Altered corollary discharge in the auditory cortex could reflect louder inner voice experience in patients with verbal hallucinations, a pilot fMRI study.

INTRODUCTION: Wide range of evidence associates auditory verbal hallucinations (AVH) with frontotemporal corollary discharge deficit. AVH likely reflect altered experiences of the inner voice and are phenomenologically diverse. The aspects of hallucinations (and related inner voice experiences) that could be explained by this deficit remain unclear. To address this important subject, we examined the temporal cortex activity during two tasks with and without corollary discharge. METHODS: We carried out an event-related BOLD fMRI study to examine temporal cortex activity in seven patients and eight healthy controls during two tasks with and without corollary discharge: reading aloud and hearing, respectively. Data were denoised by removing independent components related to head movement and subsequently processed using finite impulse response basis function to address hemodynamic response variations. To mitigate the small sample size, final analyses were carried out using permutation-based analysis of variance. RESULTS: There was a significant group interaction in the Read relative to Hear condition during the early post-stimulus stage in the left Heschl's Gyrus (p<0.01, corrected for multiple comparisons, at peak voxel [-72,53,41]). This effect was driven by a higher activity in the Read relative to the Hear condition in the same area in the patients (p<0.02, corrected). CONCLUSIONS: Our results are consistent with prior literature indicating abnormal frontotemporal disconnection in participants with hallucinations. The functional repercussions of this deficit were limited to the primary auditory cortex in early post-stimulus stage, which suggests louder experience of the inner voice in patients and could account for the loudness of their hallucinations.

Abnormal effective connectivity of reward network in first-episode schizophrenia with auditory verbal hallucinations.

OBJECTIVE: Auditory verbal hallucinations (AVHs) in schizophrenia is proved to be associated with dysfunction of mesolimbic-cortical circuits, especially during abnormal salient and internal verbal resource monitoring processing procedures. However, the information flow among areas involved in coordinated interaction implicated the pathophysiology of AVHs remains unclear. METHODS: We used spectral dynamic causal modeling (DCM) to quantify connections among eight critical hubs of reward network in 86 first-episode drug-naïve schizophrenia patients with AVHs (AVH), 93 patients without AVHs (NAVH), and 88 matched normal controls (NC) using resting-state functional magnetic resonance imaging. Group-level connection coefficients, between-group differences and correlation analysis between image measures and symptoms were performed. RESULT: DCM revealed weaker effective connectivity (EC) from right ventral striatum (RVS) to ventral tegmental area (VTA) in AVH compared to NAVH. AVH showed stronger EC from left anterior insula (AI) to RVS, stronger EC from RVS to anterior cingulate cortex (ACC), and stronger EC from VTA to posterior cingulate cortex (PCC) compared to NC. The correlation analysis results were mostly visible in the negative correlation between EC from right AI to ACC and positive sub-score, P1 sub-score, and P3 sub-score of PNASS in group-level. CONCLUSION: These findings suggest that neural causal interactions between the reward network associated with AVHs are disrupted, expanding the evidence for potential neurobiological mechanisms of AVHs. Particularly, dopamine-dependent salience attribution and top-down monitoring impairments and compensatory effects of enhanced excitatory afferents to ACC, which may provide evidence for a therapeutic target based on direct in vivo of AVHs in schizophrenia.

Alterations in the volume and shape of the basal ganglia and thalamus in schizophrenia with auditory hallucinations.

Different lines of evidence indicate that the structure and physiology of the basal ganglia and the thalamus is disturbed in schizophrenia. However, it is unknown whether the volume and shape of these subcortical structures are affected in schizophrenia with auditory hallucinations (AH), a core positive symptom of the disorder. We took structural MRI from 63 patients with schizophrenia, including 36 patients with AH and 27 patients who had never experienced AH (NAH), and 51 matched healthy controls. We extracted volumes for the left and right thalamus, globus pallidus, putamen, caudate and nucleus accumbens. Shape analysis was also carried out. When comparing to controls, the volume of the right globus pallidus, thalamus, and putamen, was only affected in AH patients. The volume of the left putamen was also increased in individuals with AH, whereas the left globus pallidus was affected in both groups of patients. The shapes of right and left putamen and thalamus were also affected in both groups. The shape of the left globus pallidus was only altered in patients lacking AH, both in comparison to controls and to cases with AH. Lastly, the general PANSS subscale was correlated with the volume of the right thalamus, and the right and left putamen, in patients with AH. We have found volume and shape alterations of many basal ganglia and thalamus in patients with and without AH, suggesting in some cases a possible relationship between this positive symptom and these morphometric alterations.

