To determine the association between blood markers of white matter injury (e.g., serum neurofilament light and phosphorylated neurofilament heavy) and a novel neuroimaging technique measuring microstructural white matter changes (e.g., diffusion kurtosis imaging) in regions (e.g., anterior thalamic radiation and uncinate fasciculus) known to be impacted in traumatic brain injury (TBI) and associated with symptoms common in those with chronic TBI (e.g., sleep disruption, cognitive and emotional disinhibition) in a heterogeneous sample of Veterans and non-Veterans with a history of remote TBI (i.e., >6 months).

Participants with complete imaging and blood data (N=24) were sampled from a larger multisite study of chronic mild-moderate TBI. Participants ranged in age from young to middle-aged (mean age = 34.17, SD age = 10.96, range = 19-58) and primarily male (66.7%). The number of distinct TBIs ranged from 1-5 and the time since most recent TBI ranged from 0-30 years. Scores on a cognitive screener (MoCA) ranged from 22-30 (mean = 26.75). We performed bivariate correlations with mean kurtosis (MK) in the anterior thalamic radiation (ATR; left, right) uncinate fasciculus (UF; left, right), and serum neurofilament light (NFL), and phosphorylated neurofilament heavy (pNFH). Both were log transformed for non-normality. Significance threshold was set at p<0.05.

pNFH was significantly and negatively correlated to MK in the right (r=-0.446) and left (r=-0.599) UF and right (r=-0.531) and left (r=-0.469) ATR. NFL showed moderate associations with MK in the right (r=-0.345) and left (r=-0.361) UF and little to small association in the right (r=-0.063) and left (r=-0.215) ATR. In post-hoc analyses, MK in both the left (r=0.434) and right (r=0.514) UF was positively associated with performance on a frontally-mediated list-learning task (California Verbal Learning Test, 2nd Edition; Trials 1-5 total).

Results suggest that serum pNFH may be a more sensitive blood marker of microstructural complexity in white matter regions frequently impacted by TBI in a chronic mild-moderate TBI sample. Further, it suggests that even years after a mild-moderate TBI, levels of pNFH may be informative regarding white matter integrity in regions related to executive functioning and emotional disinhibition, both of which are common presenting problems when these patients are seen in a clinical setting.

Transcutaneous vagus nerve stimulation (tVNS) is a promising potential intervention for Alzheimer's disease (AD) due to its influence on brain functions and mechanisms important in disease progression. Regions of interest include projection to the nucleus of the solitary tract, locus coeruleus, and hippocampus. Deterioration of the hippocampus is one of the most prominent early characteristics of AD, particularly during the mild cognitive impairment (MCI) stage. tVNS could modify function of the hippocampus. We examined resting state functional connectivity from the bilateral hippocampus in response to tVNS in patients with MCI.

Fifty older adults (28 women, 60-89 years of age) diagnosed with MCI were assessed. MCI was confirmed via diagnostic consensus conference with a neurologist and neuropsychologist (sources of information: Montreal Cognitive Assessment Test [MoCA], Clinical Dementia Rating scale [CDR], Functional Activities Questionnaire (FAQ), Hopkins Verbal Learning Test - Revised [HVLT-R] and medical record review). Resting state functional magnetic resonance imaging (fMRI) was collected on a 3T Siemens Prisma scanner while participants received either unilateral tVNS (left tragus, n = 25) or sham stimulation (left ear lobe, n = 25). fMRI data were processed using CONN toolbox v18b and hippocampal seed to voxel (whole brain) analyses were conducted with voxel and cluster level multiple comparison correction.

Contrasting tVNS and sham stimulation, whole-brain seed-to-voxel analysis demonstrated significant changes in connectivity from the left hippocampus to several cortical and subcortical regions bilaterally. Specifically, there was increased connectivity to prefrontal regions and cingulate gyri, and decreased connectivity to anterior and medial temporal lobes. A seed-to-voxel analysis from the right hippocampus indicated significant decrease in connectivity to a single cluster of regions in the left anterior temporal lobe in response to tVNS.

In conclusion, tVNS modified connectivity from the hippocampus to multiple brain regions implicated in semantic and salience functions, in which disruption correlates with deterioration in AD. These findings indicate afferent target engagement of tVNS. Future work is needed to investigate the long-term effects of tVNS in patients with MCI and whether it could contribute to meaningful cognitive change and subsequent improvements in quality of life.

