Functional Architecture Of Brain Research Articles

Resting state functional brain connectivity in child and adolescent psychiatry: where are we now?

Approaching the 30th anniversary of the discovery of resting state functional magnetic resonance imaging (rsfMRI) functional connectivity, we reflect on the impact of this neuroimaging breakthrough on the field of child and adolescent psychiatry. The study of intrinsic functional brain architecture that rsfMRI affords across a wide range of ages and abilities has yielded numerous key insights. For example, we now know that many neurodevelopmental conditions are associated with more widespread circuit alterations across multiple large-scale brain networks than previously suspected. The emergence of population neuroscience and effective data-sharing initiatives have made large rsfMRI datasets publicly available, providing sufficient power to begin to identify brain-based subtypes within heterogeneous clinical conditions. Nevertheless, several methodological and theoretical challenges must still be addressed to fulfill the promises of personalized child and adolescent psychiatry. In particular, incomplete understanding of the physiological mechanisms driving developmental changes in intrinsic functional connectivity remains an obstacle to further progress. Future directions include cross-species and multimodal neuroimaging investigations to illuminate such mechanisms. Data collection and harmonization efforts that span multiple countries and diverse cohorts are urgently needed. Finally, incorporating naturalistic fMRI paradigms such as movie watching should be a priority for future research efforts.

Diurnal fluctuations in steroid hormones tied to variation in intrinsic functional connectivity in a densely sampled male.

Most of mammalian physiology is under the control of biological rhythms, including the endocrine system with time-varying hormone secretion. Precision neuroimaging studies provide unique insights into how the endocrine system dynamically regulates aspects of the human brain. Recently, we established estrogen's ability to drive widespread patterns of connectivity and enhance the global efficiency of large-scale brain networks in a woman sampled every 24h across 30 consecutive days, capturing a complete menstrual cycle. Steroid hormone production also follows a pronounced sinusoidal pattern, with a peak in testosterone between 6-7am and nadir between 7-8pm. To capture the brain's response to diurnal changes in hormone production, we carried out a companion precision imaging study of a healthy adult man who completed MRI and venipuncture every 12-24 hours across 30 consecutive days. Results confirmed robust diurnal fluctuations in testosterone, 17β-estradiol - the primary form of estrogen - and cortisol. Standardized regression analyses revealed widespread associations between testosterone, estradiol, and cortisol concentrations and whole-brain patterns of coherence. In particular, functional connectivity in the Dorsal Attention Network was coupled with diurnally fluctuating hormones. Further, comparing dense-sampling datasets between a man and a naturally-cycling woman revealed that fluctuations in sex hormones are tied to patterns of whole-brain coherence in both sexes, and to a heightened degree in the male. Together, these findings enhance our understanding of steroid hormones as rapid neuromodulators and provide evidence that diurnal changes in steroid hormones are associated with patterns of whole-brain functional connectivity.Significance Statement Diurnal variation is an essential biorhythm, yet the relationship between diurnal fluctuations in steroid hormones and the functional architecture of the human brain is virtually unknown. This precision neuroimaging study suggests that endogenous fluctuations in testosterone, estradiol, and cortisol concentrations are tied to rhythmic changes in coherence across the brain. Precision imaging studies that track individuals across endocrine rhythms (e.g. the diurnal cycle and menstrual cycle) demonstrate steroid hormones' ability to modulate the functional architecture of the brain in both sexes and provide a roadmap for future studies to probe the functional significance of these rhythms for behavior.

