Frontal and superior temporal auditory processing abnormalities in schizophrenia

Magnetic resonance imaging of the frontal lobe in twins with schizophrenia

There is a continuous consumer demand for ever superior cosmetic products. In marketing, various forms of sensory evaluation are used to measure the consumer experience and provide data with which to improve cosmetics. Nonetheless, potential downsides of existing approaches have led to the exploration of the use of neuroimaging methods, such as functional near-infrared spectroscopy (fNIRS), to provide addition information about consumers' experiences with cosmetics. The aim of the present study was to investigate the feasibility of a real-time brain-based product evaluation method which detects the incongruency between a product, in this case lipstick, and a consumer's expectations. Thirty healthy, female, habitual lipstick users were asked to apply six different lipsticks varying in softness and to rate the softness of and their willingness to pay (WTP) for each lipstick. Cerebral hemodynamic responses in frontal areas were measured with fNIRS during lipstick application and analyzed using the general linear model (GLM). Incongruency scores between softness and expectation were calculated in order to understand how far removed each lipstick was from a participant's optimal softness preference. The correlation between brain activation (beta scores) during the application of each lipstick and the respective incongruency scores from each participant were acquired using semi-partial correlation analysis, controlling for the effects of WTP. We revealed a significant intra-subject correlation between incongruency scores and activation in the right inferior frontal gyrus (IFG). This confirms that as the texture incongruency scores increased for the lipstick samples, activation in each individual's right IFG also increased. The correlation observed between incongruency perceived by participants and activation of the right IFG not only suggests that the right IFG may play an important role in detecting incongruity when there is a discrepancy between the perceived texture and the consumer's expectations but also that measuring activity in the IFG may provide a new objective measurement of the consumer experience, thus contributing to the development of superior cosmetics.

P279 Short-latency afferent inhibition from the dorsolateral prefrontal cortex in patients with schizophrenia: A TMS-EEG study

BackgroundThe genetic etiology of schizophrenia (SCZ) overlaps with that of other major psychiatric disorders in samples of European ancestry. On the other hand, these major psychiatric disorders are distinct diagnoses that have disorder-specific genetic factors. Recently, the bipolar disorder (BIP) and SCZ Working Group of the PGC identified two genome-wide significant loci differentiating the two disorders in individuals of European descent. We hypothesized that genetic variants differentiating SCZ from BIP in Europeans as well as genetic variants related to psychiatric disorders in Europeans would overlap with genetic risk variants in Japanese SCZ patients and unaffected first-degree relatives (FRs), i.e., individuals at high risk of developing SCZ. The present study investigated transethnic polygenetic features shared between Japanese SCZ or their unaffected FRs and European patients with major psychiatric disorders by conducting polygenic risk score (PRS) analyses.MethodsTo calculate PRSs for five psychiatric disorders [SCZ, BIP, major depressive disorder (MDD), autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD)] and PRSs differentiating SCZ from BIP, we utilized large-scale European genome-wide association study (GWAS) datasets as discovery samples. PRSs derived from these GWASs were calculated for 335 Japanese target subjects [131 SCZ patients, 57 of their unaffected FRs and 147 healthy controls (HCs)]. We took these PRSs based on GWASs of European psychiatric disorders (SCZ, BIP, SCZ vs BIP, MDD, ASD and ADHD) and investigated their effect on risk in Japanese SCZ patients [(i) SCZ vs FRs vs HCs, (ii) SCZ vs HCs and (iii) SCZ vs FRs] or unaffected FRs [(iv) FRs vs HCs] by PRS analyses.ResultsThe PRSs obtained from European SCZ samples were significantly higher in Japanese patients with SCZ than in HCs [(i) SCZ vs FRs vs HCs, a maximum at PT≤1.0: adjusted R2=0.028, p=1.30×10–3; (ii) SCZ vs HCs, a maximum at PT≤1.0: Nagelkerke’s R2=0.049, p=1.66×10–3]. In addition, the PRSs related to European BIP were nominally higher in Japanese patients with SCZ than in HCs [(i) SCZ vs FRs vs HCs, a maximum at PT≤0.5: adjusted R2=0.016, p=0.012; (ii) SCZ vs HCs, a maximum at PT≤0.5: Nagelkerke’s R2=0.029, p=0.015]. Furthermore, PRSs differentiating SCZ patients from European BIP patients were marginally higher in Japanese SCZ patients than in HCs [(i) SCZ vs FRs vs HCs, a maximum at PT≤0.05: adjusted R2=0.010, p=0.043; (ii) SCZ vs HCs, a maximum at PT≤0.05: Nagelkerke’s R2=0.020, p=0.046]. Interestingly, the PRSs obtained from European ASD were marginally lower in Japanese FRs compared with HCs [(iv) FRs vs HCs, a maximum at PT≤0.01: Nagelkerke’s R2=0.045, p=0.013] and patients with SCZ [(iii) SCZ vs FRs, a maximum at PT≤0.2: Nagelkerke’s R2=0.023, p=0.084]. As childhood-onset patients with SCZ have showed higher PRSs for both SCZ and ASD than their unaffected siblings, we further investigated the correlation between age at onset and PRSs for both SCZ and ASD in our SCZ samples. Lower age at onset of SCZ was significantly associated with higher PRSs for ASD (PT≤0.05: beta=-0.20, p=7.13×10–3) but not PRSs for SCZ (p>0.05).DiscussionThese findings suggest that polygenic factors related to European SCZ and BIP and the polygenic components differentiating SCZ from BIP can transethnically contribute to SCZ risk in Japanese people. Furthermore, we suggest that reduced levels of an ASD-related genetic factor in unaffected FRs may help protect against SCZ development.

