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Cholinergic nucleus 4 (Ch4) degeneration is associated with cognitive impairment in Parkinson's disease and dementia with Lewy bodies, but it is unknown if Ch4 degeneration is also present in isolated rapid eye movement sleep behavior disorder (iRBD).The aim was to determine if there is evidence of Ch4 degeneration in patients with iRBD and if it is associated with cognitive impairment.We analyzed the clinical and neuropsychological data of 35 iRBD patients and 35 age- and sex-matched healthy controls. Regional gray matter density (GMD) was calculated for Ch4 using probabilistic maps applied to brain magnetic resonance imaging (MRI).Ch4 GMD was significantly lower in the iRBD group compared to controls (0.417 vs. 0.441, P = 0.02). Ch4 GMD was also found to be a significant predictor of letter number sequencing (β-coefficient = 58.31, P = 0.026, 95% confidence interval [7.47, 109.15]), a measure of working memory.iRBD is associated with Ch4 degeneration, and Ch4 degeneration in iRBD is associated with impairment in working memory. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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 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.

Objective: The generation and maintenance of goal-directed behavior is subserved by multiple brain regions that receive cholinergic inputs from the cholinergic nucleus 4 (Ch4). It is unknown if Ch4 degeneration contributes to apathy in Parkinson’s disease (PD). Method: We analyzed data from 106 pre-surgical patients with PD who had brain MRIs and completed the Frontal Systems Behavior Scales (FrSBe). Eighty-eight patients also completed the Beck Depression Inventory-2nd Edition. Cholinergic basal forebrain grey matter densities (GMD) were measured by applying probabilistic maps to T1 MPRAGE sequences processed using voxel-based morphometry methods. We used linear and hierarchical regression modelling to examine the association between Ch4 GMD and the FrSBe Apathy subscale scores. We used similar methods to assess the specificity of this association and potential associations between Ch4 target regions and apathy. Results: Ch4 GMD (p = .021) and Ch123 GMD (p = .032) were significantly associated with Apathy subscale scores on univariate analysis. Ch4 GMD, but not Ch123 GMD, remained significantly associated with apathy when adjusting for age, sex, levodopa equivalent doses, and disease duration. Centromedial amygdala GMD, which receives cholinergic inputs from Ch4, was also associated with apathy. Ch4 GMD was not associated with depression or disinhibition, nor was it associated with executive dysfunction when adjusting for clinical and demographic variables. Conclusions: Ch4 GMD is specifically associated with apathy in PD. Ch4 degeneration results in cholinergic denervation of multiple cortical and limbic regions, which may contribute to the cognitive and emotional-affective processing deficits that underlie the behavioral symptoms of apathy.

Puberty is a key event in adolescent development that involves significant, hormone-driven changes to many aspects of physiology including the brain. Understanding how the brain responds during this time period is important for evaluating neuronal developments that affect mental health throughout adolescence and the adult lifespan. This study examines diffusion MRI scans from the cross-sectional ABCD Study baseline cohort, a large multi-site study containing thousands of participants, to describe the relationship between pubertal development and brain microstructure. Using advanced, 3-tissue constrained spherical deconvolution methods, this study is able to describe multiple tissue compartments beyond only white matter (WM) axonal qualities. After controlling for age, sex, brain volume, subject handedness, scanning site, and sibling relationships, we observe a positive relationship between an isotropic, intracellular diffusion signal fraction and pubertal development across a majority of regions of interest (ROIs) in the WM skeleton. We also observe regional effects from an intracellular anisotropic signal fraction compartment and extracellular isotropic free water-like compartment in several ROIs. This work suggests that changes during pubertal development elicit a complex response from brain tissue that cannot be completely described by traditional methods focusing only on WM axonal properties. This work brings in vivo human neuroimaging studies more into line with work performed on animal models, which describe an interaction between increased myelination, neurogenesis, angiogenesis, and glial cell proliferation in response to pubertal hormones.

Epigenetic clocks provide powerful tools for estimating health and lifespan but their ability to predict brain degeneration and neuronal damage during the aging process is unknown. In this study, we use GrimAge, an epigenetic clock correlated to several blood plasma proteins, to longitudinally investigate brain cellular microstructure in axonal white matter from a cohort of healthy aging individuals. Given the blood plasma correlations used to develop GrimAge, a specific focus was made on white matter hyperintensities, a visible neurological manifestation of small vessel disease, and the axonal pathways throughout each individual’s brain affected by their unique white matter hyperintensity location and volume. 98 subjects over 55 years of age were scanned at baseline with 41 returning for a follow-up scan 2 years later. Using diffusion MRI lesionometry, we reconstructed subject-specific networks of affected axonal tracts and examined the diffusion cellular microstructure composition of these areas, both at baseline and longitudinally, for evidence of cellular degeneration. A chronological age-adjusted version of GrimAge was significantly correlated with baseline WMH volume and markers of neuronal decline, indicated by increased extracellular free water, increased intracellular signal, and decreased axonal signal within WMH. By isolating subject-specific axonal regions ‘lesioned’ by crossing through a WMH, age-adjusted GrimAge was also able to predict longitudinal development of similar patterns of neuronal decline throughout the brain. This study is the first to establish a relationship between accelerated epigenetic GrimAge and brain cellular microstructure in humans.

