Amy Elizabeth Ramage

Loss of cerebral white matter structural integrity tracks the gray matter metabolic decline in normal aging

Relationships between structural MRI-based markers of declining cerebral integrity, and regional PET measurements of (18)FDG uptake have not been studied well in normal aging. In this manuscript we relate changes in cerebral morphology to regional cerebral glucose uptake for 14 major cortical areas in 19 healthy older individuals (age 59-92 years). Measurements of cerebral integrity included gray matter (GM) thickness, sulcal and intergyral spans, fractional anisotropy (FA) of water diffusion and volume of hyperintense WM (HWM) lesions. (18)FDG-PET measurements were converted to standard uptake values and corrected for partial volume artifact. Following this, cortical FDG uptake was significantly correlated with several indices of WM integrity that we previously observed to be sensitive to cognitive decline in executive function, including intergyral span and HWM volumes. Our findings suggest that the age-related decline in white matter integrity, observed as increases in HWM lesions, intergyral spans and reduction in FA, correlated with a decline in the global and regional cerebral glucose uptake. Our findings support the emerging consensus that WM integrity indices are sensitive predictors of declining cerebral health in normal aging. Specifically, age-related WM degradation in the thinly myelinated association tracts appears to track the decreases in global and regional rates of glucose uptake.

Neuroimaging evidence of white matter inflammation in newly diagnosed Systemic Lupus Erythematosus

OBJECTIVE Central nervous system (CNS) involvement occurs frequently in systemic lupus erythematosus (SLE) and frequently results in morbidity. The primary pathophysiology of CNS involvement in SLE is thought to be inflammation secondary to autoantibody-mediated vasculitis. Neuroimaging studies have shown hypometabolism (representing impending cell failure) and atrophy (representing late-stage pathology), but not inflammation. The purpose of this study was to detect the presence and regional distribution of inflammation (hypermetabolism) and tissue failure, apoptosis, or atrophy (hypometabolism). METHODS Eighty-five patients with newly diagnosed SLE, who had no focal neurologic symptoms, were studied. Disease activity was quantified using the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI), a validated index of SLE-related disease activity. 18Fluorodeoxyglucose (FDG) positron emission tomography (PET) images of glucose uptake were analyzed by visual inspection and as group statistical parametric images, using the SELENA-SLEDAI score as the analysis regressor. RESULTS SELENA-SLEDAI-correlated increases in glucose uptake were found throughout the white matter, most markedly in heavily myelinated tracts. SELENA-SLEDAI-correlated decreases were found in the frontal and parietal cortex, in a pattern similar to that seen during visual inspection and presented in previous reports of hypometabolism. CONCLUSION The SELENA-SLEDAI-correlated increases in glucose consumption are potential evidence of inflammation, consistent with prior reports of hypermetabolism in inflammatory disorders. To our knowledge, this is the first imaging-based evidence of SLE-induced CNS inflammation in an SLE inception cohort. The dissociation among 18FDG uptake characteristics, spatial distribution, and disease activity correlation is in accordance with the notion that glucose hypermetabolism and hypometabolism reflect fundamentally different aspects of the pathophysiology of SLE with CNS involvement.

Frequency of perseveration in normal subjects.

Although perseveration is a recognized sign of disturbed brain function, it also occurs in normal individuals. Determination of the frequency of perseveration in normal subjects would enable clinicians to use perseveration as a marker of possible pathology. The purpose of this study was to document the extent of perseveration in normal young and older subjects. Thirty young normal individuals between the ages of 20 and 35 years and 30 older normal individuals between the ages of 60 and 75 years were given four tasks on which perseveration has been reported in brain-damaged individuals. Four percent of all responses were perseverative. No age or gender effects on frequency were observed. Of the four neuropsychological tasks, the Modified Wisconsin Card Sorting Test elicited the greatest number of perseverations.

A coordinate-based meta-analytic model of trauma processing in posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) has a well‐defined set of symptoms that can be elicited during traumatic imagery tasks. For this reason, trauma imagery tasks are often employed in functional neuroimaging studies. Here, coordinate‐based meta‐analysis (CBM) was used to pool eight studies applying traumatic imagery tasks to identify sites of task‐induced activation in 170 PTSD patients and 104 healthy controls. In this way, right anterior cingulate (ACC), right posterior cingulate (PCC), and left precuneus (Pcun) were identified as regions uniquely active in PTSD patients relative to healthy controls. To further characterize these regions, their normal interactions, and their typical functional roles, meta‐analytic connectivity modeling (MACM) with behavioral filtering was applied. MACM indicated that the PCC and Pcun regions were frequently co‐active and associated with processing of cognitive information, particularly in explicit memory tasks. Emotional processing was particularly associated with co‐activity of the ACC and PCC, as mediated by the thalamus. By narrowing the regions of interest to those commonly active across multiple studies (using CBM) and developing a priori hypotheses about directed probabilistic dependencies amongst these regions, this proposed model—when applied in the context of graphical and causal modeling—should improve model fit and thereby increase statistical power for detecting differences between subject groups and between treatments in neuroimaging studies of PTSD. Hum Brain Mapp 34:3392–3399, 2013.