Low-frequency rTMS induces modifications in cortical structural connectivity - functional connectivity coupling in schizophrenia patients with auditory verbal hallucinations.

Auditory verbal hallucinations (AVH) are distinctive clinical manifestations of schizophrenia. While low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in mitigating AVH, the precise mechanisms by which it operates remain obscure. This study aimed to investigate alternations in structural connectivity and functional connectivity (SC-FC) coupling among schizophrenia patients with AVH prior to and following treatment with 1 Hz rTMS that specifically targets the left temporoparietal junction. Initially, patients exhibited significantly reduced macroscopic whole brain level SC-FC coupling compared to healthy controls. Notably, SC-FC coupling increased significantly across multiple networks, including the somatomotor, dorsal attention, ventral attention, frontoparietal control, and default mode networks, following rTMS treatment. Significant alternations in SC-FC coupling were noted in critical nodes comprising the somatomotor network and the default mode network, such as the precentral gyrus and the ventromedial prefrontal cortex, respectively. The alternations in SC-FC coupling exhibited a correlation with the amelioration of clinical symptom. The results of our study illuminate the intricate relationship between white matter structures and neuronal activity in patients who are receiving low-frequency rTMS. This advances our understanding of the foundational mechanisms underlying rTMS treatment for AVH.

Temporal hyper-connectivity and frontal hypo-connectivity within gamma band in schizophrenia: A resting state EEG study.

OBJECTIVE: The brain network serves as the physiological foundation for information processing of the brain. Many studies have reported abnormalities of gamma oscillations in Schizophrenia. The aim of this study was to investigate the gamma-band connectivity in Schizophrenia patients. METHODS: We recorded the resting state electroencephalogram (EEG) for 15 schizophrenia patients with refractory auditory hallucinations and 14 healthy controls, with eyes open and closed. The brain network was constructed based on weighted phase lag index for gamma band. Whole scalp metrics (clustering coefficient, global efficiency and local efficiency) and local region metrics (degree and betweenness centrality) in the frontal and temporal lobes were computed. Correlation analyses between network metrics and symptom scales were examined to find associations with symptom severity. RESULTS: Schizophrenia patients had larger global efficiency and local efficiency (p < 0.05) with eyes closed, probably representing greater brain activity and information exchange. For degree and betweenness centrality, schizophrenia patients showed an increase (p < 0.05) in the temporal lobe but a decrease (p < 0.05) in the frontal lobe with eyes closed and open, potentially account for the patients' symptoms such as hallucinations and thought disorders. Local efficiency and frontal lobe degree were positively and negatively correlated with the scales, respectively (both p < 0.05). CONCLUSIONS: Altered connectivity of the resting state brain network has been revealed and may be associated with the core symptoms of schizophrenia. Our study provides promising evidence for the investigation of the pathological basis of Schizophrenia and could aid in objective diagnosis.

White matter tracts differentially associated with auditory hallucinations in first-episode psychosis: A correlational tractography diffusion spectrum imaging study.

Auditory hallucinations (AH) are a debilitating symptom in psychosis, impacting cognition and real world functioning. Recent thought conceptualizes AH as a consequence of long-range brain communication dysfunction, or circuitopathy, within the auditory sensory/perceptual, language, and cognitive control systems. Recently we showed in first-episode psychosis (FEP) that, despite overall intact white matter integrity in the cortical-cortical and cortical-subcortical language tracts and the callosal tracts connecting auditory cortices, the severity of AH correlated inversely with white matter integrity. However, that hypothesis-driven isolation of specific tracts likely missed important white matter concomitants of AH. In this report, we used a whole-brain data-driven dimensional approach using correlational tractography to associate AH severity with white matter integrity in a sample of 175 individuals. Diffusion Spectrum Imaging (DSI) was used to image diffusion distribution. Quantitative Anisotropy (QA) in three tracts was greater with increased AH severity (FDR < 0.001) and QA in three tracts was lower with increased AH severity (FDR < 0.01). White matter tracts showing associations between QA and AH were generally associated with frontal-parietal-temporal connectivity (tracts with known relevance for cognitive control and the language system), in the cingulum bundle, and in prefrontal inter-hemispheric connectivity. The results of this whole brain data-driven analysis suggest that subtle white matter alterations connecting frontal, parietal, and temporal lobes in the service of sensory-perceptual, language/semantic, and cognitive control processes impact the expression of auditory hallucination in FEP. Disentangling the distributed neural circuits involved in AH should help to develop novel interventions, such as non-invasive brain stimulation.