Chronic insomnia disorder (CID) is associated with verbal fluency deficits linked to abnormal prefrontal activation. This multichannel functional near-infrared spectroscopy (fNIRS) study compared prefrontal hemodynamic responses and functional connectivity during verbal fluency tasks (VFT) in 81 CID patients versus 100 healthy controls (HC). Cortical activation patterns and interregional connectivity were analyzed using general linear modeling and correlation matrices. CID patients exhibited significantly reduced bilateral prefrontal activation (p < 0.01), particularly in the left inferior frontal gyrus (IFG), middle frontal gyrus (MFG), and superior frontal gyrus (SFG), alongside 32-45% weaker functional connectivity compared to HC. Activation in left IFG correlated negatively with sleep latency (r=-0.32) and positively with sleep duration (r = 0.28), while right SFG activation positively associated with sleep efficiency (r = 0.31) in CID patients. Receiver operating characteristic analysis demonstrated that activation in the left superior frontal gyrus (SFG_L) alone provided fair to good discriminative capacity (AUC = 0.79). Crucially, following constructive reviewer feedback, we found that a multivariate model integrating all six prefrontal ROIs achieved a higher AUC of 0.84. Most impressively, a combined model that further incorporated behavioral performance and clinical scale scores yielded excellent discrimination (AUC = 0.91). This underscores a critical finding: while fNIRS-derived prefrontal activation is a powerful biomarker in its own right, its true clinical potential is unlocked when integrated into a multi-modal framework that captures the cognitive and affective dimensions of the disorder. These results strongly suggest that such an integrated approach, rather than relying on any single metric, is the most promising path for developing objective diagnostic aids for CID.

BackgroundBy calculating cortical thickness (CT) and cortical structural covariance (SC), we aimed to investigate cortical morphology and cortical inter-regional correlation alterations in adolescent bipolar disorder type I (BD-I) and type II (BD-II) patients.MethodsT1-weighted images from 36 BD-I and 22 BD-II patients and 19 healthy controls (HCs) were processed to estimate CT. CT values of the whole brain were compared among three groups. Cortical regions showing CT differences in groups were regarded as seeds for analyzing cortical SC differences between groups. The relationship between CT and clinical indices was further assessed.ResultsBoth BD groups showed cortical thinning in several frontal and temporal areas vs. HCs, and CT showed no significant difference between two BD subtypes. Compared to HCs, both BD groups exhibited reduced SC connections between left superior frontal gyrus (SFG) and right postcentral gyrus (PCG), left superior temporal gyrus (STG) and right pars opercularis, and left STG and right PCG. Compared with HCs, decreased SC connections between left STG and right inferior parietal gyrus (IPG) and right pars opercularis and right STG were only observed in the BD-I group, and left PCG and left SFG only in the BD-II group. CT of right middle temporal gyrus was negatively correlated with number of episodes in BD-II patients.ConclusionsAdolescent BD-I and BD-II showed commonly decreased CT while presenting commonly and distinctly declined SC connections. This study provides a better understanding of cortical morphology and cortical inter-regional correlation alterations in BD and crucial insights into neuroanatomical mechanisms and pathophysiology of different BD subtypes.

