The sensory cortex is organized into "maps" that represent sensory space across cortical space. In primary visual cortex (V1) of highly visual mammals, multiple visual feature maps are organized into a functional architecture anchored by orientation domains: regions containing neurons preferring the same stimulus orientation. Although the pinwheel-like structure of orientation domains is well-characterized in the superficial cortical layers in dorsal regions of V1, the 3D shape of orientation domains spanning all 6 cortical layers and across dorsal and ventral regions of V1 has never been revealed.

The human cerebellum is a heterogeneous structure, and the pattern of resting-state functional connectivity (rsFC) of each subregion has not yet been fully characterized. We aimed to systematically investigate rsFC pattern of each cerebellar subregion in 228 healthy young adults. Voxel-based analysis revealed that several subregions showed similar rsFC patterns, reflecting functional integration; however, different subregions displayed distinct rsFC patterns, representing functional segregation. The same vermal and hemispheric subregions showed either different patterns or different strengths of rsFCs with the cerebrum, and different subregions of lobules VII and VIII displayed different rsFC patterns. Region of interest (ROI)-based analyses also confirmed these findings. Specifically, strong rsFCs were found: between lobules I-VI and vermal VIIb-IX and the visual network; between hemispheric VI, VIIb, VIIIa and the auditory network; between lobules I-VI, VIII and the sensorimotor network; between lobule IX, vermal VIIIb and the default-mode network; between lobule Crus I, hemispheric Crus II and the fronto-parietal network; between hemispheric VIIb, VIII and the task-positive network; between hemispheric VI, VIIb, VIII and the salience network; between most cerebellar subregions and the thalamus; between lobules V, VIIb and the midbrain red nucleus; between hemispheric Crus I, Crus II, vermal VIIIb, IX and the caudate nucleus; between lobules V, VI, VIIb, VIIIa and the pallidum and putamen; and between lobules I-V, hemispheric VIII, IX and the hippocampus and amygdala. These results confirm the existence of both functional integration and segregation among cerebellar subregions and largely improve our understanding of the functional organization of the human cerebellum.

Converging evidence from both human and animal studies has highlighted the pervasive role of the neuropeptide arginine vasopressin (AVP), which is mediated by arginine vasopressin receptor 1A (AVPR1A), in both social and nonsocial learning and memory. However, the effect of genetic variants in AVPR1A on verbal learning and memory is unknown. The hippocampus is a heterogeneous structure that consists of several anatomically and functionally distinct subfields, and it is the principal target structure for the memory-enhancing effect of AVP. We tested the hypothesis that genetic variants in the RS3 and RS1 repeat polymorphisms may influence verbal learning and memory performance evaluated by the California Verbal Learning Test-II (CVLT-II) by modulating the gray matter volume (GMV) and resting-state functional connectivity (rsFC) of whole hippocampus and its subfields in a large cohort of young healthy subjects (n = 1001). Using a short/long classification scheme for the repeat length of RS3 and RS1, we found that the individuals carrying more short alleles of RS3-RS1 haplotypes had poorer learning and memory performance compared to that of those carrying more long alleles. We also revealed that individuals carrying more short alleles exhibited a significantly smaller GMV in the left cornu ammonis (CA)2/3 and weaker rsFC of the left CA2/3-bilateral thalamic (primarily in medial prefrontal subfields) compared to those carrying more long alleles. Furthermore, multiple mediation analysis confirmed that these two hippocampal imaging measures jointly and fully mediated the relationship between the genetic variants in AVPR1A RS3-RS1 haplotypes and the individual differences in verbal learning and memory performance. Our results suggest that genetic variants in AVPR1A RS3-RS1 haplotypes may affect verbal learning and memory performance in part by modulating the left hippocampal CA2/3 structure and its rsFC with the thalamus.

Pain is subjective and perceived differently in different people. However, individual differences in pain-elicited brain activations are largely overlooked and often discarded as noises. Here, we used a brain-activation-based individual identification procedure to investigate the uniqueness of the activation patterns within the whole brain or brain regions elicited by nociceptive (laser) and tactile (electrical) stimuli in each of 62 healthy participants. Specifically, brain activation patterns were used as "fingerprints" to identify each individual participant within and across sensory modalities, and individual identification accuracy was calculated to measure each individual's identifiability. We found that individual participants could be successfully identified using their brain activation patterns elicited by nociceptive stimuli, tactile stimuli, or even across modalities. However, different participants had different identifiability; importantly, the within-pain, but not within-touch or cross-modality, individual identifiability obtained from three brain regions (i.e., the left superior frontal gyrus, the middle temporal gyrus and the insular gyrus) were inversely correlated with the scores of Pain Vigilance and Awareness Questionnaire (i.e., how a person is alerted to pain) across participants. These results suggest that each individual has a unique pattern of brain responses to nociceptive stimuli which contains both modality-nonspecific and pain-specific information and may be associated with pain-related behaviors shaped by his/her own personal experiences and highlight the importance of a transition from group-level to individual-level characterization of brain activity in neuroimaging studies.

