Reduced mismatch negativity (MMN) and P300 event-related potential (ERP) components are widely replicated in schizophrenia and are also observed in individuals at clinical high risk for psychosis (CHR-P) who subsequently convert to psychosis. It is unknown whether they reflect changes in excitatory and/or inhibitory synaptic function, both implicated in schizophrenia and considered potential drug targets.
Altered static and dynamic regional homogeneity in basal ganglia–thalamocortical circuits and their association with neuropsychiatric manifestations in Wilson’s disease
PurposeWilson’s disease (WD) is an autosomal recessive disorder caused by ATP7B mutations, resulting in impaired copper metabolism and progressive neuropsychiatric manifestations. This study investigated spatiotemporal alterations in regional brain activity using static and dynamic resting-state fMRI with regional homogeneity (ReHo), and their relationships with clinical features.MethodsResting-state fMRI data were acquired from WD patients and healthy controls (HCs). Static and dynamic ReHo analyses were performed to characterize local synchronization strength and temporal variability of spontaneous neural activity. Group differences were assessed across the basal ganglia, thalamus, cerebellum, and cortical regions. Associations between altered ReHo metrics and clinical measures were evaluated with FDR correction for multiple comparisons.ResultsCompared with HCs, WD patients exhibited widespread ReHo abnormalities involving the basal ganglia (putamen and globus pallidus), thalamus, cerebellum, and cortical regions. Static ReHo in the left putamen and globus pallidus was positively associated with anxiety severity, while right putaminal ReHo was negatively associated with neurological severity and positively associated with disease duration. Dynamic ReHo in the left middle frontal gyrus showed negative associations with depression severity and disease duration. All brain–behavior correlations survived FDR correction, indicating robust effects.ConclusionWD is characterized by disrupted spatiotemporal organization of local functional synchronization within cerebellar and basal ganglia–thalamo–cortical circuits. These findings support a network-level dysfunction model involving subcortical synchronization deficits and cortical temporal instability, which together underpin neuropsychiatric manifestations and disease progression.
Interoceptive dysfunction and its neural correlates in schizophrenia: protocol for a cross-sectional multimodal MRI study
BackgroundInteroception—the perception and integration of internal bodily signals—is fundamental to emotion regulation, bodily self-awareness, and predictive coding. Emerging evidence suggests that interoceptive disturbances may contribute to core psychopathological features of schizophrenia. Our research group recently conducted a systematic review and meta-analysis demonstrating significant impairments in interoceptive accuracy and sensitivity among individuals with schizophrenia. However, the neural mechanisms underlying these deficits remain unclear.MethodsThis cross-sectional protocol will recruit 30 individuals with schizophrenia and 30 age- and sex-matched healthy controls. Participants will complete (1) behavioral interoceptive assessment using the heartbeat counting task; (2) subjective interoceptive questionnaires, including the Multidimensional Assessment of Interoceptive Awareness (MAIA) and the Body Perception Questionnaire (BPQ); (3) clinical symptom ratings (PANSS, HAM-A, HAM-D); and (4) cognitive testing (TMT, animal fluency, DSST). All participants will undergo multimodal MRI scanning, including structural T1-weighted imaging, resting-state fMRI, and diffusion tensor imaging. Neuroimaging data will be preprocessed and analyzed using DPABISurf, SPM12, and GRETNA. Expected Results: We anticipate that individuals with schizophrenia will show reduced interoceptive accuracy, altered subjective interoceptive awareness, and abnormal intrinsic neural activity and connectivity within interoception-related circuits, including the anterior insula, anterior cingulate cortex, amygdala, and thalamus. Structural abnormalities within thalamo-cortical pathways are also expected. Interoceptive deficits are hypothesized to correlate with symptom severity and cognitive performance.ConclusionsThis study will provide an integrated characterization of interoceptive dysfunction and its neural correlates in schizophrenia. Findings may advance understanding of bodily self-disturbance and emotional dysregulation and support the development of future interoception-focused therapeutic approaches.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2500110551.
