Massoud Stephane

The characteristic features of auditory verbal hallucinations in clinical and nonclinical groups: state-of-the-art overview and future directions.

Despite a growing interest in auditory verbal hallucinations (AVHs) in different clinical and nonclinical groups, the phenomenological characteristics of such experiences have not yet been reviewed and contrasted, limiting our understanding of these phenomena on multiple empirical, theoretical, and clinical levels. We look at some of the most prominent descriptive features of AVHs in schizophrenia (SZ). These are then examined in clinical conditions including substance abuse, Parkinsons disease, epilepsy, dementia, late-onset SZ, mood disorders, borderline personality disorder, hearing impairment, and dissociative disorders. The phenomenological changes linked to AVHs in prepsychotic stages are also outlined, together with a review of AVHs in healthy persons. A discussion of key issues and future research directions concludes the review.

Synchronous neural interactions assessed by magnetoencephalography: a functional biomarker for brain disorders

We report on a test to assess the dynamic brain function at high temporal resolution using magnetoencephalography (MEG). The essence of the test is the measurement of the dynamic synchronous neural interactions, an essential aspect of the brain function. MEG signals were recorded from 248 axial gradiometers while 142 human subjects fixated a spot of light for 45-60 s. After fitting an autoregressive integrative moving average (ARIMA) model and taking the stationary residuals, all pairwise, zero-lag, partial cross-correlations (PCC(ij)(0)) and their z-transforms (z(ij)(0)) between i and j sensors were calculated, providing estimates of the strength and sign (positive, negative) of direct synchronous coupling at 1 ms temporal resolution. We found that subsets of z(ij)(0) successfully classified individual subjects to their respective groups (multiple sclerosis, Alzheimers disease, schizophrenia, Sjögrens syndrome, chronic alcoholism, facial pain, healthy controls) and gave excellent external cross-validation results.

Better than mermaids and stray dogs? Subtyping auditory verbal hallucinations and its implications for research and practice

The phenomenological diversity of auditory verbal hallucinations (AVH) is not currently accounted for by any model based around a single mechanism. This has led to the proposal that there may be distinct AVH subtypes, which each possess unique (as well as shared) underpinning mechanisms. This could have important implications both for research design and clinical interventions because different subtypes may be responsive to different types of treatment. This article explores how AVH subtypes may be identified at the levels of phenomenology, cognition, neurology, etiology, treatment response, diagnosis, and voice hearer’s own interpretations. Five subtypes are proposed; hypervigilance, autobiographical memory (subdivided into dissociative and nondissociative), inner speech (subdivided into obsessional, own thought, and novel), epileptic and deafferentation. We suggest other facets of AVH, including negative content and form (eg, commands), may be best treated as dimensional constructs that vary across subtypes. After considering the limitations and challenges of AVH subtyping, we highlight future research directions, including the need for a subtype assessment tool.

Classification of schizophrenia with spectro-temporo-spatial MEG patterns in working memory.

OBJECTIVE To investigate whether temporo-spatial patterns of brain oscillations extracted from multichannel magnetoencephalogram (MEG) recordings in a working memory task can be used successfully as a biometric marker to discriminate between healthy control subjects and patients with schizophrenia. METHODS Five letters appearing sequentially on a screen had to be memorized. The letters constituted a word in one condition and a pronounceable non-word in the other. Power changes of 248 channel MEG data were extracted in frequency sub-bands and a two-step filter and search algorithm was used to select informative features that discriminated patients and controls. RESULTS The discrimination between patients and controls was greater in the word condition than in the non-word condition. Furthermore, in the word condition, the most discriminant patterns were extracted in delta (1-4 Hz), alpha (12-16 Hz) and beta (16-24 Hz) frequency bands. These features were located in the left dorso-frontal, occipital and left fronto-temporal, respectively. CONCLUSION The analysis of the oscillatory patterns of MEG recordings in the working memory task provided a high level of correct classification of patients and controls. SIGNIFICANCE We show, using a newly developed algorithm, that the temporo-spatial patterns of brain oscillations can be used as biometric marker that discriminate schizophrenia patients and healthy controls.

Evaluation of speech misattribution bias in schizophrenia.

