Martin Goldstein

Neural substrates of the interaction of emotional stimulus processing and motor inhibitory control: An emotional linguistic go/no-go fMRI study

Neural substrates of behavioral inhibitory control have been probed in a variety of animal model, physiologic, behavioral, and imaging studies, many emphasizing the role of prefrontal circuits. Likewise, the neurocircuitry of emotion has been investigated from a variety of perspectives. Recently, neural mechanisms mediating the interaction of emotion and behavioral regulation have become the focus of intense study. To further define neurocircuitry specifically underlying the interaction between emotional processing and response inhibition, we developed an emotional linguistic go/no-go fMRI paradigm with a factorial block design which joins explicit inhibitory task demand (i.e., go or no-go) with task-unrelated incidental emotional stimulus valence manipulation, to probe the modulation of the former by the latter. In this study of normal subjects focusing on negative emotional processing, we hypothesized activity changes in specific frontal neocortical and limbic regions reflecting modulation of response inhibition by negative stimulus processing. We observed common fronto-limbic activations (including orbitofrontal cortical and amygdalar components) associated with the interaction of emotional stimulus processing and response suppression. Further, we found a distributed cortico-limbic network to be a candidate neural substrate for the interaction of negative valence-specific processing and inhibitory task demand. These findings have implications for elucidating neural mechanisms of emotional modulation of behavioral control, with relevance to a variety of neuropsychiatric disease states marked by behavioral dysregulation within the context of negative emotional processing.

Diurnal cortisol amplitude and fronto-limbic activity in response to stressful stimuli

The development and exacerbation of many psychiatric and neurologic conditions are associated with dysregulation of the hypothalamic pituitary adrenal (HPA) axis as measured by aberrant levels of cortisol secretion. Here we report on the relationship between the amplitude of diurnal cortisol secretion, measured across 3 typical days in 18 healthy individuals, and blood oxygen level dependant (BOLD) response in limbic fear/stress circuits, elicited by in-scanner presentation of emotionally negative stimuli, specifically, images of the World Trade Center (WTC) attack. Results indicate that subjects who secrete a greater amplitude of cortisol diurnally demonstrate less brain activation in limbic regions, including the amygdala and hippocampus/parahippocampus, and hypothalamus during exposure to traumatic WTC-related images. Such initial findings can begin to link our understanding, in humans, of the relationship between the diurnal amplitude of a hormone integral to the stress response, and those neuroanatomical regions that are implicated as both modulating and being modulated by that response.

Frontolimbic function and cortisol reactivity in response to emotional stimuli

Frontolimbic structures involved in fear conditioning have also been associated with hypothalamic–pituitary–adrenal (HPA)-axis modulation, including amygdaloid, hippocampal, and ventromedial prefrontal cortex regions. Although HPA-axis function and endocrine changes have been investigated in the context of stress provocation, much research has not been conducted using functional neuroimaging in the study of the HPA axis and frontolimbic function in response to emotional stimuli. Using functional magnetic resonance imaging, the association of blood-oxygen-level dependent signal with salivary cortisol in response to an emotional visual scene paradigm was investigated, with prescan and postscan salivary cortisol analyzed as a covariate of interest during specific conditions. Cortisol reactivity to the paradigm was positively associated with amygdalar and hippocampal activity and negatively associated with ventromedial prefrontal cortex activity in conditions involving emotional imagery.

Caution warranted in extrapolating from Boston Naming Test item gradation construct

ABSTRACT The Boston Naming Test (BNT) was designed to present items in order of difficulty based on word frequency. Changes in word frequencies over time, however, would frustrate extrapolation in clinical and research settings based on the theoretical construct because performance on the BNT might reflect changes in ecological frequency of the test items, rather than performance across items of increasing difficulty. This study identifies the ecological frequency of BNT items at the time of publication using the American Heritage Word Frequency Book and determines changes in frequency over time based on the frequency distribution of BNT items across a current corpus, the Corpus of Contemporary American English. Findings reveal an uneven distribution of BNT items across 2 corpora and instances of negligible differentiation in relative word frequency across test items. As BNT items are not presented in order from least to most frequent, clinicians and researchers should exercise caution in relying on the BNT as presenting items in increasing order of difficulty. A method is proposed for distributing confrontation-naming items to be explicitly measured against test items that are normally distributed across the corpus of a given language.

