Delphine Pins

The multimodal connectivity of the hippocampal complex in auditory and visual hallucinations

Hallucinations constitute one of the most representative and disabling symptoms of schizophrenia. Several Magnetic Resonance Imaging (MRI) findings support the hypothesis that distinct patterns of connectivity, particularly within networks involving the hippocampal complex (HC), could be associated with different hallucinatory modalities. The aim of this study was to investigate HC connectivity as a function of the hallucinatory modality, that is, auditory or visual. Two carefully selected subgroups of schizophrenia patients with only auditory hallucinations (AH) or with audio-visual hallucinations (A+VH) were compared using the following three complementary multimodal MRI methods: resting state functional MRI, diffusion MRI and structural MRI were used to analyze seed-based Functional Connectivity (sb-FC), Tract-Based Spatial Statistics (TBSS) and shape analysis, respectively. Sb-FC was significantly higher between the HC, the medial prefrontal cortex (mPFC) and the caudate nuclei in A+VH patients compared with the AH group. Conversely, AH patients exhibited a higher sb-FC between the HC and the thalamus in comparison with the A+VH group. In the A+VH group, TBSS showed specific higher white matter connectivity in the pathways connecting the HC with visual areas, such as the forceps major and the inferior-fronto-occipital fasciculus than in the AH group. Finally, shape analysis showed localized hippocampal hypertrophy in the A+VH group. Functional results support the fronto-limbic dysconnectivity hypothesis of schizophrenia, while specific structural findings indicate that plastic changes are associated with hallucinations. Together, these results suggest that there are distinct connectivity patterns in patients with schizophrenia that depend on the sensory-modality, with specific involvement of the HC in visual hallucinations.

Visual Hallucinations in the Psychosis Spectrum and Comparative Information From Neurodegenerative Disorders and Eye Disease

Much of the research on visual hallucinations (VHs) has been conducted in the context of eye disease and neurodegenerative conditions, but little is known about these phenomena in psychiatric and nonclinical populations. The purpose of this article is to bring together current knowledge regarding VHs in the psychosis phenotype and contrast this data with the literature drawn from neurodegenerative disorders and eye disease. The evidence challenges the traditional views that VHs are atypical or uncommon in psychosis. The weighted mean for VHs is 27% in schizophrenia, 15% in affective psychosis, and 7.3% in the general community. VHs are linked to a more severe psychopathological profile and less favorable outcome in psychosis and neurodegenerative conditions. VHs typically co-occur with auditory hallucinations, suggesting a common etiological cause. VHs in psychosis are also remarkably complex, negative in content, and are interpreted to have personal relevance. The cognitive mechanisms of VHs in psychosis have rarely been investigated, but existing studies point to source-monitoring deficits and distortions in top-down mechanisms, although evidence for visual processing deficits, which feature strongly in the organic literature, is lacking. Brain imaging studies point to the activation of visual cortex during hallucinations on a background of structural and connectivity changes within wider brain networks. The relationship between VHs in psychosis, eye disease, and neurodegeneration remains unclear, although the pattern of similarities and differences described in this review suggests that comparative studies may have potentially important clinical and theoretical implications.

What visual illusions teach us about schizophrenia

Illusion, namely a mismatch between the objective and perceived properties of an object present in the environment, is a common feature of visual perception, both in normal and pathological conditions. This makes illusion a valuable tool with which to explore normal perception and its impairments. Although still debated, the hypothesis of a modified, and typically diminished, susceptibility to illusions in schizophrenia patients is supported by a growing number of studies. The current paper aimed to review how illusions have been used to explore and reveal the core features of visual perception in schizophrenia from a psychophysical, neurophysiological and functional point of view. We propose an integration of these findings into a common hierarchical Bayesian inference framework. The Bayesian formalism considers perception as the optimal combination between sensory evidence and prior knowledge, thereby highlighting the interweaving of perceptions and beliefs. Notably, it offers a holistic and convincing explanation for the perceptual changes observed in schizophrenia that might be ideally tested using illusory paradigms, as well as potential paths to explore neural mechanisms. Implications for psychopathology (in terms of positive symptoms, subjective experience or behavior disruptions) are critically discussed.

