Left-Dominant Temporal-Frontal Hypercoupling in Schizophrenia Patients With Hallucinations During Speech Perception

International audienceBackground: Task-based functional neuroimaging studies of schizophrenia have not yet replicated the increased coordinated hyperactivity in speech-related brain regions that is reported with symptom-capture and resting-state studies of hallucinations. This may be due to suboptimal selection of cognitive tasks. Methods: In the current study, we used a task that allowed experimental manipulation of control over verbal material and compared brain activity between 23 schizophrenia patients (10 hallucinators, 13 nonhallucinators), 22 psychiatric (bipolar), and 27 healthy controls. Two conditions were presented, one involving inner verbal thought (in which control over verbal material was required) and another involving speech perception (SP; in which control verbal material was not required). Results: A functional connectivity analysis resulted in a left-dominant temporal-frontal network that included speech-related auditory and motor regions and showed hypercoupling in past-week hallucinating schizophrenia patients (relative to nonhallucinating patients) during SP only. Conclusions: These findings replicate our previous work showing generalized speech-related functional network hypercoupling in schizophrenia during inner verbal thought and SP, but extend them by suggesting that hypercoupling is related to past-week hallucination severity scores during SP only, when control over verbal material is not required. This result opens the possibility that practicing control over inner verbal thought processes may decrease the likelihood or severity of hallucinations

Remembering verbally-presented items as pictures:brain activity underlying visual mental images in schizophrenia patients with visual hallucinations

Background: Previous research suggests that visual hallucinations in schizophrenia consist of mental images mistaken for percepts due to failure of the reality-monitoring processes. However, the neural substrates that underpin such dysfunction are currently unknown. We conducted a brain imaging study to investigate the role of visual mental imagery in visual hallucinations. Method: Twenty-three patients with schizophrenia and 26 healthy participants were administered a reality-monitoring task whilst undergoing an fMRI protocol. At the encoding phase, a mixture of pictures of common items and labels designating common items were presented. On the memory test, participants were requested to remember whether a picture of the item had been presented or merely its label. Results: Visual hallucination scores were associated with a liberal response bias reflecting propensity to erroneously remember pictures of the items that had in fact been presented as words. At encoding, patients with visual hallucinations differentially activated the right fusiform gyrus when processing the words they later remembered as pictures, which suggests the formation of visual mental images. On the memory test, the whole patient group activated the anterior cingulate and medial superior frontal gyrus when falsely remembering pictures. However, no differential activation was observed in patients with visual hallucinations, whereas in the healthy sample, the production of visual mental images at encoding led to greater activation of a fronto-parietal decisional network on the memory test. Conclusions: Visual hallucinations are associated with enhanced visual imagery and possibly with a failure of the reality-monitoring processes that enable discrimination between imagined and perceived events

Processing of Self versus Non-Self in Alzheimer’s Disease

Despite considerable evidence for abnormalities of self-awareness in Alzheimer’s disease (AD), the cognitive mechanisms of altered self-processing in AD have not been fully defined. Here we addressed this issue in a detailed analysis of self/non-self-processing in three patients with AD. We designed a novel neuropsychological battery comprising tests of tactile body schema coding, attribution of tactile events to self versus external agents, and memory for self- versus non-self-generated vocal information, administered in conjunction with a daily life measure of self/non-self-processing (the Interpersonal Reactivity Index). Three male AD patients (aged 54–68 years; one with a pathogenic mutation in the Presenilin 1 gene, one with a pathogenic mutation in the Amyloid Precursor Protein gene, and one with a CSF protein profile supporting underlying AD pathology) were studied in relation to a group of eight healthy older male individuals (aged 58–74 years). Compared to healthy controls, all patients had relatively intact tactile body schema processing. In contrast, all patients showed impaired memory for words previously presented using the patient’s own voice whereas memory for words presented in other voices was less consistently affected. Two patients showed increased levels of emotional contagion and reduced perspective taking on the Interpersonal Reactivity Index. Our findings suggest that AD may be associated with deficient self/non-self differentiation over time despite a relatively intact body image: this profile of altered self-processing contrasts with the deficit of tactile body schema previously described in frontotemporal dementia associated with C9orf72 mutations. We present these findings as a preliminary rationale to direct future systematic study in larger patient cohorts

Interaction of language, auditory and memory brain networks in auditory verbal hallucinations

Auditory verbal hallucinations (AVH) occur in psychotic disorders, but also as a symptom of other conditions and even in healthy people. Several current theories on the origin of AVH converge, with neuroimaging studies suggesting that the language, auditory and memory/limbic networks are of particular relevance. However, reconciliation of these theories with experimental evidence is missing. We review 50 studies investigating functional (EEG and fMRI) and anatomic (diffusion tensor imaging) connectivity in these networks, and explore the evidence supporting abnormal connectivity in these networks associated with AVH. We distinguish between functional connectivity during an actual hallucination experience (symptom capture) and functional connectivity during either the resting state or a task comparing individuals who hallucinate with those who do not (symptom association studies). Symptom capture studies clearly reveal a pattern of increased coupling among the auditory, language and striatal regions. Anatomical and symptom association functional studies suggest that the interhemispheric connectivity between posterior auditory regions may depend on the phase of illness, with increases in non-psychotic individuals and first episode patients and decreases in chronic patients. Leading hypotheses involving concepts as unstable memories, source monitoring, top-down attention, and hybrid models of hallucinations are supported in part by the published connectivity data, although several caveats and inconsistencies remain. Specifically, possible changes in fronto-temporal connectivity are still under debate. Precise hypotheses concerning the directionality of connections deduced from current theoretical approaches should be tested using experimental approaches that allow for discrimination of competing hypotheses