243 Intracranial Theta-burst Stimulation Modulates Cortical Excitability in a Dose and Location-dependent Fashion

INTRODUCTION: Direct electrical stimulation is a powerful therapeutic approach to treating a wide range of brain disorders. In particular, theta-burst stimulation (TBS) which delivers electrical pulses in rhythmic bursts of 3-8 Hz to mimic endogenous brain rhythms, has been increasingly used to improve cognitive processes and relieve symptoms of depression. However, how TBS alters underlying neural activity is poorly understood. METHODS: In nine neurosurgical epilepsy subjects undergoing intracranial monitoring, we applied direct cortical TBS at varying stimulation amplitudes and locations (prefrontal, temporal, parietal). We obtained single-pulse corticocortical evoked potentials (CCEPs) prior to stimulation to map functional connectivity. Intracranial EEG (iEEG) was recorded from non-stimulated electrodes before, during and after TBS. RESULTS: We found that TBS evoked consistent responses after each burst. These responses were observed in regions with high amplitude CCEPs and resting spontaneous delta (1-4 Hz) phase-locking to the stimulation site, consistent with our hypothesis that the underlying functional brain architecture guides information flow after stimulation. Furthermore, we observed changes in cortical excitability over time as measured by changes in amplitude of the TBS evoked responses both within stimulation burst trains and across burst trains. The degree of change in cortical excitability was modulated by anatomical location, proximity of the stimulating electrode to white matter, and current amplitude. CONCLUSIONS: These results indicate that direct cortical TBS produces neural effects that can be measured over time and correlate with baseline biophysical parameters. Thus, personalizing stimulation parameters might be critical to predictably maximize our ability to alter disease-relevant brain networks.

Personalized connectivity-based network targeting model of transcranial magnetic stimulation for treatment of psychiatric disorders: computational feasibility and reproducibility.

Repetitive transcranial magnetic stimulation (rTMS) holds promise for treating psychiatric disorders; however, the variability in treatment efficacy among individuals underscores the need for further improvement. Growing evidence has shown that TMS induces a broad network modulatory effect, and its effectiveness may rely on accurate modulation of the pathological network specific to each disorder. Therefore, determining the optimal TMS coil setting that will engage the functional pathway delivering the stimulation is crucial. Compared to group-averaged functional connectivity (FC), individual FC provides specific information about a person's brain functional architecture, offering the potential for more accurate network targeting for personalized TMS. However, the low signal-to-noise ratio (SNR) of FC poses a challenge when utilizing individual resting-state FC. To overcome this challenge, the proposed solutions include increasing the scan duration and employing the cluster method to enhance the stability of FC. This study aimed to evaluate the stability of a personalized FC-based network targeting model in individuals with major depressive disorder or schizophrenia with auditory verbal hallucinations. Using resting-state functional magnetic resonance imaging data from the Human Connectome Project, we assessed the model's stability. We employed longer scan durations and cluster methodologies to improve the precision in identifying optimal individual sites. Our findings demonstrate that a scan duration of 28 minutes and the utilization of the cluster method achieved stable identification of individual sites, as evidenced by the intraindividual distance falling below the ~1cm spatial resolution of TMS. The current model provides a feasible approach to obtaining stable personalized TMS targets from the scalp, offering a more accurate method of TMS targeting in clinical applications.

Cortical changes in the brain of patients with hemifacial spasm.

Hemifacial spasm (HFS) is a movement disorder characterized by involuntary muscle contractions on one side of the face. It is associated with disturbances in the brain's functional architecture. Despite this, the structural alterations in the brain related to HFS remain poorly understood. In this study, we investigated the cortical morphology changes in patients with HFS compared to healthy controls (HCs). We analyzed 3D T1-weighted MRI images from 33 patients with left-sided primary HFS and 33 age- and sex-matched HCs. Measurements of cortical thickness (CTh), sulcal depth, local gyrification index (lGI), and fractal dimension were taken using a computational anatomy toolbox. A general linear model, accounting for age, gender, and total brain volume, was applied for statistical analyses. Significant clusters were then assessed for correlations with clinical parameters. The HFS patients displayed several cortical abnormalities when compared to HCs, including reduced CTh in the contralateral precentral gyrus and left orbitofrontal cortex, decreased sulcal depth in the left orbitofrontal cortex, and increased lGI in the right insula and superior temporal cortex. However, fractal dimension did not differ significantly between the groups. Additionally, in HFS patients, a notable negative correlation was found between the sulcal depth in the left orbitofrontal cortex and the Beck Depression Inventory-II scores. Our findings reveal that HFS is associated with specific surface-based morphological changes in the brain. These alterations contribute to a deeper understanding of the neurophysiological mechanisms involved in HFS and may have implications for future research and treatment strategies.

