Depression in bipolar disorder (BD-II) is frequently misdiagnosed as unipolar depression (UD) leading to inappropriate treatment and downstream complications for many bipolar sufferers. In this study, we evaluated whether neuromelanin-MR signal and volume changes in the substantia nigra (SN) can be used as potential biomarkers to differentiate BD-II from UD. The signal intensities and volumes of the SN regions were measured, and contrast-to-noise ratio (CNR) to the decussation of the superior cerebellar peduncles were calculated and compared between healthy controls (HC), BD-II and UD subjects. Results showed that compare to HC, both BD-II and UD subjects had significantly decreased CNR and increased volume on the right and left sides. Moreover, the volume in BD-II group was significantly increased compared to UD group. The area under the receiver operating characteristic curve (AUC) for discriminating BD from HC was the largest for the Volume-L (AUC, 0.85; 95% confidence interval [CI]: 0.77, 0.93). The AUC for discriminating UD from HC was the largest for the Volume-L (AUC, 0.76; 95% CI: 0.65, 0.86). Furthermore, the AUC for discriminating BD from UD was the largest for the Volume-R (AUC, 0.73; 95% CI: 0.62, 0.84). Our findings suggest that neuromelanin-sensitive magnetic resonance imaging techniques can be used to differentiate BD-II from UD.

Autism spectrum disorder (ASD) is characterized by etiological and phenotypic heterogeneity. Despite efforts to categorize ASD into subtypes, research on specific functional connectivity changes within ASD subgroups based on clinical presentations is limited. This study proposed a symptom-based clustering approach to identify subgroups of ASD based on multiple clinical rating scales and investigate their distinct Electroencephalogram (EEG) functional connectivity patterns. Eyes-opened resting-state EEG data were collected from 72 children with ASD and 63 typically developing (TD) children. A data-driven clustering approach based on Social Responsiveness Scales-Second Edition and Vinland-3 scores was used to identify subgroups. EEG functional connectivity and topological characteristics in four frequency bands were assessed. Two subgroups were identified: mild ASD (mASD, n = 37) and severe ASD (sASD, n = 35). Compared to TD, mASD showed increased functional connectivity in the beta band, while sASD exhibited decreased connectivity in the alpha band. Significant between-group differences in global and regional topological abnormalities were found in both alpha and beta bands. The proposed symptom-based clustering approach revealed the divergent functional connectivity patterns in the ASD subgroups that was not observed in typical ASD studies. Our study thus provides a new perspective to address the heterogeneity in ASD research.

Recognizing a stimulus as familiar is an important capacity in our everyday life. Recent investigation of visual processes has led to important insights into the nature of the neural representations of familiarity for human faces. Still, little is known about how familiarity affects the neural dynamics of non-face stimulus processing. Here we report the results of an EEG study, examining the representational dynamics of personally familiar scenes. Participants viewed highly variable images of their own apartments and unfamiliar ones, as well as personally familiar and unfamiliar faces. Multivariate pattern analyses were used to examine the time course of differential processing of familiar and unfamiliar stimuli. Time-resolved classification revealed that familiarity is decodable from the EEG data similarly for scenes and faces. The temporal dynamics showed delayed onsets and peaks for scenes as compared to faces. Familiarity information, starting at 200ms, generalized across stimulus categories and led to a robust familiarity effect. In addition, familiarity enhanced category representations in early (250-300ms) and later (>400ms) processing stages. Our results extend previous face familiarity results to another stimulus category and suggest that familiarity as a construct can be understood as a general, stimulus-independent processing step during recognition.