The inferior parietal lobule (IPL) is a functionally and anatomically heterogeneous region. Much of the information about the anatomical connectivity and parcellation of this region was obtained from histological studies on non-human primates. However, whether these findings from non-human primates can be applied to the human inferior parietal lobule, especially the left inferior parietal lobule, which shows evidence of considerable evolution from primates to humans, remains unclear. In this study, diffusion MRI was employed to investigate the anatomical connectivities of the human left inferior parietal lobule. Using a new algorithm, spectral clustering with edge-weighted centroidal voronoi tessellations, to search for regional variations in the probabilistic connectivity profiles of all left inferior parietal lobule voxels with all the rest of the brain identified six subregions with distinctive connectivity properties in the left inferior parietal lobule. Consistent with cytoarchitectonic findings, four subregions were found in the left supramarginal gyrus and two subregions in the left angular gyrus. The specific connectivity patterns of each subregion of the left inferior parietal lobule were supported by both the anatomical and functional connectivity properties for each subregion, as calculated by a meta-analysis-based target method and by voxel-based whole brain anatomical and functional connectivity analyses. The proposed parcellation scheme for the human left inferior parietal lobule and the maximum probability map for each subregion may facilitate more detailed future studies of this brain area.

In this study, we introduced a length-normalized parameterization method to establish anatomical correspondence of white matter fiber tracts across subjects and applied this method to investigate the presence of abnormal diffusion along the pyramidal tract (PYT) of relapsing neuromyelitis optica (RNMO) patients without visible brain lesions. In this approach, the part of the PYT between the lowest slice of the cerebral peduncle and the uppermost slice of the lateral ventricle was reconstructed to establish the anatomical correspondence across subjects using diffusion tensor tractography. Then it was parameterized by normalizing its length and dividing equally the normalized length into a certain number of segments, so that the comparability of each segment across subjects along the PYT was established. Tract-specific diffusion indices, including directionally averaged diffusivity (D(av)), fractional anisotropy (FA), primary diffusivity (lambda(1)) and transverse diffusivity (lambda(23)), were obtained from each segment. Thus, the distribution maps of these indices along the PYT were obtained. The distribution maps of D(av), FA, and lambda(23) of RNMO patients were significantly different from those of healthy controls, especially in the lower part of the PYT. The differences may be caused by secondary degeneration to lesions in the spinal cord. In conclusion, a length-normalized parameterization method is proposed to establish anatomical correspondence for the PYT. Compared with existed methods, a major merit of our method is to provide comparability across subjects along the PYT on the basis of diffusion tensor tractography and to make it possible for the quantitative analysis along the fiber tract. This method can also be used to quantitatively analyze other white matter fiber tracts between two definite anatomic landmarks in many neurological or psychiatric diseases.

A large body of research suggests that oxytocin receptor (OXTR) gene polymorphisms may influence both social behaviors and psychiatric conditions related to social deficits, such as autism spectrum disorders (ASDs), schizophrenia, and mood and anxiety disorders. However, the neural mechanism underlying these associations is still unclear. Relative to controls, patients with these psychiatric conditions show differences in brain structure, and in resting state fMRI (rs-fMRI) signal synchronicity among default mode network (DMN) regions (also known as functional connectivity). We used a stepwise imaging genetics approach in 328 healthy young adults to test the hypothesis that 10 SNPs in OXTR are associated with differences in DMN synchronicity and structure of some of the associated brain regions. As OXTR effects may be sex-dependent, we also tested whether our findings were modulated by sex. OXTR rs2254298 A allele carriers had significantly lower rsFC with PCC in a cluster extending from the right fronto-insular cortex to the putamen and globus pallidus, and in bilateral dorsal anterior cingulate cortex (dACC) compared to individuals with the GG genotype; all observed effects were found only in males. Moreover, compared to the male individuals with GG genotype ofrs2254298, the male A allele carriers demonstrated significantly thinner cortical gray matter in the bilateral dACC. Our findings suggest that there may be sexually dimorphic mechanisms by which a naturally occurring variation of the OXTR gene may influence brain structure and function in DMN-related regions implicated in neuropsychiatric disorders.