Florbetapir F18 PET identification of beta-amyloid in the living brain: A consecutive clinical case series

P2-082 FLORBETAPIR F18 PET IDENTIFICATION OF BETA-AMYLOID IN THE LIVING BRAIN: A CONSECUTIVE CLINICAL CASE SERIES Effie Mitsis, Heidi Bender, Lale Kostakoglu, Josef Machac, Jane Martin, Jennifer Woehr, Martin Goldstein, Mary Sano, SamGandy, Mount Sinai School of Medicine, New York, New York, United States; Mt. Sinai School of Medicine, New York, New York, United States; Mount Sinai Medical Center, New York, New York, United States; Icahn School of Medicine at Mount Sinai, New York, New York, United States; Mount Sinai School of Medicine & James J Peters VAMC, New York, New York, United States; Icahn School of Medicine at Mount Sinai, New York City, New York, United States. Contact e-mail: effie.mitsis@mssm.edu

Florbetapir scanning excludes Alzheimer's disease in a retired NFL player with delayed cognitive impairment

OBJECTIVE: We sought to determine whether [18F] Florbetapir PET imaging would clarify diagnosis in an aging NFL player with cognitive decline.BACKGROUND: Single severe traumatic brain injury (TBI) is believed to increase risk for Alzheimer’s disease (AD), while chronic repetitive TBI in boxers is believed to increase the risk for tangle-only disease, or tauopathy, known as dementia pugilistica (DP). DP-like pathology has been observed in retired NFL players and in military veterans exposed to blast where the term chronic traumatic encephalopathy (CTE) is applied. The clinical distinction of AD from other causes of what we term “delayed post-traumatic cognitive impairment (DPTCI)” is challenging, but accurate diagnosis is required to avoid including subjects without cerebral amyloidosis in trials of Aβ-reducing agents. DESIGN/METHODS: A retired NFL player was evaluated for progressive cognitive impairment. During his 10-year professional career in the 1960s-1970s, the patient reported experiencing multiple concussions. By twelve hours post-game, he was at times unable to name which team he had just played against. Neuropsychological testing revealed impaired information processing speed, impaired verbal comprehension, and impaired immediate and delayed recall but intellectual function and learning ability were preserved. An NFL Neurological Care Program team -- consisting of a neurologist, a neurologist-psychiatrist, a neuropsychologist, and two neuroradiologists -- evaluated the patient.RESULTS: All evaluators agreed on the diagnosis of possible DPTCI, but they were unable to reach unanimity on the inclusion of possible AD. Two independent neuropsychologists from the ADRC reviewed the test results and supported the inclusion of possible AD, although the primary examining team (with the exception of one of the neurologists) opposed the inclusion of possible AD. Florbetapir scanning excluded cerebral amyloidosis -- thereby excluding AD -- and the patient was given a diagnosis of DPTCI without amyloidosis with possible CTE. CONCLUSIONS: This case illustrates the potential for brain amyloid imaging to prevent the inappropriate inclusion of non-AD patients (including those with a history of TBI) in trials of Aβ-reducing agents. Disclosure: Dr. Mitsis has nothing to disclose. Dr. Riggio has nothing to disclose. Dr. D9Antonio has nothing to disclose. Dr. Goldstein has nothing to disclose. Dr. DeKosky has received personal compensation in an editorial capacity for UpToDate. Dr. Naidich has nothing to disclose. Dr. Delman has nothing to disclose. Dr. Machac has nothing to disclose. Dr. Kostakoglu has nothing to disclose. Dr. Elder has nothing to disclose. Dr. Sano has received personal compensation for activities with Aventis Pharmaceuticals Inc., Bayer Pharmaceutical Corp., Forest Laboratories Inc., GlaxoSmithKline Inc., Janssen, Medication, Bristol-Myer Squibb Co., OrthoMcNeil, and Takeda. Dr. Gandy has received personal compensation for activities with Johnson & Johnson, Pfizer Inc, Alzheimer Immunotherapy Alliance, Diagenic, Amicus, and Baxter. Dr. Gordon has nothing to disclose.