The individualized neural tuning model: Precise and generalizable cartography of functional architecture in individual brains

Abstract Quantifying how brain functional architecture differs from person to person is a key challenge in human neuroscience. Current individualized models of brain functional organization are based on brain regions and networks, limiting their use in studying fine-grained vertex-level differences. In this work, we present the individualized neural tuning (INT) model, a fine-grained individualized model of brain functional organization. The INT model is designed to have vertex-level granularity, to capture both representational and topographic differences, and to model stimulus-general neural tuning. Through a series of analyses, we demonstrate that (a) our INT model provides a reliable individualized measure of fine-grained brain functional organization, (b) it accurately predicts individualized brain response patterns to new stimuli, and (c) for many benchmarks, it requires only 10–20 minutes of data for good performance. The high reliability, specificity, precision, and generalizability of our INT model affords new opportunities for building brain-based biomarkers based on naturalistic neuroimaging paradigms.

Brain functional segregation, handedness and cognition in situs inversus totalis: A replication study

Situs inversus totalis (SIT) is a rare congenital anomaly in which the arrangement of the visceral organs is completely left-right mirrored. A previous study by our lab suggests that SIT (N = 15) correlated with more heterogeneous asymmetrical brain organization and increased left-handedness. In addition, visceral reversal correlated with poorer cognitive performance, especially when hemisphere organization was atypical. The current study sought to replicate these findings in a larger sample. We scanned 23 volunteers with SIT as well as an equal number of controls with usual organ arrangement, and used fMRI to determine their hemisphere dominance for two left hemisphere functions (language and manual praxis) and two right hemisphere functions (spatial attention and face recognition). Effects of SIT etiology were explored by pooling data from the original cohort with the replication sample. Our results reveal that each of those four cognitive functions demonstrated the expected population dominance in SIT, albeit they were less pronounced – but not significantly so – compared to controls. Unusual patterns of hemispheric crowding and mirror-reversal of functional brain organization was observed more often in SIT (48%) than in the controls (30%), but this difference also did not reach statistical significance. However, left-handedness was found to be significantly more common in SIT (26%) than in the overall population (10.6%). Finally, cognitive ability, as assessed by a neuropsychological test battery, was not associated with organ situs or hemisphere organization. Taken together, our data adds to the growing evidence that the determinants of visceral and neural asymmetries are largely independent from one another and that complete situs inversus does not co-occur with an obligatory transposition of the brain's functional architecture. There nevertheless might be instances in which (genetic) mechanisms could simultaneously cause complete visceral reversal and atypical brain laterality.

Perceived financial well-being and its association with frontostriatal functional connectivity, real-life anticipatory experiences, and everyday happiness

Perceived financial well-being (FWB) is an important aspect of life that can affect one’s attitude toward future experiences and happiness. However, the relationship between FWB, anticipatory experiences, and happiness, and the brain’s functional architecture underlying this relationship remain unknown. Here, we combined an experience sampling method, multilevel modeling, and functional neuroimaging to identify the neural correlates of FWB and their associations with real-world anticipatory experiences and everyday happiness. Behaviorally, we found that individuals with greater FWB felt more positive and more interested when they expected positive events to occur, which in turn resulted in increased everyday happiness. Furthermore, the level of FWB was significantly associated with the strength of functional connectivity (FC) between the nucleus accumbens (NAc) and ventromedial prefrontal cortex (vmPFC) and the local coherence within the vmPFC. The frontostriatal FC and local coherence within the vmPFC were further predictive of everyday happiness via the anticipatory response involving interestedness during positive expectations. Our findings suggest that individual differences in FWB could be reflected in the functional architecture of brain’s reward system that may contribute to shaping positive anticipatory experiences and happiness in daily life.

Alterations in the global brain network in older adults with poor sleep quality: A resting-state fMRI study

ObjectivesOlder adults often experience more fragmented and less restful sleep than younger individuals. However, the mechanisms in the brain that underlie these phenomena have been rarely studied. The aim of this study was to identify the differences in global brain network properties between older adults with good and poor sleep quality and to explore the relationship between these network properties and symptoms of insomnia. MethodsWe performed a graph-theoretic analysis of resting-state functional magnetic resonance imaging data from two groups of older adults: 59 with good sleep quality and 59 with poor sleep quality. Functional connectivity among 264 brain regions of interest was estimated, and undirected graphs were constructed. Network topological properties were compared using one-way repeated-measures analysis of variance. Pearson's correlation analysis assessed the relationship between the mean scores of the global network properties across network sparsity and insomnia symptoms, as measured using the global Pittsburgh Sleep Quality Index score. ResultsOlder adults with poor sleep quality displayed increased small-world-ness, global efficiency and modularity in the functional brain network during rest. Conversely, they exhibited decreased local efficiency, characteristic path length and clustering coefficient. In the total population, we found associations between insomnia symptoms and global network characteristics, except for betweenness centrality and modularity. ConclusionsIn older adults with poor sleep quality, global network measures revealed a functional brain architecture that tended towards integration rather than segregation. Further research is needed to better understand what these findings mean about the effects of aging on poor sleep quality.