Functional Brain Networks of Minor and Well-Structured Major Hallucinations in Parkinson's Disease.

BACKGROUND: Minor hallucinations (mHs) and well-structured major hallucinations (MHs) are common symptoms of Parkinson's disease (PD) psychosis. OBJECTIVES: To investigate the resting-state networks (RSNs) in patients with PD without hallucinations (PD-nH), with mH (PD-mH), and with MH (PD-MH). METHODS: A total of 73 patients with PD were enrolled (27 PD-nH, 23 PD-mH, and 23 PD-MH). Using seed-based functional connectivity analyses, we investigated the RSNs supposedly related to hallucinations in PD: the default mode network (DMN), executive control network (ECN), dorsal attention network (DAN), ventral attention network (VAN), and visual network (VN). We compared the cognitive function and RSN connectivity among the three groups. In addition, we performed a seed-to-seed analysis to examine the inter-network connectivity within each group using the corresponding RSN seeds. RESULTS: PD-MH group had lower test scores for attention and visuospatial functions compared with those in the other groups. The connectivity of the right intracalcarine cortex within the DAN was lower in the PD-MH group than in the others. The PD-mH and PD-MH groups showed higher connectivity in the left orbitofrontal cortex within DMN compared with the PD-nH group, whereas the connectivity was lower in the right middle frontal gyrus (MFG) within ECN, precuneus cortex within VAN, right middle temporal gyrus and precuneus cortex within DAN, and left MFG within VN. The PD-mH and PD-MH groups showed different inter-network connectivity between the five RSNs, especially regarding DAN connectivity. CONCLUSIONS: DAN dysfunction may be a key factor in the progression from mH to MH in patients with PD. © 2023 International Parkinson and Movement Disorder Society.

Rich-club reorganization of white matter structural network in schizophrenia patients with auditory verbal hallucinations following 1 Hz rTMS treatment.

The human brain comprises a large-scale structural network of regions and interregional pathways, including a selectively defined set of highly central and interconnected hub regions, often referred to as the "rich club", which may play a pivotal role in the integrative processes of the brain. A quintessential symptom of schizophrenia, auditory verbal hallucinations (AVH) have shown a decrease in severity following low-frequency repetitive transcranial magnetic stimulation (rTMS). However, the underlying mechanism of rTMS in treating AVH remains elusive. This study investigated the effect of low-frequency rTMS on the rich-club organization within the brain in patients diagnosed with schizophrenia who experience AVH using diffusion tensor imaging data. Through by constructing structural connectivity networks, we identified several critical rich hub nodes, which constituted a rich-club subnetwork, predominantly located in the prefrontal cortices. Notably, our findings revealed enhanced connection strength and density within the rich-club subnetwork following rTMS treatment. Furthermore, we found that the decreased connectivity within the subnetwork components, including the rich-club subnetwork, was notably enhanced in patients following rTMS treatment. In particular, the increased connectivity strength of the right median superior frontal gyrus, which functions as a critical local bridge, with the right postcentral gyrus exhibited a significant correlation with improvements in both positive symptoms and AVH. These findings provide valuable insights into the role of rTMS in inducing reorganizational changes within the rich-club structural network in schizophrenia and shed light on potential mechanisms through which rTMS may alleviate AVH.

Associations of resting-state perfusion and auditory verbal hallucinations with and without emotional content in schizophrenia.

