Diffusion magnetic resonance spectroscopy captures microglial reactivity related to gut-derived systemic lipopolysaccharide: A preliminary study.

Neuroinflammation is a key component underlying multiple neurological disorders, yet non-invasive and cost-effective assessment of in vivo neuroinflammatory processes in the central nervous system remains challenging. Diffusion weighted magnetic resonance spectroscopy (dMRS) has shown promise in addressing these challenges by measuring diffusivity properties of different neurometabolites, which can reflect cell-specific morphologies. Prior work has demonstrated dMRS utility in capturing microglial reactivity in the context of lipopolysaccharide (LPS) challenges and serious neurological disorders, detected as changes of microglial metabolite diffusivity properties. However, the extent to which such dMRS metrics are capable of detecting subtler and more nuanced levels of neuroinflammation in populations without overt neuropathology is unknown. Here we examined the relationship between intrinsic, gut-derived levels of systemic LPS and dMRS-based apparent diffusion coefficients (ADC) of choline, creatine, and N-acetylaspartate (NAA) in two brain regions: the thalamus and the corona radiata. Higher plasma LPS concentrations were significantly associated with increased ADC of choline and NAA in the thalamic region, with no such relationships observed in the corona radiata for any of the metabolites examined. As such, dMRS may have the sensitivity to measure microglial reactivity across populations with highly variable levels of neuroinflammation, and holds promising potential for widespread applications in both research and clinical settings.

Abnormal Cerebrovascular Activity, Perfusion, and Glymphatic Clearance in Lewy Body Diseases.

Cerebrovascular activity is not only crucial to optimal cerebral perfusion, but also plays an important role in the glymphatic clearance of interstitial waste, including α-synuclein. This highlights a need to evaluate how cerebrovascular activity is altered in Lewy body diseases. This review begins by discussing how vascular risk factors and cardiovascular autonomic dysfunction may serve as upstream or direct influences on cerebrovascular activity. We then discuss how patients with Lewy body disease exhibit reduced and delayed cerebrovascular activity, hypoperfusion, and reductions in measures used to capture cerebrospinal fluid flow, suggestive of a reduced capacity for glymphatic clearance. Given the lack of an existing framework, we propose a model by which these processes may foster α-synuclein aggregation and neuroinflammation. Importantly, this review highlights several avenues for future research that may lead to treatments early in the disease course, prior to neurodegeneration. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Parkinson's disease cerebrovascular reactivity pattern: A feasibility study.

A mounting body of research points to cerebrovascular dysfunction as a fundamental element in the pathophysiology of Parkinson's disease (PD). In the current feasibility study, blood-oxygen-level-dependent (BOLD) MRI was used to measure cerebrovascular reactivity (CVR) in response to hypercapnia in 26 PD patients and 16 healthy controls (HC), and aimed to find a multivariate pattern specific to PD. Whole-brain maps of CVR amplitude (i.e., magnitude of response to CO2) and latency (i.e., time to reach maximum amplitude) were computed, which were further analyzed using scaled sub-profile model principal component analysis (SSM-PCA) with leave-one-out cross-validation. A meaningful pattern based on CVR latency was identified, which was named the PD CVR pattern (PD-CVRP). This pattern was characterized by relatively increased latency in basal ganglia, sensorimotor cortex, supplementary motor area, thalamus and visual cortex, as well as decreased latency in the cerebral white matter, relative to HC. There were no significant associations with clinical measures, though sample size may have limited our ability to detect significant associations. In summary, the PD-CVRP highlights the importance of cerebrovascular dysfunction in PD, and may be a potential biomarker for future clinical research and practice.

Comparison of automated and manual quantification methods for neuromelanin-sensitive MRI in Parkinson's disease.