Altered stability of dynamic brain functional architecture in primary open-angle glaucoma: a surface-based resting-state fMRI study.

Delineating the neuropathological characteristics of primary open-angle glaucoma (POAG) is critical for understanding its pathophysiology. While temporal stability represents a crucial aspect of the brain's functional architecture, the specific patterns underlying its contribution to POAG remain unclear. This study aims to analyze the brain functional abnormalities in POAG using functional stability, a dynamic functional connectivity (DFC) approach based on resting-state functional magnetic resonance imaging (rs-fMRI). Seventy patients with POAG and forty-five healthy controls underwent rs-fMRI and ophthalmological examinations. The stability of DFC was calculated as the concordance of DFC over time using a sliding-window approach, and the differences in stability between the two groups were compared. Subsequently, Spearman's correlation analyses were conducted to examine the relationship between functional stability and clinical indicators. Compared with healthy controls, patients with POAG exhibited significantly decreased functional stability in the visual network, including the early visual center, ventral and dorsal stream visual cortex in both hemispheres. Conversely, stability values increased in the bilateral inferior parietal gyrus and right inferior frontal cortex. In POAG patients, the dynamic stability of the left early visual cortex and ventral stream visual cortex correlated with the mean deviation of visual field defects (r = 0.251, p = 0.037). The evidence from this study suggests that functional stability may provide a new understanding of brain alterations in the progression of POAG.

Effects of Fmr1 Gene Mutations on Sex Differences in Autism-Like Behavior and Dendritic Spine Development in Mice and Transcriptomic Studies

Fragile X syndrome (FXS) is the most common single gene disorder contributing to autism spectrum disorder (ASD). Although significant sex differences are observed in FXS, few studies have focused on the phenotypic characteristics as well as the differences in brain pathological changes and gene expression in FXS by sex. Therefore, we analyzed sex differences in autism-like behavior and dendritic spine development in two-month-old male and female Fmr1 KO and C57 mice and evaluated the mechanisms at transcriptome level. Results suggest that Fmr1 KO mice display sex differences in autism-like behavior and dendritic spine density. Compared to females, male had more severe effects on anxiety, repetitive stereotype-like behaviors, and socializing, with higher dendritic spine density. Furthermore, two male-biased and five female-biased expressed genes were screened based on KEGG pathway enrichment and protein–protein interaction (PPI) analyses. In conclusion, our findings show mutations in the Fmr1 gene lead to aberrant expression of related genes and affect the sex-differentiated behavioral phenotypes of Fmr1 KO mice by affecting brain development and functional architecture, and suggest future studies should focus on including female subjects to comprehensively reflect the differentiation of FXS in both sexes and develop more precise and effective therapeutic strategies.

Improved Functionnectome by dissociating the contributions of white matter fiber classes to functional activation.

Integrating the underlying brain circuit's structural and functional architecture is required to explore the functional organization of cognitive networks. In that regard, we recently introduced the Functionnectome. This structural-functional method combines an fMRI acquisition with tractography-derived white matter connectivity data to map cognitive processes onto the white matter. However, this multimodal integration faces three significant challenges: (1) the necessarily limited overlap between tractography streamlines and the grey matter, which may reduce the amount of functional signal associated with the related structural connectivity; (2) the scrambling effect of crossing fibers on functional signal, as a single voxel in such regions can be structurally connected to several cognitive networks with heterogeneous functional signals; and (3) the difficulty of interpretation of the resulting cognitive maps, as crossing and overlapping white matter tracts can obscure the organization of the studied network. In the present study, we tackled these problems by developing a streamline-extension procedure and dividing the white matter anatomical priors between association, commissural, and projection fibers. This approach significantly improved the characterization of the white matter involvement in the studied cognitive processes. The new Functionnectome priors produced are now readily available, and the analysis workflow highlighted here should also be generalizable to other structural-functional approaches. We improved the Functionnectome approach to better study the involvement of white matter in brain function by separating the analysis of the three classes of white matter fibers (association, commissural, and projection fibers). This step successfully clarified the activation maps and increased their statistical significance.