Facial palsy therapies based on cortical plasticity are in development, but facial synkinesis progress is limited. Studying neural plasticity characteristics, especially network organization and its constitutive elements (nodes/edges), is the key to overcome the bottleneck. We studied 55 participants (33 facial synkinesis patients, 22 healthy controls) with clinical assessments, functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI). We analyzed rich-club organization and metrics of structural brain networks (rich-club coefficients, strength, degree, density, and efficiency). Functional brain network metrics, including functional connectivity and its coupling with the structural network, were also computed. Patients displayed reduced strength and density of rich-club nodes and edges, as well as decreased global efficiency. All nodes exhibited decreased nodal efficiency in patients. Patients had significantly increased functional connectivity and decreased structural-functional coupling strength in rich-club nodes, rich-club edges, and feeder edges. Our study indicates that facial synkinesis patients have weakened structural connections but enhanced functional transmission from rich-club nodes. The loss of connections and efficiency in structural network may trigger compensatory increases in functional connectivity of rich-club nodes. Two potential biomarkers, rich-club edge density and structural-functional coupling strength, may serve as indicators of disease outcome. These findings provide valuable insights into synkinesis mechanisms and offer potential targets for cortical intervention.

Motor imagery can, similarly to physical practice, improve motor performance through experience-based plasticity. Using magnetoencephalography, we investigated changes in brain activity associated with offline consolidation of motor sequence learning through physical practice or motor imagery. After an initial training session with either physical practice or motor imagery, participants underwent overnight consolidation. As control condition, participants underwent wake-related consolidation after training with motor imagery. Behavioral analyses revealed that overnight consolidation of motor learning through motor imagery outperformed wake-related consolidation (95% CI [0.02, 0.07], P < 0.001, RP2 = 0.05). As regions of interest, we selected the generators of event-related synchronization/desynchronization of alpha (8-12Hz) and beta (15-30Hz) oscillations, which predicted the level of performance on the motor sequence. This yielded a primary sensorimotor-premotor network for alpha oscillations and a cortico-cerebellar network for beta oscillations. The alpha network exhibited increased neural desynchronization after overnight consolidation compared to wake-related consolidation. By contrast, the beta network exhibited an increase in neural synchronization after wake-related consolidation compared to overnight consolidation. We provide the first evidence of parallel brain plasticity underlying behavioral changes associated with sleep-dependent consolidation of motor skill learning through motor imagery and physical practice.

Electroencephalography can assess connectivity between brain hemispheres, potentially influencing cognitive functions. Much of the existing electroencephalography research primarily focuses on undirected connectivity, leaving uncertainties about directed connectivity alterations between left-right brain hemispheres or frontal-posterior lobes in mild cognitive impairment. We analyzed resting-state electroencephalography data from 34 mild cognitive impairment individuals and 23 normal controls using directed transfer function and graph theory for directed network analysis. Concerning the dominance within left-right hemispheres or frontal-posterior lobes, the mild cognitive impairment group exhibited decreased connectivity within the frontal compared with posterior brain regions in the delta and theta bands. Regarding the dominance between the brain hemispheres or lobes, the mild cognitive impairment group showed reduced connectivity from the posterior to the frontal regions versus the reverse direction in the same bands. Among all participants, the intra-lobe frontal-posterior dominance correlated positively with executive function in the delta and alpha bands. Inter-lobe dominance between frontal and posterior regions also positively correlated with executive function, attention, and language in the delta band. Additionally, interhemispheric dominance between the left and right hemispheres positively correlated with attention in delta and theta bands. These findings suggest altered cerebral dominance in mild cognitive impairment, potentially serving as electrophysiological markers for neurocognitive disorders.