Neuromelanin-sensitive magnetic resonance imaging quantitative analysis methods have provided promising biomarkers that can noninvasively quantify degeneration of the substantia nigra in patients with Parkinson's disease. However, there is a need to systematically evaluate the performance of manual and automated quantification approaches. We evaluate whether spatial, signal-intensity, or subject specific abnormality measures using either atlas based or manually traced identification of the substantia nigra better differentiate patients with Parkinson's disease from healthy controls using logistic regression models and receiver operating characteristics. Inference was performed using bootstrap analyses to calculate 95% confidence interval bounds. Pairwise comparisons were performed by generating 10,000 permutations, refitting the models, and calculating a paired difference between metrics. Thirty-one patients with Parkinson's disease and 22 healthy controls were included in the analyses. Signal intensity measures significantly outperformed spatial and subject specific abnormality measures, with the top performers exhibiting excellent ability to differentiate patients with Parkinson's disease and healthy controls (balanced accuracy = 0.89; area under the curve = 0.81; sensitivity =0.86; and specificity = 0.83). Atlas identified substantia nigra metrics performed significantly better than manual tracing metrics. These results provide clear support for the use of automated signal intensity metrics and additional recommendations. Future work is necessary to evaluate whether the same metrics can best differentiate atypical parkinsonism, perform similarly in de novo and mid-stage cohorts, and serve as longitudinal monitoring biomarkers.

Longitudinal hippocampal subfields, CSF biomarkers, and cognition in patients with Parkinson disease.

Objective: Hippocampal atrophy is an indicator of emerging dementia in PD, though it is unclear whether cerebral spinal fluid (CSF) Abeta-42, t-tau, or alpha-syn predict hippocampal subfield atrophy in a de novo cohort of PD patients. To examine whether levels of CSF alpha-synuclein (alpha-syn), beta-amyloid 1-42 (Abeta-42), or total-tau (t-tau) are associated with hippocampal subfield volumes over time. Methods: We identified a subset of Parkinson's Progression Markers Initiative (PPMI) de novo PD patients with longitudinal T1-weighted imaging (baseline plus at least two additional visits across 12, 24, and 48 months) and CSF biomarkers available at baseline. We performed cross-sectional, regression, and linear mixed model analyses to evaluate the baseline and longitudinal CSF biomarkers, hippocampal subfields, and cognition. A false discovery rate (FDR) was used to correct for multiple comparisons. Results: 88 PD-CN and 21 PD-MCI had high quality longitudinal data. PD-MCI patients exhibited reduced bilateral CA1 volumes relative to PD-CN, though there were no significant differences in CSF biomarkers between these groups. Relationships between CSF biomarkers and hippocampal subfields changed over time, with a general pattern that lower CSF Abeta-42, higher t-tau and higher alpha-syn were associated with smaller hippocampal subfields, primarily in the right hemisphere. Conclusion: We replicated prior reports that demonstrated reduced CA1 volumes in PD-MCI in a de novo PD cohort. CSF biomarkers were associated with individual subfields, with evidence that the increased CSF t-tau was associated with smaller subiculum volumes at baseline and over time, though there was no clear indication that the subfields associated with cognition (CA1 and HATA) were associated with CSF biomarkers.

Lesion network mapping of eye-opening apraxia.

Apraxia of eyelid opening (or eye-opening apraxia) is characterized by the inability to voluntarily open the eyes because of impaired supranuclear control. Here, we examined the neural substrates implicated in eye-opening apraxia through lesion network mapping. We analysed brain lesions from 27 eye-opening apraxia stroke patients and compared them with lesions from 20 aphasia and 45 hemiballismus patients serving as controls. Lesions were mapped onto a standard brain atlas using resting-state functional MRI data derived from 966 healthy adults in the Harvard Dataverse. Our analyses revealed that most eye-opening apraxia-associated lesions occurred in the right hemisphere, with subcortical or mixed cortical/subcortical involvement. Despite their anatomical heterogeneity, these lesions functionally converged on the bilateral dorsal anterior and posterior insula. The functional connectivity map for eye-opening apraxia was distinct from those for aphasia and hemiballismus. Hemiballismus lesions predominantly mapped onto the putamen, particularly the posterolateral region, while aphasia lesions were localized to language-processing regions, primarily within the frontal operculum. In summary, in patients with eye-opening apraxia, disruptions in the dorsal anterior and posterior insula may compromise their capacity to initiate the appropriate eyelid-opening response to relevant interoceptive and exteroceptive stimuli, implicating a complex interplay between salience detection and motor execution.

