Speeded Near Infrared Spectroscopy (NIRS) Response Detection

The hemodynamic response measured by Near Infrared Spectroscopy (NIRS) is temporally delayed from the onset of the underlying neural activity. As a consequence, NIRS based brain-computer-interfaces (BCIs) and neurofeedback learning systems, may have a latency of several seconds in responding to a change in participants' behavioral or mental states, severely limiting the practical use of such systems. To explore the possibility of reducing this delay, we used a multivariate pattern classification technique (linear support vector machine, SVM) to decode the true behavioral state from the measured neural signal and systematically evaluated the performance of different feature spaces (signal history, history gradient, oxygenated or deoxygenated hemoglobin signal and spatial pattern). We found that the latency to decode a change in behavioral state can be reduced by 50% (from 4.8 s to 2.4 s), which will enhance the feasibility of NIRS for real-time applications

A pilot randomized trial to examine effects of a hybrid closed-loop insulin delivery system on neurodevelopmental and cognitive outcomes in adolescents with type 1 diabetes

Type 1 diabetes (T1D) is associated with lower scores on tests of cognitive and neuropsychological function and alterations in brain structure and function in children. This proof-of-concept pilot study (ClinicalTrials.gov Identifier NCT03428932) examined whether MRI-derived indices of brain development and function and standardized IQ scores in adolescents with T1D could be improved with better diabetes control using a hybrid closed-loop insulin delivery system. Eligibility criteria for participation in the study included age between 14 and 17 years and a diagnosis of T1D before 8 years of age. Randomization to either a hybrid closed-loop or standard diabetes care group was performed after pre-qualification, consent, enrollment, and collection of medical background information. Of 46 participants assessed for eligibility, 44 met criteria and were randomized. Two randomized participants failed to complete baseline assessments and were excluded from final analyses. Participant data were collected across five academic medical centers in the United States. Research staff scoring the cognitive assessments as well as those processing imaging data were blinded to group status though participants and their families were not. Forty-two adolescents, 21 per group, underwent cognitive assessment and multi-modal brain imaging before and after the six month study duration. HbA1c and sensor glucose downloads were obtained quarterly. Primary outcomes included metrics of gray matter (total and regional volumes, cortical surface area and thickness), white matter volume, and fractional anisotropy. Estimated power to detect the predicted treatment effect was 0.83 with two-tailed, α = 0.05. Adolescents in the hybrid closed-loop group showed significantly greater improvement in several primary outcomes indicative of neurotypical development during adolescence compared to the standard care group including cortical surface area, regional gray volumes, and fractional anisotropy. The two groups were not significantly different on total gray and white matter volumes or cortical thickness. The hybrid closed loop group also showed higher Perceptual Reasoning Index IQ scores and functional brain activity more indicative of neurotypical development relative to the standard care group (both secondary outcomes). No adverse effects associated with study participation were observed. These results suggest that alterations to the developing brain in T1D might be preventable or reversible with rigorous glucose control. Long term research in this area is needed

Social Brain Development in Williams Syndrome: The Current Status and Directions for Future Research

Williams syndrome (WS) is a neurodevelopmental condition that occurs as a result of a contiguous deletion of ∼26–28 genes on chromosome 7q11.23. WS is often associated with a distinctive social phenotype characterized by an increased affinity toward processing faces, reduced sensitivity to fear related social stimuli and a reduced ability to form concrete social relationships. Understanding the biological mechanisms that underlie the social phenotype in WS may elucidate genetic and neural factors influencing the typical development of the social brain. In this article, we review available studies investigating the social phenotype of WS throughout development and neuroimaging studies investigating brain structure and function as related to social and emotional functioning in this condition. This review makes an important contribution by highlighting several neuro-behavioral mechanisms that may be a cause or a consequence of atypical social development in WS. In particular, we discuss how distinctive social behaviors in WS may be associated with alterations or delays in the cortical representation of faces, connectivity within the ventral stream, structure and function of the amygdala and how long- and short-range connections develop within the brain. We integrate research on typical brain development and from existing behavioral and neuroimaging research on WS. We conclude with a discussion of how genetic and environmental factors might interact to influence social brain development in WS and how future neuroimaging and behavioral research can further elucidate social brain development in WS. Lastly, we describe how ongoing studies may translate to improved social developmental outcomes for individuals with WS

Neural bases of social feedback processing and self–other distinction in late childhood: The role of attachment and age

