied the role of electroencephalography (EEG) in the diagnosis of Alzheimer-type dementia in patients with Down's syndrome. 197 patients with Down's syndrome were monitored for 5 to 8 years. Aspects of cognitive functioning were assessed twice yearly. EEGs were scored in a blind fashion, and changes in the EEG were compared to changes in cognitive functioning. When possible, a neuropathological post-mortem examination was performed. Cognitive functioning was drastically reduced in 29 patients. The dominant occipital rhythm became slower at the onset of the cognitive deterioration, and eventually disappeared. In 11 of these patients neuropathological examination showed a severe form of Alzheimer's disease. Changes in the frequency of the dominant occipital rhythm could distinguish between Alzheimer's disease or other causes as underlying the cognitive decline. Slowing of the dominant occipital rhythm seems to be related to Alzheimer's disease in patients with Down's syndrome, and the frequency of the dominant occipital activity decreases at the onset of cognitive deterioration. The EEG is thus an important tool in the clinical diagnosis of Alzheimer-type dementia in patients with Down's syndrome.     

Postnatal cerebral maturation in Down's syndrome children: a developmental EEG coherence study.

Eyes-closed EEG was recorded from 19 scalp locations in thirty Down's Syndrome children and young adults, aged 9 months to 26 years. These subjects were age-matched to normal children and normal young adults. EEG coherence was computed for five groups of electrode pairings: 1--anterior-to-posterior, 2--posterior-to-anterior, 3--posterior temporal, 4--anterior temporal and 5--interhemispheric. The results showed that EEG coherence strongly and consistently discriminated between the two groups. Developmental trajectories in the Down's group were weakly linear and often with negative slopes. In contrast, normal children showed strong linear and nonlinear developmental trajectories with only positive slopes. The greatest differences between groups was in the left hemisphere and in posterior cortical regions as compared to frontal regions. The normal children exhibited growth spurts in EEG coherence at particular postnatal ages, whereas the Down's Syndrome children failed to exhibit strong growth spurts in EEG development.     

Observation of EEG coherence after repetitive transcranial magnetic stimulation.

OBJECTIVE: The effects before and after repetitive transcranial magnetic stimulation (rTMS) on EEG activity were investigated. METHODS: Nineteen healthy subjects received two trains (10 Hz, 100% of motor threshold, 3 s/train) of rTMS to the left frontal area. Directed coherence and ordinary coherence were calculated from EEG epochs recorded before and after (1 approximately 3 and 3 approximately 5 min) rTMS. The results were compared and demonstrated on maps. RESULTS: Directed coherence between cortical areas increased after rTMS (F=5.62, P<0.005), with the intra-hemispheric change being more pronounced than the inter-hemispheric change. Connections from the stimulated site to other sites were selectively reinforced. In contrast, ordinary coherence did not change after the stimulation. rTMS did not influence the dominant frequency at which maximal coherence was calculated. Differences in the directed coherence with opposite directions after rTMS were significantly correlated with the differences before rTMS (r=0.88, 0.89, P<0.001). CONCLUSIONS: (1) rTMS can enhance the connections between cortical areas, especially connections between the stimulated cortex and other sites in the brain. (2) Comparing with connections from the parietal area to frontal area, connections from the frontal area to parietal area are obviously improved by rTMS in both hemispheres. (3) The effects of rTMS can last for several minutes. Therefore, the necessity of EEG monitoring in rTMS studies is suggested.     

Alzheimer-like neurotransmitter deficits in adult Down''s syndrome brain tissue.

Brain tissue taken at necropsy from five cases of Down's syndrome and six controls was analysed for changes in neurotransmitter markers. Concentrations of noradrenaline (NA), dopamine (DA) and its major metabolite homovanillic acid (HVA), 5-hydroxytryptamine (5HT) and its metabolite 5-hydroxyindoleacetic acid (5HIAA) were determined by means of HPLC, whilst choline acetyltransferase (ChAT) was measured by a radiochemical technique. Significant reductions in NA, 5HT and ChAT were found in most cortical and subcortical regions of the Down's syndrome tissue investigated. The neuropathological lesions were assessed using a fluorescent stain for neuritic plaques and neurofibrillary tangles. These were present to varying extents in every Down's syndrome case except the youngest but were not found in control tissue of comparable age. The results indicate profound transmitter deficits and neuropathological abnormalities in adult patients with Down's syndrome, which closely resemble those of Alzheimer's disease.     

Down's syndrome: intellectual and behavioural functioning during adulthood

ABSTRACT. Previous cross–sectional studies of Down's syndrome have suggested thatdeficits in cognitive and neurological functioning after the age of 35 years are symptomatic of Alzheimer's disease. It has been claimed that this pattern corresponds to post-mortem neuropathological findings of Alzheimer's disease in all Down's syndrome patients who die aged over 35 years. In the present study of Down's syndrome patients aged between 19 and 49 years, results showed that, for those over 35 years, intellectual deterioration had occurred in less than a third. No relationship was found between chronological age and the level of self care skills or the presence of disturbed behaviour. Results are discussed in terms of the interpretation of the existing neuropathological literature, the methodology of future studies and clinicaldecisions regarding hospitalized patients with Down's syndrome.     

Abnormal inter- and intra-hemispheric integration in male paranoid schizophrenia: a graph-theoretical analysis

Background

The human brain is a complex network of regions that are structurally interconnected by white matter (WM) tracts. Schizophrenia (SZ) can be conceptualized as a disconnection syndrome characterized by widespread disconnections in WM pathways.

Aims

To assess whether or not anatomical disconnections are associated with disruption of the topological properties of inter- and intra-hemispheric networks in SZ.

Methods

We acquired the diffusion tensor imaging data from 24 male patients with paranoid SZ during an acute phase of their illness and from 24 healthy age-matched male controls. The brain FA-weighted (fractional anisotropy-weighted) structural networks were constructed and the inter- and intra-hemispheric integration was assessed by estimating the average characteristic path lengths (CPLs) between and within the left and right hemisphere networks.

Results

The mean CPLs for all 18 inter-and intra-hemispheric CPLs assessed were longer in the SZ patient group than in the control group, but only some of these differences were significantly different: the CPLs for the overall inter-hemispheric and the left and right intra-hemispheric networks; the CPLs for the interhemisphere subnetworks of the frontal lobes, temporal lobes, and subcortical structures; and the CPL for the intra- frontal subnetwork in the right hemisphere. Among the 24 patients, the CPL of the inter-frontal subnetwork was positively associated with negative symptom severity, but this was the only significant result among 72 assessed correlations, so it may be a statistical artifact.

Conclusions

Our findings suggest that the integrity of intra- and inter-hemispheric WM tracts is disrupted in males with paranoid SZ, supporting the brain network disconnection model (i.e., the ^‘connectivity hypothesis^’) of schizophrenia. Larger studies with less narrowly defined samples of individuals with schizophrenia are needed to confirm these results.