Sarael Alcauter

Functional Network Development During the First Year: Relative Sequence and Socioeconomic Correlations

The first postnatal year is characterized by the most dramatic functional network development of the human lifespan. Yet, the relative sequence of the maturation of different networks and the impact of socioeconomic status (SES) on their development during this critical period remains poorly characterized. Leveraging a large, normally developing infant sample with multiple longitudinal resting-state functional magnetic resonance imaging scans during the first year (N = 65, scanned every 3 months), we aimed to delineate the relative maturation sequence of 9 key brain functional networks and examine their SES correlations. Our results revealed a maturation sequence from primary sensorimotor/auditory to visual to attention/default-mode, and finally to executive control networks. Network-specific critical growth periods were also identified. Finally, marginally significant positive SES-brain correlations were observed at 6 months of age for both the sensorimotor and default-mode networks, indicating interesting SES effects on functional brain maturation. To the best of our knowledge, this is the first study delineating detailed longitudinal growth trajectories of all major functional networks during the first year of life and their SES correlations. Insights from this study not only improve our understanding of early brain development, but may also inform the critical periods for SES expression during infancy.

Development of Thalamocortical Connectivity during Infancy and Its Cognitive Correlations

Although commonly viewed as a sensory information relay center, the thalamus has been increasingly recognized as an essential node in various higher-order cognitive circuits, and the underlying thalamocortical interaction mechanism has attracted increasing scientific interest. However, the development of thalamocortical connections and how such development relates to cognitive processes during the earliest stages of life remain largely unknown. Leveraging a large human pediatric sample (N = 143) with longitudinal resting-state fMRI scans and cognitive data collected during the first 2 years of life, we aimed to characterize the age-dependent development of thalamocortical connectivity patterns by examining the functional relationship between the thalamus and nine cortical functional networks and determine the correlation between thalamocortical connectivity and cognitive performance at ages 1 and 2 years. Our results revealed that the thalamus–sensorimotor and thalamus–salience connectivity networks were already present in neonates, whereas the thalamus–medial visual and thalamus–default mode network connectivity emerged later, at 1 year of age. More importantly, brain–behavior analyses based on the Mullen Early Learning Composite Score and visual–spatial working memory performance measured at 1 and 2 years of age highlighted significant correlations with the thalamus–salience network connectivity. These results provide new insights into the understudied early functional brain development process and shed light on the behavioral importance of the emerging thalamocortical connectivity during infancy.

Intersubject Variability of and Genetic Effects on the Brain's Functional Connectivity during Infancy

Infancy is a period featuring a high level of intersubject variability but the brain basis for such variability and the potential genetic/environmental contributions remain largely unexplored. The assessment of the brains functional connectivity during infancy by the resting state functional magnetic resonance imaging (rsfMRI) technique (Biswal et al., 1995) provides a unique means to probe the brain basis of intersubject variability during infancy. In this study, an unusually large typically developing human infant sample including 58 singletons, 132 dizygotic twins, and 98 monozygotic twins with rsfMRI scans during the first 2 years of life was recruited to delineate the spatial and temporal developmental patterns of both the intersubject variability of and genetic effects on the brains functional connectivity. Through systematic voxelwise functional connectivity analyses, our results revealed that the intersubject variability at birth features lower variability in primary functional areas but higher values in association areas. Although the relative pattern remains largely consistent, the magnitude of intersubject variability undergoes an interesting U-shaped growth during the first 2 years of life. Overall, the intersubject variability patterns during infancy show both adult-like and infant-specific characteristics (Mueller et al., 2013). On the other hand, age-dependent genetic effects were observed showing significant but bidirectional relationships with intersubject variability. The temporal and spatial patterns of the intersubject variability of and genetic contributions to the brains functional connectivity documented in this study shed light on the largely uncharted functional development of the brain during infancy.