Reduced and Delayed Cerebrovascular Reactivity in Patients with Parkinson's Disease.

BACKGROUND: Cerebrovascular dysfunction in Parkinson's disease (PD) is heterogeneous and may contribute to disease pathophysiology or progression. There is a need to understand the mechanisms by which cerebrovascular dysfunction is altered in participants with PD. OBJECTIVES: The objective of this study is to test the hypothesis that participants with PD exhibit a significant reduction in the ability of the cerebral vessels to dilate in response to vasoactive challenges relative to healthy controls (HC). METHODS: The current study uses a vasodilatory challenge while participants undergo functional magnetic resonance imaging to quantify the amplitude and delay of cerebrovascular reactivity in participants with PD relative to age and sex-matched HC. An analysis of covariance was used to evaluate differences in cerebrovascular reactivity amplitude and latency between PD participants and HC. RESULTS: A significant main effect of group was observed for whole-brain cerebrovascular reactivity amplitude (F(1, 28) = 4.38, p = 0.046, Hedge's g = 0.73) and latency (F(1, 28) = 16.35, p < 0.001, Hedge's g = 1.42). Participants with PD exhibited reduced whole-brain amplitude and increased latencies in cerebrovascular reactivity relative to HC. The evaluation of regional effects indicates that the largest effects were observed in the cuneus, precuneus, and parietal regions. CONCLUSIONS: PD participants exhibited reduced and delayed cerebrovascular reactivity. This dysfunction may play an important role in chronic hypoxia, neuroinflammation, and protein aggregation, mechanisms that could lead to disease progression. Cerebrovascular reactivity may serve as an important biomarker and target for future interventions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Test-Retest Reliability of a Semi-Structured Interview to Aid in Pediatric Traumatic Brain Injury Diagnosis.

OBJECTIVE: Retrospective self-report is typically used for diagnosing previous pediatric traumatic brain injury (TBI). A new semi-structured interview instrument (New Mexico Assessment of Pediatric TBI; NewMAP TBI) investigated test-retest reliability for TBI characteristics in both the TBI that qualified for study inclusion and for lifetime history of TBI. METHOD: One-hundred and eight-four mTBI (aged 8-18), 156 matched healthy controls (HC), and their parents completed the NewMAP TBI within 11 days (subacute; SA) and 4 months (early chronic; EC) of injury, with a subset returning at 1 year (late chronic; LC). RESULTS: The test-retest reliability of common TBI characteristics [loss of consciousness (LOC), post-traumatic amnesia (PTA), retrograde amnesia, confusion/disorientation] and post-concussion symptoms (PCS) were examined across study visits. Aside from PTA, binary reporting (present/absent) for all TBI characteristics exhibited acceptable (≥0.60) test-retest reliability for both Qualifying and Remote TBIs across all three visits. In contrast, reliability for continuous data (exact duration) was generally unacceptable, with LOC and PCS meeting acceptable criteria at only half of the assessments. Transforming continuous self-report ratings into discrete categories based on injury severity resulted in acceptable reliability. Reliability was not strongly affected by the parent completing the NewMAP TBI. CONCLUSIONS: Categorical reporting of TBI characteristics in children and adolescents can aid clinicians in retrospectively obtaining reliable estimates of TBI severity up to a year post-injury. However, test-retest reliability is strongly impacted by the initial data distribution, selected statistical methods, and potentially by patient difficulty in distinguishing among conceptually similar medical concepts (i.e., PTA vs. confusion).

DNA methylation under the major depression pathway predicts pediatric quality of life four-month post-pediatric mild traumatic brain injury.