Prospective memory (PM) impairment is among the most frequent memory complaints, yet little is known about the underlying neural mechanisms. PM for a planned intention may be achieved through strategic monitoring of the environment for cues, involving ongoing attentional processes, or through spontaneous retrieval. We hypothesized that parietal spectral power modulation accompanies prospectively encoded intention retrieval, irrespective of PM retrieval approach. A cognitively engaging arithmetic-based ongoing task (OGT) was employed to encourage spontaneous retrieval, with a focal, internally generated PM cue to eliminate OGT/PM trial differentiation based on perceptual or conceptual PM cue features. Two PM repetition frequencies were used to vary the extent of strategic monitoring. We observed a transient parietal alpha/beta spectral power reduction directly preceding the response, which was distinguishable on a single trial basis, as revealed by an OGT/PM trial classification rate exceeding 70% using linear discriminant analysis. The alpha/beta idling rhythm reflects cortical inhibition. A disengagement of task-relevant neural assemblies from this rhythm, reflected in alpha/beta power reduction, is deemed to increase information content, facilitate information integration, and enable engagement of neural assemblies in task-related cortical networks. The observed power reduction is consistent with the Dual Pathways model, where PM strategies converge at the PM retrieval stage.

Complement signaling is thought to serve as an opsonization signal to promote the phagocytosis of synapses by microglia. However, while its role in synaptic remodeling has been demonstrated in the retino-thalamic system, it remains unclear whether complement signaling mediates synaptic pruning in the brain more generally. Here we found that mice lacking the Complement receptor 3, the major microglia complement receptor, failed to show a deficit in either synaptic pruning or axon elimination in the developing mouse cortex. Instead, mice lacking Complement receptor 3 exhibited a deficit in the perinatal elimination of neurons in the cortex, a deficit that is associated with increased cortical thickness and enhanced functional connectivity in these regions in adulthood. These data demonstrate a role for complement in promoting neuronal elimination in the developing cortex.

The comprehension of metaphor, a vivid and figurative language, is a complex endeavor requiring cooperation among multiple cognitive systems. There are still many important questions regarding neural mechanisms implicated in specific types of metaphor. To address these questions, we conducted activation likelihood estimation meta-analyses on 30 studies (containing data of 480 participants) and meta-analytic connectivity modeling analyses. First, the results showed that metaphor comprehension engaged the inferior frontal gyrus, middle temporal gyrus, fusiform gyrus, lingual gyrus, and middle occipital gyrus-all in the left hemisphere. In addition to the commonly reported networks of language and attention, metaphor comprehension engaged networks of visual. Second, sub-analysis showed that the contextual complexity can modulate figurativeness, with the convergence on the left fusiform gyrus during metaphor comprehension at discourse-level. Especially, right hemisphere only showed convergence in studies of novel metaphors, suggesting that the right hemisphere is more associated with difficulty than metaphorical. The work here extends knowledge of the neural mechanisms underlying metaphor comprehension in individual brain regions and neural networks.

Brian imaging-derived phenotypes (IDPs) have been suggested to be associated with ischemic stroke, but the causality between them remains unclear. In this bidirectional two-sample Mendelian randomization (MR) study, we explored the potential causal relationship between 461 imaging-derived phenotypes (n = 33,224, UK Biobank) and ischemic stroke (n = 34,217 cases/406,111 controls, Multiancestry Genome-Wide Association Study of Stroke). Forward MR analyses identified five IDPs associated with ischemic stroke, including mean diffusivity (MD) in the right superior fronto-occipital fasciculus (1.22 [95% CI, 1.11-1.34]), MD in the left superior fronto-occipital fasciculus (1.30 [1.17-1.44]), MD in the anterior limb of the right internal capsule (1.36 [1.22-1.51]), MD in the right anterior thalamic radiation (1.17 [1.09-1.26]), and MD in the right superior thalamic radiation (1.23 [1.11-1.35]). In the reverse MR analyses, ischemic stroke was identified to be associated with three IDPs, including high isotropic or free water volume fraction in the body of corpus callosum (beta, 0.189 [95% confidence interval, 0.107-0.271]), orientation dispersion index in the pontine crossing tract (0.175 [0.093-0.257]), and volume of the third ventricle (0.219 [0.138-0.301]). This bidirectional two-sample MR study suggested five predictors and three diagnostic markers for ischemic stroke at the brain-imaging level. Further studies are warranted to replicate our findings and clarify underlying mechanisms.