Resting-State Functional MRI Metrics in Patients With Chronic Mild Traumatic Brain Injury and Their Association With Clinical Cognitive Performance

Mild traumatic brain injury (mTBI) accounts for more than 80% of people experiencing brain injuries. Symptoms of mTBI include short-term and long-term adverse clinical outcomes. In this study, resting-state functional magnetic resonance imaging (rs-fMRI) was conducted to measure voxel-based indices including fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) in patients suffering from chronic mTBI; 64 patients with chronic mTBI at least 3 months post injury and 40 healthy controls underwent rs-fMRI scanning. Partial correlation analysis controlling for age and gender was performed within mTBI cohort to explore the association between rs-fMRI metrics and neuropsychological scores. Compared with controls, chronic mTBI patients showed increased fALFF in the left middle occipital cortex (MOC), right middle temporal cortex (MTC), and right angular gyrus (AG), and increased ReHo in the left MOC and left posterior cingulate cortex (PCC). Enhanced FC was observed from left MOC to right precuneus; from right MTC to right superior temporal cortex (STC), right supramarginal, and left inferior parietal cortex (IPC); and from the seed located at right AG to left precuneus, left superior medial frontal cortex (SMFC), left MTC, left superior temporal cortex (STC), and left MOC. Furthermore, the correlation analysis revealed a significant correlation between neuropsychological scores and fALFF, ReHo, and seed-based FC measured from the regions with significant group differences. Our results demonstrated that alterations of low-frequency oscillations in chronic mTBI could be representative of disruption in emotional circuits, cognitive performance, and recovery in this cohort.

Three heads are better than one: Cooperative learning brains wire together when a consensus is reached

Theories of human learning converge on the view that individuals working together learn better than do those working alone. Little is known, however, about the neural mechanisms of learning through cooperation. We addressed this research gap by leveraging functional near-infrared spectroscopy (fNIRS) to record the brain activity of triad members in a group simultaneously. Triads were instructed to analyze an ancient Chinese poem either cooperatively or independently. Four main findings emerged. First, we observed significant within-group neural synchronization (GNS) in the left superior temporal cortex, supramarginal gyrus, and postcentral gyrus during cooperative learning compared to independent learning. Second, the enhancement of GNS in triads was amplified when a consensus was reached (vs. elaboration or argument) during cooperative learning. Third, GNS was predictive of learning outcome at an early stage (156-170 s after learning was initiated). Fourth, social factors such as social closeness (e.g., how much learners liked one other) were reflected in GNS and co-varied with learning engagement. These results provide neurophysiological support for Piaget's theory of cognitive development and favor the notion that successful learning through cooperation involves dynamic consensus building, which is captured in neural patterns shared across learners in a group.

Categorical encoding of voice in human superior temporal cortex

The ability to recognize abstract features of voice during auditory perception is a complex, yet poorly understood, feat of human audition. For the listener, this occurs in near-automatic fasion to seamlessly extract complex cues from a highly variable auditory signal. Voice perception depends on specialized regions of auditory cortex, including superior temporal gyrus (STG) and superior temporal sulcus (STS). However, the nature of voice encoding at the cortical level remains poorly understoood. We leverage intracerebral recordings across human auditory cortex during presentation of voice and non-voice acoustic stimuli to examine voice encoding in auditory cortex, in eight patient-participants undergoing epilepsy surgery evaluation. We show that voice-selectivity increases along the auditory hierarchy from supratemporal plane (STP) to the STG and STS. Results show accurate decoding of vocalizations from human auditory cortical activity even in the complete absence of linguistic content. These findings show an early, less-selective temporal window of neural activity in the STG and STS followed by a sustained, strongly voice-selective window. We then developed encoding models that demonstrate divergence in the encoding of acoustic features along the auditory hierarchy, wherein STG/STS responses were best explained by voice category as opposed to the acoustic features of voice stimuli. This is in contrast to neural activity recorded from STP, in which responses were accounted for by acoustic features. These findings support a model of voice perception that engages categorical encoding mechanisms within STG and STS.

Ventral Prefrontal Cortex

The ventral prefrontal cortex learns to associate objects, faces, and vocalizations, and its connectional fingerprint explains why it alone can do so. It receives visual inputs from the inferior temporal cortex and auditory ones from the superior temporal cortex. It combines these inputs with those from the orbital prefrontal (PF) cortex so as to specify the goal that is currently desirable. This is then transformed into the target of search via connections with the frontal eye field and the target for manual retrieval via connections with the premotor areas. The ventral PF cortex can also learn to form associations between objects, for example by linking them into categories. These can be retrieved from long-term memory via connections with the hippocampus.