BACKGROUND: Major depression has been recognized as the most commonly diagnosed psychiatric complication of mild traumatic brain injury (mTBI). Moreover, major depression is associated with poor outcomes following mTBI; however, the underlying biological mechanisms of this are largely unknown. Recently, genomic and epigenetic factors have been increasingly implicated in the recovery following TBI. RESULTS: This study leveraged DNA methylation within the major depression pathway, along with demographic and behavior measures (features used in the clinical model) to predict post-concussive symptom burden and quality of life four-month post-injury in a cohort of 110 pediatric mTBI patients and 87 age-matched healthy controls. The results demonstrated that including DNA methylation markers in the major depression pathway improved the prediction accuracy for quality of life but not persistent post-concussive symptom burden. Specifically, the prediction accuracy (i.e., the correlation between the predicted value and observed value) of quality of life was improved from 0.59 (p = 1.20 × 10-3) (clinical model) to 0.71 (p = 3.89 × 10-5); the identified cytosine-phosphate-guanine sites were mainly in the open sea regions and the mapped genes were related to TBI in several molecular studies. Moreover, depression symptoms were a strong predictor (with large weights) for both post-concussive symptom burden and pediatric quality of life. CONCLUSION: This study emphasized that both molecular and behavioral manifestations of depression symptoms played a prominent role in predicting the recovery process following pediatric mTBI, suggesting the urgent need to further study TBI-caused depression symptoms for better recovery outcome.

The clinical relevance of gray matter atrophy and microstructural brain changes across the psychosis continuum.

Patients with psychotic spectrum disorders (PSD) exhibit similar patterns of atrophy and microstructural changes that may be associated with common symptomatology (e.g., symptom burden and/or cognitive impairment). Gray matter concentration values (proxy for atrophy), fractional anisotropy (FA), mean diffusivity (MD), intracellular neurite density (Vic) and isotropic diffusion volume (Viso) measures were therefore compared in 150 PSD (schizophrenia, schizoaffective disorder, and bipolar disorder Type I) and 63 healthy controls (HC). Additional analyses evaluated whether regions showing atrophy and/or microstructure abnormalities were better explained by DSM diagnoses, symptom burden or cognitive dysfunction. PSD exhibited increased atrophy within bilateral medial temporal lobes and subcortical structures. Gray matter along the left lateral sulcus showed evidence of increased atrophy and MD. Increased MD was also observed in homotopic fronto-temporal regions, suggesting it may serve as a precursor to atrophic changes. Global cognitive dysfunction, rather than DSM diagnoses or psychotic symptom burden, was the best predictor of increased gray matter MD. Regions of decreased FA (i.e., left frontal gray and white matter) and Vic (i.e., frontal and temporal regions and along central sulcus) were also observed for PSD, but were neither spatially concurrent with atrophic regions nor associated with clinical symptoms. Evidence of expanding microstructural spaces in gray matter demonstrated the greatest spatial overlap with current and potentially future regions of atrophy, and was associated with cognitive deficits. These results suggest that this particular structural abnormality could potentially underlie global cognitive impairment that spans traditional diagnostic categories.

Severity of Ongoing Post-Concussive Symptoms as a Predictor of Cognitive Performance Following a Pediatric Mild Traumatic Brain Injury.

