EXAMINING BRAIN NETWORK MODULARITY IN U.S. MILITARY PERSONNEL WITH BLAST VS. NON-BLAST RELATED MILD TRAUMATIC BRAIN INJURY

Problem: Traumatic brain injury (TBI) is a major health concern to the public, accounting for alarming numbers of hospitalizations and emergency department visits per year. mTBI is of particular concern because of the injury’s ‘invisible’ nature. There are a lack of clinical findings on current evidence-based diagnostic protocols, and sufferers of this “silent” injury persistently complain of changes in functioning compared to their baseline abilities. Methods: 103 active duty service members from the SCORE study comprised 3 groups: mTBI resulting from blast (bmTBI; n=32), mTBI not resulting from blast (e.g. falls, motor vehicle accidents) (mTBI; n=29), and orthopedic controls (OC; n=42). Participants completed an fMRI task assessing effort and a standardized neuropsychological battery. Whole-brain network modularity analysis was completed to determine the pathophysiology secondary to TBI, whether the pathophysiology differs based on the nature of injury, and whether altered modularity relates to cognition. Results: Analysis of variance tests (ANOVA) revealed greater modularity in bmTBI than mTBI and OC at increased effort levels. Repeated measures ANOVAs revealed that increasing modularity values (Q) in bmTBI corresponded with increased effort level demands, while the Q in mTBI and OC was consistent across effort levels. Pearson correlations revealed minimal associations between Q and measures of processing speed. No significant correlations between Q and neuropsychological measures were observed in the OC group. Conclusions: This study suggests that the pathophysiology of blast injury alters the modular structure of the brain in TBI to a greater extent than in TBI from other etiologies

Magnetoencephalography abnormalities in adult mild traumatic brain injury: a systematic review

Background The global incidence of traumatic brain injuries is rising, with at least 80% being classified as mild. These mild injuries are not visible on routine clinical imaging. The potential clinical role of a specific imaging biomarker be it diagnostic, prognostic or directing and monitoring progress of personalised treatment and rehabilitation has driven the exploration of several new neuroimaging modalities. This systematic review examined the evidence for magnetoencephalography (MEG) to provide an imaging biomarker in mild traumatic brain injury (mTBI). Methods Our review was prospectively registered on PROSPERO: CRD42019151387. We searched EMBASE, MEDLINE, trial registers, PsycINFO, Cochrane Library and conference abstracts and identified 37 papers describing MEG changes in mTBI eligible for inclusion. Since meta-analysis was not possible, based on the heterogeneity of reported outcomes, we provide a narrative synthesis of results. Results The two most promising MEG biomarkers are excess resting state low frequency power, and widespread connectivity changes in all frequency bands. These may represent biomarkers with potential for diagnostic application, which reflect time sensitive changes, or may be capable of offering clinically relevant prognostic information. In addition, the rich data that MEG produces are well-suited to new methods of machine learning analysis, which is now being actively explored. Interpretation MEG reveals several promising biomarkers, in the absence of structural abnormalities demonstrable with either computerised tomography or magnetic resonance imaging. This review has not identified sufficient evidence to support routine clinical use of MEG in mTBI currently. However, verifying MEG’s potential would help meet an urgent clinical need within civilian, sports and military medicine

Developing neuroimaging biomarkers of blast-induced traumatic brain injury

In the past two decades, the awareness of the physical and emotional effects and sequalae of traumatic brain injuries (TBI) has grown considerably, especially in the case of soldiers returning from their deployment in Iraq and Afghanistan, after sustaining blast-induced TBI (bTBI). While the understanding of bTBI and how it compares to civilian non-blast TBI is essential for proper prevention, diagnosis and treatment, it is currently limited, especially in human in-vivo studies. Developing neuroimaging biomarkers of bTBI is key in understanding primary blast injury mechanism. I therefore investigated the patterns of white matter and grey matter injuries that are specific to bTBI and aren¶t commonl\ seen in civilians Zho suffered from head trauma using advanced neuroimaging techniques. However, because of significant methodological issues and limitations, I developed and tested a new pipeline capable of running the analysis of white matter abnormalities in soldiers, called subject-specific diffusion segmentation (SSDS). I also used standard methodologies to investigate changes at the level of the grey matter structures, and more particularly the limbic system. Finally, I trained a machine learning algorithm that builds decision trees with the aim of classifying between patients with TBI and controls, and between different TBI mechanisms as an example of what could potentially be applied in the context of bTBI. I found three main neuroimaging biomarkers specific to bTBI. The first one is a microstructural white matter abnormality at the level of the middle cerebellar peduncle, characterized by a decrease of diffusivity measures. The second is also a decrease in diffusivity properties, at the level of the white matter boundary, and the third one is a loss of hippocampal volume, with no association to post-traumatic stress disorder. Finally, I demonstrated that SSDS can be used in tandem with a machine learning algorithm for potential diagnosis of TBI with high accuracy. These findings provide mechanistic insights into bTBI and the effect of primary blast injuries on the human brain. This work also identifies important neuroimaging biomarkers that might facilitate prevention and diagnosis in soldiers who suffered from bTBI.Open Acces