Both volumetry and functional connectivity of Heschl's gyrus are associated with auditory P300 in first episode schizophrenia

Background: Although some Magnetic Resonance Imaging (MRI) studies have investigated the relationship between clinical severity and neuroanatomical alterations in patients with schizophrenia (SCZ), the biological signature associated with illness severity in schizophrenia is still uncertain. Therefore, this study aims to investigate structural brain abnormalities in SCZ, with particular regards to the identification of potential deficits associated with the severity of illness. Methods: In total, 1.5T MRI data were acquired for 61 subjects with SCZ and 59 matched healthy controls (HC). The patient group was divided in two sub-groups based on clinical severity, one composed of 34 mild-to-moderately ill patients, and the other of 27 severely ill patients, and compared with matched HC. Results: The whole group of patients with SCZ had significantly reduced grey matter (GM) volumes in the left inferior and middle temporal gyrus compared to HC (p < 0.05, pFWE corrected). Furthermore, compared to HC, patients with mild-to-moderate illness showed decreased GM volumes in the inferior and middle temporal gyrus, whereas those with severe illness had reduced GM volumes in the middle temporal gyrus and cerebellum bilaterally (all p < 0.001 uncorrected). No differences were observed between the two sub-groups of patients. Conclusion: The results showed significant GM volume reductions in temporal regions in patients with SCZ compared to matched HC, confirming the role of these regions in the pathophysiology of SCZ. Furthermore, specific cerebellar grey matter volume reductions were identified in patients with severe illness, which may contribute to stratifying patients with SCZ according to their clinical phenotype expression, ultimately helping in guiding targeted therapeutic/rehabilitation interventions.

Evidence of Timing Deficit in Developmental Dyslexia From Movement Related Potentials and Directed Effective Connectivity at the Sources

Assessing brain structural associations with working-memory related brain patterns in schizophrenia and healthy controls using linked independent component analysis

Symposium Title: Motion and Emotion in Developmental Disorders: A Spherical Psychophysiological Perspective

In groups of patients suffering from schizophrenia (SZ), redox dysregulation was reported in both peripheral fluids and brain. It has been hypothesized that such dysregulation, including alterations of the glutathione (GSH) cycle could participate in the brain white matter (WM) abnormalities in SZ due to the oligodendrocytes' susceptibility to oxidative stress. In this study we aim to assess the differences between 82 schizophrenia patients (PT) and 86 healthy controls (HC) in GSH-redox peripheral blood markers: GSH peroxidase (GPx), reductase (GR) enzymatic activities and their ratio (GPx/GR-ratio), evaluating the hypotheses that alterations in the homeostasis of the systemic GSH cycle may be associated with pathological mechanisms in the brain WM in PT. To do so, we employ the advanced diffusion MRI methods: Diffusion Kurtosis Imaging (DKI) and White Matter Tract Integrity-Watson (WMTI-W), which provide excellent sensitivity to demyelination and neuroinflammation. We show that GPx levels are higher (p=0.00041) in female control participants and decrease with aging (p=0.026). We find differences between PT and HC in the association of GR and mean kurtosis (MK, p<0.0001). Namely, lower MK was associated with higher blood GR activity in HC, but not in PT, suggesting that high GR activity (a hallmark of reductive stress) in HC was linked to changes in myelin integrity. However, GSH-redox peripheral blood markers did not explain the WM anomalies detected in PT, or the design of the present study could not detect subtle phenomenon, if present.

