Discriminating between bipolar and major depressive disorder using a machine learning approach and resting-state EEG data.

OBJECTIVE: Distinguishing major depressive disorder (MDD) from bipolar disorder (BD) is a crucial clinical challenge as effective treatment is quite different for each condition. In this study electroencephalography (EEG) was explored as an objective biomarker for distinguishing MDD from BD using an efficient machine learning algorithm (MLA) trained by a relatively large and balanced dataset. METHODS: A 3 step MLA was applied: (1) a multi-step preprocessing method was used to improve the quality of the EEG signal, (2) symbolic transfer entropy (STE), an effective connectivity measure, was applied to the resultant EEG and (3) the MLA used the extracted STE features to distinguish MDD (N = 71) from BD (N = 71) subjects. RESULTS: 14 connectivity features were selected by the proposed algorithm. Most of the selected features were related to the frontal, parietal, and temporal lobe electrodes. The major involved regions were the Broca region in the frontal lobe and the somatosensory association cortex in the parietal lobe. These regions are near electrodes FC5 and CPz and are involved in processing language and sensory information, respectively. The resulting classifier delivered an evaluation accuracy of 88.5% and a test accuracy of 89.3%, using 80% of the data for training and evaluation and the remaining 20% for testing, respectively. CONCLUSIONS: The high evaluation and test accuracies of our algorithm, derived from a large balanced training sample suggests that this method may hold significant promise as a clinical tool. SIGNIFICANCE: The proposed MLA may provide an inexpensive and readily available tool that clinicians may use to enhance diagnostic accuracy and shorten time to effective treatment.

A Machine Learning Algorithm to Discriminating Between Bipolar and Major Depressive Disorders Based on Resting EEG Data.

Distinguishing major depressive disorder (MDD) from bipolar disorder (BD) is a crucial clinical challenge due to the lack of known biomarkers. Conventional methods of diagnosis rest exclusively on symptomatic presentation, and personal and family history. As a result, BD-depressed episode (BD-DE) is often misdiagnosed as MDD, and inappropriate therapy is given. Electroencephalography (EEG) has been widely studied as a potential source of biomarkers to differentiate these disorders. Previous attempts using machine learning (ML) methods have delivered insufficient sensitivity and specificity for clinical use, likely as a consequence of the small training set size, and inadequate ML methodology. We hope to overcome these limitations by employing a training dataset of resting-state EEG from 71 MDD and 71 BD patients. We introduce a robust 3 steps ML technique: 1) a multi-step preprocessing method is used to improve the quality of the EEG signal 2) symbolic transfer entropy (STE), which is an effective connectivity measure, is applied to the resultant EEG signals 3) the ML algorithm uses the extracted STE features to distinguish MDD from BD patients. Clinical Relevance--- The accuracy of our algorithm, derived from a large sample of patients, suggests that this method may hold significant promise as a clinical tool. The proposed method delivered total accuracy, sensitivity, and specificity of 84.9%, 83.4%, and 87.1%, respectively.

Neuroleptics reverse attention asymmetries in schizophrenic patients.

Discussions of hemispheric asymmetry in psychopathology are often confounded by the effects of medication. We examined the effect of neuroleptic drugs on attention asymmetries in acutely psychotic patients admitted for the first time to a psychiatric hospital before the initiation of drug treatment and again after a period of treatment with neuroleptics. Overall performance did not change significantly; however, attention asymmetry was clearly related to the medication status of the patient: unmedicated patients showed inattention to the right hemispace, which changed to more prominent left-sided inattention when medicated. A longer time on medication or a higher daily dose were associated with a shift of inattention from the right to left hemispace. This suggests that neuroleptics may normalize left hemisphere performance, at the expense of deteriorated right hemisphere performance.

A neuropsychological study of the stable syndrome of hysteria.

Ten patients with the stable syndrome of hysteria were matched for age, sex, handedness, and full-scale WAIS IQ with ten controls, ten psychotic depressives and ten schizophrenics. All were subjected to an extensive neuropsychological test battery. Compared to the controls, the hysteria group exhibited bifrontal impairment (R = L) and, globally, greater dysfunction of the nondominant hemisphere. A G analysis provided a complete separation between the hysteria and controls. However, a D-index analysis showed that the hysteria group was more impaired than normals and depressives because of greater dysfunction of the dominant hemisphere, whilst schizophrenia showed greater nondominant hemisphere dysfunction than hysteria. Further, a cluster analysis on the 40 subjects produced three clusters: normal controls, depressives, and a schizophrenia-hysteria grouping. These findings are interpreted as suggesting that dominant hemisphere dysfunction is fundamentally related to the syndrome of hysteria and that the dysfunction of the nondominant hemisphere is brought about by associated features: the female excess, the emotional instability and dysphoric mood, the presence of asymmetrical pain, and conversion symptomatology. It is further argued, in view of the familial associations, that hysteria in the female is a syndrome equivalent to psychopathy in the male (who also exhibits dominant hemisphere dysfunction) and might represent in the female a (relatively benign) variant of schizophrenia characterized by imprecise verbal communications, a subtle form of affective incongruity, together with the conversion parameter.