Auditory Verbal Hallucinations (AVH) are highly prevalent in patients with schizophrenia. AVH with high emotional content lead to particularly poor functional outcome. Increasing evidence shows that AVH are associated with alterations in structure and function in language and memory related brain regions. However, neural correlates of AVH with emotional content remain unclear. In our study (n = 91), we related resting-state cerebral perfusion to AVH and emotional content, comparing four groups: patients with AVH with emotional content (n = 13), without emotional content (n = 14), without hallucinations (n = 20) and healthy controls (n = 44). Patients with AVH and emotional content presented with increased perfusion within the amygdala and the ventromedial and dorsomedial prefrontal cortex (vmPFC/ dmPFC) compared to patients with AVH without emotional content. In addition, patients with any AVH showed hyperperfusion within the anterior cingulate gyrus, the vmPFC/dmPFC, the right hippocampus, and the left pre- and postcentral gyrus compared to patients without AVH. Our results indicate metabolic alterations in brain areas critical for the processing of emotions as key for the pathophysiology of AVH with emotional content. Particularly, hyperperfusion of the amygdala may reflect and even trigger emotional content of AVH, while hyperperfusion of the vmPFC/dmPFC cluster may indicate insufficient top-down amygdala regulation in patients with schizophrenia.

Pulvinar quantitative susceptibility mapping predicts visual hallucinations post-deep brain stimulation in Parkinson's disease.

PURPOSE: We have reported the relationship between low pulvinar nuclei (PN) intensity in susceptibility-weighted imaging and the appearance of visual hallucinations and cognitive function. The aim of the study was to examine the changes in the quantitative susceptibility mapping (QSM) in patients with Parkinson's disease (PD) who underwent deep brain stimulation (DBS) and verify whether the PN susceptibility value (SV) on QSM can predict visual hallucination and cognitive changes after DBS. METHODS: This study examined 24 patients with PD who underwent DBS along with QSM imaging on magnetic resonance imaging (MRI). All MRIs were performed within 3 months before surgery. The PN SV was further assessed based on the QSM. Then, associations were examined among cognitive changes, hallucination, and PN SV. The cognitive function of the patient was compared immediately before surgery and at 1 year postoperatively. RESULTS: Visual hallucinations were observed in seven patients during the follow-up period. The PN SV was ≥0.045 ppm in nine patients with PD, and six of them had visual hallucinations, whereas only one of 15 patients with PD with SV of <0.045 ppm had visual hallucinations (Fisher's exact test, p = .0037). CONCLUSIONS: The SV of >0.045 ppm at the PN in QSM in patients with PD may provide useful information suggesting visual hallucination and cognitive deterioration after DBS treatment.

Alterations in brain connectivity patterns in schizophrenia patients with auditory verbal hallucinations during low frequency repetitive transcranial magnetic stimulation.

OBJECTIVE: Auditory verbal hallucinations (AVH) are a characteristic symptom of schizophrenia. Although low-frequency repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to alleviate the severity of AVH, its exact neurophysiological mechanisms remain unclear. This study aimed to elucidate the alterations in brain connectivity patterns in schizophrenia patients with AVH after low frequency rTMS. Furthermore, the relationship between these alterations and clinical outcomes was examined, thereby identifying potential biomarkers for rTMS treatment efficacy. METHODS: A total of 30 schizophrenia patients with AVH and 33 healthy controls were recruited. The patients received 1 Hz rTMS applied to the left temporoparietal junction region over 15 days. Resting-state functional magnetic resonance imaging scans were conducted for all participants. Subsequently, degree centrality (DC) and seed-based functional connectivity (FC) analyses were employed to identify specific alterations in brain connectivity patterns after rTMS treatment. RESULTS: At baseline, patients exhibited divergent DC patterns in the frontal, occipital, and limbic lobes compared to healthy controls. In addition, prior to treatment, patients demonstrated altered FC from the superior frontal gyrus seeds that linked to the frontal, temporal, and somatosensory regions. Following rTMS treatment, these abnormalities were notably reversed, correlating with improved clinical outcomes. CONCLUSIONS: These findings demonstrate that schizophrenia patients with AVH exhibited atypical interactions within the frontal and temporal lobes. These alterations might be crucial biomarkers for predicting the efficacy of low frequency rTMS.

Behavioral and neural correlates of pareidolic illusions in dementia with Lewy bodies.