Functional connectome fingerprinting across the lifespan.

Systematic changes have been observed in the functional architecture of the human brain with advancing age. However, functional connectivity (FC) is also a powerful feature to detect unique "connectome fingerprints," allowing identification of individuals among their peers. Although fingerprinting has been robustly observed in samples of young adults, the reliability of this approach has not been demonstrated across the lifespan. We applied the fingerprinting framework to the Cambridge Centre for Ageing and Neuroscience cohort (n = 483 aged 18 to 89 years). We found that individuals are "fingerprintable" (i.e., identifiable) across independent functional MRI scans throughout the lifespan. We observed a U-shape distribution in the strength of "self-identifiability" (within-individual correlation across modalities), and "others-identifiability" (between-individual correlation across modalities), with a decrease from early adulthood into middle age, before improving in older age. FC edges contributing to self-identifiability were not restricted to specific brain networks and were different between individuals across the lifespan sample. Self-identifiability was additionally associated with regional brain volume. These findings indicate that individual participant-level identification is preserved across the lifespan despite the fact that its components are changing nonlinearly.

Altered intrinsic functional brain architecture in patients with functional constipation: a surface-based network study.

Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID). Studies have indicated a higher likelihood of psychiatric disorders, such as anxiety, depression, sleep disturbances, and impaired concentration, among patients with FCon. However, the underlying pathophysiological mechanisms responsible for these symptoms in FCon patients remain to be fully elucidated. The human brain is a complex network architecture with several fundamental organizational properties. Neurological interactions between gut symptoms and psychiatric issues may be closely associated with these complex networks. In the present study, a total of 35 patients with FCon and 40 healthy controls (HC) were recruited for a series of clinical examinations and resting-state functional magnetic imaging (RS-fMRI). We employed the surface-based analysis (SBA) approach, utilizing the Schaefer cortical parcellation template and Tikhonov regularization. Graph theoretical analysis (GTA) and functional connectivity (FC) analysis of RS-fMRI were conducted to investigate the aberrant network alterations between the two groups. Additionally, correlation analyses were performed between the network indices and clinical variables in patients with FCon. At the global level, we found altered topological properties and networks in patients with FCon, mainly including the significantly increased clustering coefficient (CP), local efficiency (Eloc), and shortest path length (LP), whereas the decreased global efficiency (Eglob) compared to HC. At the regional level, patients with FCon exhibited increased nodal efficiency in the frontoparietal network (FPN). Furthermore, FC analysis demonstrated several functional alterations within and between the Yeo 7 networks, particularly including visual network (VN), limbic network (LN), default mode network (DMN), and somatosensory-motor network (SMN) in sub-network and large-scale network analysis. Correlation analysis revealed that there were no significant associations between the network metrics and clinical variables in the present study. These results highlight the altered topological architecture of functional brain networks associated with visual perception abilities, emotion regulation, sensorimotor processing, and attentional control, which may contribute to effectively targeted treatment modalities for patients with FCon.

Ex-utero third trimester developmental changes in functional brain network organization in infants born very and extremely preterm.

The latter half of gestation is a period of rapid brain development, including the formation of fundamental functional brain network architecture. Unlike in-utero fetuses, infants born very and extremely preterm undergo these critical maturational changes in the extrauterine environment, with growing evidence suggesting this may result in altered brain networks. To date, however, the development of functional brain architecture has been unexplored. From a prospective cohort of preterm infants, graph parameters were calculated for fMRI scans acquired prior to reaching term equivalent age. Eight graph properties were calculated, Clustering Coefficient (C), Characteristic Path Length (L), Modularity (Q), Local Efficiency (LE), Global Efficiency (GE), Normalized Clustering (λ), Normalized Path Length (γ), and Small-Worldness (σ). Properties were first compared to values generated from random and lattice networks and cost efficiency was evaluated. Subsequently, linear mixed effect models were used to assess relationship with postmenstrual age and infant sex. A total of 111 fMRI scans were acquired from 85 preterm infants born at a mean GA 28.93 ± 2.8. Infants displayed robust small world properties as well as both locally and globally efficient networks. Regression models found that GE increased while L, Q, λ, γ, and σ decreased with increasing postmenstrual age following multiple comparison correction (r2Adj range 0.143-0.401, p < 0048), with C and LE exhibited trending increases with age. This is the first direct investigation on the extra-uterine formation of functional brain architecture in preterm infants. Importantly, our results suggest that changes in functional architecture with increasing age exhibit a different trajectory relative to in utero fetus. Instead, they exhibit developmental changes more similar to the early postnatal period in term born infants.