Brain networks involved in source monitoring in schizophrenia

Schizophrenia is characterized by cognitive deficits in many domains. One of the domains in which these deficits are commonly found is in self-other source monitoring. Source monitoring refers to the set of processes by which individuals recall the conditions and contextual details surrounding the encoding of a memory episode, and self-other source monitoring specifically involves differentiating between actions performed by oneself versus those performed by another person. In this study, the goal was to investigate the neural basis of self-other source monitoring, and to discover how this neural activity differs in schizophrenia. The results of this study indicate that schizophrenia patients and healthy control subjects utilize essentially the same neural network for self-other source monitoring, and that this network involves brain areas that have been described as belonging to the task-positive and task-negative networks. Multiple statistical methods were used to analyze this dataset in order to provide a comprehensive set of results, as well as to determine the agreement between them. Although differences exist between the methods employed herein, in both the matrices that are used as input, and the mathematical operations performed on them, the results suggest that all the methods identified a common signal in the data.Medicine, Faculty ofGraduat

Multimodal examination of brain networks involved in attentional biasing in schizophrenia

Schizophrenia is a serious, chronic mental illness that is characterized by perceptual abnormalities and cognitive deficits. Although the illness is commonly associated with perceptual abnormalities, the cognitive deficits have the greater impact on functional outcomes in patients. Some of the most profound deficits in schizophrenia have been observed in a domain referred to as cognitive control. Cognitive control is defined as the ability to adaptively adjust behaviour in response to environmental changes. Given the broadness of this definition, cognitive control is often fractionated into constituent cognitive operations, such as goal representation and maintenance, attentional biasing, conflict resolution, and stimulus-response mapping. In this study, the goal was to examine the brain basis for deficits in the attentional biasing aspect of cognitive control in schizophrenia. Behavioural and brain mechanisms of attentional biasing were assessed by manipulating the number of features that participants would have to ignore for each experimental trial. As schizophrenia is characterized by changes to both brain structure and function, a further aim was to use multi-modal brain imaging to develop a comprehensive picture of changes that underlie difficulties in attentional biasing. The results of this study indicated that although schizophrenia patients exhibit changes in brain structure, they still utilized the same brain networks as neurologically healthy individuals to bias attention towards relevant stimulus features. For the functional magnetic resonance imaging results, a functional brain network underlying attentional biasing, which included the dorsal anterior cingulate cortex, was identified and showed a positive relationship between the number of irrelevant stimulus features and increases in brain activity. Patients, however, showed reduced compensatory modulations in brain activity as the number of irrelevant stimulus dimensions increased. The magnetoencephalography results showed differences between the schizophrenia patients and healthy participants, but these differences were not as hypothesized, and may reflect cognitive differences related to language processing in schizophrenia. This work suggests that brain activity in patients is less efficient at higher levels of task difficulty when performing an attentional biasing task but these results are clouded by underlying changes in brain structure and a high variability in task activity in the patients.Medicine, Faculty ofGraduat

Aberrant default network activations during verbal thought generation may contribute to hallucinations in schizophrenia

International audienceSchizophrenia, particularly hallucinations, has been associated with impairments in source monitoring, whereby hallucinating patients tend to misattribute the source of a speech event to an external agent. Previous research proposed that abnormalities in generating thoughts may induce more vivid auditory sensations, which could account for misattribution from an internal to external source, possibly leading to auditory verbal hallucinations. In the present study, we investigated the neural underpinnings of a verbal thought generation (VTG) task using fMRI in 12 healthy controls and in 5 schizophrenia patients (DSM-IV). Two conditions were examined. In the first condition, participants were required to mentally generate a definition of a frequent word presented on the screen. In the second condition, participants were required to listen to the definition of a frequent word presented on the screen. An event-related fMRI protocol was used over 2 sessions of 8 minutes each. Analysis using constrained principal component analysis with a finite impulse response (FIR) model indicated that, during the mental generation task, default network regions including bilateral posterior cingulate cortex (BA 30-31), medial frontal gyrus bilaterally (BA10) and left precuneus (BA 7-19) showed less complete deactivation in schizophrenia patients relative to healthy controls. No group differences were found in task-positive networks, or the listening only condition. These results suggest abnormalities in the default network associated with the generation of thoughts, which may play a part in the genesis of auditory verbal hallucinations

More than a surprise: The bivalency effect in task switching

When switching tasks, if stimuli are presented that contain features that cue two of the tasks in the set (i.e., bivalent stimuli), performance slowing is observed on all tasks. This generalized slowing extends to tasks in the set which have no features in common with the bivalent stimulus and is referred to as the bivalency effect. In previous work, the bivalency effect was invoked by presenting occasionally occurring bivalent stimuli; therefore, the possibility that the generalized slowing is simply due to surprise (as opposed to bivalency) has not yet been discounted. This question was addressed in two task switching experiments where the occasionally occurring stimuli were either bivalent (bivalent version) or merely surprising (surprising version). The results confirmed that the generalized slowing was much greater in the bivalent version of both experiments, demonstrating that the magnitude of this effect is greater than can be accounted for by simple surprise. This set of results confirms that slowing task execution when encountering bivalent stimuli may be fundamental for efficient task switching, as adaptive tuning of response style may serve to prepare the cognitive system for possible future high conflict trials