Impaired olfaction and reduced cholinergic nucleus 4 (Ch4) volume both predict greater cognitive decline in Parkinson's disease (PD). We examined the relationship between olfaction, longitudinal change in cholinergic basal forebrain nuclei and their target regions, and cognition in early PD.We analyzed a cohort of 97 PD participants from the Parkinson's Progression Markers Initiative with brain MRIs at baseline, 1 year, 2 years, and 4 years. Using probabilistic maps, regional grey matter density (GMD) was calculated for Ch4, cholinergic nuclei 1, 2, and 3 (Ch123), and their target regions.Baseline University of Pennsylvania Smell Identification Test score correlated with change in GMD of all regions of interest (all p 0.05). Rate of change of Ch4 GMD was correlated with rate of change of Ch123 (p = 0.034), cortex (p = 0.001), and amygdala GMD (p 0.001), but not hippocampus GMD (p = 0.38). Rate of change of Ch123 GMD was correlated with rate of change of cortex (p = 0.001) and hippocampus (p 0.001), but not amygdala GMD (p = 0.133). In a linear regression model including change in GMD of all regions of interest and age as predictors, change in cortex GMD (βˆImpaired olfaction is associated with degeneration of the cholinergic basal forebrain and bilateral cortex, amygdala, and hippocampus in PD. The relationship between impaired olfaction and cognitive decline may be mediated by greater atrophy of the cortex and hippocampus.

The prognosis of lower grade glioma (LGG) patients depends (in large part) on both isocitrate dehydrogenase (IDH) gene mutation and chromosome 1p/19q codeletion status. IDH-mutant LGG without 1p/19q codeletion (IDHmut-Noncodel) often exhibit a unique imaging appearance that includes high apparent diffusion coefficient (ADC) values not observed in other subtypes. The purpose of this study was to develop an ADC analysis-based approach that can automatically identify IDHmut-Noncodel LGG. Whole-tumor ADC metrics, including fractional tumor volume with ADC > 1.5 × 10−3mm2/s (VADC>1.5), were used to identify IDHmut-Noncodel LGG in a cohort of N = 134 patients. Optimal threshold values determined in this dataset were then validated using an external dataset containing N = 93 cases collected from The Cancer Imaging Archive. Classifications were also compared with radiologist-identified T2-FLAIR mismatch sign and evaluated concurrently to identify added value from a combined approach. VADC>1.5 classified IDHmut-Noncodel LGG in the internal cohort with an area under the curve (AUC) of 0.80. An optimal threshold value of 0.35 led to sensitivity/specificity = 0.57/0.93. Classification performance was similar in the validation cohort, with VADC>1.5 ≥ 0.35 achieving sensitivity/specificity = 0.57/0.91 (AUC = 0.81). Across both groups, 37 cases exhibited positive T2-FLAIR mismatch sign—all of which were IDHmut-Noncodel. Of these, 32/37 (86%) also exhibited VADC>1.5 ≥ 0.35, as did 23 additional IDHmut-Noncodel cases which were negative for T2-FLAIR mismatch sign. Tumor subregions with high ADC were a robust indicator of IDHmut-Noncodel LGG, with VADC>1.5 achieving > 90% classification specificity in both internal and validation cohorts. VADC>1.5 exhibited strong concordance with the T2-FLAIR mismatch sign and the combination of both parameters improved sensitivity in detecting IDHmut-Noncodel LGG.

There is evidence that cortical cholinergic denervation contributes to gait and balance impairment in Parkinson’s Disease (PD), especially reduced gait speed. The objective of this study was to determine the relationship between cholinergic basal forebrain gray matter density (GMD) and gait in PD patients. We 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. Reduced 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). Reduced 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.

Finite element (FE) models of the brain are crucial for investigating the mechanisms of traumatic brain injury (TBI). However, FE brain models are often limited to a single neuroanatomy because the manual development of subject-specific models is time consuming. The objective of this study was to develop a pipeline to automatically generate subject-specific FE brain models using previously developed nonlinear image registration techniques, preserving both external and internal neuroanatomical characteristics. To verify the morphing-induced mesh distortions did not influence the brain deformation response, strain distributions predicted using the morphed model were compared to those from manually created voxel models of the same subject. Morphed and voxel models were generated for 44 subjects ranging in age, and simulated using head kinematics from a football concussion case. For each subject, brain strain distributions predicted by each model type were consistent, and differences in strain prediction was less than 4% between model type. This automated technique, taking approximately 2 h to generate a subject-specific model, will facilitate interdisciplinary research between the biomechanics and neuroimaging fields and could enable future use of biomechanical models in the clinical setting as a tool for improving diagnosis.

Purpose Several recent studies have used a three-tissue constrained spherical deconvolution pipeline to obtain quantitative metrics of brain tissue microstructure from diffusion-weighted MRI data. The three tissue compartments, consisting of white matter, gray matter, and CSF-like (free water) signals, are potentially useful in the evaluation of brain microstructure in a range of pathologies. However, the reliability and long-term stability of these metrics have not yet been evaluated. Methods This study examined estimates of whole-brain microstructure for the three tissue compartments, in three separate test-retest cohorts. Each cohort had different lengths of time between baseline and retest, ranging from within the same scanning session in the shortest interval to 3 months in the longest interval. Each cohort was also collected with different acquisition parameters. Results The CSF-like compartment displayed the greatest reliability across all cohorts, with intraclass correlation coefficient (ICC) values being above 0.95 in each cohort. White matter-like and gray matter-like compartments both demonstrated very high reliability in the immediate cohort (both ICC > 0.90); however, this declined in the 3-month interval cohort to both compartments having ICC > 0.80. Regional CSF-like signal fraction was examined in bilateral hippocampus and had an ICC > 0.80 in each cohort. Conclusion The three-tissue constrained spherical deconvolution techniques provide reliable and stable estimates of tissue-microstructure composition, up to 3 months longitudinally in a control population. This forms an important basis for further investigations using three-tissue constrained spherical deconvolution techniques to track changes in microstructure across a variety of brain pathologies.