Neuropsychological and power spectral EEG investigations of the obsessive-compulsive syndrome.

Eleven consecutive patients with primary obsessive-compulsive syndrome were studied neuropsychologically and the power spectral EEG characteristic of ten of these patients unmedicated, at rest, and during cognitive tasks were analyzed. The finding of predominantly left frontal dysfunction in the obsessional syndrome is discussed in the light of neurophysiological and psychosurgical evidence which suggest that perturbation of the cingulate-orbital frontal connections modulates obsessive-compulsive symptomatology.

Imbalance of hemispheric functions in the major psychoses: a study of handedness in the People's Republic of China.

A study of hand preference and eye dominance in schizophrenia, manic-depressive psychosis, and normal controls was carried out in the People's Republic of China. An excess of sinistrality was found in both men and women schizophrenics, but not in manic-depressive patients. Both the manic-depressive and schizophrenic psychoses are characterized by a significant excess of left eye dominance and by an increasing divergence between eye and hand dominance when compared to the controls. The major published studies investigating hand preference in psychopathology are reviewed, and possible interpretations of the conflicting findings are suggested.

Asymmetrical olfactory acuity and neuroleptic treatment in schizophrenia.

Uni-rhinal olfactory acuity in schizophrenia was investigated in two experiments. The first assessed the presence of a predicted atypical asymmetry of nostril laterality and the second assessed the effect of antipsychotic treatment on the asymmetry. Although olfactory identification impairment has been well documented in schizophrenia, olfactory acuity has been neglected. This may be an oversight as cerebral structures of the mesial temporal lobe important to olfactory perception have often been implicated in the pathophysiology of schizophrenia and it is thus reasonable to postulate a primary impairment of olfactory acuity in schizophrenia. In addition, unmedicated patients with schizophrenia have exhibited asymmetrical laterality favouring the right over the left hemisphere in studies of visual, haptic, and auditory perception, and the few published prospective treatment studies have suggested a reversal of this asymmetry with first generation neuroleptic treatments. In experiment 1 a generalization of the perceptual asymmetry to olfactory acuity was examined by measurement of n-butanol olfactory thresholds with the Connecticut Chemosensory Perception Exam (CCPE) in an unmedicated sample of 17 patients with schizophrenia and 17 age, gender, and handedness matched normal controls. The patient sample showed an asymmetrical impairment of the left nostril that was not apparent in the normal control sample. In experiment 2, the CCPE was administered to a new sample of 10 patients with schizophrenia before and after neuroleptic treatment. The asymmetry observed in experiment 1 was replicated, and the relative advantage of the right nostril shifted to a relative advantage of the left nostril over the course of 8weeks of treatment. Results are discussed in relation to cerebral aspects of schizophrenia and potential implications to cognitive change from treatment.

Electroconvulsive therapy and lateralized affective systems.

The neurophysiological systems subtending generalized seizures (activated by ECT) and temporal-limbic seizures are described as well as the interactions existing between the two seizure systems. There are correlations between schizophrenia and the limbic seizure system on the one hand and the manic-depressive or bipolar syndromes and the generalized seizure system on the other which are theoretically related to the different (although overlapping) neural substrates underlying the two major syndromes of psychosis. Evidence is reviewed that indicates that in ECT-responsive depression (with both bilateral and unilateral nondominant ECT) the modus operandi hinges on right-hemispheric neural events. Neurophysiological, neurological, and acoustic threshold evidence is discussed: all of which emphasizes the importance of the nondominant hemisphere in the genesis of endogenous depressions and in their treatment with convulsive therapies. In addition, studies showing that psychotropic agents with specific antidepressant effects produce asymmetric activation of the right hemisphere (EEG) are related to the above issues.

Influence of gender in schizophrenia as related to other psychopathological syndromes.

The evidence indicating that the forms of schizophrenia in men and women represent different morbid states is reviewed. Age of onset and gender are considered to be of fundamental importance in determining the different symptomatological and evolutionary features of the syndrome in the two sexes. Early-onset forms in males are associated with chronicity, absence of familial predisposition for psychosis, and the presence of structural cerebral pathology specifically involving the dominant hemisphere. Later onset forms in females are characterized by more florid symptoms, more affective features, more familial psychosis, and more favorable outcome with no or less pronounced structural cerebral involvement. It is argued that these differential characteristics derive from the differential hemispheric organization of the male and female brain--which also determines the male susceptibility to other psychopathological syndromes such as psychopathy and sexual deviations as well as the excess in women of schizoaffective states, affective disorders, and late-onset schizophrenia.

Statistical quantitative EEG studies of depression, mania, schizophrenia and normals.