BACKGROUND The attribution of self-generated speech to others could explain the experience of verbal hallucinations. To test this hypothesis, we developed a task to simultaneously evaluate (A) operations of self-other distinction and (B) operations that have the same cognitive demands as in A apart from self-other distinction. By adjusting A to B, operations of self-other distinction were specifically evaluated. METHOD Thirty-nine schizophrenia patients and 26 matched healthy controls were required to distinguish between self-generated, other-generated and non-generated (self or other) sentences. The sentences were in the first, second or third person and were read in a male or female voice in equal proportions. Mixed multi-level logistic regression models were used to investigate the effect of group, sentence source, pronoun and gender of the heard sentences on response accuracy. RESULTS Patients differed from controls in the recognition of self-generated and other-generated sentences but not in general recognition ability. Pronoun was a significant predictor of response accuracy but without any significant interaction with group. Differences in the gender of heard sentences were not significant. Misattribution bias differentiated groups only in the self-other direction. CONCLUSIONS These data support the theory that misattribution of self-generated speech to others could result in verbal hallucinations. The syntactic (pronoun) factor could impact self-other distinction in subtypes of verbal hallucinations that are phenomenologically defined whereas the acoustic factor (gender of heard speech) is unlikely to affect self-other distinction.

Multidimensional analysis of the abnormal neural oscillations associated with lexical processing in schizophrenia.

The neural mechanisms of language abnormalities, the core symptoms in schizophrenia, remain unclear. In this study, a new experimental paradigm, combining magnetoencephalography (MEG) techniques and machine intelligence methodologies, was designed to gain knowledge about the frequency, brain location, and time of occurrence of the neural oscillations that are associated with lexical processing in schizophrenia. The 248-channel MEG recordings were obtained from 12 patients with schizophrenia and 10 healthy controls, during a lexical processing task, where the patients discriminated correct from incorrect lexical stimuli that were visually presented. Event-related desynchronization/synchronization (ERD/ERS) was computed along the frequency, time, and space dimensions combined, that resulted in a large spectral–spatial–temporal ERD/ERS feature set. Machine intelligence techniques were then applied to select a small subset of oscillation patterns that are abnormal in patients with schizophrenia, according to their discriminating power in patient and control classification. Patients with schizophrenia showed abnormal ERD/ERS patterns during both lexical encoding and post-encoding periods. The top-ranked features were located at the occipital and left frontal–temporal areas, and covered a wide frequency range, including δ (1-4 Hz), α (8-12 Hz), β (12-32 Hz), and γ (32-48 Hz) bands. These top features could discriminate the patient group from the control group with 90.91% high accuracy, which demonstrates significant brain oscillation abnormalities in patients with schizophrenia at the specific frequency, time, and brain location indicated by these top features. As neural oscillation abnormality may be due to the mechanisms of the disease, the spectral, spatial, and temporal content of the discriminating features can offer useful information for helping understand the physiological basis of the language disorder in schizophrenia, as well as the pathology of the disease itself.

The dynamic architecture of working memory in schizophrenia

BACKGROUND The capacity to hold information in working memory is greater for the first and/or last items of a sequence of information (architecture), and varies according to the retention interval (dynamic) and the type of stimuli. Although working memory deficits in schizophrenia have been documented widely, it is not clear how its architecture and dynamics are affected by the disease. METHODS Using two Sternberg paradigms - the recognition and the context-recall tasks - we investigated the effect of serial position, retention interval, type of stimuli, and task (type of encoding for the serial position) on working memory capacity in 26 schizophrenia patients and 20 healthy control subjects. A mixed model analysis of variance was applied to the proportion of correct responses and reaction time data. RESULTS All the experimental factors had significant effects. However, the most important effects were those of group, groupxserial position, and groupxdelay interactions. The last two effects were driven by a reduced primacy effect and by a reduced performance with longer delay in schizophrenia compared to control subjects. The serial positionxdelay interaction was significant without triple interaction with group. Groupxtype of stimuli and groupxtask for the serial position interactions were not significant. CONCLUSION Schizophrenia patients exhibited normal dynamics but abnormal architecture of working memory (reduced primacy effect), and faster decay of information. These impairments affected equally verbal, spatial and object stimuli and operated with implicit and explicit encoding of the serial position. Although these impairments were not correlated with the clinical picture, they are likely to contribute to the pathogenesis of the difficulties with which schizophrenia patients are faced. Consequently, addressing these specific impairments could alleviate these difficulties.