Scene perception and visuospatial memory converge at the anterior edge of visually-responsive cortex.

To fluidly engage with the world, our brains must simultaneously represent both the scene in front of us and our memory of the immediate surrounding environment (i.e., local visuospatial context). How does the brain's functional architecture enable sensory and mnemonic representations to closely interface, while also avoiding sensory-mnemonic interference? Here, we asked this question using first-person, head-mounted virtual reality (VR) and fMRI. Using VR, human participants of both sexes learned a set of immersive, real-world visuospatial environments in which we systematically manipulated the extent of visuospatial context associated with a scene image in memory across three learning conditions, spanning from a single field-of-view to a city street. We used individualized, within-subject fMRI to determine which brain areas support memory of the visuospatial context associated with a scene during recall (Exp. 1) and recognition (Exp. 2). Across the whole brain, activity in three patches of cortex was modulated by the amount of known visuospatial context, each located immediately anterior to one of the three scene perception areas of high-level visual cortex. Individual subject analyses revealed that these anterior patches corresponded to three functionally-defined place memory areas, which selectively respond when visually recalling personally familiar places. In addition to showing activity levels that were modulated by the amount of visuospatial context, multivariate analyses showed that these anterior areas represented the identity of the specific environment being recalled. Together, these results suggest a convergence zone for scene perception and memory of the local visuospatial context at the anterior edge of high-level visual cortex.Significance statement:As we move through the world, the visual scene around us is integrated with our memory of the wider visuospatial context. Here, we sought to understand how the functional architecture of the brain enables coexisting representations of the current visual scene and memory of the surrounding environment. Using a combination of immersive virtual reality and fMRI, we show that memory of visuospatial context outside the current field-of-view is represented in a distinct set of brain areas immediately anterior and adjacent to the perceptually-oriented scene-selective areas of high-level visual cortex. This functional architecture would allow efficient interaction between immediately adjacent mnemonic and perceptual areas, while also minimizing mnemonic-perceptual interference.

A paraventricular thalamus to insular cortex glutamatergic projection gates “emotional” stress-induced binge eating in females

It is well-established that stress and negative affect trigger eating disorder symptoms and that the brains of men and women respond to stress in different ways. Indeed, women suffer disproportionately from emotional or stress-related eating, as well as associated eating disorders such as binge eating disorder. Nevertheless, our understanding of the precise neural circuits driving this maladaptive eating behavior, particularly in women, remains limited. We recently established a clinically relevant model of ‘emotional’ stress-induced binge eating whereby only female mice display binge eating in response to an acute “emotional” stressor. Here, we combined neuroanatomic, transgenic, immunohistochemical and pathway-specific chemogenetic approaches to investigate whole brain functional architecture associated with stress-induced binge eating in females, focusing on the role of Vglut2 projections from the paraventricular thalamus (PVTVglut2+) to the medial insular cortex in this behavior. Whole brain activation mapping and hierarchical clustering of Euclidean distances revealed distinct patterns of coactivation unique to stress-induced binge eating. At a pathway-specific level, PVTVglut2+ cells projecting to the medial insular cortex were specifically activated in response to stress-induced binge eating. Subsequent chemogenetic inhibition of this pathway suppressed stress-induced binge eating. We have identified a distinct PVTVglut2+ to insular cortex projection as a key driver of “emotional” stress-induced binge eating in female mice, highlighting a novel circuit underpinning this sex-specific behavior.

Associations between infant amygdala functional connectivity and social engagement following a stressor: A preliminary investigation.

