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In an uncontrolled, open-label pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy. Adverse effects included persistent paresthesias in four patients. The study was too small to assess the safety of this procedure. Essential tremor, the most common movement disorder, with a prevalence as high as 4%, is characterized by a rhythmic oscillation of agonist and antagonist muscle groups, typically between 8 and 12 Hz. 1 The cause of this disorder remains unknown, although there is often a familial component with a link to a particular polymorphism in the gene encoding leucine-rich repeat and immunoglobulin domain–containing protein 1 ( LINGO1 ). Although essential tremor is not medically dangerous, it is progressive and disabling in the home and workplace. 2 The degree of tremor does not always correlate with the severity of disability, 3 and patients with . . .

The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a new approach to calculating axonal conduction velocity termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1w/T2w ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves MRI-measurable in vivo differences of myelin and axonal development with implications for neuronal and behavioral function. We also introduce a novel formulation for calculating aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD.

A growing body of literature associates increases in electronic screen time with a vast array of psychological consequences amongst adolescents, but little is known about the neurological underpinnings of this relationship. This longitudinal study examines structural and diffusion brain MRI scans from two timepoints collected from the Adolescent Brain Cognitive Development (ABCD) Study-a large, multi-site study with thousands of participants. By assessing both gray matter density (GMD) and gray matter measurements of diffusion microstructure in the adolescent brain, we describe how the developmental trajectory of the brain changes with screen-based media consumption at the subcellular level. Gray matter microstructure was measured across 13 bilateral regions functionally implicated with screen time use and associated with either the control or reward system. After controlling for age, sex, total brain volume, scanning site, sibling relationships, physical activity, and socioeconomic status, this study finds significant positive correlations between increased screen time and axonal signal across six of the 13 regions selected, while also finding significantly decreased intracellular signaling in eight regions, primarily in regions functionally associated with cognitive control. Comparing these associations to normal developmental trajectories suggests adolescent age-related brain development may be accelerated by increased screen time in brain areas associated with reward processing, while age-related brain development may be decelerated in regions of the control system. Highlighting the sensitivity of microstructural analysis, no significant relationships with increased screen time were found using GMD or fractional anisotropy. This work suggests that increased screen usage during adolescent development has a complex association with brain tissue that cannot be completely described by traditional quantifications of tissue microstructure.

Preterm birth is a major risk factor for disrupted brain development and subsequent neurodevelopmental disorders, yet the underlying mechanisms remain poorly understood. Further, typical neuroimaging analyses are particularly challenging in the neonatal brain: data is frequently low quality, and a lack of cellular development violates the assumptions relied on by many commonly-used techniques. In this study, we develop and present an advanced diffusion magnetic resonance imaging method to examine the microstructural organization of white matter in a clinically-acquired cohort of premature neonates. Using a novel approach that resolves multiple tissue compartments within the brain, we provide highly detailed orientation and quantification of white matter fibers and tissue signal fraction. We also utilize a series of automated segmentation algorithms to identify and measure these metrics across key tracts and subcortical regions. We investigate how these measures relate to postmenstrual age, as well as to clinical factors reflecting neonatal illness severity. We report successful segmentation and reconstruction of numerous white matter tracts throughout the neonatal brain. We further demonstrate the utility and functionality of microstructural analysis in a variety of pathologies commonly encountered in the neonatal clinical environment. Our results demonstrate tract-specific developmental trajectories, with early-maturing pathways showing higher microstructural organization. Exploratory analyses suggest that neonatal illness severity has modest, tissue-specific associations with microstructural properties. This work demonstrates that advanced microstructural imaging methods can extract meaningful white matter measurements from clinically-acquired scans, providing a practical framework for studying neonatal brain development in real-world hospital settings. These metrics are able to be calculated at extremely young ages, potentially allowing non-invasive study of vulnerable populations before detailed behavioral or neurological assessments are feasible.