Attachment plays a key role in how children process information about the self and others. Here, we examined the neural bases of interindividual differences in attachment in late childhood and tested whether social cognition-related neural activity varies as function of age. In a small sample of 8-year-old to 12-year-old children (n = 21/19), we used functional magnetic resonance imaging to measure neural responses during social feedback processing and self–other distinction. Attachment was assessed using child self-report. The social feedback processing task presented smiling and angry faces either confirming or disconfirming written information about participant performance on a perceptual game. In addition to observing main effects of facial emotion and performance, an increase in age was related to a shift from negative (i.e., angry faces/bad performance) to positive (i.e., smiling faces/good performance) information processing in the left amygdala/hippocampus, bilateral fusiform face area, bilateral anterior temporal pole (ATP), and left anterior insula. There were no effects of attachment on social feedback processing. The self–other distinction task presented digital morphs between children’s own faces and faces of their mother or stranger females. We observed differential activation in face processing and mentalizing regions in response to self and mother faces versus morphed faces. Furthermore, left ATP activity was associated with attachment anxiety such that greater attachment anxiety was related to a shift from heightened processing of self and mother faces to morphed faces. There were no effects of age on self–other distinction. We discuss our preliminary findings in the context of attachment theory and previous work on social evaluation and self–other processing

A preliminary study of orbitofrontal activation and hypersociability in Williams Syndrome

Individuals with Williams syndrome (WS) demonstrate an abnormally positive social bias. However, the neural substrates of this hypersociability, i.e., positive attribution bias and increased drive toward social interaction, have not fully been elucidated. Methods: We performed an event-related functional magnetic resonance imaging study while individuals with WS and typically developing controls (TD) matched positive and negative emotional faces. WS compared to TD showed reduced right amygdala activation during presentation of negative faces, as in the previous literature. In addition, WS showed a unique pattern of right orbitofrontal cortex activation. While TD showed medial orbitofrontal cortex activation in response to positive, and lateral orbitofrontal cortex activation to negative, WS showed the opposite pattern. In light of the general notion of a medial/lateral gradient of reward/punishment processing in the orbitofrontal cortex, these findings provide an additional biological explanation for, or correlate of positive attribution bias and hypersociability in WS

Aberrant Neural Function During Emotion Attribution in Female Subjects With Fragile X Syndrome

Objective: Fragile X (FraX) syndrome is caused by mutations of the FraX mental retardation-1 gene—a gene responsible for producing FraX mental retardation protein. The neurocognitive phenotype associated with FraX in female subjects includes increased risk for emotional disorders including social anxiety, depression, and attention deficit. Here, the authors investigated the neurobiological systems underlying emotion attribution in female subjects with FraX syndrome. Method: While undergoing functional magnetic resonance imaging, 10 high-functioning female subjects with FraX syndrome and 10 typically developing (TD) female subjects were presented with photographs of happy, sad, and neutral faces and instructed to determine the facial emotion. Results: No significant group differences were found for the recognition of happy faces, although the FraX group showed a trend toward a significant difference for the recognition of sad faces and significantly poorer recognition of neutral faces. Controlling for between-group differences in IQ and performance accuracy, the TD group had greater activation than the FraX group in the anterior cingulate cortex (ACC) for neutral faces compared with scrambled faces and the caudate for sad faces compared with scrambled faces (but not for sad faces compared with neutral faces). In the FraX group, FraX mental retardation protein levels positively correlated with activation in the dorsal ACC for neutral, happy, and sad faces when independently compared with scrambled faces. Significantly greater negative correlation between IQ and insula activation for neutral faces relative to scrambled faces was observed in the FraX group compared with the TD group. Significantly greater positive correlation between IQ and ACC activation for neutral faces relative to scrambled faces was observed in the TD group compared with the FraX group. Conclusions: Although emotion recognition is generally spared in FraX syndrome, the emotion circuit (i.e., ACC, caudate, insula) that modulates emotional responses to facial stimuli may be disrupted

Humor Modulates the Mesolimbic Reward Centers

AbstractHumor plays an essential role in many facets of human life including psychological, social, and somatic functioning. Recently, neuroimaging has been applied to this critical human attribute, shedding light on the affective, cognitive, and motor networks involved in humor processing. To date, however, researchers have failed to demonstrate the subcortical correlates of the most fundamental feature of humor—reward. In an effort to elucidate the neurobiological substrate that subserves the reward components of humor, we undertook a high-field (3 Tesla) event-related functional MRI study. Here we demonstrate that humor modulates activity in several cortical regions, and we present new evidence that humor engages a network of subcortical regions including the nucleus accumbens, a key component of the mesolimbic dopaminergic reward system. Further, the degree of humor intensity was positively correlated with BOLD signal intensity in these regions. Together, these findings offer new insight into the neural basis of salutary aspects of humor