Schizoaffective disorder (SA) is distinguished from schizophrenia (SZ) based on the presence of prominent mood symptoms over the illness course. Despite this clinical distinction, SA and SZ patients are often combined in research studies, in part because data supporting a distinct pathophysiological boundary between the disorders are lacking. Indeed, few studies have addressed whether neurobiological abnormalities associated with SZ, such as the widely replicated reduction and delay of the P300 event-related potential (ERP), are also present in SA. Scalp EEG was acquired from patients with DSM-IV SA (n = 15) or SZ (n = 22), as well as healthy controls (HC; n = 22) to assess the P300 elicited by infrequent target (15%) and task-irrelevant distractor (15%) stimuli in separate auditory and visual ”oddball” tasks. P300 amplitude was reduced and delayed in SZ, relative to HC, consistent with prior studies. These SZ abnormalities did not interact with stimulus type (target vs. task-irrelevant distractor) or modality (auditory vs. visual). Across sensory modality and stimulus type, SA patients exhibited normal P300 amplitudes (significantly larger than SZ patients and indistinguishable from HC). However, P300 latency and reaction time were both equivalently delayed in SZ and SA patients, relative to HC. P300 differences between SA and SZ patients could not be accounted for by variation in symptom severity, socio-economic status, education, or illness duration. Although both groups show similar deficits in processing speed, SA patients do not exhibit the P300 amplitude deficits evident in SZ, consistent with an underlying pathophysiological boundary between these disorders.

Structural and functional brain abnormalities in schizophrenia (SZ) are well-documented, yet the role of the glymphatic system remains largely unexplored. Given emerging evidence linking the microbiome-gut-brain axis to SZ, this study aims to investigate the glymphatic system function in SZ patients using diffusion tensor image analysis along the perivascular space (DTI-ALPS) and to explore its associations with gut microbiota and cognitive performance. Multi-omics data were obtained from a cohort of 87 SZ patients and 70 healthy controls (HCs), including fecal 16S rRNA sequencing, DTI-ALPS index analysis, and cognitive assessments. Correlation and mediation analyses were conducted to explore the relationships among the gut microbiome, DTI-ALPS index, and cognitive performance. Compared to HCs, patients with SZ exhibited significantly lower DTI-ALPS indices in the left, right, and bilateral hemispheres. These indices were positively associated with multiple cognitive domains. In addition, gut microbial dysbiosis was observed in SZ, characterized by a decrease in butyrate-producing bacteria and an increase in pathogenic bacteria. Exploratory analyses further revealed a tripartite link among the key microbial genera, DTI-ALPS indices, and cognitive performance. Notably, the higher abundance of Proteus as well as the lower abundance of Blautia and Faecalibacterium may contribute to poorer cognitive performance, potentially through disruptions in the right DTI-ALPS index. These findings provide novel insights into glymphatic dysfunction in SZ and highlight a potential microbiota–glymphatic–cognition pathway contributing to cognitive impairments.

BackgroundThe aim of this study was to investigate potential morphological alterations of gray and white matter in patients with optic neuritis (ON) and their relationship with behavioral performance, using voxel-based morphometry (VBM).Material/MethodsTwelve (4 males, 8 females) patients with ON and 12 (4 males, 8 females) age-, sex-, and education-matched healthy controls (HCs) underwent magnetic resonance imaging (MRI). Imaging data were analyzed using two-sample t tests to identify group differences in gray and white matter volume (GMV, WMV). Correlation analysis was used to explore relationships between observed GMV and WMV of different areas and visual evoked potential (VEP) in ON.ResultsCompared with HCs, ON patients had: significantly decreased GMV in the left postcentral gyrus, left inferior frontal gyrus, left anterior cingulate, left and right middle frontal gyrus, and right inferior parietal lobule; decreased WMV in the left middle frontal gyrus, right superior frontal gyrus, left precentral gyrus and right inferior parietal lobule; and increased WMV in the left fusiform gyrus and left inferior parietal lobule. VEP latency of the right eye in ON correlated positively with WMV signal value of the left fusiform gyrus (r=0.726, p=0.008), and negatively with GMV signal value of the right inferior parietal lobule (r=−0.611, p=0.035). Duration of ON correlated negatively with WMV signal value of the right superior frontal gyrus (r=−0.662, p=0.019), while best-corrected visual acuity (VA) of the right eye correlated negatively with WMV signal value of the left middle frontal gyrus (r=−0.704, p=0.011).ConclusionsThese results suggest significant brain involvement in ON, which may reflect the underlying pathologic mechanism. Correlational results demonstrate that VEP in ON is closely associated with WMV and GMV atrophy in many brain regions.