Consistent Anterior–Posterior Segregation of the Insula During the First 2 Years of Life

The human insula is a complex region characterized by heterogeneous cytoarchitecture, connectivity, and function. Subregional parcellation of the insula in adults has revealed an interesting anterior-posterior subdivision pattern that is highly consistent with its functional differentiation. However, the development of the insulas subregional segregation during the first 2 years of life remains unknown. The aim of this study was to test the hypothesis that similar segregation of the insula exists during this critical time period based on the resting-state functional magnetic resonance imaging study of a large cohort of infants (n = 143) with longitudinal scans. Our results confirmed a consistent anterior-posterior subdivision of the insula during the first 2 years of life with dissociable connectivity patterns associated with each cluster. Specifically, the anterior insula coupled more with frontal association areas, whereas the posterior insula integrated more with sensorimotor-related regions. More importantly, dramatic development of each subregions functional network was observed, providing important neuronal correlates for the rapid advancement of its related functions during this time period.

Hemispheric asymmetries of functional connectivity and grey matter volume in the default mode network

Resting state networks such as the default mode network have been widely reported. Although a plethora of information on its functional relevance has been generated, little is known about lateralization or hemisphere asymmetry within the DMN. We used high-resolution resting state fMRI and T1 3D data to investigate such asymmetries in two groups of healthy subjects, one right-handed and one left-handed. Independent component analysis and the dual regression approach were carried out to identify functional asymmetries, while voxel-based morphometry was used to identify structural asymmetries in grey matter volume within the DMN. Greater leftward functional connectivity was observed in the posterior cingulate gyrus (PCG) for both groups. Leftward functional asymmetry was observed in the thalamus and rightward functional asymmetries were observed in the middle frontal and middle/superior temporal gyrus in the right-handed group. Rightward asymmetries in grey matter volume were observed in the posterior portion of the PCG for both groups. The right-handed group exhibited leftward structural asymmetries in the anterior portion of the PCG and in the middle frontal and posterior portion of the middle temporal gyrus, while rightward asymmetries were observed in the posterior portion of the PCG and anterior portions of temporal regions. These results suggest that functional connectivity and grey matter volume are not equally distributed between hemispheres within the DMN, and that functional asymmetries are not always reflected or determined by structural asymmetries.

The dynamic reorganization of the default-mode network during a visual classification task

The default-mode network has been reported to possess highly versatile and even contrasting functions but the underlying functioning mechanism remains elusive. In this study, we adopt a dynamic view of the default-mode network structure and hypothesize that it could potentially contribute to different functions through dynamic reorganization of its functional interaction pattern within and across network boundaries depending on the ongoing cognitive demands. With four experimental states and functional connectivity magnetic resonance imaging, we show that the default-mode network is characterized by within-network desynchronization and outside-network integration during the transition from resting state to an external visual classification task. Such default-mode network dynamics are task demand-dependent and return to their original status during the transition back to resting. More importantly, the degree of within-network desynchronization correlates with reaction time while the level of outside-network integration indexes task performance accuracy. Overall, the documented dynamic reorganization of the default-mode network and the significant behavioral correlations provide new insights into our understanding of this complex network and emphasize a dynamic view in future studies of its functioning mechanism.

Network Connectivity Abnormality Profile Supports a Categorical-Dimensional Hybrid Model of ADHD