OBJECTIVE: This study aimed to examine the predictors of cognitive performance in patients with pediatric mild traumatic brain injury (pmTBI) and to determine whether group differences in cognitive performance on a computerized test battery could be observed between pmTBI patients and healthy controls (HC) in the sub-acute (SA) and the early chronic (EC) phases of injury. METHOD: 203 pmTBI patients recruited from emergency settings and 159 age- and sex-matched HC aged 8-18 rated their ongoing post-concussive symptoms (PCS) on the Post-Concussion Symptom Inventory and completed the Cogstate brief battery in the SA (1-11 days) phase of injury. A subset (156 pmTBI patients; 144 HC) completed testing in the EC (~4 months) phase. RESULTS: Within the SA phase, a group difference was only observed for the visual learning task (One-Card Learning), with pmTBI patients being less accurate relative to HC. Follow-up analyses indicated higher ongoing PCS and higher 5P clinical risk scores were significant predictors of lower One-Card Learning accuracy within SA phase, while premorbid variables (estimates of intellectual functioning, parental education, and presence of learning disabilities or attention-deficit/hyperactivity disorder) were not. CONCLUSIONS: The absence of group differences at EC phase is supportive of cognitive recovery by 4 months post-injury. While the severity of ongoing PCS and the 5P score were better overall predictors of cognitive performance on the Cogstate at SA relative to premorbid variables, the full regression model explained only 4.1% of the variance, highlighting the need for future work on predictors of cognitive outcomes.

Differing functional mechanisms underlie cognitive control deficits in psychotic spectrum disorders.

Background: Functional underpinnings of cognitive control deficits in unbiased samples (i.e., all comers) of patients with psychotic spectrum disorders (PSD) remain actively debated. While many studies suggest hypofrontality in the lateral prefrontal cortex (PFC) and greater deficits during proactive relative to reactive control, few have examined the full hemodynamic response. Methods: Patients with PSD (n = 154) and healthy controls (n = 65) performed the AX continuous performance task (AX-CPT) during rapid (460 ms) functional neuroimaging and underwent full clinical characterization. Results: Behavioural results indicated generalized cognitive deficits (slower and less accurate) across proactive and reactive control conditions in patients with PSD relative to healthy controls. We observed a delayed/prolonged neural response in the left dorsolateral PFC, the sensorimotor cortex and the superior parietal lobe during proactive control for patients with PSD. These proactive hemodynamic abnormalities were better explained by negative rather than by positive symptoms or by traditional diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR), with subsequent simulations unequivocally demonstrating how these abnormalities could be erroneously interpreted as hypoactivation. Conversely, true hypoactivity, unassociated with clinical symptoms or DSM-IV-TR diagnoses, was observed within the ventrolateral PFC during reactive control. Limitations: In spite of guidance for AX-CPT use in neuroimaging studies, one-third of patients with PSD could not perform the task above chance and were more clinically impaired. Conclusion: Current findings question the utility of the AX-CPT for neuroimaging-based appraisal of cognitive control across the full spectrum of patients with PSD. Previously reported lateral PFC "hypoactivity" during proactive control may be more indicative of a delayed/prolonged neural response, important for rehabilitative purposes. Negative symptoms may better explain certain behavioural and hemodynamic abnormalities in patients with PSD relative to DSM-IV-TR diagnoses.

Resting-State Power and Regional Connectivity After Pediatric Mild Traumatic Brain Injury.

BACKGROUND: Physiological recovery from pediatric mild traumatic brain injury (pmTBI) as a function of age remains actively debated, with the majority of studies relying on subjective symptom report rather than objective markers of brain physiology. PURPOSE: To examine potential abnormalities in fractional amplitude of low-frequency fluctuations (fALFF) or regional homogeniety (ReHo) during resting-state fMRI following pmTBI. STUDY TYPE: Prospective cohort. POPULATION: Consecutively recruited pmTBI (N = 105; 8-18 years old) and age- and sex-matched healthy controls (HC; N = 113). FIELD STRENGTH/SEQUENCE: 3T multiecho gradient T1 -weighted and single-shot gradient-echo echo-planar imaging. ASSESSMENT: All pmTBI participants were assessed 1 week and 4 months postinjury (HC assessed at equivalent timepoints after the first visit). Comprehensive demographic, clinical, and cognitive batteries were performed in addition to primary investigation of fALFF and ReHo. All pmTBI were classified as "persistent" or "recovered" based on both assessment periods. STATISTICAL TESTS: Chi-square, nonparametric, and generalized linear models for demographic data. Generalized estimating equations for clinical and cognitive data. Voxelwise general linear models (AFNI's 3dMVM) for fALFF and ReHo assessment. RESULTS: Evidence of recovery was observed for some, but not all, clinical and cognitive measures at 4 months postinjury. fALFF was increased in the left striatum for pmTBI relative to HC both at 1 week and 4 months postinjury; whereas no significant group differences (P > 0.001) were observed for ReHo. Age-at-injury did not moderate either resting-state metric across groups. In contrast to analyses of pmTBI as a whole, there were no significant (P > 0.001) differences in either fALFF or ReHo in patients with persistent postconcussive symptoms compared to recovered patients and controls at 4 months postinjury. DATA CONCLUSIONS: Our findings suggest prolonged clinical recovery and alterations in the relative amplitude of resting-state fluctuations up to 4 months postinjury, but no clear relationship with age-at-injury or subjective symptom report. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: 2 J. MAGN. RESON. IMAGING 2020;52:1701-1713.