In December 2019, the first reports came from China about cases of pneumonia caused by a previously unknown coronavirus, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), responsible for a disease called COVID-19. Since then, the pandemic has spread worldwide, affecting people’s physical and mental health and as well as quality of life. Currently, many people are experiencing the health consequences of contracting COVID-19, also due to the impact this disease has on the central nervous system. As a result, in addition to well-known ailments, such as headaches, chronic fatigue or smell and taste disorders, COVID-19 survivors may develop neuropsychological problems such as executive-attentional deficits. However, the specificity of these executive-attentional problems has not been determined. Thus, the purpose of this study was to learn if survivors of COVID-19 may present with more generalized or rather specific dysfunction(s) of the anterior attentional-executive system.

The study group consisted of 37 individuals who underwent COVID-19 (age M=44, education M=17). The comparison group consisted of 25 matched controls tested before the COVID-19 pandemia. The experimental procedures included (1) a clinical interview, (2) an assessment of selected cognitive functions (3) and attentionalexecutive functioning, which was assessed using the ROtman-Baycrest Battery to Investigate Attention (ROBBIA); a battery was designed to measure three attentional processes (i.e., energizing, task setting, and monitoring). Overall, four reaction time (RT) subtests from ROBBIA were administered: (1) Simple RT, (2) Choice RT, (3), Prepare RT, and (4) Concentrate. For each subtest, the instruction was to press an appropriate button on a response pad as quickly as possible when a target stimulus (one of the following capital letters: A, B, C, or D) is detected, but also (in Choice RT, Prepare RT and Concentrate) to make as few errors as possible.

Overall, the analyses revealed that individuals who survived COVID-19 exhibited a different effect of the warning stimulus compared to controls. Specifically, COVID19 survivors presented an increase in reaction time from 1s warning condition to 3s warning condition being significantly greater than the control group’s increase (p < .05). Also, only in the COVID-19 group, reaction time in the Concentrate task tended to be longer (p = 0.01). No group differences in monitoring (e.g., number of errors) or task setting emerged.

The patients’ problems appear analogous to those observed in other chronic somatic diseases, likely due to the impact of COVID-19 on the frontal lobe’s medial regions. However, due to a small sample size, future neuroimaging research, including computerized studies of attentional-execution networks, is needed to confirm that COVID-19 may predominantly affect the energization system that contributes to these patient’s cognitive slowing and defective ability to sustain attention.

Obesity is associated with adverse effects on brain health, including increased risk for neurodegenerative diseases. Changes in cerebral metabolism may underlie or precede structural and functional brain changes. While bariatric surgery is known to be effective in inducing weight loss and improving obesity-related medical comorbidities, few studies have examined whether it may be able to improve brain metabolism. In the present study, we examined change in cerebral metabolite concentrations in participants with obesity who underwent bariatric surgery.

35 patients with obesity (BMI > 35 kg/m2) were recruited from a bariatric surgery candidate nutrition class. They completed single voxel 1H-proton magnetic resonance spectroscopy at baseline (pre-surgery) and within one year post-surgery. Spectra were obtained from a large medial frontal brain region. Tissue-corrected absolute concentrations for metabolites including choline-containing compounds (Cho), myo-inositol (mI), N-acetylaspartate (NAA), creatine (Cr), and glutamate and glutamine (Glx) were determined using Osprey. Paired t-tests were used to examine within-subject change in metabolite concentrations, and correlations were used to relate these changes to other health-related outcomes, including weight loss and glycemic control.

Bariatric surgery was associated with a reduction in cerebral Cho (f[34j = -3.79, p < 0.001, d = -0.64) and mI (f[34] = -2.81, p < 0.01, d = -0.47) concentrations. There were no significant changes in NAA, Glx, or Cr concentrations. Reductions in Cho were associated with greater weight loss (r = 0.40, p < 0.05), and reductions in mI were associated with greater reductions in HbA1c (r = 0.44, p < 0.05).

Participants who underwent bariatric surgery exhibited reductions in cerebral Cho and mI concentrations, which were associated with improvements in weight loss and glycemic control. Given that elevated levels of Cho and mI have been implicated in neuroinflammation, reduction in these metabolites after bariatric surgery may reflect amelioration of obesity-related neuroinflammatory processes. As such, our results provide evidence that bariatric surgery may improve brain health and metabolism in individuals with obesity.

To determine the association between in-vivo spectroscopy metabolite data, the local connectome, and markers of initial injury severity (I.e., history of loss of consciousness; LoC) in traumatic brain injury (TBI), in a heterogenous sample of Veterans and non-Veterans with a history of remote mild-to-moderate TBI (I.e., >6 months).