Temporospatial Characterization of Brain Oscillations (TSCBO) Associated with Subprocesses of Verbal Working Memory in Schizophrenia

The studies of the neural correlates of verbal working memory in schizophrenia are somewhat inconsistent. This could be related to experimental paradigms that engage differentially working memory components or methodological limitations in terms of characterization of brain activity. Magnetoencephalographic recordings were obtained on 10 schizophrenia patients and 11 healthy controls while performing a modified Sternberg paradigm to investigate subprocesses of verbal working memory. A new method for temporospatial characterization of brain oscillations was applied to whole head recordings and a 1–48 Hz frequency range. Patients differed from controls in event-related synchronization/desynchronization (ERS/ERD) patterns during the encode phase, the mid-maintain phase, and the end of the maintain phase. During the encode phase, patients did not show 1–4 Hz ERS in the left anterior frontal and left parietal lobes. In the mid-maintain phase, the left anterior frontal and left parietal lobes 1–4 Hz ERS, and the bilateral occipital lobes 8–32 Hz ERS were not observed in patients. At the end of the maintain phase, patients did not exhibit 12–48 Hz ERD in the left frontal and parietal lobes. The behavioral data showed reduced primacy effect In schizophrenia, the encode and maintain subprocesses were associated with less ERS and less ERD, respectively. These ERS/ERD abnormalities had specificity in terms of frequency and spatial location. Less ERD reflects reduced complexity of the neural activity, while reduced ERS reflects failure of the neural systems to resume idle state. The impaired primacy effect appears related to specific ERS/ERD patterns in the encode and maintain phases.

Auditory verbal hallucinations result from combinatoric associations of multiple neural events

While Auditory Verbal Hallucinations (AVH) refer to specific experiences shared by all subjects who have AVH—the perception of auditory speech without corresponding external stimuli, the characteristics of these experiences differ from one subject to another. These characteristics include aspects such as the location of AVH (inside or outside the head), the linguistic complexity of AVH (hearing words, sentences, or conversations), the range of content of AVH (repetitive or systematized content), and many other variables. In another word, AVH are phenomenologically heterogeneous experiences. After decades of research focused on a few explanatory mechanisms for AVH, it is apparent that none of these mechanisms alone explains the wide phenomenological range of AVH experiences. To date, our phenomenological understanding of AVH remains largely disjointed from our understanding of the mechanisms of AVH. For a cohesive understanding of AVH, I review the phenomenology and the cognitive and neural basis of AVH. This review indicates that the phenomenology of AVH is not a pointless curiosity. How a subject describes his AVH experiences could inform about the neural events that resulted in AVH. I suggest that a subject-specific combinatoric associations of different neural events result in AVH experiences phenomenologically diverse across subjects.

Selection of spectro-temporal patterns in multichannel MEG with support vector machines for schizophrenia classification

We present a new framework for the diagnosis of schizophrenia based on the spectro-temporal patterns selected by a support vector machine from multichannel magnetoencephalogram (MEG) recordings in a verbal working memory task. In the experimental paradigm, five letters appearing sequentially on a screen were memorized by subjects. The letters constituted a word in one condition and a pronounceable nonword in the other. Power changes were extracted as features in frequency subbands of 248 channel MEG data to form a rich feature dictionary. A support vector machine has been used to select a small subset of features with recursive feature elimination technique (SVM-RFE) and the reduced subset was used for classification. We note that the discrimination between patients and controls in the word condition was higher than in the non-word condition (91.8% vs 83.8%). Furthermore, in the word condition, the most discriminant patterns were extracted in delta (1–4 Hz), theta (4–8Hz) and alpha (12–16 Hz) frequency bands. We note that these features were located around the left frontal, left temporal and occipital areas, respectively. Our results indicate that the proposed approach can quantify discriminative neural patterns associated to a functional task in spatial, spectral and temporal domain. Moreover these features provide interpretable information to the medical expert about physiological basis of the illness and can be effectively used as a biometric marker to recognize schizophrenia in clinical practice.