Use of magnetic source imaging to assess recovery after severe traumatic brain injury—an MEG pilot study

RationaleSevere TBI (sTBI) is a devastating neurological injury that comprises a significant global trauma burden. Early comprehensive neurocritical care and rehabilitation improve outcomes for such patients, although better diagnostic and prognostic tools are necessary to guide personalized treatment plans.MethodsIn this study, we explored the feasibility of conducting resting state magnetoencephalography (MEG) in a case series of sTBI patients acutely after injury (~7 days), and then about 1.5 and 8 months after injury. Synthetic aperture magnetometry (SAM) was utilized to localize source power in the canonical frequency bands of delta, theta, alpha, beta, and gamma, as well as DC–80 Hz.ResultsAt the first scan, SAM source maps revealed zones of hypofunction, islands of preserved activity, and hemispheric asymmetry across bandwidths, with markedly reduced power on the side of injury for each patient. GCS scores improved at scan 2 and by scan 3 the patients were ambulatory. The SAM maps for scans 2 and 3 varied, with most patients showing increasing power over time, especially in gamma, but a continued reduction in power in damaged areas and hemispheric asymmetry and/or relative diminishment in power at the site of injury. At the group level for scan 1, there was a large excess of neural generators operating within the delta band relative to control participants, while the number of neural generators for beta and gamma were significantly reduced. At scan 2 there was increased beta power relative to controls. At scan 3 there was increased group-wise delta power in comparison to controls.ConclusionIn summary, this pilot study shows that MEG can be safely used to monitor and track the recovery of brain function in patients with severe TBI as well as to identify patient-specific regions of decreased or altered brain function. Such MEG maps of brain function may be used in the future to tailor patient-specific rehabilitation plans to target regions of altered spectral power with neurostimulation and other treatments

Effects of Diversity and Neuropsychological Performance in an NFL Cohort

Objective: The aim of this study was to examine the effect of ethnicity on neuropsychological test performance by comparing scores of white and black former NFL athletes on each subtest of the WMS. Participants and Methods: Data was derived from a de-identified database in South Florida consisting of 63 former NFL white (n=28, 44.4%) and black (n=35, 55.6%) athletes (Mage= 50.38; SD= 11.57). Participants completed the following subtests of the WMS: Logical Memory I and II, Verbal Paired Associates I and II, and Visual Reproduction I and II. Results: A One-Way ANOVA yielded significant effect between ethnicity and performance on several subtests from the WMS-IV. Black athletes had significantly lower scores compared to white athletes on Logical Memory II: F(1,61) = 4.667, p= .035, Verbal Paired Associates I: F(1,61) = 4.536, p = .037, Verbal Paired Associates: II F(1,61) = 4.677, p = .034, and Visual Reproduction I: F(1,61) = 6.562, p = .013. Conclusions: Results suggest significant differences exist between white and black athletes on neuropsychological test performance, necessitating the need for proper normative samples for each ethnic group. It is possible the differences found can be explained by the psychometric properties of the assessment and possibility of a non-representative sample for minorities, or simply individual differences. Previous literature has found white individuals to outperform African-Americans on verbal and non-verbal cognitive tasks after controlling for socioeconomic and other demographic variables (Manly & Jacobs, 2002). This highlights the need for future investigators to identify cultural factors and evaluate how ethnicity specifically plays a role on neuropsychological test performance. Notably, differences between ethnic groups can have significant implications when evaluating a sample of former athletes for cognitive impairment, as these results suggest retired NFL minorities may be more impaired compared to retired NFL white athletes

Distinguishing Performance on Tests of Executive Functions Between Those with Depression and Anxiety

