Julia E. Slocomb

Comparison of retinal vasodilator and constrictor responses in type 2 diabetes

Purpose:  The retinal blood vessels provide a unique way to directly examine the human microvasculature, which is frequently damaged in individuals with diabetes. Previous studies have demonstrated that retinal flickering light‐induced vasodilation and hyperoxia‐induced vasoconstriction may operate by enhancing or reducing similar vasoregulatory factor(s), but a comparison between these two provocative stimuli in individuals with diabetes has not been studied. The purpose of the study was to examine the association between retinal flickering light‐induced vasodilation and retinal hyperoxia‐induced vasoconstriction in type 2 diabetic subjects and in healthy controls.

Impaired retinal vasodilator responses in prediabetes and type 2 diabetes

Purpose:  In diabetes, endothelial dysfunction and subsequent structural damage to blood vessels can lead to heart attacks, retinopathy and strokes. However, it is unclear whether prediabetic subjects exhibit microvascular dysfunction indicating early stages of arteriosclerosis and vascular risk. The purpose of this study was to examine whether retinal reactivity may be impaired early in the hyperglycaemic continuum and may be associated with markers of inflammation.

The Less BOLD, the Wiser: Support for the latent resource hypothesis after traumatic brain injury

Previous studies of the BOLD response in the injured brain have revealed neural recruitment relative to controls during working memory tasks in several brain regions, most consistently the right prefrontal cortex and anterior cingulate cortices. We previously proposed that the recruitment observed in this literature represents auxiliary support resources, and that recruitment of PFC is not abnormal or injury specific and should reduce as novelty and challenge decrease. The current study directly tests this hypothesis in the context of practice of a working memory task. It was hypothesized that individuals with brain injury would demonstrate recruitment of previously indicated regions, behavioral improvement following task practice, and a reduction in the BOLD signal in recruited regions after practice. Individuals with traumatic brain injury and healthy controls performed the n‐back during fMRI acquisition, practiced each task out of the scanner, and returned to the scanner for additional fMRI n‐back acquisition. Statistical parametric maps demonstrated a number of regions of recruitment in the 1‐back in individuals with brain injury and a number of corresponding regions of reduced activation in individuals with brain injury following practice in both the 1‐back and 2‐back. Regions of interest demonstrated reduced activation following practice, including the anterior cingulate and right prefrontal cortices. Individuals with brain injury demonstrated modest behavioral improvements following practice. These findings suggest that neural recruitment in brain injury does not represent reorganization but a natural extension of latent mechanisms that engage transiently and are contingent upon cerebral challenge. Hum Brain Mapp, 2012.

Dispositional optimism and outcome following traumatic brain injury

Objective: Despite vast literature examining the predictors of patient outcome following traumatic brain injury (TBI), the complicated relationship between personality and psychological, cognitive and functional outcomes remains poorly understood. The present study examined the relationship between the personality trait of dispositional optimism (DO) and outcome after moderate and severe TBI in the context of a proposed theoretical model. Methods: Forty-five individuals who had sustained moderate-to-severe TBI were recruited through mailings and completed the Symptom Checklist Questionnaire-90 Revised (SCL-90-R), the Telephone Interview for Cognitive Status (TICS), the Craig Handicap Assessment Reporting Technique (CHART) and the Life Orientation Test-Revised (LOT-R). Analyses were conducted to test a model predicting the relationship between personality and patient outcome after TBI. Results: DO was significantly correlated with psychological distress, but did not predict functional outcome. In addition, two significant mediating relationships were demonstrated: (1) psychological distress was shown to mediate the relationship between dispositional optimism and cognitive ability and (2) cognitive ability mediated the relationship between psychological distress and functional outcome. Conclusion: These findings illustrate that higher levels of DO in individuals sustaining moderate-to-severe TBI are related to better psychological functioning which in turn predicts improved cognitive and functional outcomes.

Impaired coronary and retinal vasomotor function to hyperoxia in Individuals with Type 2 diabetes.

PURPOSE Adults with diabetes are at a high risk of developing coronary heart disease. The purpose of this study was to assess coronary artery vascular function non-invasively in individuals with and without Type 2 diabetes and to compare these coronary responses to another microvascular bed (i.e. retina). We hypothesized that individuals with diabetes would have impaired coronary reactivity and that these impairments would be associated with impairments in retinal reactivity. METHODS Coronary blood velocity (Transthoracic Doppler Echocardiography) and retinal diameters (Dynamic Vessel Analyzer) were measured continuously during five minutes of breathing 100% oxygen (i.e. hyperoxia) in 15 persons with Type 2 diabetes and 15 age-matched control subjects. Using fundus photographs, retinal vascular calibers were also measured (central retinal arteriole and venule equivalents). RESULTS Individuals with diabetes compared to controls had impaired coronary (-2.34±16.64% vs. -14.27±10.58%, P=0.03) and retinal (arteriole: -0.04±3.34% vs. -3.65±5.07%, P=0.03; venule: -1.65±3.68% vs. -5.23±5.47%, P=0.05) vasoconstrictor responses to hyperoxia, and smaller central arteriole-venule equivalent ratios (0.83±0.07 vs. 0.90±0.07, P=0.014). Coronary reactivity was associated with central retinal arteriole equivalents (r=-0.516, P=0.005) and retinal venular reactivity (r=0.387, P=0.034). CONCLUSION Diabetes impairs coronary and retinal microvascular function to hyperoxia. Impaired vasoconstrictor responses may be part of a systemic diabetic vasculopathy, which may contribute to adverse cardiovascular events in individuals with diabetes.