As concerns about head impact in American football have grown, similar concerns have started to extend to other sports thought to experience less head impact, such as soccer and lacrosse. However, the amount of head impact experienced in soccer and lacrosse is relatively unknown, particularly compared with the substantial amount of data from football. This pilot study quantifies and compares head impact from four different types of sports teams: college football, high school football, college soccer, and college lacrosse. During the 2013 and 2014 seasons, 61 players wore mastoid patch accelerometers to quantify head impact during official athletic events (i.e., practices and games). In both practices and games, college football players experienced the most or second-most impacts per athletic event, highest average peak resultant linear and rotational acceleration per impact, and highest cumulative linear and rotational acceleration per athletic event. For average peak resultant linear and rotational acceleration per individual impact, college football was followed by high school football, then college lacrosse, and then college soccer, with similar trends in both practices and games. In the four teams under study, college football players experienced a categorically higher burden of head impact. However, for cumulative impact burden, the high school football cohort was not significantly different from the college soccer cohort. The results suggest that head impact in sport substantially varies by both the type of sport (football vs. soccer vs. lacrosse) and level of play (college vs. high school).

BackgroundThere is evidence that cortical cholinergic denervation contributes to gait and balance impairment in Parkinson’s Disease (PD), especially reduced gait speed.ObjectivesThe objective of this study was to determine the relationship between cholinergic basal forebrain gray matter density (GMD) and gait in PD patients.MethodsWe investigated 66 PD patients who underwent a pre-surgical evaluation for a neurosurgical procedure to treat motor symptoms of PD. As part of this evaluation patients had a brain MRI and formal gait assessments. By applying probabilistic maps of the cholinergic basal forebrain to voxel-based morphometry of brain MRI, we calculated gray matter density (GMD) for cholinergic nucleus 4 (Ch4), cholinergic nucleus 1, 2, and 3 (Ch123), and the entire cortex.ResultsReduced Ch4 GMD was associated with reduced Fast Walking Speed in the “on” medication state (FWSON, p = 0.004). Bilateral cortical GMD was also associated with FWSON (p = 0.009), but Ch123 GMD was not (p = 0.1). Bilateral cortical GMD was not associated with FWSON after adjusting for Ch4 GMD (p = 0.44). While Ch4 GMD was not associated with improvement in Timed Up and Go (TUG) or Cognitive TUG in the “on” medication state, reduced Ch4 GMD was associated with greater percent worsening based on dual tasks (p = 0.021).ConclusionsReduced Ch4 GMD is associated with slower gait speed in PD and greater percent worsening in TUG during dual tasks in patients with PD. These findings have implications for planning of future clinical trials investigating cholinergic therapies to improve gait impairment in PD.

Functional connectivity between the amygdala and the medial prefrontal cortex (mPFC) has been identified as a neural substrate of emotion regulation that undergoes changes throughout development, with a mature profile typically emerging at 10 years of age. Maternal bonding in childhood has been shown to buffer amygdala reactivity and to influence the trajectory of amygdala–mPFC coupling. The oxytocinergic system is critical in the development of social behavior and maternal bonding. Early-life parental care influences the methylation status of the oxytocin receptor (OXTRm) in animal models and humans, and higher OXTRm is associated with lower amygdala–PFC functional connectivity in adults. Using a neuroimaging-epigenetic approach, we investigated saliva-derived OXTRm as a biological marker of structural and functional connectivity maturation in 57 typically developing children (P < 0.05). We utilized seed-based connectivity analysis during a novel abstract movie paradigm and find that higher levels of OXTRm are associated with a more adult-like functional connectivity profile. Concurrently, more adult-like functional connectivity was associated with higher reported self-control and more diffusion streamlines between the amygdala and mPFC. OXTRm mediates the association between structural and functional connectivity with higher levels of OXTRm being associated with more streamlines. Lastly, we also find that lower OXTRm blunts the association between amygdala–mPFC connectivity and future internalizing behaviors in early adolescence. These findings implicate OXTRm as a biological marker at the interface of the social environment and amygdala–mPFC connectivity in emotional and behavioral regulation. Ultimately, identification of neurobiological markers may lead to earlier detection of children at risk for socio-emotional dysfunction.