Background Fluorescence in situ hybridization (FISH) is a standard method for 1p/19q codeletion testing in diffuse gliomas but occasionally renders erroneous results. Purpose To determine whether MRI/CT analysis identifies isocitrate dehydrogenase (IDH)-mutant gliomas misassigned to 1p/19q codeletion status with FISH. Materials and Methods Data in patients with IDH-mutant lower-grade gliomas (World Health Organization grade II/III) and 1p/19q codeletion status determined with FISH that were accrued from January 1, 2010 to October 1, 2017, were included in this retrospective study. Two neuroradiologist readers analyzed the pre-resection MRI findings (and CT findings, when available) to predict 1p/19q status (codeleted or noncodeleted) and provided a prediction confidence score (1 = low, 2 = moderate, 3 = high). Percentage concordance between the consensus neuroradiologist 1p/19q prediction and the FISH result was calculated. For gliomas where (a) consensus neuroradiologist 1p/19q prediction differed from the FISH result and (b) consensus neuroradiologist confidence score was 2 or greater, further 1p/19q testing was performed with chromosomal microarray analysis (CMA). Nine control specimens were randomly chosen from the remaining study sample for CMA. Percentage concordance between FISH and CMA among the CMA-tested cases was calculated. Results A total of 112 patients (median age, 38 years [interquartile range, 31-51 years]; 57 men) were evaluated (112 gliomas). Percentage concordance between the consensus neuroradiologist 1p/19q prediction and the FISH result was 84.8% (95 of 112; 95% confidence interval: 76.8%, 90.9%). Among the 17 neuroradiologist-FISH discordances, there were nine gliomas associated with a consensus neuroradiologist confidence score of 2 or greater. In six (66.7%) of these nine gliomas, the 1p/19q codeletion status as determined with CMA disagreed with the FISH result and agreed with the consensus neuroradiologist prediction. For the nine control specimens, there was 100% agreement between CMA and FISH for 1p/19q determination. Conclusion MRI and CT analysis can identify diffuse gliomas misassigned to 1p/19q codeletion status with fluorescence in situ hybridization (FISH). Further molecular testing should be considered for gliomas with discordant neuroimaging and FISH results. © RSNA, 2019 Online supplemental material is available for this article.

ObjectiveA major contributor to dementia in Parkinson disease (PD) is degeneration of the cholinergic basal forebrain. This study determined whether cholinergic nucleus 4 (Ch4) density is associated with cognition in early and more advanced PD.MethodsWe analysed brain MRIs and neuropsychological test scores for 228 newly diagnosed PD participants from the Parkinson’s Progression Markers Initiative (PPMI), 101 healthy controls from the PPMI and 125 more advanced PD patients from a local retrospective cohort. Cholinergic basal forebrain nuclei densities were determined by applying probabilistic maps to MPRAGE T1 sequences processed using voxel-based morphometry methods. Relationships between grey matter densities and cognitive scores were analysed using correlations and linear regression models.ResultsIn more advanced PD, greater Ch4 density was associated with Montreal Cognitive Assessment (MoCA) score (β=14.2; 95% CI=1.5 to 27.0; p=0.03), attention domain z-score (β=3.2; 95% CI=0.8 to 5.5; p=0.008) and visuospatial domain z-score (β=7.9; 95% CI=2.0 to 13.8; p=0.009). In the PPMI PD cohort, higher Ch4 was associated with higher scores on MoCA (β=9.2; 95% CI=1.9 to 16.5; p=0.01), Judgement of Line Orientation (β=20.4; 95% CI=13.8 to 27.0; pConclusionIn de novo and more advanced PD, lower Ch4 density is associated with impaired global cognition, attention and visuospatial function.

Contains fulltext : 244253.pdf (Publisher’s version ) (Open Access) BACKGROUND: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated. OBJECTIVE: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging. METHODS: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effects models. Patients grouped according to Hoehn and Yahr stage were compared with age- and sex-matched controls. Within the patient sample, we investigated associations with Montreal Cognitive Assessment score. RESULTS: Overall, patients showed a thinner cortex in 38 of 68 regions compared with controls (d(max) = -0.20, d(min) = -0.09). The bilateral putamen (d(left) = -0.14, d(right) = -0.14) and left amygdala (d = -0.13) were smaller in patients, whereas the left thalamus was larger (d = 0.13). Analysis of staging demonstrated an initial presentation of thinner occipital, parietal, and temporal cortices, extending toward rostrally located cortical regions with increased disease severity. From stage 2 and onward, the bilateral putamen and amygdala were consistently smaller with larger differences denoting each increment. Poorer cognition was associated with widespread cortical thinning and lower volumes of core limbic structures. CONCLUSIONS: Our findings offer robust and novel imaging signatures that are generally incremental across but in certain regions specific to disease stages. Our findings highlight the importance of adequately powered multicenter collaborations. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