Perseverative behaviour in fluent and non-fluent aphasic adults

Perseveration by type (recurrent, continuous, or stuck-in-set) was examined for 30 stroke patients, 20 of whom exhibited fluent aphasia, and 10 with non-fluent aphasia. Comparisons were made between the two aphasic subject groups on two verbal and two non-verbal tasks. Twenty-eight of the patients (93%) produced at least one instance of perseveration. The most commonly occurring type was recurrent perseveration. Instances of continuous perseveration also were common and were produced by 18 patients. Stuck-in-set perseveration was uncommon with only two patients exhibiting this form of perseveration. No differences were observed in the frequency of perseveration across the four tasks between fluent and non-fluent aphasic patients. Perseveration was significantly correlated with aphasia severity, but not with time post-onset.

Central sensitization as a component of post-deployment syndrome

Many service members and veterans report chronic unexplained symptoms such as pain, fatigue and memory complaints, which have most recently been characterized as post-deployment syndrome (PDS). Chronic widespread pain is a component of this syndrome, producing significant disability and considerable health care costs. The similarity between the nature of these complaints and other medically unexplained illnesses such as fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome suggest that they may share a common mechanism. Here, we provide support for PDS as a consequence of pain and sensory amplification secondary to neuroplastic changes within the central nervous system, a phenomenon often termed central sensitization. We also discuss how factors such as stress and genetics may promote chronic widespread pain in veterans and service members who develop PDS.

Regional cerebral glucose metabolism differentiates danger- and non-danger-based traumas in post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is presumably the result of life threats and conditioned fear. However, the neurobiology of fear fails to explain the impact of traumas that do not entail threats. Neuronal function, assessed as glucose metabolism with (18)fluoro-deoxyglucose positron emission tomography, was contrasted in active duty, treatment-seeking US Army Soldiers with PTSD endorsing either danger- (n = 19) or non-danger-based (n = 26) traumas, and was compared with soldiers without PTSD (Combat Controls, n = 26) and Civilian Controls (n = 24). Prior meta-analyses of regions associated with fear or trauma script imagery in PTSD were used to compare glucose metabolism across groups. Danger-based traumas were associated with higher metabolism in the right amygdala than the control groups, while non-danger-based traumas associated with heightened precuneus metabolism relative to the danger group. In the danger group, PTSD severity was associated with higher metabolism in precuneus and dorsal anterior cingulate and lower metabolism in left amygdala (R(2 )= 0.61). In the non-danger group, PTSD symptom severity was associated with higher precuneus metabolism and lower right amygdala metabolism (R(2 )= 0.64). These findings suggest a biological basis to consider subtyping PTSD according to the nature of the traumatic context.

Drawing from experience: The development of alternative communication strategies

Abstract We present a case report of a right-handed man who experienced a left hemisphere stroke and the onset of severe, persistent aphasia at age 52. This man is of interest because of his remarkable use of drawing for communication that was initiated at two years post-onset of aphasia. We provide an overview of his course of treatment from one to 5 years postonset and describe the development of his effective multimodal approach to communication.

Thinking outside the (Black) box

the fruitless search for the flight recorders from the Air France Airbus A330 that crashed into the Atlantic Ocean on June 1 has stirred new interest in the development of alternate methods of delivering vital black box data to accident investigators.1 One alternative — the deployable flight incident recorder — has been in use for decades on military aircraft; the future of a second alternative — transmission of flight data to a ground station — is intertwined with technological advances that are improving computer data transmission between air and ground. “Both ideas have advantages and disadvantages that must be carefully evaluated,” said Sandy Angers, a spokeswoman for Boeing Commercial Airplanes. In almost all crashes, the flight data recorder (FDR) and cockpit voice recorder (CVR) are recovered without much difficulty. But on some occasions, as in the case of the Air France A330 and a Yemenia Airways A310 that crashed in the Indian Ocean on June 30, 2009,2 the search has gone on for weeks or months — continuing even after the end of the 30-day period in which underwater locator beacons, or “pingers,” transmit signals to alert searchers to the location of the boxes. Historically, most accidents in which flight recorders have been pronounced “not recoverable” have not been in water but rather in “unusually inhospitable terrain, such as mountaintops,” Angers said. Years ago, recorders sometimes were so badly damaged by post-impact fire or by water that some of their information was irretrievable. In recent years, however, as solid-state digital media have replaced tapes, this has happened less frequently, said James Cash, the U.S. National Transportation Safety Board’s (NTSB’s) chief technical adviser for recorders. “If anything, it’s fire that did the recorders in,” Cash said. “We’ve never lost one because of impact damage, but ... older, tape-based units were more easily damaged by fire.”