The four-region model with 7 specified subregions represents a theoretical construct of functionally segregated divisions of the cingulate cortex based on integrated neurobiological assessments. Under this framework, we aimed to investigate the functional specialization of the human cingulate cortex by analyzing the resting-state functional connectivity (FC) of each subregion from a network perspective. In 20 healthy subjects we systematically investigated the FC patterns of the bilateral subgenual (sACC) and pregenual (pACC) anterior cingulate cortices, anterior (aMCC) and posterior (pMCC) midcingulate cortices, dorsal (dPCC) and ventral (vPCC) posterior cingulate cortices and retrosplenial cortices (RSC). We found that each cingulate subregion was specifically integrated in the predescribed functional networks and showed anti-correlated resting-state fluctuations. The sACC and pACC were involved in an affective network and anti-correlated with the sensorimotor and cognitive networks, while the pACC also correlated with the default-mode network and anti-correlated with the visual network. In the midcingulate cortex, however, the aMCC was correlated with the cognitive and sensorimotor networks and anti-correlated with the visual, affective and default-mode networks, whereas the pMCC only correlated with the sensorimotor network and anti-correlated with the cognitive and visual networks. The dPCC and vPCC involved in the default-mode network and anti-correlated with the sensorimotor, cognitive and visual networks, in contrast, the RSC was mainly correlated with the PCC and thalamus. Based on a strong hypothesis driven approach of anatomical partitions of the cingulate cortex, we could confirm their segregation in terms of functional neuroanatomy, as suggested earlier by task studies or exploratory multi-seed investigations.

The oxytocin receptor gene (OXTR) rs53576A has been associated with autism spectrum disorders (ASDs). A smaller hypothalamic volume has been reported in healthy male A-allele carriers than in male GG homozygotes and in patients with ASDs than in healthy controls. These findings prompt the hypothesis that male AA homozygotes may have weaker hypothalamic functional connectivity when compared to male G-allele carriers. We calculated local functional connectivity density (FCD) using a voxel-wise data-driven approach based on resting-state functional MRI data in 270 young healthy subjects. Both the main effect of genotype and the gender-by-genotype interaction were considered. Of the whole brain, only the local FCD of the hypothalamus exhibited the main effect of genotype. Post-hoc testing revealed significantly lower local FCD in male AA homozygotes compared to male G-allele carriers although there was only a trend of significance in the gender-by-genotype interaction. We further analyzed the resting-state functional connectivity (rsFC) of the hypothalamic region that demonstrating significant genotype differences in local FCD. We found a significant gender-by-genotype interaction in rsFC between the hypothalamic region and the left dorsolateral prefrontal cortex, but no significant main effect of genotype was found. Post-hoc testing revealed that this rsFC was significantly weaker in male AA homozygotes compared to male G-allele carriers. Our findings identify gender-dependent mechanisms of OXTR rs53576 gene variation impacting the functional connectivity of the hypothalamus in healthy individuals and suggest that these mechanisms are important for understanding ASDs.

Much Research has been done on extrinsic and intrinsic systems, which consist of brain regions associated with the processing of externally and internally oriented stimuli, respectively. However, understanding of the underlying relationships within and between these two systems is relatively limited. To improve our understanding of these underlying relationships, we investigated the positive and negative correlations of three regions of interest (ROIs) located in the auditory, visual and somatosensory systems by using resting state functional MRI (fMRI) with a large sample size. We found that all three sensory systems exhibited significant negative correlation with the intrinsic system. In contrast, positive correlations between these sensory cortices and brain regions outside their respective system were limited. The present study extended former findings by indicating that multiple subsystems rather than a single subsystem of the extrinsic system are inherently negatively correlated with the intrinsic system. We suggest that these negative correlations between the extrinsic and intrinsic systems may explain the phenomenon that externally and internally oriented processes can always disturb or even interrupt each other.

Many functional imaging studies have been performed to explore the neural basis of intelligence by detecting brain activity changes induced by intelligence-related tasks, such as reasoning or working memory. However, little is known about whether the spontaneous brain activity at rest is relevant to the differences in intelligence. Here, 59 healthy adult subjects (Wechsler Adult Intelligence Scale score, 90-138) were studied with resting state fMRI. We took the bilateral dorsolateral prefrontal cortices (DLPFC) as the seed regions and investigated the correlations across subjects between individual intelligence scores and the strength of the functional connectivity (FC) between the seed regions and other brain regions. We found that the brain regions in which the strength of the FC significantly correlated with intelligence scores were distributed in the frontal, parietal, occipital and limbic lobes. Stepwise linear regression analysis also revealed that the FCs within the frontal lobe and between the frontal and posterior brain regions were both important predictive factors for the differences in intelligence. These findings support a network view of intelligence, as suggested in previous studies. More importantly, our findings suggest that brain activity may be relevant to the differences in intelligence even in the resting state and in the absence of an explicit cognitive demand. This could provide a new perspective for understanding the neural basis of intelligence.