Fetal cortical activation to sound at 33 weeks of gestation: a functional MRI study.

Hearing already functions before birth, but little is known about the neural basis of fetal life experiences. Recent imaging studies have validated the use of functional magnetic resonance imaging (fMRI) in pregnant women at 38-weeks of gestation. The aim of the present study was to examine fetal brain activation to sound, using fMRI at the beginning of the third trimester of pregnancy. 6 pregnant women between 28- and 34-weeks of gestation were scanned using a magnetic strength of 1.5 T, with an auditory stimulus applied to their abdomen. 3 fetuses with a gestational age of 33 weeks, showed significant activation to sound in the left temporal lobe, measured using a new data-driven approach (Independent Component Analysis for fMRI time series). Only 2 of these fetuses showed left temporal activation, when the standard voxel-wise analysis method was used (p=0.007; p=0.001). Moreover, motion parameters added as predictors of the General Linear Model confirmed that motion cannot account for the signal variance in the fetal temporal cortex (p=0.01). Comparison between the statistical maps obtained from MRI scans of the fetuses with those obtained from adults, made it possible to confirm our hypothesis, that there is brain activation in the primary auditory cortex in response to sound. Measurement of the fetal hemodynamic response revealed an average fMRI signal change of +3.5%. This study shows that it is possible to use fMRI to detect early fetal brain function, but also confirms that sound processing occurs beyond the reflexive sub-cortical level, at the beginning of the third trimester of pregnancy.

Neural functional organization of hallucinations in schizophrenia: Multisensory dissolution of pathological emergence in consciousness

Although complex hallucinations are extremely vivid, painful symptoms in schizophrenia, little is known about the underlying mechanisms of multisensory integration in such a phenomenon. We investigated the neural basis of these altered states of consciousness in a patient with schizophrenia, by combining state of the art neuroscientific exploratory methods like functional MRI, diffusion tensor imaging, cortical thickness analysis, electrical source reconstruction and trans-cranial magnetic stimulation. The results shed light on the functional architecture of the hallucinatory processes, in which unimodal information from different modalities is strongly functionally connected to higher-order integrative areas.

REM sleep behaviour disorder and visuoperceptive dysfunction: a disorder of the ventral visual stream?

In idiopathic rapid eye movement sleep behaviour disorder (RBD), an association with visuoperceptive disorders has been described. However, such an association has not been clearly established in RBD secondary to Parkinson’s disease (PD). We compared visuoperceptive function in four groups of non-demented patients (parkinsonian patients with or without RBD, patients with idiopathic RBD and control participants) via a procedure enabling the analysis of the various components of visual information processing and in order to answer the following question: is RBD associated with visuoperceptive and/or attentional disorders in PD and, if so, where is the dysfunction located along the visual pathway? Sensorial aspects of visual information were evaluated using a contrast sensitivity test, perceptual aspects were assessed using a contour-based object identification test and visual attention was measured in an attentional capture paradigm. The diagnosis of RBD was confirmed by polysomnography. We observed a higher object identification threshold (OIT) (1) in PD patients with RBD compared with PD patients without RBD and with controls and (2) in idiopathic RBD patients compared with controls. There were no significant OIT differences between PD patients with RBD and idiopathic RBD patients or between PD patients without RBD and controls. We did not find any significant inter-group differences in any of the other visuoperceptive tests. RBD, idiopathic or secondary to PD, is associated with perceptual closure dysfunction. Our results suggest that this perceptual dysfunction is specifically associated with RBD and may be related to a non-dopaminergic impairment.