Polygenic Risk for Schizophrenia, Brain Structure and Environmental Risk in UK Biobank

Schizophrenia is a heritable neurodevelopmental disorder characterized by neuroanatomical changes in the brain but exactly how increased genetic burden for schizophrenia influences brain structure is unknown. Similarly, the impact of environmental risk factors for schizophrenia on brain structure is not fully understood. We investigated how genetic burden for schizophrenia (indexed by a polygenic risk score, PRS-SCZ) was associated with cortical thickness (CT), cortical surface area (SA), cortical volume (CV) and multiple subcortical structures within 18,147 White British ancestry participants from UK Biobank. We also explored whether environmental risk factors for schizophrenia (cannabis use, childhood trauma, low birth weight and Townsend social deprivation index) exacerbated the impact of PRS-SCZ on brain structure. We found that PRS-SCZ was significantly associated with lower CT in the frontal lobe, insula lobe, lateral orbitofrontal cortex, medial orbitofrontal cortex, posterior cingulate cortex and inferior frontal cortex, as well as reduced SA and CV in the supramarginal cortex and superior temporal cortex, but not with differences in subcortical volumes. When models included environmental risk factors as covariates, PRS-SCZ was only associated with lower SA/CV within the supramarginal cortex, superior temporal cortex and inferior frontal cortex. Moreover, no interactions were observed between PRS-SCZ and each of the environmental risk factors on brain structure. Overall, we identified brain structural correlates of PRS-SCZ predominantly within frontal and temporal regions. Some of these associations were independent of environmental risk factors, suggesting that they may represent biomarkers of genetic risk for schizophrenia.

Neural patterns of word processing differ in children with dyslexia and isolated spelling deficit

There is an ongoing debate concerning the extent to which deficits in reading and spelling share cognitive components and whether they rely, in a similar fashion, on sublexical and lexical pathways of word processing. The present study investigates whether the neural substrates of word processing differ in children with various patterns of reading and spelling deficits. Using functional magnetic resonance imaging, we compared written and auditory processing in three groups of 9–13-year olds (N = 104): (1) with age-adequate reading and spelling skills; (2) with reading and spelling deficits (i.e., dyslexia); (3) with isolated spelling deficits but without reading deficits. In visual word processing, both deficit groups showed hypoactivations in the posterior superior temporal cortex compared to typical readers and spellers. Only children with dyslexia exhibited hypoactivations in the ventral occipito-temporal cortex compared to the two groups of typical readers. This is the result of an atypical pattern of higher activity in the occipito-temporal cortex for non-linguistic visual stimuli than for words, indicating lower selectivity. The print–speech convergence was reduced in the two deficit groups. Impairments in lexico-orthographic regions in a reading-based task were associated primarily with reading deficits, whereas alterations in the sublexical word processing route could be considered common for both reading and spelling deficits. These findings highlight the partly distinct alterations of the language network related to reading and spelling deficits.

Integrative analysis identifies bHLH transcription factors as contributors to Parkinson’s disease risk mechanisms

Genome-wide association studies (GWAS) have identified multiple genetic risk signals for Parkinson’s disease (PD), however translation into underlying biological mechanisms remains scarce. Genomic functional annotations of neurons provide new resources that may be integrated into analyses of GWAS findings. Altered transcription factor binding plays an important role in human diseases. Insight into transcriptional networks involved in PD risk mechanisms may thus improve our understanding of pathogenesis. We analysed overlap between genome-wide association signals in PD and open chromatin in neurons across multiple brain regions, finding a significant enrichment in the superior temporal cortex. The involvement of transcriptional networks was explored in neurons of the superior temporal cortex based on the location of candidate transcription factor motifs identified by two de novo motif discovery methods. Analyses were performed in parallel, both finding that PD risk variants significantly overlap with open chromatin regions harboring motifs of basic Helix-Loop-Helix (bHLH) transcription factors. Our findings show that cortical neurons are likely mediators of genetic risk for PD. The concentration of PD risk variants at sites of open chromatin targeted by members of the bHLH transcription factor family points to an involvement of these transcriptional networks in PD risk mechanisms.