BackgroundBrain structure abnormalities throughout the course of Parkinson’s disease (PD) have yet to be fully elucidated. Inconsistent findings across studies may be partly due to small sample sizes and heterogeneous analysis methods. Using a multicenter approach and harmonized analysis methods, we aimed to overcome these limitations and shed light on disease stage-specific profiles of PD pathology as suggested by in vivo neuroimaging.MethodsIndividual brain MRI and clinical data from 2,367 PD patients and 1,183 healthy controls were collected from 19 sites, deriving from 20 countries. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effect linear models. Patients were grouped according to the Hoehn & Yahr (HY) disease stages and compared to age- and sex-matched controls. Within the PD sample, we investigated associations between Montreal Cognitive Assessment (MoCA) scores and brain morphology.FindingsThe main analysis showed a thinner cortex in 38 of 68 regions in PD patients compared to controls (dmax = −0·25, dmin = −0·13). The bilateral putamen (left: d = −0·16, right: d = −0·16) and left amygdala (d = −0·15) were smaller in patients, while the left thalamus was larger (d = 0·17). HY staging indicated that a thinner cortex initially presents in the occipital, parietal and temporal cortex, and extends towards caudally located brain regions with increased disease severity. From HY stage 2 and onwards the bilateral putamen and amygdala were consistently smaller with larger effects denoting each increment. Finally, we found that poorer cognitive performance was associated with widespread cortical thinning as well as lower volumes of core limbic structures.InterpretationOur findings offer robust and novel imaging signatures that are specific to the disease severity stages and in line with an ongoing neurodegenerative process, highlighting the importance of such multicenter collaborations.FundingNIH Big Data to Knowledge program, ENIGMA World Aging Center, and ENIGMA Sex Differences Initiative, and other international agencies (listed in full in the Acknowledgments).

Finite element (FE) models of the brain are crucial for investigating the mechanisms of traumatic brain injury (TBI). However, FE brain models are often limited to a single neuroanatomy because the manual development of subject-specific models is time consuming. The objective of this study was to develop a pipeline to automatically generate subject-specific FE brain models using previously developed nonlinear image registration techniques, preserving both external and internal neuroanatomical characteristics. To verify the morphing-induced mesh distortions did not influence the brain deformation response, strain distributions predicted using the morphed model were compared to those from manually created voxel models of the same subject. Morphed and voxel models were generated for 44 subjects ranging in age, and simulated using head kinematics from a football concussion case. For each subject, brain strain distributions predicted by each model type were consistent, and differences in strain prediction was less than 4% between model type. This automated technique, taking approximately 2 h to generate a subject-specific model, will facilitate interdisciplinary research between the biomechanics and neuroimaging fields and could enable future use of biomechanical models in the clinical setting as a tool for improving diagnosis.

There is evidence that cortical cholinergic denervation contributes to gait and balance impairment in Parkinson's Disease (PD), especially reduced gait speed.The objective of this study was to determine the relationship between cholinergic basal forebrain gray matter density (GMD) and gait in PD patients.We 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.Reduced 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).Reduced 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.

In this study, twenty volunteers were subjected to three, non-injurious lateral head impacts delivered by a 3.7 kg padded impactor at 2 m/s at varying levels of muscle activation (passive, co-contraction, and unilateral contraction). Electromyography was used to quantify muscle activation conditions, and resulting head kinematics were recorded using a custom-fit instrumented mouthpiece. A multi-modal battery of diagnostic tests (evaluated using neurocognitive, balance, symptomatic, and neuroimaging based assessments) was performed on each subject pre- and post-impact. The passive muscle condition resulted in the largest resultant head linear acceleration (12.1 ± 1.8 g) and angular velocity (7.3 ± 0.5 rad/s). Compared to the passive activation, increasing muscle activation decreased both peak resultant linear acceleration and angular velocity in the co-contracted (12.1 ± 1.5 g, 6.8 ± 0.7 rad/s) case and significantly decreased in the unilateral contraction (10.7 ± 1.7 g, 6.5 ± 0.7 rad/s) case. The duration of angular velocity was decreased with an increase in neck muscle activation. No diagnostic metric showed a statistically or clinically significant alteration between baseline and post-impact assessments, confirming these impacts were non-injurious. This study demonstrated that isometric neck muscle activation prior to impact can reduce resulting head kinematics. This study also provides the data necessary to validate computational models of head impact.

There are concerns about the effects of subconcussive head impacts in sport, but the effects of subconcussion on brain connectivity are not well understood. We hypothesized that college football players experience changes in brain functional connectivity not found in athletes competing in lower impact sports or healthy controls. These changes may be spatially heterogeneous across participants, requiring analysis methods that go beyond mass-univariate approaches commonly used in functional MRI (fMRI). To test this hypothesis, we analyzed resting-state fMRI data from college football (n = 15), soccer (n = 12), and lacrosse players (n = 16), and controls (n = 29) collected at preseason and postseason time points. Regional homogeneity (ReHo) and degree centrality (DC) were calculated as measures of local and long-range functional connectivity, respectively. Standard voxel-wise analysis and paired support vector machine (SVM) classification studied subconcussion’s effects on local and global functional connectivity. Voxel-wise analyses yielded minimal findings, but SVM classification had high accuracy for college football’s ReHo (87%, p = 0.009) and no other group. The findings suggest subconcussion results in spatially heterogeneous changes in local functional connectivity that may only be detectible with multivariate analyses. To determine if voxel-wise and SVM analyses had similar spatial patterns, region-average t-statistic and SVM weight values were compared using a measure of ranking distance. T-statistic and SVM weight rankings exhibited significantly low ranking distance values for all groups and metrics, demonstrating that the analyses converged on a similar underlying effect. Overall, this research suggests that subconcussion in football may produce local functional connectivity changes similar to concussion.