Spatial evolution in temporal dynamics of hemodynamic response function in human superior colliculi with ultra-high-resolution MRI at 9.4T
The superior colliculus (SC) plays a crucial role in multisensory integration, visual information processing, saccadic target selection, visual selective attention, and decision making. In particular, the SC has a key role in oculomotor coordination, following a rostro-caudal organization. The rostral SC, which corresponds to foveal representation, is linked to fixation, microsaccades, smooth pursuit, and vergence adjustments. In contrast, the caudal SC, representing more peripheral visual field, is associated with the large gaze shifts (saccades). However, evidence regarding whether this functional gradient is preserved in the human SC remains limited. In this study, we employed a sequence-following visual-motor task to specifically engage SC activity. We measured blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to brief neural activity, known as hemodynamic response function (HRF). We showed a spatial gradient of the BOLD positive HRFs (pHRF) along the rostro-caudal axis of the SC. The pHRF was primarily located in the rostral SC, and it gradually weakened toward the caudal SC, where negative HRF (nHRF) was often observed. The systematic rostro-caudal evolution of HRFs were consistent both within and across subjects, consistent with results from previous electrophysiological studies. Our work showed the feasibility of using ultra-high-field fMRI to non-invasively examine neurovascular dynamics in a small and deeply located subcortical structures of the human brain.
Baseline Mismatch Negativity Amplitude Predicts Direction and Magnitude of Ketamine Effect in Healthy Volunteers — A “Disordinal” Effect
Mismatch negativity (MMN) is a component of the auditory event-related potential (ERP) that is elicited during a passive oddball paradigm where task-irrelevant infrequent deviants are presented in a stream of more frequent standard stimuli. MMN is believed to index a pre-attentive stage of auditory information processing closely linked to N-methyl-D-aspartate receptors (NMDAR) function. Ketamine is thought to act primarily as an NMDAR antagonist, has been used in clinical trials to model the symptoms of schizophrenia and is increasingly used in the clinic to treat depression.
Speech in noise prediction by use of cortical auditory evoked potentials in normal hearing and sensorineural hearing loss: a systematic review
IntroductionSpeech perception in noise (SPiN) is a critical challenge for individuals with sensorineural hearing loss (SNHL), and current behavioral assessments can be unreliable in populations with language barriers or cognitive impairment. Cortical auditory evoked potentials (CAEPs) can serve as a supplementary measurement as they often show strong correlations with SPiN outcomes across diverse hearing profiles.MethodsFollowing PRISMA and SWiM guidelines, this systematic review includes studies from PubMed, Web of Science, and Scopus databases that examined the relationship between non-task related CAEPs and SPiN outcomes in adults with normal hearing, SNHL, or cochlear implants.ResultsSixteen studies were included, encompassing 238 participants with SNHL and 204 participants with normal hearing. Across studies, N1 latency, P2 latency, and N1-P2 amplitude of the onset CAEP and acoustic change complex (ACC) are most consistently correlated with SPiN performance, particularly in sentence-based tests. The mismatch negativity (MMN) showed limited predictive value, as findings varied by age and hearing status. A meta-analysis was not conducted due to methodological heterogeneity.ConclusionOnset CAEP and ACC N1 and P2 latencies together with N1-P2 amplitudes particularly demonstrate potential as electrophysiological indicators of SPiN performance. Their clinical utility is promising for populations where behavioral testing can be unreliable, such as CI users or individuals with cognitive or language barriers. However, standardization of protocols and further longitudinal research are needed to validate their application in clinical settings.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42023404158, identifier PROSPERO (CRD42023404158).
The Parafascicular Role in Updating Action from a Spatial to a Visual Strategy Is Driven by Its Glutamatergic Mesencephalic Locomotor Region Inputs
The ability to update actions depends on the thalamus’s parafascicular nucleus (PF); however, which PF’s inputs control this function is unknown. Here, using fiber photometry, retrograde labeling, ex vivo electrophysiology, and optogenetic manipulations, we identify the contribution of the PF and its glutamatergic inputs to the update from a spatial to a visually guided strategy in a set-shifting task conducted in mice (of either sex). Our results show the following: (1) GCaMP signals from the PF recorded along the update from a spatial to a visual strategy correlate with the probability of selecting the correct action based on a light stimulus. (2) Optogenetic inhibition of the PF during this update decreases the probability of selecting the correct action. (3) The mesencephalic locomotor region (MLR) was found to have the highest probability of synaptic connections with the PF. (4) GCaMP recordings from the MLR->PF input support it as a main driver in allowing the PF update function. (5) Inhibition of the MLR->PF connection decreases the probability of updating the contingency. These findings identify the inputs from the MLR as a crucial driver of the PF’s role in controlling the update of actions.