Participants with complete PRESS magnetic resonance spectroscopy (MRS) and diffusion weighted imaging (DWI) data (N = 41) were sampled from a larger multisite study of chronic mild-to-moderate TBI (Nmiid = 38; Nmoderate = 3; 54% with LoC; 46% with multiple TBI). The sample was predominantly male (76%) with ages ranging from 23-59 (M = 36.9, SD = 10.1), with 98% holding at least a high school degree (M = 14.5 years of education, SD = 2.4). Fully tissue-and-relaxation-corrected metabolite concentration estimates in the dorsal anterior cingulate (30x30x30mm voxel) were modeled using Osprey 2.4.0. Total creatine (tCr), total choline (tCho), total N-acetylaspartate (tNAA), glutamate/glutamine (Glx), and myo-inositol (mI) were analyzed. Logistic regression was used to measure the association between metabolites and history of TBI with LoC. Correlational connectometry using the normalized spin distribution function was performed for metabolites associated with LoC, to characterize the local connectome associated with metabolites of interest, controlling for age and sex, and correcting for multiple comparisons (FDR < .050 with 4000 permutations). A profile approach was used to interpret diffusion metrics, contrasting quantitative anisotropy (QA) with fractional anisotropy (FA). Local connectome tracks were then clustered to identify the larger white matter tract.

Glx (p = .008) and tCr (p = .032) were significantly associated with history of TBI with LoC. Increased Glx was associated with increased QA in 11,001 tracks, accounting for 1.4% of the total white matter tracks in the brain. 90% of tracks were identified in bilateral cingulum (33%), bilateral thalamic (13%), bilateral corticospinal (13%), corpus callosum (12%), left arcuate fasciculus (9%), left frontoparietal aslant tracts (6%), and bilateral inferior fronto-occipital fasciculus (4%) tracts. In contrast, FA was not associated with Glx. The same pattern emerged for tCr, with 10,542 tracks identified predominantly in bilateral cingulum (29%), corpus callosum (21%), bilateral corticospinal (15%), bilateral corticostriatal (7%), bilateral medial lemniscus (7%), left cortico-pontine (3%), left thalamic (2%), and bilateral superior longitudinal fasciculus (2%) tracts. Post-hoc exploratory analyses of mean QA across regions of cingulum found that increased QA was associated with self-report measures of headache intensity, fatigue, and perceived change in executive functioning.

Results provided evidence that multimodal imaging can identify subtle markers of initial TBI severity years after injury. Neurometabolite concentrations were associated with diffuse changes in the local connectome; the pattern of discrepancy between FA and QA was suggestive of reduced potential for neuroplasticity. Exploratory analyses further indicated that variability in white matter density in the cingulum, an important connection for limbic regions, was associated with a range of problems commonly reported in clinical settings, which may be informative for diagnosis and treatment planning.

Determine associations between cognitive outcomes in remote TBI (i.e., at least 6 months post injury), a blood marker of neural degeneration (i.e., Tau), and diffusion kurtosis imaging (DKI) measures (e.g., mean or radial kurtosis). Because DKI imaging is sensitive to the environmental complexity of the imaged area, we sought to investigate regions known to be associated with the cognitive and emotional sequalae of TBI, such as the anterior thalamic radiations, uncinate fasciculus, and the corpus callosum.

41 individuals with mild-to-moderate TBI and a mean age(SD) of 36.1(10.4) years underwent DKI, a blood draw, and neuropsychological assessments. 23 healthy controls (HC) with a mean age(SD) of 35.2(15.2) years underwent the blood draw and assessments, but no imaging. Higher diffusion kurtosis indicates more restricted diffusion, possibly due to greater complexity within the imaged region. Thus, in the context of TBI, DKI can be used as a proxy measurement for biological processes that alter the complexity of imaged environments, such as reactive gliosis. Some people show cognitive deficits long after TBI and this could be associated with increased inflammation and membrane protein aggregates in damaged brain regions. We used bivariate correlations and general linear models to investigate the association of mean kurtosis (MK) in long white matter tracts and Tau (total or phosphorylated) to color-word Stroop scores; a measure of fronto-subcortical function.

In patients with TBI, MK was significantly associated with serum total Tau (TTau) in the right (r=-0.396) and left (r=-0.555) uncinate fasciculus (UF), right (r=-0.402) and left (r=-0.504) anterior thalamic radiations (ATR), and the genu (r=-0.526) and body (r=-0.404) of the corpus callosum (CC). TTau had a significant association with word Stroop scores, F(1,63)=-2.546, p=0.013. However, there was no significant effect of group (i.e., TBI or HC), F(2,63)=-0.426, p=0.672, on cognitive performance. When models were implemented that included both TTau and MK in either the UF or ATR as explanatory variables to predict word Stroop scores, TTau levels and MK in the right UF explained a significant amount of the variance in Stroop performance, F(1,29)=2.215, p=0.025. Further, there was also a significant association between radial kurtosis in the right UF and Stroop word scores (r= 0.366).