INTRODUCTION: Pareidolia, a form of visual illusions phenomenologically similar to complex visual hallucinations, is a phenomenon that is associated with visual hallucinations in dementia with Lewy bodies (DLB). This study aimed to identify commonalities and differences in behavioral and neural correlates between pareidolic illusions and visual hallucinations in DLB. METHODS: Forty-three patients with DLB underwent the scene pareidolia test, which evokes and measures pareidolic illusions, and standardized neuropsychological and behavioral assessments. Regional cerebral blood flow (rCBF) was measured by single-photon emission computed tomography. Factor analysis was performed to assess the relationships among pareidolic illusions, cognitive functions, and behavioral symptoms. Partial least squares correlation analysis was used to investigate the relationship between these symptoms and rCBF. RESULTS: Factor analysis yielded three behavior factors: the first factor (hallucinations/fluctuations) consisted of pareidolic illusions, visual hallucinations, and fluctuating cognition; the second factor (general cognitive function) consisted of general cognitive function and working memory; and the third factor (visual processing) consisted of visual processing and pareidolic illusions. Partial least squares correlation analysis identified two brain-behavior correlation patterns: (1) rCBF reduction in the frontal and perisylvian/periventricular regions was associated with lower general cognitive function and lower visual processing; and (2) rCBF reduction in the bilateral occipitotemporal cortex was associated with more severe hallucinations/fluctuations and lower visual processing. CONCLUSIONS: At the behavioral level, pareidolic illusions are associated with visual hallucinations, fluctuating cognition, and visual processing in DLB. At the neural level, pareidolic illusions may arise from the synergistic effects of global neuropathological changes and occipitotemporal cortical dysfunctions.

Cerebral blood flow changes in schizophrenia patients with auditory verbal hallucinations during low-frequency rTMS treatment.

Auditory verbal hallucinations (AVH) are a prominent symptom of schizophrenia. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been evidenced to improve the treatment of AVH in schizophrenia. Although abnormalities in resting-state cerebral blood flow (CBF) have been reported in schizophrenia, the perfusion alterations specific to schizophrenia patients with AVH during rTMS require further investigation. In this study, we used arterial spin labeling (ASL) to investigate changes in brain perfusion in schizophrenia patients with AVH, and their associations with clinical improvement following low-frequency rTMS treatment applied to the left temporoparietal junction area. We observed improvements in clinical symptoms (e.g., positive symptoms and AVH) and certain neurocognitive functions (e.g., verbal learning and visual learning) following treatment. Furthermore, at baseline, the patients showed reductions in CBF in regions associated with language, sensory, and cognition compared to controls, primarily located in the prefrontal cortices (e.g., left inferior frontal gyrus and left middle frontal gyrus), occipital lobe (e.g., left calcarine cortex), and cingulate cortex (e.g., bilateral middle cingulate cortex), compared to controls. Conversely, we observed increased CBF in the left inferior temporal gyrus and bilateral putamen in patients relative to controls, regions known to be involved in AVH. However, the hypoperfusion or hyperperfusion patterns did not persist and instead were normalized, and were related to clinical response (e.g., AVH) in patients during low-frequency rTMS treatment. Importantly, the changes in brain perfusion were related to clinical response (e.g., AVH) in patients. Our findings suggest that low-frequency rTMS can regulate brain perfusion involving critical circuits by its remote effect in schizophrenia, and may play an important mechanistic role in the treatment of AVH.

Structural and Functional Imaging Correlates of Visual Hallucinations in Parkinson's Disease.

PURPOSE OF REVIEW: To review recent structural and functional MRI studies of visual hallucinations in Parkinson's disease. RECENT FINDINGS: Previously, neuroimaging had shown inconsistent findings in patients with Parkinson's hallucinations, especially in studies examining grey matter volume. However, recent advances in structural and functional MRI techniques allow better estimates of structural connections, as well as the direction of connectivity in functional MRI. These provide more sensitive measures of changes in structural connectivity and allow models of the changes in directional functional connectivity to be tested. We identified 27 relevant studies and found that grey matter imaging continues to show heterogeneous findings in Parkinson's patients with visual hallucinations. Newer approaches in diffusion imaging and functional MRI are consistent with emerging models of Parkinson's hallucinations, suggesting shifts in attentional networks. In particular, reduced bottom-up, incoming sensory information, and over-weighting of top-down signals appear to be important drivers of visual hallucinations in Parkinson's disease.

Visual networks: Electric brain stimulation and diffusion tensor imaging.