Retinal vasoreactivity as a marker for chronic ischemic white matter disease

UNLABELLED The cerebral microvasculature cannot be easily studied non-invasively. Because the retina and brain share embryological, anatomical and physiological similarities, studies of retinal blood vessels may prove to be useful as a surrogate marker for cerebrovascular disease. In epidemiological studies abnormal retinal arteriovenous ratios (AVRs) predict the risk of stroke and vascular dementia. However, the association between retinal vasoreactivity, cerebral small vessel ischemic disease, and cerebral blood vessel function remains unknown. STUDY GOALS To examine (1) the association between cerebral ischemic white matter disease (WMD) and retinal microvessel behavior and (2) the relationship between retinal blood vessel reactivity and measures of cerebrovascular function. METHODS Cohort study of 12 patients with ischemic WMD and 14 healthy controls. Retinal vasoreactivity was measured following high frequency flicker light stimulation. Middle cerebral artery (MCA) vasoreactivity was measured using transcranial Doppler ultrasound (TCD). Magnetic resonance imaging scans (MRIs) were reviewed for evidence of ischemic WMD. RESULTS Patients with ischemic WMD had attenuated retinal venous (2.2% ± 0.27 SD, vs. controls 6% ± 0.7 SD, p=0.002, CI 95%) and arterial (1.9% ± 0.8 SD, vs. controls 4.9% ± 0.8 SD, p=0.004, CI 95%) vasoreactivity compared to controls. An attenuated retinal venous light flicker response was associated with a significant decrease of MCA vasoreactivity (r=0.45, p=0.05, CI 95%). Decreased AVRs, an indicator for altered retinal vessel architecture in patients with cerebral chronic ischemic WMD, were also significantly correlated with dysfunction of cerebral vasoreactivity (r=0.69, p=0.001, CI 95%). CONCLUSION In this study functional and structural impairment of the retinal microvasculature were associated with ischemic WMD and measures of cerebral vascular function. Microvascular dysfunction in the eye may predict cerebral small vessel disease, but validation by larger studies is needed.

Modeling distinct imaging hemodynamics early after TBI: the relationship between signal amplitude and connectivity

Over the past decade, fMRI studies of cognitive change following traumatic brain injury (TBI) have investigated blood oxygen level dependent (BOLD) activity during working memory (WM) performance in individuals in early and chronic phases of recovery. Recently, BOLD fMRI work has largely shifted to focus on WM and resting functional connectivity following TBI. However, fundamental questions in WM remain. Specifically, the effects of injury on the basic relationships between local and interregional functional neuroimaging signals during WM processing early following moderate to severe TBI have not been examined. This study employs a mixed effects model to examine prefrontal cortex and parietal lobe signal change during a WM task, the n-back, and whether there is covariance between regions of high amplitude signal change, (synchrony of elicited activity (SEA) very early following TBI. We also examined whether signal change and SEA differentially predict performance during WM. Overall, percent signal change in the right prefrontal cortex (rPFC) was and important predictor of both reaction time (RT) and SEA in early TBI and matched controls. Right prefrontal cortex (rPFC) percent signal change positively predicted SEA within and between persons regardless of injury status, suggesting that the link between these neurodynamic processes in WM-activated regions remains unaffected even very early after TBI. Additionally, rPFC activity was positively related to RT within and between persons in both groups. Right parietal (rPAR) activity was negatively related to RT within subjects in both groups. Thus, the local signal intensity of the rPFC in TBI appears to be a critical property of network functioning and performance in WM processing and may be a precursor to recruitment observed in chronic samples. The present results suggest that as much research moves toward large scale functional connectivity modeling, it will be essential to develop integrated models of how local and distant neurodynamics promote WM performance after TBI.

Impaired Retinal Vasoreactivity: An Early Marker of Stroke Risk in Diabetes

Diabetes is a common cause of small vessel disease leading to stroke and vascular dementia. While the function and structure of large cerebral vessels can be easily studied, the brains microvasculature remains difficult to assess. Previous studies have demonstrated that structural changes in the retinal vessel architecture predict stroke risk, but these changes occur at late disease stages. Our goal was to examine whether retinal vascular status can predict cerebral small vessel dysfunction during early stages of diabetes. Retinal vasoreactivity and cerebral vascular function were measured in 78 subjects (19 healthy controls, 22 subjects with prediabetes, and 37 with type‐2 diabetes) using a new noninvasive retinal imaging device (Dynamic Vessel Analyzer) and transcranial Doppler studies, respectively. Cerebral blood vessel responsiveness worsened with disease progression of diabetes. Similarly, retinal vascular reactivity was significantly attenuated in subjects with prediabetes and diabetes compared to healthy controls. Subjects with prediabetes and diabetes with impaired cerebral vasoreactivity showed mainly attenuation of the retinal venous flicker response. This is the first study to explore the relationship between retinal and cerebral vascular function in diabetes. Impairment of venous retinal responsiveness may be one of the earliest markers of vascular dysfunction in diabetes possibly indicating subsequent risk of stroke and vascular dementia.