Background: The effects of head impact in sports are of growing interest for clinicians, scientists, and athletes. Soccer is the most popular sport worldwide, but the burden of head impact in collegiate soccer is still unknown. Purpose: To quantify head impact associated with practicing and playing collegiate soccer using wearable accelerometers. Study Design: Descriptive epidemiological study. Methods: Mastoid patch accelerometers were used to quantify head impact in soccer, examining differences in head impact as a function of sex and event type (practice vs game). Seven female and 14 male collegiate soccer players wore mastoid patch accelerometers that measured head impacts during team events. Data were summarized for each athletic exposure, and statistical analyses evaluated the mean number of impacts, mean peak linear acceleration, mean peak rotational acceleration, and cumulative linear and rotational acceleration, each grouped by sex and event type. Results: There were no differences in the frequency or severity of head impacts between men’s and women’s soccer practices. For men’s soccer, games resulted in 285% more head impacts than practices, but there were no event-type differences in mean impact severity. Men’s soccer games resulted in more head impacts than practices across nearly all measured impact severities, which also resulted in men’s soccer games producing a greater cumulative impact burden. Conclusion: Similar to other sports, men’s soccer games have a greater impact burden when compared with practices, and this effect is driven by the quantity rather than severity of head impacts. In contrast, there were no differences in the quantity or severity of head impacts in men’s and women’s soccer practices. These data could prompt discussions of practical concern to collegiate soccer, such as understanding sex differences in head impact and whether games disproportionately contribute to an athlete’s head impact burden.

Sport concussion affects millions of athletes each year at all levels of sport. Increasing evidence demonstrates clinical and physiological recovery are becoming more divergent definitions, as evidenced by several studies examining blood-based biomarkers of inflammation and imaging studies of the central nervous system (CNS). Recent studies have shown elevated microglial activation in the CNS in active and retired American football players, as well as in active collegiate athletes who were diagnosed with a concussion and returned to sport. These data are supportive of discordance in clinical symptomology and the inflammatory response in the CNS upon symptom resolution. In this review, we will summarize recent advances in the understanding of the inflammatory response associated with sport concussion and broader mild traumatic brain injury, as well as provide an outlook for important research questions to better align clinical and physiological recovery.

Purpose Diffuse lower grade gliomas (LGG) with isocitrate dehydrogenase ( IDH ) gene mutations ( IDH MUT ) have a distinct survival advantage compared with IDH wild-type ( IDH WT ) cases but the mechanism underlying this disparity is not well understood. Diffusion Tensor Imaging (DTI) has identified infiltrated non-enhancing tumor regions that are characterized by low isotropic ( p ) and high anisotropic ( q ) diffusion tensor components that associate with poor survival in glioblastoma. We hypothesized that similar regions are more prevalent in IDH WT (vs. IDH MUT ) LGG. Methods p and q maps were reconstructed from preoperative DTI scans in N = 41 LGG patients with known IDH mutation and 1p/19q codeletion status. Enhancing and non-enhancing tumor volumes were autosegmented from standard (non-DTI) MRI scans. Percentage non-enhancing tumor volumes exhibiting low p and high q (V inf ) were then determined using threshold values ( p  = 2 × 10 −3 mm 2 /s, q  = 3 × 10 –4 mm 2 /s) and compared between IDH WT and IDH MUT LGG, and between IDH MUT LGG with and without 1p/19q codeletion. Results V inf volumes were significantly larger in IDH WT LGG than in IDH MUT LGG (35.4 ± 18.3% vs. 15.9 ± 7.6%, P < 0.001). V inf volumes did not significantly differ between IDH MUT LGG with and without 1p/19q codeletion (17.1 ± 9.5% vs. 14.8 ± 5.8%, P = 1.0). Conclusion IDH WT LGG exhibited larger volumes with suppressed isotropic diffusion ( p ) and high anisotropic diffusion ( q ) which reflects regions with increased cell density but non-disrupted neuronal structures. This may indicate a greater prevalence of infiltrative tumor in IDH WT LGG.