OBJECTIVE: The present study investigated the networks of visual functional areas using electric brain stimulation (EBS) and diffusion tensor imaging (DTI). METHODS: Thirteen patients with intractable focal epilepsy in which visual functional areas were identified by EBS were enrolled. An electric stimulation at 50Hz was applied to electrodes during several tasks. DTI was used to identify subcortical fibers originating from the visual functional areas identified by EBS. RESULT: The electrical stimulation induced three types of visual symptoms: visual illusions (change of vision), visual hallucinations (appearance of a new object), and blurred vision. Visual illusions were associated with stimulation of lateral temporo-parieto-occipital areas, and visual hallucinations with stimulation of lateral/basal temporal areas, the occipital lobe and the precuneus. Stimulus intensities eliciting visual illusions were significantly higher than those for visual hallucinations. Tractography revealed that the superior fronto-occipital fasciculus was associated with visual illusions and the middle longitudinal fasciculus with visual hallucinations, and both symptoms shared several subcortical fibers such as the vertical occipital fasciculus, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, inferior longitudinal fasciculus, optic radiations, and commissural fibers. CONCLUSION: The present study revealed the characteristic cortical regions and networks of visual functional areas. The results obtained provide information on human visual functions and are a practical guide for electrical cortical stimulation.

Time varying dynamics of hallucinations in clinical and non-clinical voice-hearers.

Auditory verbal hallucinations (AVH) are frequently associated with psychotic disorders, yet also occur in non-clinical voice-hearers. AVH in this group are similar to those within clinical voice-hearers in terms of several phenomenological aspects, but non-clinical voice-hearers report to have more control over their AVH and attribute less emotional valence to them. These dissimilarities may stem from differences on the neurobiological level, as it is still under debate whether the mechanisms involved in AVH are the same in clinical and non-clinical voice-hearers. In this study, 21 clinical and 21 non-clinical voice-hearers indicated the onset and offsets of AVH during an fMRI scan. Using a method called leading eigenvector dynamics analysis (LEiDA), we examined time-varying dynamics of functional connectivity involved in AVH with a sub-second temporal resolution. We assessed differences between groups, and between hallucination and rest periods in dwell time, switching frequency, probability of occurrence, and transition probabilities of nine recurrent states of functional connectivity with a permutation ANOVA. Deviations in dwell times, switching frequencies, and switch probabilities in the hallucination period indicated more erratic dynamics during this condition regardless of their clinical status. Post-hoc analyses of the dwell times exhibited the most distinct differences between the rest and hallucination condition for the non-clinical sample, suggesting stronger differences between the two conditions in this group. Overall, these findings suggest that the neurobiological mechanisms involved in AVH are similar in clinical and non-clinical individuals.

Structural Correlates of Lifetime Voice-Hearing in Patients with Borderline Personality Disorder: A Pilot Study.

INTRODUCTION: Auditory verbal hallucinations (AVH) are transdiagnostic phenomena that can occur in several mental disorders, including borderline personality disorder (BPD). Despite the transdiagnostic relevance of these symptoms, very little is known about neural signatures of AVH in BPD. METHODS: We used structural magnetic resonance imaging to investigate multiple markers of brain morphology in BPD patients presenting with a lifetime history of AVH (AVH, n = 6) versus BPD patients without AVH (nAVH, n = 10) and healthy controls (HC, n = 12). The Computational Anatomy Toolbox (CAT12) was used for surface-based morphometric analyses that considered cortical thickness (CTh), gyrification (CG), and complexity of cortical folding (CCF). Factorial models were used to explore differences between AVH patients and HC, as well as between the patient groups. RESULTS: Compared to HC, AVH patients showed distinct abnormalities in key regions of the language network, i.e., aberrant CTh and CG in right superior temporal gyrus and abnormal CCF in left inferior frontal gyrus. Further abnormalities were found in right prefrontal cortex (CTh) and left orbitofrontal cortex (CCF). Compared to nAVH patients, individuals with AVH showed abnormal CTh in right prefrontal cortex, along with CCF differences in right transverse temporal, superior parietal, and parahippocampal gyri. CG differences between the patient groups were found in left orbitofrontal cortex. CONCLUSION: The data suggest a transdiagnostic neural signature of voice-hearing that converges on key regions involved in speech generation and perception, memory and executive control. It is possible that cortical features of distinct evolutionary and genetic origin, i.e., CTh and CG/CCF, differently contribute to AVH vulnerability in BPD.

Multimodal visual system analysis as a biomarker of visual hallucinations in Parkinson's disease.