Attention‐deficit/hyperactivity disorder (ADHD) is characterized by inattention, hyperactivity, and impulsivity, but there is no consensus regarding whether ADHD exists on the extreme end of a continuum of normal behavior or represents a discrete disorder. In this study, we sought to characterize both the categorical and dimensional variations in network functional connectivity in order to identify neural connectivity mechanisms of ADHD. Functional connectivity analyses of resting‐state fMRI data from 155 children with ADHD and 145 typically developing children (TDC) defined the dorsal attention network (DA), default mode network (DM), salience processing network (SAL) and executive control network (CON). Regional alterations in connectivity associated with categorical diagnoses and dimensional symptom measures (inattention and hyperactivity/impulsivity) as well as their interaction were systematically characterized. Dimensional relationships between symptom severity measures and functional connectivity that did not differ between TDC and children with ADHD were observed for each network, supporting a dimensional characterization of ADHD. However, categorical differences in functional connectivity magnitude between TDC and children with ADHD were detected after accounting for dimensional relationships, indicating the existence of categorical mechanisms independent of dimensional effects. Additionally, differential dimensional relationships for TDC versus ADHD children demonstrated categorical differences in brain–behavior relationships. The patterns of network functional organization associated with categorical versus dimensional measures of ADHD accentuate the complexity of this disorder and support a dual characterization of ADHD etiology featuring both dimensional and categorical mechanisms. Hum Brain Mapp 35:4531–4543, 2014.

Disruption of visual and motor connectivity in spinocerebellar ataxia type 7

Spinocerebellar ataxia type 7 (SCA7) is an autosomal‐dominant neurodegenerative disorder characterized by progressive ataxia and retinal dystrophy. It is caused by a CAG trinucleotide expansion in the ataxin7 gene. Anatomical studies have shown severe cerebellar degeneration and region‐specific neocortical atrophy in SCA7 patients. However, the impact of the neurodegeneration on the functional integration of the remaining tissue is still unknown. The aim of this study was to examine functional connectivity abnormalities in areas with significant gray matter atrophy in SCA7 patients and their relationship with number of CAG repeats. Using a combination of voxel‐based morphometry and resting‐state fMRI, we studied 26 genetically confirmed SCA7 patients and aged‐matched healthy controls. In SCA7 patients we found reduced functional interaction between the cerebellum and the middle and superior frontal gyri, disrupted functional connectivity between the visual and motor cortices, and increased functional coordination between atrophied areas of the cerebellum and a range of visual cortical areas compared with healthy controls. The degree of mutation expansion showed a negative effect on both the functional interaction between the right anterior cerebellum and the left superior frontal gyrus and the connectivity between the right anterior cerebellum and left parahippocampal gyrus. We found abnormal functional connectivity patterns, including both hypo‐ and hyperconnectivity, compared with controls. These abnormal patterns show reasonable association with the severity of gene mutation. Our findings suggest that aberrant changes are prevalent in both motor and visual systems, adding significantly to our understanding of the pathophysiology of SCA7.

Music reduces pain and increases resting state fMRI BOLD signal amplitude in the left angular gyrus in fibromyalgia patients.

Music reduces pain in fibromyalgia (FM), a chronic pain disease, but the functional neural correlates of music-induced analgesia (MIA) are still largely unknown. We recruited FM patients (n = 22) who listened to their preferred relaxing music and an auditory control (pink noise) for 5 min without external noise from fMRI image acquisition. Resting state fMRI was then acquired before and after the music and control conditions. A significant increase in the amplitude of low frequency fluctuations of the BOLD signal was evident in the left angular gyrus (lAnG) after listening to music, which in turn, correlated to the analgesia reports. The post-hoc seed-based functional connectivity analysis of the lAnG showed found higher connectivity after listening to music with right dorsolateral prefrontal cortex (rdlPFC), the left caudate (lCau), and decreased connectivity with right anterior cingulate cortex (rACC), right supplementary motor area (rSMA), precuneus and right precentral gyrus (rPreG). Pain intensity (PI) analgesia was correlated (r = 0.61) to the connectivity of the lAnG with the rPreG. Our results show that MIA in FM is related to top-down regulation of the pain modulatory network by the default mode network (DMN).

Frequency of spontaneous BOLD signal shifts during infancy and correlates with cognitive performance

Highlights • Peak-frequency of spontaneous BOLD signal increases during infancy.• Increments of power at the peak-frequency showed spatially dependent patterns.• Power at the peak-frequency in 1-year olds correlates with cognitive performance.