Abstract& Stress-induced activation of the locus ceruleus-norepinephrine (LC-NE) system produces significant cognitive and behavioral effects, including enhanced arousal and attention. Improvements in discrimination task performance and memory have been attributed to this stress response. In contrast, for other cognitive functions that require cognitive flexibility, increased activity of the LC-NE system may produce deleterious effects. The aim of the present study was to determine the effect of pharmacological modulation of the LC-NE system on stress-induced impairments in cognitive flexibility performance in healthy individuals. Cognitive performance, plus psychological and physiological parameters for 16 adults without any history of anxiety disorders, was assessed during four test sessions: stress and no-stress, with each condition tested after administration of propranolol and placebo. The Trier Social Stress Test, a public-speaking and mental arithmetic stressor, was presented to participants for the stress sessions, whereas a similar, but nonstressful, control task (reading, counting) was utilized for the no-stress sessions. Tests of cognitive flexibility included lexical-semantic and associative problem-solving tasks (anagrams, Compound Remote Associates Test). Visuospatial memory and motor processing speed tests served as control tasks. Results indicate that (1) stress impaired performance on cognitive flexibility tasks, but not control tasks; (2) compared to placebo, cognitive flexibility improved during stress with propranolol. Therefore, psychological stress, such as public speaking, negatively impacts performance on tasks requiring cognitive flexibility in normal individuals, and this effect is reversed by beta-adrenergic antagonism. This may provide support for the hypothesis that stress-related impairments in cognitive flexibility are related to the noradrenergic system. &

Functional magnetic resonance imaging (fMRI) was used to assess neural activation as participants learned to segment continuous streams of speech containing syllable sequences varying in their transitional probabilities. Speech streams were presented in four runs, each followed by a behavioral test to measure the extent of learning over time. Behavioral performance indicated that participants could discriminate statistically coherent sequences (words) from less coherent sequences (partwords). Individual rates of learning, defined as the difference in ratings for words and partwords, were used as predictors of neural activation to ask which brain areas showed activity associated with these measures. Results showed significant activity in the pars opercularis and pars triangularis regions of the left inferior frontal gyrus (LIFG). The relationship between these findings and prior work on the neural basis of statistical learning is discussed, and parallels to the frontal/subcortical network involved in other forms of implicit sequence learning are considered.

Removal of the anterior temporal lobe (ATL) is an effective surgical treatment for intractable temporal lobe epilepsy but carries a risk of language and verbal memory deficits. Preoperative localization of functional zones in the ATL might help reduce these risks, yet fMRI protocols in current widespread use produce very little activation in this region. Based on recent evidence suggesting a role for the ATL in semantic integration, we designed an fMRI protocol comparing comprehension of brief narratives (Story task) with a semantically shallow control task involving Corresponding Author: Jeffrey R. Binder, MD, MEB Room 4550, 8701 Watertown Plank Road, Milwaukee, WI 53226 USA, Phone: 1-414-456-4662, Fax: 1-414-456-6562, jbinder@mcw.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroimage. Author manuscript; available in PMC 2012 January 15. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript serial arithmetic (Math task). The Story > Math contrast elicited strong activation throughout the ATL, lateral temporal lobe, and medial temporal lobe bilaterally in an initial cohort of 18 healthy participants. The task protocol was then implemented at 6 other imaging centers using identical methods. Data from a second cohort of participants scanned at these centers closely replicated the results from the initial cohort. The Story-Math protocol provides a reliable method for activation of surgical regions of interest in the ATL. The bilateral activation supports previous claims that conceptual processing involves both temporal lobes. Used in combination with language lateralization measures, reliable ATL activation maps may be useful for predicting cognitive outcome in ATL surgery, though the validity of this approach needs to be established in a prospective surgical series.

HIV infected individuals with severe immune suppression are more likely to develop HIV-associated neurocognitive disorders than those with preserved immune function. While partial immune reconstitution occurs in those with severe immune suppression after starting combined antiretroviral therapy, it is not established whether improvement in immune function reverses or prevents injury to the central nervous system (CNS). To address this question, 50 participants (nadir CD4 counts ≤200cells/mm3, on a stable antiretroviral regimen for at least 12 consecutive weeks prior to study) and 13 HIV negative participants underwent a comprehensive neurological evaluation followed by diffusion tensor imaging (DTI). 84% of the 50 HIV participants were neurologically asymptomatic (HIVNA) and 16% had mild cognitive impairment (HIVCI). Tract-Based Spatial Statistics (TBSS) on DTI data revealed that mean diffusivity (MD) increased significantly in the posterior aspect of both hemispheres in HIVNA compared to controls. In HIVCI, compared to controls and HIVNA, increased MD extended to prefrontal areas. Fractional anisotropy (FA) decreased only in HIVCI, compared to either controls or HIVNA. Furthermore, DTI showed significant correlations to duration of HIV infection and significant associations with multiple cognitive domains. This study highlights that in partial immune reconstitution, injury to the CNS is present even in those that are neurologically asymptomatic and there are discrete spatial patterns of white matter injury in HIVNA subjects compared to HIVCI subjects. Our results also show that quantitative analysis of DTI using TBSS is a sensitive approach to evaluate HIV-associated white matter disease and thus valuable in monitoring central nervous system injury.

Background/Objectives Vision-based speed of processing (VSOP) training is a promising cognitive intervention for older adults. However, it is unknown whether VSOP training can affect cognitive processing in individuals at high risk for dementia. Here, we examined cognitive and neural effects of VSOP training in older adults with amnestic mild cognitive impairment (aMCI) and contrasted those effects with an active control (mental leisure activities; MLA). Design A randomized single-blinded controlled pilot trial. Setting An academic medical center. Participants Twenty-one participants with aMCI. Intervention A 6-week computerized VSOP training. Measurements Multiple cognitive processing measures, instrumental activities of daily living (IADL), and two key resting state neural networks regulating cognitive processing: central executive network (CEN) and default mode network (DMN). Results We found that, compared to MLA control, VSOP training led to significant improvements in trained (processing speed and attention: F1,19 = 6.61, Partial η2 = 0.26, p = .019) and untrained cognitive domains (working memory: F1,19 = 7.33, Partial η2 = 0.28, p = .014; IADL: F1,19 = 5.16, Partial η2 = 0.21, p = .035), and protective maintenance in DMN (F1, 9 = 14.63, Partial η2 = 0.62, p = .004). Additionally, VSOP training, but not MLA, resulted in a significant improvement in CEN connectivity (Z = −2.37, p = .018). Conclusion We identified both target and transfer effects of VSOP training and revealed links between VSOP training and two key neural networks associated with aMCI. These findings highlight the potential of VSOP training to slow cognitive decline in aMCI. Further delineation of mechanisms underlying VSOP-induced plasticity is necessary to understand in what populations and conditions such training may be most effective.