Visual hallucinations (VH) are present in up to 75% of Parkinson's disease (PD) patients. However, their neural bases and participation of the visual system in VH are not well-understood in PD. Seventy-four participants, 12 PD with VH (PDVH), 35 PD without VH (PDnoVH) and 27 controls underwent a battery of primary visual function and visual cognition tests, retinal optical coherence tomography and structural and resting-state functional brain MRI. We quantified cortical thickness with Freesurfer and functional connectivity (FC) of Visual (VIS), Fronto-Parietal (FP), Ventral Attention (VAN) and Dorsal Attention (DAN) networks with CONN toolbox. Group comparisons were performed with MANCOVA. Area Under the Curve (AUC) was computed to assess the ability of visual variables to differentiate PDVH and PDnoVH. There were no significant PDVH vs PDnoVH differences in disease duration, motor manifestations, general cognition or dopamine agonist therapy (DA) use. Compared to PDnoVH and HC, and regardless of DA use, PDVH showed significantly reduced contrast sensitivity, visuoperceptive and visuospatial abilities, increased retina photoreceptor layer thickness, reduced cortical thickness mostly in right visual associative areas, decreased between-network VIS-VAN and VAN-DAN connectivity and increased within-network DAN connectivity. The combination of clinical and imaging variables that best discriminated PDVH and PDnoVH (highest AUC), where within-network DAN FC, photoreceptor layer thickness and cube analysis test from Visual Object and Space Perception Battery (accuracy of 81.8%). Compared to PDnoVH, PDVH have specific functional and structural abnormalities within the visual system, which can be quantified non-invasively and could potentially constitute biomarkers for VH in PD.

Structural brain abnormalities in schizophrenia patients with a history and presence of auditory verbal hallucination.

Although many studies have demonstrated structural brain abnormalities associated with auditory verbal hallucinations (AVH) in schizophrenia, the results remain inconsistent because of the small sample sizes and the reliability of clinical interviews. We compared brain morphometries in 204 participants, including 58 schizophrenia patients with a history of AVH (AVH + ), 29 without a history of AVH (AVH-), and 117 healthy controls (HCs) based on a detailed inspection of medical records. We further divided the AVH+ group into 37 patients with and 21 patients without hallucinations at the time of the MRI scans (AVH++ and AVH+-, respectively) via clinical interviews to explore the morphological differences according to the persistence of AVH. The AVH + group had a smaller surface area in the left caudal middle frontal gyrus (F = 7.28, FDR-corrected p = 0.0008) and precentral gyrus (F = 7.68, FDR-corrected p = 0.0006) compared to the AVH- group. The AVH+ patients had a smaller surface area in the left insula (F = 7.06, FDR-corrected p = 0.001) and a smaller subcortical volume in the bilateral hippocampus (right: F = 13.34, FDR-corrected p = 0.00003; left: F = 6.80, FDR-corrected p = 0.001) compared to the HC group. Of these significantly altered areas, the AVH++ group showed significantly smaller bilateral hippocampal volumes compared to the AVH+- group, and a smaller surface area in the left precentral gyrus and caudal middle frontal gyrus compared to the AVH- group. Our findings highlighted the distinct pattern of structural alteration between the history and presence of AVH in schizophrenia, and the importance of integrating multiple criteria to elucidate the neuroanatomical mechanisms.

Brain correlates of speech perception in schizophrenia patients with and without auditory hallucinations.

The experience of auditory verbal hallucinations (AVH, "hearing voices") in schizophrenia has been found to be associated with reduced auditory cortex activation during perception of real auditory stimuli like tones and speech. We re-examined this finding using 46 patients with schizophrenia (23 with frequent AVH and 23 hallucination-free), who underwent fMRI scanning while they heard words, sentences and reversed speech. Twenty-five matched healthy controls were also examined. Perception of words, sentences and reversed speech all elicited activation of the bilateral superior temporal cortex, the inferior and lateral prefrontal cortex, the inferior parietal cortex and the supplementary motor area in the patients and the healthy controls. During the sentence and reversed speech conditions, the schizophrenia patients as a group showed reduced activation in the left primary auditory cortex (Heschl's gyrus) relative to the healthy controls. No differences were found between the patients with and without hallucinations in any condition. This study therefore fails to support previous findings that experience of AVH attenuates speech-perception-related brain activations in the auditory cortex. At the same time, it suggests that schizophrenia patients, regardless of presence of AVH, show reduced activation in the primary auditory cortex during speech perception, a finding which could reflect an early information processing deficit in the disorder.