Our results show that an indicator of biological complexity (DKI) in cognitively important brain regions is associated with cognitive performance and Tau in patients with remote mild-to-moderate TBI. The UF is a critical fronto-temporal/subcortical pathway that has previously been implicated in the manifestation of executive dysfunction and mood dysregulation in TBI. Tau is an important marker of neurodegeneration implicated in Alzheimer’s disease, Parkinson’s disease, and chronic traumatic encephalopathy (CTE), and DKI is potentially sensitive to markers of neurodegeneration. The association of Tau and DKI measures is novel and shows concordance between blood and brain imaging markers and cognitive performance in patients with mild to moderate TBI.

The prism adaptation (PA) with rightward shifting lenses is a promising rehabilitation technique for left hemispatial neglect. The PA has also been applied in healthy individuals to investigate cognitive mechanism(s) underlining such adaptation. Importantly, studies have suggested that PA may primarily impact the functions of the dorsal or the ventral attentional stream, and we have previously reported that PA to the upward and downward shifting lenses leads to a significant aftereffect in vertical line bisection task. However, this post-adaptation effect, similarly to that seen in the horizontal plane, might have been modified by the presence of the vertical pseudoneglect healthy participants often experience prior to PA. Thus, the aim of this study was to test this hypothesis.

30 right-handed healthy adults (age M=22,4) performed a computerized line bisection (LB) in vertical and horizontal condition. The bisections were performed twice: before and after PA procedure. Participants took experimental procedure three times, each in at least 24 h of break, each time in one of three conditions of shifting lenses; down, up, control. Both LB tasks (vertical and horizontal) consisted of 24 lines, each centered on 23" touch screen. The participants were asked to find the middle of the line. Throughout the experiment, participants were comfortably seated with their head positioned on a chinrest. Participants were fitted with prismatic goggles that deviated their visual field by 10 degrees. For the adaptation we used the Peg-the-mole procedure consisting of 120 pointing movements.

To assess the effect of the vertical PA on landmark judgments we performed a repeated measures ANOVA with direction of PA (upward/downward), the condition of LB (vertical/ horizontal) and pre- vs post adaptation as a between-subjects factor. This analysis revealed a main effect of the direction of PA (p< 0.001) and a main effect of condition (p< 0.001). Overall, however, only adaptation in up-shifting lenses led to significant aftereffects (p<0.05). Further, when we excluded participants who did not exhibited horizontal pseudoneglect in preadaptation LB, the effect of PA in downshifting PA emerged in vertical LB (p<0.05). Further, this group also exhibited the aftereffect of PA in up-shifting lenses for the horizontal (p<0.01) and the vertical LB (p<0.05). Additionally, these participants exhibited a congruent tendency after upward and downward PA, and tended to allocate their attention more upward and rightward.

The results of this study confirm that the vertical PA evokes a visuo-spatial bias. Moreover, the PA aftereffect seems to be modified by the presence of the pre-adaptation pseudoneglect. Whereas the mechanism inducing this bias is not fully known, it might be explained in light of the interhemispheric activation-inhibition balance. Both the upward and downward PA may primarily lead to activation of the posterior regions of the right hemisphere, and this activation may result with the upward and rightward bias in the LB task. However, future research with neuroimaging techniques is needed to test this hypothesis.

Among patients with a history of ESBL infection, uncertainty remains regarding whether all of these patients require ESBL-targeted therapy when presenting with a subsequent infection. We sought to determine the risks associated with a subsequent ESBL infection to help inform empiric antibiotic decisions.

A retrospective cohort study of adult patients with positive index culture for Escherichia coli or Klebsiella pneumoniae (EC/KP) receiving medical care during 2017 was conducted. Risk assessments were performed to identify factors associated with subsequent infection caused by ESBL-producing EC/KP.

In total, 200 patients were included in the cohort, 100 with ESBL-producing EC/KP and 100 with ESBL-negative EC/KP. Of 100 patients (50%) who developed a subsequent infection, 22 infections were ESBL-producing EC/KP, 43 were other bacteria, and 35 had no or negative cultures. Subsequent infection caused by ESBL-producing EC/KP only occurred when the index culture was also ESBL-producing (22 vs 0). Among those with ESBL-producing index culture, the incidences of subsequent infection caused by ESBL-producing EC/KP versus other bacterial subsequent infection were similar (22 vs 18; P = .428). Factors associated with subsequent infection caused by ESBL-producing EC/KP include history of ESBL-producing index culture, time ≤180 days between index culture and subsequent infection, male sex, and Charlson comorbidity index score >3.

History of ESBL-producing EC/KP culture is associated with subsequent infection caused by ESBL-producing EC/KP, particularly within 180 days after the historical culture. Among patients presenting with infection and a history of ESBL-producing EC/KP, other factors should be considered in making empiric antibiotic decisions, and ESBL-targeted therapy may not always be warranted.