Models which assess the progression of Lewy pathology in Parkinson's disease have proposed ascending spread in a caudal-rostral pattern. In-vivo human evidence for this theory is limited, in part because there are no biomarkers that allow for direct assessment of Lewy pathology. Here, we measured neurodegeneration via MRI, an outcome which may serve as a proxy for a more direct assessment of ascending models using a combination of (1) MRI-based measures of gray matter density and (2) regions of interest (ROIs) corresponding to cortical and subcortical loci implicated in past MRI and stereological studies of Parkinson's disease. Gray matter density was measured using brain MRI voxel-based morphometry from three cohorts: (1) early Parkinson's disease, (2) more advanced Parkinson's disease and (3) healthy controls. Early Parkinson's disease patients (N = 228, mean age = 61.9 years, mean disease duration = 0.6 years) were newly diagnosed by the Parkinson's Progression Markers Initiative (PPMI). Advanced Parkinson's disease patients (N = 136, mean age = 63.5 years, mean disease duration = 8.0 years) were collected retrospectively from a local cohort undergoing evaluation for functional neurosurgery. Control subjects (N = 103, mean age = 60.2 years) were from PPMI. Comparative analyses focused on gray matter regions ranging from deep gray subcortical structures to the neocortex. ROIs were defined with existing probabilistic cytoarchitectonic brain maps. For subcortical regions of the basal forebrain, amygdala, and entorhinal cortex, advanced Parkinson's disease patients had significantly lower gray matter density when compared to both early Parkinson's disease and healthy controls. No differences were seen in neocortical regions that are "higher" in any proposed ascending pattern. Across early and advanced Parkinson's disease, gray matter density from nearly all subcortical regions significantly decreased with disease duration; no neocortical regions showed this effect. These results demonstrate that atrophy in advanced Parkinson's patients compared to early patients and healthy controls is largely confined to subcortical gray matter structures. The degree of atrophy in subcortical brain regions was linked to overall disease duration, suggesting an organized pattern of atrophy across severity.

Background Fluorescence in situ hybridization (FISH) is a standard method for 1p/19q codeletion testing in diffuse gliomas but occasionally renders erroneous results. Purpose To determine whether MRI/CT analysis identifies isocitrate dehydrogenase (

The clinical and pathological progression of Alzheimer's disease often proceeds rapidly, but little is understood about its structural characteristics over short intervals. This study evaluated the short temporal characteristics of the brain structure in Alzheimer's disease through the application of cytoarchitectonic probabilistic brain mapping to measurements of gray matter density, a technique which may provide advantages over standard volumetric MRI techniques. Gray matter density was calculated using voxel-based morphometry of T1-weighted MRI obtained from Alzheimer's disease patients and healthy controls evaluated at intervals of 0.5, 1.5, 3.5, 6.5, 9.5, 12, 18, and 24 months by the MIRIAD study. The Alzheimer's disease patients had 19.1% less gray matter at 1st MRI, and this declined 81.6% faster than in healthy controls. Atrophy in the hippocampus, amygdala, and basal forebrain distinguished the Alzheimer's disease patients. Notably, the CA2 of the hippocampus was found to have atrophied significantly within 1 month. Gray matter density measurements were reliable, with intraclass correlation coefficients exceeding 0.8. Comparative atrophy in the Alzheimer's disease group agreed with manual tracing MRI studies of Alzheimer's disease while identifying atrophy on a shorter time scale than has previously been reported. Cytoarchitectonic mapping of gray matter density is reliable and sensitive to small-scale neurodegeneration, indicating its use in the future study of Alzheimer's disease.

PurposeSeveral recent studies have utilized a 3-tissue constrained spherical deconvolution pipeline to obtain quantitative metrics of brain tissue microstructure from diffusion-weighted MRI data. The three tissue compartments, comprising white matter-, grey matter-, and CSF-like (free water) signals, are potentially useful in the evaluation of brain microstructure in a range of pathologies. However, the reliability and long-term stability of these metrics has not yet been evaluated.MethodsThis study examined estimates of whole brain microstructure for the three tissue compartments, in three separate test-retest cohorts. Each cohort has different lengths of time between baseline and retest, ranging from within the same scanning session in the shortest interval to three months in the longest interval. Each cohort was also collected with different acquisition parameters.ResultsThe CSF-like compartment displayed the greatest reliability across all cohorts, with intraclass correlation coefficient (ICC) values being above 0.95 in each cohort. White matter-like and grey matter-like compartments both demonstrated very high reliability in the immediate cohort (both ICC>0.90), however this declined in the 3 month interval cohort to both compartments having ICC>0.80. Regional CSF-like signal fraction was examined in bilateral hippocampus and had an ICC>0.80 in each cohort.ConclusionThe 3-tissue CSD techniques provide reliable and stable estimates of tissue microstructure composition, up to 3 months longitudinally in a control population. This forms an important basis for further investigations utilizing 3-tissue CSD techniques to track changes in microstructure across a variety of brain pathologies.

Diffuse lower grade gliomas (LGG) with isocitrate dehydrogenase (IDH) gene mutations (IDHMUT) have a distinct survival advantage compared with IDH wild-type (IDHWT) 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 IDHWT (vs. IDHMUT) LGG. 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 (Vinf) were then determined using threshold values (p = 2 × 10−3mm2/s, q = 3 × 10–4 mm2/s) and compared between IDHWT and IDHMUT LGG, and between IDHMUT LGG with and without 1p/19q codeletion. Vinf volumes were significantly larger in IDHWT LGG than in IDHMUT LGG (35.4 ± 18.3% vs. 15.9 ± 7.6%, P

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).