Objective: To see if there are differences in executive functions between those diagnosed with Major Depressive Disorder (MDD) and those with Generalized Anxiety Disorder (GAD).Participants and Methods: The data were chosen from a de-identified database at a neuropsychological clinic in South Florida. The sample used was adults diagnosed with MDD (n=75) and GAD (n=71) and who had taken the Halstead Category Test, Trail Making Test, Stroop Test, and the Wisconsin Card Sorting Test. Age (M=32.97, SD=11.75), gender (56.7% female), and race (52.7% White) did not differ between groups. IQ did not differ but education did (MDD=13.41 years, SD=2.45; GAD=15.11 years, SD=2.40), so it was ran as a covariate in the analyses. Six ANCOVAs were run separately with diagnosis being held as the fixed factor and executive function test scores held as dependent variables. Results: The MDD group only performed worse on the Category Test than the GAD group ([1,132]=4.022, p\u3c .05). Even though both WCST scores used were significantly different between the two groups, both analyses failed Levene’s test of Equality of Error Variances, so the data were not interpreted. Conclusions: Due to previous findings that those diagnosed with MDD perform worse on tests of executive function than normal controls (Veiel, 1997), this study wanted to compare executive function performance between those diagnosed with MDD and those with another common psychological disorder. The fact that these two groups only differed on the Category Test shows that there may not be much of a difference in executive function deficits between those with MDD and GAD. That being said, not being able to interpret the scores on the WCST test due to a lack of homogeneity of variance indicates that a larger sample size is needed to compare these two types of patients, as significant differences may be found. The results of this specific study, however, could mean that the Category Test could be used in assisting the diagnosis of a MDD patient

The Effect of Ethnicity on Neuropsychological Test Performance of Former NFL Athletes

Objective: To investigate the effect of ethnicity on neuropsychological test performance by specifically exploring differences between white and black former NFL athletes on subtests of the WAIS-IV. Participants and Methods: Data was derived from a de-identified database in Florida consisting of 63 former NFL athletes (Mage=50.38; SD=11.57); 28 white and 35 black. Participants completed the following subtests of the WAIS-IV: Block Design, Similarities, Digit Span, Matrix Reasoning, Arithmetic, Symbol Search, Visual Puzzles, Coding, and Cancellation. Results: One-Way ANOVA yielded a significant effect between ethnicity and performance on several subtests. Black athletes had significantly lower scaled scores than white athletes on Block Design F(1,61)=14.266, p\u3c.001, Similarities F(1,61)=5.904, p=.018, Digit Span F(1,61)=8.985, p=.004, Arithmetic F(1,61)=16.07, p\u3c.001 and Visual Puzzles F(1,61)=16.682, p\u3c .001. No effect of ethnicity was seen on performance of Matrix Reasoning F(1,61)=2.937, p=.092, Symbol Search F(1,61)=3.619, p=.062, Coding F(1,61)=3.032, p=.087 or Cancellation F(1,61)=2.289, p=.136. Conclusions: Results reveal significant differences between white and black athletes on all subtests of the WAIS-IV but those from the Processing Speed Scale and Matrix Reasoning. These findings align with previous literature that found white individuals to outperform African-Americans on verbal and non-verbal tasks after controlling for socioeconomic and demographic variables (Manly & Jacobs, 2002). These differences may also be a reflection of the WAIS-IV’s psychometric properties and it is significant to consider the normative sample used may not be appropriate for African-Americans. This study highlights the need for future research to identify how ethnicity specifically influences performance, sheds light on the importance of considering cultural factors when interpreting test results, and serves as a call to action to further understand how and why minorities may not be accurately represented in neuropsychological testing

Regional Cerebral Blood Flow Patterns in Children vs. Adults with ADHD Combined and Inattentive Types: A SPECT Study

Objective: The current study sought to determine whether ADHD Combined Type (ADHD-C) and ADHD Primarily Inattentive Type (ADHD-PI) showed differential regional cerebral blood flow (rCBF) patterns in children vs. adults. Participants and Methods: The overall sample (N=1484) was effectively split into four groups: adults with ADHD-PI (n=519), adults with ADHD-C (n=405), children with ADHD-PI (n=192), children with ADHD-C (n=368). All participants were void of bipolar, schizophrenia, autism, neurocognitive disorders, and TBI. The data were collected from a de-identified archival database of individuals who underwent SPECT scans at rest. Results: Using αConclusions: Overall, the current study suggested that children may show rCBF differences between different ADHD subtypes, but adults may not. The current study did not find significance in any of the 17 brain regions examined when comparing adults with ADHD-C to adults with ADHD-PI. All significant findings were attributed to the children with ADHD-C group showing aberrant blood flow rate than at least one other group. Previous research has supported that the differentiation of these subtypes as distinctive disorders is difficult to make in adults (Sobanski et al., 2006). Other research has indicated the potential of imaging techniques to differentiate the two in children (Al-Amin, Zinchenko, & Geyer, 2018). The current findings support nuanced ways in which rCBF patterns of ADHD-C and ADHD-PI differ between children and adults