Functional architecture of the infant brain, especially functional connectivity (FC) within the amygdala network and between the amygdala and other networks (i.e., default-mode [DMN] and salience [SAL] networks), provides a neural basis for infant socioemotional functioning. Yet, little is known about the extent to which early within- and between-network amygdala FC are related to infant stress recovery across the first year of life. In this study, we examined associations between amygdala FC (i.e., within-network amygdala connectivity, and between-network amygdala connectivity with the DMN and SAL) at 3 months and infant recovery from a mild social stressor at 3, 6 and 9 months. At 3 months, thirty-five infants (13 girls) underwent resting-state functional magnetic resonance imaging during natural sleep. Infants and their mothers completed the still-face paradigm at 3, 6, and 9 months, and infant stress recovery was assessed at each time point as the proportion of infant social engagement during the reunion episode. Bivariate correlations indicated that greater positive within-network amygdala FC and greater positive amygdala-SAL FC, but not amygdala-DMN FC, at 3 months predicted lower levels of stress recovery at 3 and 6 months, but were nonsignificant at 9 months. These findings provide preliminary evidence that early functional synchronization within the amygdala network, as well as segregation between the amygdala and the SAL, may contribute to infant stress recovery in the context of infant-mother interaction.

Understanding brain functional architecture through robotics.

Robotics is increasingly seen as a useful test bed for computational models of the brain functional architecture underlying animal behavior. We provide an overview of past and current work, focusing on probabilistic and dynamical models, including approaches premised on the free energy principle, situating this endeavor in relation to evidence that the brain constitutes a layered control system. We argue that future neurorobotic models should integrate multiple neurobiological constraints and be hybrid in nature.

Stepwise functional brain architecture from disease epicenter correlates with atrophy in progressive supranuclear palsy (P11-6.001)

<h3>Objective:</h3> This study applied SFC to test the hypothesis that topological stepwise architecture propagating from the disease epicenter would shape patterns of grey matter (GM) atrophy in a cohort of patients with progressive supranuclear palsy (PSP). <h3>Background:</h3> MRI connectomics is an ideal tool to test the model of network-based spread of pathological protein aggregates in neurodegenerative disorders. Stepwise functional connectivity (SFC) is a graph-theory-based neuroimaging method, which detects whole-brain functional couplings of a selected region of interest, at increasing link-step topological distances. <h3>Design/Methods:</h3> Twenty-eight patients with PSP and 50 healthy controls underwent brain magnetic resonance imaging (MRI) on a 3T scanner, including 3D-T1 weighted and resting-state functional MRI sequences. GM was parcellated into 90 regions using the Automated Anatomical Labeling (AAL) atlas. Correlations between SFC architecture in controls and atrophy patterns in PSP patients were tested. The disease epicenter was identified as the peak of atrophy observed in an independent cohort of 13 cases with <i>post mortem</i> confirmation of PSP pathology, and used as seed region for SFC analysis. <h3>Results:</h3> The disease epicenter was identified in the left midbrain tegmental region. Compared with controls, PSP patients showed prevalent atrophy in the subcortical GM (mostly, in the thalami and caudate nuclei), but also in frontal, parietal and cerebellar cortical regions. For each region of the AAL atlas, a strong correlation was found between average link-step distance from the left midbrain in controls and mean normalized GM volume in PSP patients (r=0.37, p&lt;0.001). <h3>Conclusions:</h3> Our findings demonstrate that the brain architectural topology, as described by SFC propagating from the disease epicenter, shapes the pattern of atrophic changes in PSP, supporting the view of a network-based pathology propagation in this disease and holding the promise to be used to model disease progression in future longitudinal studies. <b>Disclosure:</b> Dr. Spinelli has nothing to disclose. Miss Ghirelli has nothing to disclose. Miss Bottale has nothing to disclose. Silvia Basaia has nothing to disclose. Ms. Cividini has nothing to disclose. Dr. Volonte has nothing to disclose. Mr. Galantucci has nothing to disclose. Giuseppe Magnani has nothing to disclose. Dr. Caso has nothing to disclose. The institution of Elisa Canu has received research support from Italian Ministry of Health . Dr. Castelnovo has nothing to disclose. Paola Caroppo has nothing to disclose. Sara Prioni has nothing to disclose. Miss Villa has nothing to disclose. Dr. Josephs has nothing to disclose. Dr. Whitwell has nothing to disclose. Federica Agosta has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Philips. Federica Agosta has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier INC. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).