A 45-year-old woman presented with 2 years of progressive bilateral leg weakness and stiffness. She had a history of severe asthma and had been on high-dose steroids for 13 years. On examination, she had a Cushingoid appearance and spastic paraparesis. Sequential MRIs of her thoracic spine demonstrated increased T1 signal in the epidural space consistent with epidural lipomatosis, eventually causing severe cord compression (figures 1 and 2). The epidural space normally contains adipose tissue, but in patients who are obese or on long-term steroids, this can become pathologically enlarged.1 The treatment consists of weight loss, steroid weaning, and in severe cases, decompressive surgery.2

SUMMARY: The past decade has seen impressive advances in the types of neuroimaging information that can be acquired in patients with traumatic brain injury. However, despite this increase in information, understanding of the contribution of this information to prognostic accuracy and treatment pathways for patients is limited. Available techniques often allow us to infer the presence of microscopic changes indicative of alterations in physiology and function in brain tissue. However, because histologic confirmation is typically lacking, conclusions reached by using these techniques remain solely inferential in almost all cases. Hence, a need exists for validation of these techniques by using data from large population samples that are obtained in a uniform manner, analyzed according to well-accepted procedures, and correlated with closely monitored clinical outcomes. At present, many of these approaches remain confined to population-based research rather than diagnosis at an individual level, particularly with regard to traumatic brain injury that is mild or moderate in degree. A need and a priority exist for patient-centered tools that will allow advanced neuroimaging tools to be brought into clinical settings. One barrier to developing these tools is a lack of an age-, sex-, and comorbidities-stratified, sequence-specific, reference imaging data base that could provide a clear understanding of normal variations across populations. Such a data base would provide researchers and clinicians with the information necessary to develop computational tools for the patient-based interpretation of advanced neuroimaging studies in the clinical setting. The recent “Joint ASNR-ACR HII-ASFNR TBI Workshop: Bringing Advanced Neuroimaging for Traumatic Brain Injury into the Clinic” on May 23, 2014, in Montreal, Quebec, Canada, brought together neuroradiologists, neurologists, psychiatrists, neuropsychologists, neuroimaging scientists, members of the National Institute of Neurologic Disorders and Stroke, industry representatives, and other traumatic brain injury stakeholders to attempt to reach consensus on issues related to and develop consensus recommendations in terms of creating both a well-characterized normative data base of comprehensive imaging and ancillary data to serve as a reference for tools that will allow interpretation of advanced neuroimaging tests at an individual level of a patient with traumatic brain injury. The workshop involved discussions concerning the following: 1) designation of the policies and infrastructure needed for a normative data base, 2) principles for characterizing normal control subjects, and 3) standardizing research neuroimaging protocols for traumatic brain injury. The present article summarizes these recommendations and examines practical steps to achieve them.

Imaging plays an essential role in identifying intracranial injury in patients with traumatic brain injury (TBI). The goals of imaging include (1) detecting injuries that may require immediate surgical or procedural intervention, (2) detecting injuries that may benefit from early medical therapy or vigilant neurologic supervision, and (3) determining the prognosis of patients to tailor rehabilitative therapy or help with family counseling and discharge planning. In this article, the authors perform a review of the evidence on the utility of various imaging techniques in patients presenting with TBI to provide guidance for evidence-based, clinical imaging protocols. The intent of this article is to suggest practical imaging recommendations for patients presenting with TBI across different practice settings and to simultaneously provide the rationale and background evidence supporting their use. These recommendations should ultimately assist referring physicians faced with the task of ordering appropriate imaging tests in particular patients with TBI for whom they are providing care. These recommendations should also help radiologists advise their clinical colleagues on appropriate imaging utilization for patients with TBI.

ObjectiveDetermining baseline predictors of future psychosis in Parkinson disease (PD) may identify those at risk for more rapidly progressive disease, i.e., a more malignant PD subtype.MethodsThis cohort study evaluated 423 patients with newly diagnosed PD collected as part of the Parkinson's Progression Markers Initiative. Psychotic symptoms were assessed with the Movement Disorders Society–Unified Parkinson Disease Rating Scale item 1.2, which assesses hallucinations and psychosis over the past week. At baseline, participants completed the Scales for Outcomes in Parkinson's Disease–Autonomic, the REM Sleep Behavior Disorder (RBD) Screening Questionnaire, and the Epworth Sleepiness Scale. Cholinergic nucleus 4 (Ch4) density was calculated for 228 participants with PD and 101 healthy controls.ResultsMultivariate logistic regression adjusted for age and sex found that greater autonomic symptoms (p = 0.002), RBD (p = 0.021), and excessive daytime sleepiness (EDS) (p = 0.003) at baseline were associated with increased risk of reporting psychotic symptoms on ≥2 occasions. Having 2 or 3 of these baseline symptoms was associated with lower Ch4 density (p = 0.007). In a logistic regression model adjusted for age and sex, higher Ch4 gray matter density was associated with lower risk of reporting psychotic symptoms on ≥2 occasions (odds ratio 0.96 [for an increase in density of 1 unit], p = 0.03).ConclusionsThis study confirms that RBD, EDS, and greater autonomic symptom burden are associated with greater risk of future psychotic symptoms in PD. Reduced Ch4 density at baseline is associated with future psychotic symptoms and a greater burden of RBD, EDS, and autonomic symptoms.

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.

Background Complete or partial agenesis of the falx cerebri may occur in pediatric patients with developmental anomalies. However, isolated agenesis of the falx in a developmentally normal adult is exceptionally rare. We describe the first reported case of a patient with a third ventricular mass associated with partial agenesis of the anterior falx cerebri, a circumstance that influenced surgical access to a third ventricular epidermoid cyst. Case Description A 60-year-old developmentally normal woman presented with progressively worsening aphasia and altered mental status. Brain magnetic resonance imaging showed obstructive hydrocephalus from a third ventricular mass. An anterior interhemispheric transcallosal approach was planned to remove the tumor. However, upon dural opening there was no evidence of a falx cerebri, an anomaly visible but not reported on the prior imaging studies. An interhemispheric fissure was present, but the medial frontal lobes were densely adherent, with multiple traversing veins within the superficial arachnoid of the fissure. Therefore, a left frontal transcortical approach was performed for microsurgical resection of the tumor. Histopathologic analysis identified the lesion to be an epidermoid cyst. Conclusions Partial agenesis of the falx cerebri is exceedingly rare in a developmentally normal adult, particularly in the presence of an anatomically normal superior sagittal sinus. If present, however, it is important to note this association preoperatively because partial agenesis of the falx cerebri precludes an interhemispheric transcallosal approach to the lateral and third ventricles.