Concurrent fNIRS and EEG for brain function investigation: A systematic, methodology-focused review

Electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) stand as state-of-the-art techniques for non-invasive functional neuroimaging. On a unimodal basis, EEG has poor spatial resolution while presenting high temporal resolution. In contrast, fNIRS offers better spatial resolution, though it is constrained by its poor temporal resolution. One important merit shared by the EEG and fNIRS is that both modalities have favorable portability and could be integrated into a compatible experimental setup, providing a compelling ground for the development of a multimodal fNIRS-EEG integration analysis approach. Despite a growing number of studies using concurrent fNIRS-EEG designs reported in recent years, the methodological reference of past studies remains unclear. To fill this knowledge gap, this review critically summarizes the status of analysis methods currently used in concurrent fNIRS-EEG studies, providing an up-to-date overview and guideline for future projects to conduct concurrent fNIRS-EEG studies. A literature search was conducted using PubMed and Web of Science through 31 August 2021. After screening and qualification assessment, 92 studies involving concurrent fNIRS-EEG data recordings and analyses were included in the final methodological review. Specifically, three methodological categories of concurrent fNIRS-EEG data analyses, including EEG-informed fNIRS analyses, fNIRS-informed EEG analyses, and parallel fNIRS-EEG analyses, were identified and explained with detailed description. Finally, we highlighted current challenges and potential directions in concurrent fNIRS-EEG data analyses in future research

Longitudinal identification of clinically distinct neurophenotypes in young children with fragile X syndrome

Fragile X syndrome (FXS), due to mutations of the FMR1 gene, is the most common known inherited cause of developmental disability. The cognitive, behavioral, and neurological phenotypes observed in affected individuals can vary considerably, making it difficult to predict outcomes and determine the need for interventions. We sought to examine early structural brain growth as a potential marker for identification of clinically meaningful subgroups. Participants included 42 very young boys with FXS who completed a T1-weighted anatomical MRI and cognitive/behavioral assessment at two longitudinal time points, with mean ages of 2.89 y and 4.91 y. Topological data analysis (TDA), an unsupervised approach to multivariate pattern analysis, was applied to the longitudinal anatomical data to identify coherent but heretofore unknown subgroups. TDA revealed two large subgroups within the study population based solely on longitudinal MRI data. Post hoc comparisons of cognition, adaptive functioning, and autism severity scores between these groups demonstrated that one group was consistently higher functioning on all measures at both time points, with pronounced and significant unidirectional differences (P < 0.05 for time point 1 and/or time point 2 for each measure). These results support the existence of two longitudinally defined, neuroanatomically distinct, and clinically relevant phenotypes among boys with FXS. If confirmed by additional analyses, such information may be used to predict outcomes and guide design of targeted therapies. Furthermore, TDA of longitudinal anatomical MRI data may represent a useful method for reliably and objectively defining subtypes within other neuropsychiatric disorders

Influence of the X-chromosome on neuroanatomy: evidence from Turner and Klinefelter syndromes.

Studies of sex effects on neurodevelopment have traditionally focused on animal models investigating hormonal influences on brain anatomy. However, more recent evidence suggests that sex chromosomes may also have direct upstream effects that act independently of hormones. Sex chromosome aneuploidies provide ideal models to examine this framework in humans, including Turner syndrome (TS), where females are missing one X-chromosome (45X), and Klinefelter syndrome (KS), where males have an additional X-chromosome (47XXY). As these disorders essentially represent copy number variants of the sex chromosomes, investigation of brain structure across these disorders allows us to determine whether sex chromosome gene dosage effects exist. We used voxel-based morphometry to investigate this hypothesis in a large sample of children in early puberty, to compare regional gray matter volumes among individuals with one (45X), two (typically developing 46XX females and 46XY males), and three (47XXY) sex chromosomes. Between-group contrasts of TS and KS groups relative to respective sex-matched controls demonstrated highly convergent patterns of volumetric differences with the presence of an additional sex chromosome being associated with relatively decreased parieto-occipital gray matter volume and relatively increased temporo-insular gray matter volumes. Furthermore, z-score map comparisons between TS and KS cohorts also suggested that this effect occurs in a linear dose-dependent fashion. We infer that sex chromosome gene expression directly influences brain structure in children during early stages of puberty, extending our understanding of genotype-phenotype mechanisms underlying sex differences in the brain