It is difficult to completely differentiate patients with relapsing neuromyelitis optica (RNMO) from relapsing-remitting multiple sclerosis (RRMS) for their similarities in clinical manifestation. In this study, we proposed a novel approach, using two-dimensional histogram of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the brain derived from diffusion tensor imaging (DTI) as classification feature, to discriminate patients with RNMO from RRMS. In this approach, two-dimensional principal component analysis (2D-PCA) was used to extract feature and reduce dimensionality of matrix-formed data efficiently. Then linear discriminant analysis (LDA) was performed on these extracted features to find the best projection direction to separate patients with RNMO from RRMS. Finally, a minimum distance classifier was generated on the basis of projection scores. The correct recognition rate of our method reached 85.7%, validated by the leave-one-out method. This result was much higher than that using feature of ADC or FA separately (59.5% for ADC, 76.2% for FA). In conclusion, the proposed method on the basis of combined features is more effective for classification than those merely using the features separately, and it may be helpful in differentiating RNMO from RRMS patients.

Although both schizophrenia and gray matter volume (GMV) show high heritability, however, genes accounting for GMV alterations in schizophrenia remain largely unknown. Based on risk genes identified in schizophrenia by the genome-wide association study of the Schizophrenia Working Group of the Psychiatric Genomics Consortium, we used transcription-neuroimaging association analysis to test that which of these genes are associated with GMV changes in schizophrenia. For each brain tissue sample, the expression profiles of 196 schizophrenia risk genes were extracted from six donated normal brains of the Allen Human Brain Atlas, and GMV differences between patients with schizophrenia and healthy controls were calculated based on five independent case-control structural MRI datasets (276 patients and 284 controls). Genes associated with GMV changes in schizophrenia were identified by performing cross-sample spatial correlations between expression levels of each gene and case-control GMV difference derived from the five MRI datasets integrated by harmonization and meta-analysis. We found that expression levels of 98 genes consistently showed significant cross-sample spatial correlations with GMV changes in schizophrenia. These genes were functionally enriched for chemical synaptic transmission, central nervous system development, and cell projection. Overall, this study provides a set of genes possibly associated with GMV changes in schizophrenia, which could be used as candidate genes to explore biological mechanisms underlying the structural impairments in schizophrenia.

Studies have indicated that the dorsal attention network (DAN) and the ventral attention network (VAN) functionally interact via several fronto-parietal connector hubs. However, the anatomical connectivity profiles of these connector hubs, and the coupling between the anatomical and functional connectivities of them, are still unknown. In the present study, we found that functional connector hubs anatomically bridged the DAN and VAN based on multimodal magnetic resonance imaging data from the Human Connectome Project (HCP) Consortium and an independent Chinese cohort. The three hubs had unique anatomical connectivity patterns with the attention sub-networks. For each connector hub, the pattern of anatomical connectivity resembled the functional one. Finally, the strength of the anatomical connectivity of these connector hubs was positively associated with the functional connectivity at the group- and individual-levels. Our findings help to better understand the anatomical mechanisms underlying the functional interactions between the DAN and the VAN.

Nociceptive and tactile information is processed in the somatosensory system via reciprocal (i.e., feedforward and feedback) projections between the thalamus, the primary (S1) and secondary (S2) somatosensory cortices. The exact hierarchy of nociceptive and tactile information processing within this 'thalamus-S1-S2' network and whether the processing hierarchy differs between the two somatosensory submodalities remains unclear. In particular, two questions related to the ascending and descending pathways have not been addressed. For the ascending pathways, whether tactile or nociceptive information is processed in parallel (i.e., 'thalamus-S1' and 'thalamus-S2') or in serial (i.e., 'thalamus-S1-S2') remains controversial. For the descending pathways, how corticothalamic feedback regulates nociceptive and tactile processing also remains elusive. Here, we aimed to investigate the hierarchical organization for the processing of nociceptive and tactile information in the 'thalamus-S1-S2' network using dynamic causal modeling (DCM) combined with high-temporal-resolution fMRI. We found that, for both nociceptive and tactile information processing, both S1 and S2 received inputs from thalamus, indicating a parallel structure of ascending pathways for nociceptive and tactile information processing. Furthermore, we observed distinct corticothalamic feedback regulations from S1 and S2, showing that S1 generally exerts inhibitory feedback regulation independent of external stimulation whereas S2 provides additional inhibition to the thalamic activity during nociceptive and tactile information processing in humans. These findings revealed that nociceptive and tactile information processing have similar hierarchical organization within the somatosensory system in the human brain.