Evidence for asymmetric inhibitory activity during motor planning phases of sensorimotor synchronization.

Sensorimotor synchronization (SMS) is frequently dependent on coordination of excitatory and inhibitory activity across hemispheres, as well as the cognitive control over environmental distractors. However, the timing (motor planning versus execution) and cortical regions involved in these processes remain actively debated. Functional magnetic resonance imaging data were therefore analyzed from 34 strongly right-handed healthy adults performing a cued (to initiate motor planning) SMS task with either their right or left hand (motor execution phase) based on spatially congruent or incongruent visual stimuli. Behavioral effects of incongruent stimuli were limited to the first stimulus. Functionally, greater activation was observed in left sensorimotor cortex (SMC) and right cerebellar Lobule V for congruent versus incongruent stimuli. A negative blood-oxygen level dependent response, a putative marker of neural inhibition, was present in bilateral SMC, right supplemental motor area (SMA) and bilateral cerebellar Lobule V during the motor planning, but not execution phase. The magnitude of the inhibitory response was greater in right cortical regions and cerebellar Lobule V. Homologue connectivity was associated with inhibitory activity in the right SMA, suggesting that individual differences in intrinsic connectivity may mediate transcallosal inhibition. In summary, results suggest increased inhibition (i.e., greater negative BOLD response) within the right relative to left hemisphere, which was released once motor programs were executed. Both task and intrinsic functional connectivity results highlight a critical role of the left SMA in interhemispheric inhibition and motor planning.

Neurosensory Screening and Symptom Provocation in Pediatric Mild Traumatic Brain Injury.

OBJECTIVE: To evaluate diagnostic/prognostic implications of neurosensory testing during the subacute stage in patients with pediatric mild traumatic brain injury (pmTBI). SETTING: Recruitment from pediatric emergency department and urgent care clinics, assessment in a controlled environment. PARTICIPANTS: In total, 146 pmTBI patients evaluated 7.4 ± 2.3 days and approximately 4 months postinjury; 104 age/sex-matched healthy controls (HCs) at equivalent time points. DESIGN: Prospective cohort study. MAIN MEASURES: Neurosensory examination based on sequence of 10 established tests of vestibular-ocular, oculomotor, vestibulospinal, and visual functioning. RESULTS: The amount of symptom provocation (positive change from pretest symptomatology) was significantly increased in pmTBI relative to HCs on every subtest 1 week postinjury, as were deficits in monocular accommodative amplitude and King-Devick Test errors. However, symptom provocation did not meaningfully alter diagnostic sensitivity/specificity relative to more easily obtained pretest symptom ratings. Evidence of clinically significant symptom provocation 1 week postinjury improved sensitivity (Δ = +12.9%) of identifying patients with persistent postconcussive symptoms 4 months postinjury on an independent symptom measure. CONCLUSIONS: The diagnostic sensitivity/specificity of neurosensory testing in acutely concussed youth may be limited at 1 week postinjury as a function of natural recovery occurring in most emergency department cohorts. Neurosensory screening may have greater utility for identifying patients who experience delayed recovery.