To use diffusion-tensor (DT) magnetic resonance (MR) imaging in patients with essential tremor who were treated with transcranial MR imaging-guided focused ultrasound lesion inducement to identify the structural connectivity of the ventralis intermedius nucleus of the thalamus and determine how DT imaging changes correlated with tremor changes after lesion inducement.With institutional review board approval, and with prospective informed consent, 15 patients with medication-refractory essential tremor were enrolled in a HIPAA-compliant pilot study and were treated with transcranial MR imaging-guided focused ultrasound surgery targeting the ventralis intermedius nucleus of the thalamus contralateral to their dominant hand. Fourteen patients were ultimately included. DT MR imaging studies at 3.0 T were performed preoperatively and 24 hours, 1 week, 1 month, and 3 months after the procedure. Fractional anisotropy (FA) maps were calculated from the DT imaging data sets for all time points in all patients. Voxels where FA consistently decreased over time were identified, and FA change in these voxels was correlated with clinical changes in tremor over the same period by using Pearson correlation.Ipsilateral brain structures that showed prespecified negative correlation values of FA over time of -0.5 or less included the pre- and postcentral subcortical white matter in the hand knob area; the region of the corticospinal tract in the centrum semiovale, in the posterior limb of the internal capsule, and in the cerebral peduncle; the thalamus; the region of the red nucleus; the location of the central tegmental tract; and the region of the inferior olive. The contralateral middle cerebellar peduncle and bilateral portions of the superior vermis also showed persistent decrease in FA over time. There was strong correlation between decrease in FA and clinical improvement in hand tremor 3 months after lesion inducement (P.001).DT MR imaging after MR imaging-guided focused ultrasound thalamotomy depicts changes in specific brain structures. The magnitude of the DT imaging changes after thalamic lesion inducement correlates with the degree of clinical improvement in essential tremor.

Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare complication of angiogenesis inhibitors. Anti-vascular endothelial growth factor-directed therapies, including the novel vascular endothelial growth factor multikinase inhibitor regorafenib, are used in metastatic colorectal cancer. A 46-year-old man presented with seizures, agitation, altered mental status, and hypertension 4 days after starting regorafenib. Magnetic resonance imaging of the brain suggested RPLS. After discontinuation of regorafenib and the management of hypertension, no further seizure activity occurred and his mental status improved. Antineoplastic agents, including the new oral angiogenesis inhibitors, sunitinib, sorafenib, and pazopanib, have been linked to RPLS. The literature review indicates our case is the first published report of RPLS during regorafenib treatment.

Aside effect of our aging population is an increasing incidence of dementia. Historically, the role of imaging in dementia has been directed at ruling out the various treatable etiologies. Now a variety of imaging techniques are available or under development for evaluating the structural, biochemical, and functional changes seen in neurodegenerative disease. The advent of these new imaging techniques can help differentiate diseases that have overlapping symptomatology and offers the possibility of diagnosing conditions before they become clinically apparent. The following review is intended to discuss the currently available imaging tools specific to dementia and to introduce some research techniques that may play a clinical role in the future. Given our emphasis on new and emerging techniques, this review is necessarily restricted to the most common causes of dementia, namely Alzheimer disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD).

BACKGROUND AND PURPOSE: MR imaging–guided focused sonography surgery is a new stereotactic technique that uses high-intensity focused sonography to heat and ablate tissue. The goal of this study was to describe MR imaging findings pre- and post-ventralis intermedius nucleus lesioning by MR imaging–guided focused sonography as a treatment for essential tremor and to determine whether there was an association between these imaging features and the clinical response to MR imaging–guided focused sonography. MATERIALS AND METHODS: Fifteen patients with medication-refractory essential tremor prospectively gave consent; were enrolled in a single-site, FDA-approved pilot clinical trial; and were treated with transcranial MR imaging–guided focused sonography. MR imaging studies were obtained on a 3T scanner before the procedure and 24 hours, 1 week, 1 month, and 3 months following the procedure. RESULTS: On T2-weighted imaging, 3 time-dependent concentric zones were seen at the site of the focal spot. The inner 2 zones showed reduced ADC values at 24 hours in all patients except one. Diffusion had pseudonormalized by 1 month in all patients, when the cavity collapsed. Very mild postcontrast enhancement was seen at 24 hours and again at 1 month after MR imaging–guided focused sonography. The total lesion size and clinical response evolved inversely compared with each other (coefficient of correlation = 0.29, P value = .02). CONCLUSIONS: MR imaging–guided focused sonography can accurately ablate a precisely delineated target, with typical imaging findings seen in the days, weeks, and months following the treatment. Tremor control was optimal early when the lesion size and perilesional edema were maximal and was less later when the perilesional edema had resolved.