The EEG characteristics of 63 depressive psychotics, 75 manics and 53 schizophrenic patients, consecutive admissions satisfying research criteria, are presented. Statistical comparisons between the psychotic groups and of each psychotic group against 60 normal controls (all dextral) were undertaken for power, coherence and phase characteristics in the 8-13 Hz frequency band. The characteristic EEG-myogenic power spectra for frequencies up to 60 Hz, expressed as the log of the right/left parietal and temporal power ratios for the four groups are also graphically displayed. The results suggest the presence of increasing disorganization of the right hemisphere (least in depression, intermediate in mania and maximal in schizophrenia) together with left hemisphere disorganization (in both mania and schizophrenia; again maximal in schizophrenia).

The effect of brain function on coherence patterns in the bipolar EEG.

Studies of the functional organization of the brain based on measurements of coherence in the EEG have, in the past, suffered from a methodological defect which has made interpretation of the results difficult. The effect involved is the use of an active common reference for the recording of the EEG. As a consequence, inferences related to the functional connectivity of brain between the non-referential sites using coherence have probably been wrong. To avoid the problem with the common reference, we have used bipolar derivations of the EEG and used measurements of coherence to reflect synchrony not between individual sites but between regions of the brain. The EEGs in a population of normal volunteers were examined with respect to coherence. Changes in the patterning of coherence were induced by utilizing EEGs from the volunteers during 3 different functional brain states. The first of these was the resting state, the second the verbal motor state and the third, the spatial motor state. The stepwise discriminant analysis method was used to study differences in the patterning of coherences in the 3 states. The results show that the spatial motor state was the most distinct in this regard amongst the 3 states. They results also interpreted as indicating that changes in the patterning of coherence from that in the resting state consisted of both functionally specific and functionally non-specific components.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurophysiological and neuropsychological study of two cases of multiple personality syndrome and comparison with chronic hysteria.

Two cases of multiple personality were studied neurophysiologically and neuropsychologically. Bilateral frontal (Right greater than Left) and left temporal dysfunction was present in both cases, on neuropsychological indicators. Both cases on EEG analysis, were in a state of relative left hemisphere activation, across all cerebral regions and task conditions. The one case who was cured with hypnotherapy, after recovery showed normal left hemisphere functions neuropsychologically but remained in a state of relative left hemisphere activation electrophysiologically. This is in contrast to women with chronic hysteria who exhibit relative right hemisphere activation in all regions and across all conditions. Both patients were unmedicated throughout. A neurophysiological model to account for these findings is presented.

Quantitative EEG studies of pedophilia.

Ninety six pedophiles, whose sexual orientation was confirmed by phallometric response to sexual stimuli, were investigated with quantitative EEG and compared to age- and sex-matched healthy controls. The EEG analysis showed a pattern of increased frontal delta, theta and alpha power (especially during verbal processing) and a pattern of reduced interhemispheric and increased intrahemispheric-interhemispheric coherence, right and left (only during verbal processing), an effect that was restricted to those who showed maximal erotic arousal for sexual partners aged 6-12 years. These findings will be discussed in the context of recent studies which suggest that sexual deviations in the male relate to altered dominant hemispheric functions with disruption of frontal interhemispheric relationships.

[Cerebral mechanisms of the efficacy of electroshock therapy]. / Mécanismes cérébraux de l'efficacité des électrochocs.

There are correlations between schizophrenia and the limbic seizure system on the one hand and the manic-depressive or bipolar syndromes and the generalized seizure system on the other hand, which are theoretically related to the different (although overlapping) neural substrates underlying the two major syndromes of psychosis. Evidence is reviewed that indicates that in ECT-responsive depression (with both bilateral and unilateral nondominant ECT) the modus operandi hinges on right-hemispheric neural events. At the same time the relevance of the complex interactions existing between limbic and generalized seizures, REM suppression, right limbic epilepsy and REM activation is discussed as well as the role of carbamazepine in these interactions.

[The obsessive-compulsive syndrome: reflection of fronto-caudate dysregulation of the left hemisphere?]. / Le syndrome obsessionnel-compulsif: reflet d'un défaut de régulation fronto-caudée de l'hémisphère gauche?

Neuropsychological studies of the obsessional syndrome reveal bilateral frontal dysfunction. Early onset is characteristic of males, who have a more chronic course than females, and who are more often non-dextral. Hypermetabolic activity of the frontal and caudate, bilaterally, is found in most PET investigations, although one report is of relative hypofrontality and global cortical hypometabolism for absolute values. Given the frequency with which basal ganglia disease leads to obsessive-compulsive phenomena (Cf Sydenham's Chorea, Gilles de La Tourette) and frontal lobe inertia, a perturbation of frontal-caudate regulatory motor and ideational sub-systems in the obsessional syndrome appears probable. Bilateral caudate atrophy on CT scan has been reported. Further, EP investigations, both somatosensory and auditory, implicate the left hemisphere in obsessions; together with reduced P300 latencies and during imaginal flooding there is increased left (frontal) hemisphere flow (rCBF). Single case studies document the relationship of obsessions to left frontal-left caudate unilateral pathology. It is suggested that lateralized dysregulation of the left fronto-caudate network is the major cerebral determinant of obsessive-compulsive states.