Neural correlates of implicit object identification

The present study sought to assess neural correlates of implicit identification of objects by means of fMRI, using tasks that require matching of the physical properties of objects. Behavioural data suggests that there is automatic access to object identity when observers attend to a physical property of the form of an object (e.g. the objects orientation) and no evidence for semantic processing when subjects attend to colour. We evaluated whether, in addition to neural areas associated with decisions to specific perceptual properties, areas associated with access to semantic information were activated when tasks demanded processing of the global configuration of pictures. We used two perceptual matching tasks based on the global orientation or on the colour of line drawings. Our results confirmed behavioural data. Activations in the inferior occipital cortex, fusiform and inferior temporal gyri in both tasks (orientation and colour) account for perceptual and structural processing involved in each task. In contrast, activations in the posterior and medial parts of the fusiform gyrus, shown to be involved in explicit semantic judgements, were more pronounced in the orientation-matching task, suggesting that semantic information from the pictures is processed in an implicit way even when not required by the task. Thus, this study suggests that cortical regions usually involved in explicit semantic processing are also activated when implicit processing of objects occurs.

Automatic object identification: an fmri study

Boucart and Humphreys reported an automatic access to object identity when observers attend to a physical property of the form of an object (e.g. the orientation) but not to its colour. We sought evidence for automatic identification in a brain imaging study using fMRI. In an orientation decision task participants decided whether a picture was vertical or horizontal. In the colour decision task participants decided if a picture was blue or green. Activation of areas 18–19 was found for both color and orientation. Activation of the temporal area 37 occurred more frequently in the orientation than in the colour decision task. This result suggests that automatic identification activates the same brain area as overt processing of semantic information.

Time compression increases with eccentricity: a magnocellular property.

Accurate time perception is crucial in peripheral vision especially for the spatial perception during actions. To investigate the dynamics of time perception in peripheral vision, parvocellular-biased and magnocellular-biased flashes were presented at different eccentricities (0–48°) in an interflash interval discrimination task. Results showed an increase in time compression with eccentricity for both stimuli (magnocellular-biased and parvocellular-biased flashes). Nevertheless, when stimulus visibility was ‘equalized’ across the visual field, the increase in time compression was only found for magnocellular-biased stimuli. Thus, we suggest that the magnocellular pathway accounts for time underestimation. Moreover, its increase with eccentricity could be an inherent property of the magnocellular system more than a result of a decrease in stimulus visibility.

fmri capture of auditory hallucinations: Validation of the two‐steps method

Our purpose was to validate a reliable method to capture brain activity concomitant with hallucinatory events, which constitute frequent and disabling experiences in schizophrenia. Capturing hallucinations using functional magnetic resonance imaging (fMRI) remains very challenging. We previously developed a method based on a two‐steps strategy including (1) multivariate data‐driven analysis of per‐hallucinatory fMRI recording and (2) selection of the components of interest based on a post‐fMRI interview. However, two tests still need to be conducted to rule out critical pitfalls of conventional fMRI capture methods before this two‐steps strategy can be adopted in hallucination research: replication of these findings on an independent sample and assessment of the reliability of the hallucination‐related patterns at the subject level. To do so, we recruited a sample of 45 schizophrenia patients suffering from frequent hallucinations, 20 schizophrenia patients without hallucinations and 20 matched healthy volunteers; all participants underwent four different experiments. The main findings are (1) high accuracy in reporting unexpected sensory stimuli in an MRI setting; (2) good detection concordance between hypothesis‐driven and data‐driven analysis methods (as used in the two‐steps strategy) when controlled unexpected sensory stimuli are presented; (3) good agreement of the two‐steps method with the online button‐press approach to capture hallucinatory events; (4) high spatial consistency of hallucinatory‐related networks detected using the two‐steps method on two independent samples. By validating the two‐steps method, we advance toward the possible transfer of such technology to new image‐based therapies for hallucinations. Hum Brain Mapp 38:4966–4979, 2017.