Recent advances have enabled delivery of high-intensity focused ultrasound through the intact human cranium with magnetic resonance imaging (MRI) guidance. This preliminary study investigates the use of transcranial MRI-guided focused ultrasound thalamotomy for the treatment of essential tremor.From February 2011 through December 2011, in an open-label, uncontrolled study, we used transcranial MRI-guided focused ultrasound to target the unilateral ventral intermediate nucleus of the thalamus in 15 patients with severe, medication-refractory essential tremor. We recorded all safety data and measured the effectiveness of tremor suppression using the Clinical Rating Scale for Tremor to calculate the total score (ranging from 0 to 160), hand subscore (primary outcome, ranging from 0 to 32), and disability subscore (ranging from 0 to 32), with higher scores indicating worse tremor. We assessed the patients' perceptions of treatment efficacy with the Quality of Life in Essential Tremor Questionnaire (ranging from 0 to 100%, with higher scores indicating greater perceived disability).Thermal ablation of the thalamic target occurred in all patients. Adverse effects of the procedure included transient sensory, cerebellar, motor, and speech abnormalities, with persistent paresthesias in four patients. Scores for hand tremor improved from 20.4 at baseline to 5.2 at 12 months (P=0.001). Total tremor scores improved from 54.9 to 24.3 (P=0.001). Disability scores improved from 18.2 to 2.8 (P=0.001). Quality-of-life scores improved from 37% to 11% (P=0.001).In this pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy. Large, randomized, controlled trials will be required to assess the procedure's efficacy and safety. (Funded by the Focused Ultrasound Surgery Foundation; ClinicalTrials.gov number, NCT01304758.).

Background: Concussion and repetitive head impact in sports has increased interest and concern for clinicians, scientists, and athletes. Lacrosse is the fastest growing sport in the United States, but the burden of head impact in lacrosse is unknown. Purpose: The goal of this pilot study was to quantify head impact associated with practicing and playing collegiate lacrosse while subjects were fitted with wearable accelerometers. Study Design: Descriptive epidemiology study. Methods: In a single year, a collegiate cohort of 14 women’s and 15 men’s lacrosse players wore mastoid-patch accelerometers to measure the frequency and severity of head impacts during official practices and games. Average impact severity, mean number of impacts, and cumulative acceleration were evaluated, stratified by sport and event type. Results: Men’s and women’s collegiate lacrosse players did not significantly differ in the number of head impacts received during games (11.5 for men vs 9.2 for women) or practices (3.1 vs 3.1). Men’s lacrosse players had significantly higher average head acceleration per impact during games compared with women (21.1 g vs 14.7 g) but not during practices (21.3 g vs 18.1 g). For both men and women, more impacts occurred during games than during practices (men, 11.5 vs 3.1; women, 9.2 vs 3.1), but impact severity did not significantly differ between events for either sport (men, 21.1 g vs 21.3 g; women, 14.7 g vs 18.1 g). Conclusion: The study data suggest a higher impact burden during games compared with practices, but this effect is driven by the quantity rather than severity of impacts. In contrast, sex-based effects in impact burden are driven by average impact severity rather than quantity. Data collected from larger multisite trials and/or different age groups could be used to inform ongoing debates, including headgear and practice regulations, that might appreciably affect the burden of head impacts in lacrosse. Clinical Relevance: While most head impacts do not result in a clinical diagnosis of concussion, evidence indicates that subconcussive head impacts may increase susceptibility to concussion and contribute to long-term neurodegeneration.

Determine the MRI characteristics of large post-traumatic cervical spine extra-arachnoid collections managed conservatively in clinically stable patients and whether evidence of clinical or imaging deterioration materialized. Following IRB approval, we conducted a retrospective search for all patients (>16 years old) over a 17-months period who had an extra-arachnoid fluid collection reported on a post-traumatic cervical spine MRI. Patients were excluded if they had surgery for an unstable fracture (n = 21), emergent decompression (n = 1) or lacked a follow-up MRI within 15 days (n = 1). Two MSK radiologists recorded the size, morphology and MRI signal characteristics of the collections. Eight patients (5 male, 3 female) met the inclusion criteria (mean age 40 years; range 19–78 years). Seven of the eight patients had fluid collections that demonstrated thin, tapered margins, extended >7 vertebral bodies and involved >180 degrees of the spinal canal. The signal characteristics of these collections varied: hyper-T1/iso-T2 (n = 1), iso-T1/T2 (n = 3), hyper-T1/hypo-T2 (n = 3) and mixed-T1/T2 (n = 1). Six of seven collections were ventral. Follow-up MRI demonstrated resolution/significant decrease in size (n = 4 between 1 and 12 days) or no change/slight decrease in size (n = 3; between 2 and 11 days). None of the seven fluid collections enlarged, no patient had abnormal cord signal, and no patient’s neurologic symptoms worsened. One of eight patients had a dorsal “mass-like” collection that was slightly smaller 9 days later. In stable patients with large, tapered post-traumatic cervical spine extra-arachnoid collections managed non-surgically, none developed (1) clinical worsening, (2) abnormal cord signal or (3) collection enlargement, regardless of the collection’s signal characteristics.

Anatomic structures have been linked to the mnemonic component of working memory, but the neural network underlying associated decision processes remains elusive. Here we present an event-related functional magnetic resonance imaging study that measured activity during the decision period of a delayed face recognition task. A double dissociation of activity between anterior cingulate cortex (ACC), and a network including left fusiform face area (FFA) and left dorsolateral prefrontal cortex (DLPFC), reflected whether a probe face matched the remembered face at the time of decision. Greater activity in the left FFA and left DLPFC correlated with probe faces that matched the remembered face; in contrast, activity in ACC was greater when the probe face did not match the remembered face. These results support a model where frontal regions act in concert with stimulus-specific temporal structures to make recognition decisions about visual stimuli.