The frontal aslant tract (FAT) and its role in speech, language and executive function

In this review, we examine the structural connectivity of a recently-identified fiber pathway, the frontal aslant tract (FAT), and explore its function. We first review structural connectivity studies using tract-tracing methods in non-human primates, and diffusion-weighted imaging and electrostimulation in humans. These studies suggest a monosynaptic connection exists between the lateral inferior frontal gyrus and the pre-supplementary and supplementary motor areas of the medial superior frontal gyrus. This connection is termed the FAT. We then review research on the left FAT's putative role in supporting speech and language function, with particular focus on speech initiation, stuttering and verbal fluency. Next, we review research on the right FAT's putative role supporting executive function, namely inhibitory control and conflict monitoring for action. We summarize the extant body of empirical work by suggesting that the FAT plays a domain general role in the planning, timing, and coordination of sequential motor movements through the resolution of competition among potential motor plans. However, we also propose some domain specialization across the hemispheres. On the left hemisphere, the circuit is proposed to be specialized for speech actions. On the right hemisphere, the circuit is proposed to be specialized for general action control of the organism, especially in the visuo-spatial domain. We close the review with a discussion of the clinical significance of the FAT, and suggestions for further research on the pathway

Enlarged perivascular spaces in infancy and autism diagnosis, cerebrospinal fluid volume, and later sleep problems

IMPORTANCE: Perivascular spaces (PVS) and cerebrospinal fluid (CSF) are essential components of the glymphatic system, regulating brain homeostasis and clearing neural waste throughout the lifespan. Enlarged PVS have been implicated in neurological disorders and sleep problems in adults, and excessive CSF volume has been reported in infants who develop autism. Enlarged PVS have not been sufficiently studied longitudinally in infancy or in relation to autism outcomes or CSF volume. OBJECTIVE: To examine whether enlarged PVS are more prevalent in infants who develop autism compared with controls and whether they are associated with trajectories of extra-axial CSF volume (EA-CSF) and sleep problems in later childhood. DESIGN, SETTING, AND PARTICIPANTS: This prospective, longitudinal cohort study used data from the Infant Brain Imaging Study. Magnetic resonance images were acquired at ages 6, 12, and 24 months (2007-2017), with sleep questionnaires performed between ages 7 and 12 years (starting in 2018). Data were collected at 4 sites in North Carolina, Missouri, Pennsylvania, and Washington. Data were analyzed from March 2021 through August 2022. EXPOSURE: PVS (ie, fluid-filled channels that surround blood vessels in the brain) that are enlarged (ie, visible on magnetic resonance imaging). MAIN OUTCOMES AND MEASURES: Outcomes of interest were enlarged PVS and EA-CSF volume from 6 to 24 months, autism diagnosis at 24 months, sleep problems between ages 7 and 12 years. RESULTS: A total of 311 infants (197 [63.3%] male) were included: 47 infants at high familial likelihood for autism (ie, having an older sibling with autism) who were diagnosed with autism at age 24 months, 180 high likelihood infants not diagnosed with autism, and 84 low likelihood control infants not diagnosed with autism. Sleep measures at school-age were available for 109 participants. Of infants who developed autism, 21 (44.7%) had enlarged PVS at 24 months compared with 48 infants (26.7%) in the high likelihood but no autism diagnosis group (P = .02) and 22 infants in the control group (26.2%) (P = .03). Across all groups, enlarged PVS at 24 months was associated with greater EA-CSF volume from ages 6 to 24 months (β = 4.64; 95% CI, 0.58-8.72; P = .002) and more frequent night wakings at school-age (F = 7.76; η2 = 0.08; P = .006). CONCLUSIONS AND RELEVANCE: These findings suggest that enlarged PVS emerged between ages 12 and 24 months in infants who developed autism. These results add to a growing body of evidence that, along with excessive CSF volume and sleep dysfunction, the glymphatic system could be dysregulated in infants who develop autism

Development of Prefrontal Structure and Connectivity in Typical Children and Children with ADHD: Association with Language and Executive Function

The structure and connectivity of the prefrontal cortex has been extensively studied for its contribution to language and executive function (EF) development, but many questions still remain whether its microstructural tissue properties can reliably predict behavioral outcomes in very young typically and atypically developing populations. In particular, the bilateral frontal aslant tract (FAT) has garnered increasing interest with respect to its potential association with both language and EF, but has yet to be examined in childhood attention disorders, such Attention Deficit Hyperactivity Disorder (ADHD). At the same time, with advances in diffusion weighted imaging (DWI), new diffusion models offer more nuanced characterizations of specific tissue properties, namely neurite (axonal and dendritic) density and organization. Restricted diffusion imaging (RDI) and neurite orientation dispersion and density diffusion imaging (NODDI) are two advanced approaches to measuring density \textit{in vivo} that have been tested in animal, infant, and adult studies, but have been sparsely examined in regards to their association with behavioral outcomes in young children. We can now apply these diffusion methods to the analysis of microstructure of the frontal lobe and its association with language and EF. Thus, across three studies, this dissertation aims to answer the following questions: Does the FAT show age-related change during the sensitive developmental period between 4- to 7-years of age, and do age-related differences differ in children diagnosed with ADHD? Can the microstructural properties of the FAT differentially predict language and EF outcomes in ADHD and control samples? Are novel DWI methods capable of reliably mapping neurite density in children and adults and expanding what we currently know about brain microstructure and maturation? And finally, can neurite density and orientation within prefrontal and subcortical brain regions predict behavioral outcomes in typically and atypically developing children? To answer these questions, we used three DWI reconstruction methods to better elucidate neural tissue development, and examined its association to a battery of language and EF measures. We present compelling evidence that the FAT is a potential biomarker for ADHD, capable of differentially predicting aspects of language and EF across these groups. Furthermore, we show that more precise diffusion-weighted imaging methods can inform our understanding of typical and atypical brain development as it relates to behavior in the domains of language and EF

Sleep, cerebrospinal fluid, and the glymphatic system : A systematic review

Current theories of the glymphatic system (GS) hypothesize that it relies on cerebrospinal fluid (CSF) circulation to disseminate growth factors and remove metabolic waste from the brain with increased CSF production and circulation during sleep; thereby, linking sleep disturbance with elements of CSF circulation and GS exchange. However, our growing knowledge of the relations between sleep, CSF, and the GS are plagued by variability in sleep and CSF measures across a wide array of pathologies. Hence, this review aims to summarize the dynamic relationships between sleep, CSF-, and GS-related features in samples of typically developing individuals and those with autoimmune/inflammatory, neurodegenerative, neurodevelopmental, sleep-related, neurotraumatic, neuropsychiatric, and skull atypicalities. One hundred and ninety articles (total n = 19,129 participants) were identified and reviewed for pathology, CSF circulation and related metrics, GS function, and sleep. Numerous associations were documented between sleep problems and CSF metabolite concentrations (e.g., amyloid-beta, orexin, tau proteins) and increased CSF volumes or pressure. However, these relations were not universal, with marked differences across pathologies. It is clear that elements of CSF circulation/composition and GS exchange represent pathways influenced by sleep; however, carefully designed studies and advances in GS measurement are needed to delineate the nuanced relationships