Neural and cognitive biomarkers of binge and heavy drinking

BACKGROUND: Theories suggest two motivations that drive people to consume alcohol at pathological levels: (1) seeking of short-term pleasurable effects and (2) alleviation of unpleasant states. The former is associated with binge drinking (BD; i.e. high intake during fewer occasions) and the latter with heavy drinking (HD; substantial intake during more occasions). Although direct comparisons have not been made, BD has been associated with impairments in top-down executive control (related to frontal-parietal regions) and HD has been linked to bottom-up changes in internal mentation (related to the default mode network anatomical structure and function). This dissertation compares the two drinking patterns with the goal of testing for differential neurocognitive and neuroanatomical characteristics that would be indicative of two disorder subtypes. METHODS: The sample consisted of adult participants with a history of adolescent onset: BD (N = 16), HD (N = 15), and Healthy Controls (HC; N = 21). All groups were equated on age, education, amount of lifetime alcohol consumed (BD and HD groups), as well as other factors. The study compared group performance on an affective go/no go task and group differences in brain volume and cortical thickness based on structural MRI. RESULTS: Behavioral results showed a higher number of errors for the HD group, in comparison to other groups. Volumetric results indicated a smaller bilateral ventral diencephalon in both BD and HD, in comparison to the HC, and smaller bilateral globus pallidus in BD only. Cortical thickness analyses revealed a thinner left superior parietal region (overlapping with the dorsal attention and fronto-parietal networks) in BD, whereas a left medial occipito-parietal region was thicker in HD (overlapping mainly with the visual network). CONCLUSION: These data, interpreted in the context of prior studies, suggest that BD findings might be indicative of an executive control dysregulation that could contribute to continued BD. HD findings might be indicative of tissue damage due to frequent drinking. Prior research has found the occipital region to have the highest concentration γ-Aminobutyric acid receptors that are affected by alcohol, which might explain the thicker occipital region findings in the HD group

COMBAT-RELATED STRESSORS ON SPECIAL OPERATIONS FORCES COMBAT SERVICE MEMBERS’ RESILIENCE AND MENTAL HEALTH

Military service is psychologically and physically taxing and involves exposure to mild traumatic brain injury (mTBI). This may have negative mental health consequences. The impact on positive mental health should also be considered. Predicting health and performance via intrapersonal characteristics, such as resilience, may enhance our knowledge in this area but there is no measurement gold standard. Additionally, military stress may negatively impact resilience. We described resilience using three valid and reliable psychometric assessments and compared Special Operations Forces (SOF) combat service members (SMs) who selected and assigned to SOF organizations (career start) or had been with their organization for several years (mid-career). We found SOF career stage differences in the most psychometrically sound resilience psychometric, the Ego Resiliency Scale (ER89) (t52 = -2.51, p = 0.04). This relationship was partially a function of total military service years. Post-hoc contrasts revealed that mid-career SOF combat SMs with low and moderate total military service tended to report lower ER89 scores than career start SMs (ts52 = -2.69 and -2.66, ps = 0.01), but ER89 scores between career stages were not significantly different with high total military service (t52 = -1.1, p = 0.27). Resilience and SOF career stage had significant interaction effects on subjective well-being (2(1) = 5.89, p = 0.02), anxiety (2(1) = 5.45, p = 0.02), and posttraumatic stress symptoms (2(1) = 6.03, p = 0.01). The expected associations between resilience and mental health symptoms were not seen in SOF mid-career SMs, preliminarily indicating resilience’s adaptive associations with mental health may be blunted in combat SMs having served multiple years in SOF or we are looking to early in the resilience process for complete mental health to be achieved. Future research should replicate these findings within SOF combat SMs to better understand when resilience and mental health decay may begin during SOF service.Doctor of Philosoph