Comparison of Methods for Classifying Persistent Post-Concussive Symptoms in Children.

Pediatric mild traumatic brain injury (pmTBI) has received increased public scrutiny over the past decade, especially regarding children who experience persistent post-concussive symptoms (PPCS). However, several methods for defining PPCS exist in clinical and scientific literature, and even healthy children frequently exhibit non-specific, concussive-like symptoms. Inter-method agreement (six PPCS methods), observed misclassification rates, and other psychometric properties were examined in large cohorts of consecutively recruited adolescent patients with pmTBI (n = 162) 1 week and 4 months post-injury and in age/sex-matched healthy controls (HC; n = 117) at equivalent time intervals. Six published PPCS methods were stratified into Simple Change (e.g., International Statistical Classification of Diseases and Related Health Problems, 10th revision [ICD-10]) and Standardized Change (e.g., reliable change indices) algorithms. Among HC, test-retest reliability was fair to good across the 4-month assessment window, with evidence of bias (i.e., higher symptom ratings) during retrospective relative to other assessments. Misclassification rates among HC were higher (>30%) for Simple Change algorithms, with poor inter-rater reliability of symptom burden across HC and their parents. A 49% spread existed in terms of the proportion of pmTBI patients "diagnosed" with PPCS at 4 months, with superior inter-method agreement among standardized change algorithms. In conclusion, the self-reporting of symptom burden is only modestly reliable in typically developing adolescents over a 4-month period, with additional evidence for systematic bias in both adolescent and parental ratings. Significant variation existed for identifying pmTBI patients who had "recovered" (i.e., those who did not meet individual criteria for PPCS) from concussion across the six definitions, representing a considerable challenge for estimating the true incidence rate of PPCS in published literature. Although relatively straightforward to obtain, current findings question the utility of the most commonly used Simple Change scores for diagnosis of PPCS in clinical settings.

Persistent alterations in cerebrovascular reactivity in response to hypercapnia following pediatric mild traumatic brain injury.

Much attention has been paid to the effects of mild traumatic brain injury (mTBI) on cerebrovascular reactivity in adult populations, yet it remains understudied in pediatric injury. In this study, 30 adolescents (12-18 years old) with pediatric mTBI (pmTBI) and 35 age- and sex-matched healthy controls (HC) underwent clinical and neuroimaging assessments during sub-acute (6.9 ± 2.2 days) and early chronic (120.4 ± 11.7 days) phases of injury. Relative to controls, pmTBI reported greater initial post-concussion symptoms, headache, pain, and anxiety, resolving by four months post-injury. Patients reported increased sleep issues and exhibited deficits in processing speed and attention across both visits. In grey-white matter interface areas throughout the brain, pmTBI displayed increased maximal fit/amplitude of a time-shifted end-tidal CO2 regressor to blood oxygen-level dependent response relative to HC, as well as increased latency to maximal fit. The alterations persisted through the early chronic phase of injury, with maximal fit being associated with complaints of ongoing sleep disturbances during post hoc analyses but not cognitive measures of processing speed or attention. Collectively, these findings suggest that deficits in the speed and degree of cerebrovascular reactivity may persist longer than current conceptualizations about clinical recovery within 30 days.

Radiologic common data elements rates in pediatric mild traumatic brain injury.

OBJECTIVE: The nosology for classifying structural MRI findings following pediatric mild traumatic brain injury (pmTBI) remains actively debated. Radiologic common data elements (rCDE) were developed to standardize reporting in research settings. However, some rCDE are more specific to trauma (probable rCDE). Other more recently proposed rCDE have multiple etiologies (possible rCDE), and may therefore be more common in all children. Independent cohorts of patients with pmTBI and controls were therefore recruited from multiple sites (New Mexico and Ohio) to test the dual hypothesis of a higher incidence of probable rCDE (pmTBI > controls) vs similar rates of possible rCDE on structural MRI. METHODS: Patients with subacute pmTBI (n = 287), matched healthy controls (HC; n = 106), and orthopedically injured (OI; n = 71) patients underwent imaging approximately 1 week postinjury and were followed for 3-4 months. RESULTS: Probable rCDE were specific to pmTBI, occurring in 4%-5% of each sample, rates consistent with previous large-scale CT studies. In contrast, prevalence rates for incidental findings and possible rCDE were similar across groups (pmTBI vs OI vs HC). The prevalence of possible rCDE was also the only finding that varied as a function of site. Possible rCDE and incidental findings were not associated with postconcussive symptomatology or quality of life 3-4 months postinjury. CONCLUSION: Collectively, current findings question the trauma-related specificity of certain rCDE, as well how these rCDE are radiologically interpreted. Refinement of rCDE in the context of pmTBI may be warranted, especially as diagnostic schema are evolving to stratify patients with structural MRI abnormalities as having a moderate injury.

Proactive inhibition deficits with normal perfusion after pediatric mild traumatic brain injury.

Although much attention has been generated in popular media regarding the deleterious effects of pediatric mild traumatic brain injury (pmTBI), a paucity of empirical evidence exists regarding the natural course of biological recovery. Fifty pmTBI patients (12-18 years old) were consecutively recruited from Emergency Departments and seen approximately 1 week and 4 months post-injury in this prospective cohort study. Data from 53 sex- and age-matched healthy controls (HC) were also collected. Functional magnetic resonance imaging was obtained during proactive response inhibition and at rest, in conjunction with independent measures of resting cerebral blood flow. High temporal resolution imaging enabled separate modeling of neural responses for preparation and execution of proactive response inhibition. A priori predictions of failed inhibitory responses (i.e., hyperactivation) were observed in motor circuitry (pmTBI>HC) and sensory areas sub-acutely and at 4 months post-injury. Paradoxically, pmTBI demonstrated hypoactivation (HC>pmTBI) during target processing, along with decreased activation within prefrontal cognitive control areas. Functional connectivity within motor circuitry at rest suggested that deficits were limited to engagement during the inhibitory task, whereas normal resting cerebral perfusion ruled out deficits in basal perfusion. In conclusion, current results suggest blood oxygen-level dependent deficits during inhibitory control may exceed commonly held beliefs about physiological recovery following pmTBI, potentially lasting up to 4 months post-injury.

A comparison of denoising pipelines in high temporal resolution task-based functional magnetic resonance imaging data.

It has been known for decades that head motion/other artifacts affect the blood oxygen level-dependent signal. Recent recommendations predominantly focus on denoising resting state data, which may not apply to task data due to the different statistical relationships that exist between signal and noise sources. Several blind-source denoising strategies (FIX and AROMA) and more standard motion parameter (MP) regression (0, 12, or 24 parameters) analyses were therefore compared across four sets of event-related functional magnetic resonance imaging (erfMRI) and block-design (bdfMRI) datasets collected with multiband 32- (repetition time [TR] = 460 ms) or older 12-channel (TR = 2,000 ms) head coils. The amount of motion varied across coil designs and task types. Quality control plots indicated small to moderate relationships between head motion estimates and percent signal change in both signal and noise regions. Blind-source denoising strategies eliminated signal as well as noise relative to MP24 regression; however, the undesired effects on signal depended both on algorithm (FIX > AROMA) and design (bdfMRI > erfMRI). Moreover, in contrast to previous results, there were minimal differences between MP12/24 and MP0 pipelines in both erfMRI and bdfMRI designs. MP12/24 pipelines were detrimental for a task with both longer block length (30 ± 5 s) and higher correlations between head MPs and design matrix. In summary, current results suggest that there does not appear to be a single denoising approach that is appropriate for all fMRI designs. However, even nonaggressive blind-source denoising approaches appear to remove signal as well as noise from task-related data at individual subject and group levels.