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). Visuo-spatial 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.
• fMRI was used to study the neural bases of statistical learning during word segmentation. • Participants acquired statistical regularities in a continuous syllable stream. • Analyses related ...learning at multiple time points to changes in neural activity. • Results showed the central involvement of the LIFG in this type of learning.
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.
Frontal and temporal white matter pathways play key roles in language processing, but the specific computations supported by different tracts remain a matter of study. A role in speech planning has ...been proposed for a recently described pathway, the frontal aslant tract (FAT), which connects the posterior inferior frontal gyrus to the pre-SMA. Here, we use longitudinal functional and structural MRI and behavioral testing to evaluate the behavioral consequences of a lesion to the left FAT that was incurred during surgical resection of a frontal glioma in a 60-year-old woman, Patient AF. The pattern of performance in AF is compared, using the same measures, with that in a 37-year-old individual who underwent a left anterior temporal resection and hippocampectomy (Patient AG). AF and AG were both cognitively intact preoperatively but exhibited specific and doubly dissociable behavioral deficits postoperatively: AF had dysfluent speech but no word finding difficulty, whereas AG had word finding difficulty but otherwise fluent speech. Probabilistic tractography showed that the left FAT was lesioned postoperatively in AF (but not AG) whereas the inferior longitudinal fasciculus was lesioned in AG (but not AF). Those structural changes were supported by corresponding changes in functional connectivity to the posterior inferior frontal gyrus: decreased functional connectivity postoperatively between the posterior inferior frontal gyrus and pre-SMA in AF (but not AG) and decreased functional connectivity between the posterior inferior frontal gyrus and the middle temporal gyrus in AG (but not AF). We suggest from these findings that the left FAT serves as a key communicative link between sentence planning and lexical access processes.
To investigate the relationship between pathological brain iron deposition and white matter hyperintensities (WMHs) in cerebral small vessel disease (CSVD), via Monte Carlo simulations of magnetic ...susceptibility imaging and the development of a novel imaging marker called the Expected Iron Coefficient (EIC).
A synthetic pathological model of a different number of impenetrable spheres at random locations was employed to represent pathological iron deposition. The diffusion process was simulated with a Monte Carlo method with adjustable parameters to manipulate sphere size, distribution, and extracellular properties. Quantitative susceptibility mapping (QSM) was performed in a clinical dataset to study CSVD to derive and evaluate QSM, R2*, the iron microenvironment coefficient (IMC), and the EIC in the presence of WMHs.
The simulations show that QSM signals increase in the presence of increased tissue iron, confirming that the EIC increases with pathology. Clinical results demonstrate that while QSM, R2*, and the IMC do not show significant differences in brain iron, the EIC does in the context of CSVD.
The EIC is more sensitive to subtle changes in brain iron deposition caused by pathology, even when QSM, R2*, and the IMC fail.
Objectives
To examine the cognitive and neural effects of vision‐based speed‐of‐processing (VSOP) training in older adults with amnestic mild cognitive impairment (aMCI) and contrast those effects ...with an active control (mental leisure activities (MLA)).
Design
Randomized single‐blind controlled pilot trial.
Setting
Academic medical center.
Participants
Individuals with aMCI (N = 21).
Intervention
Six‐week computerized VSOP training.
Measurements
Multiple cognitive processing measures, instrumental activities of daily living (IADLs), and two resting state neural networks regulating cognitive processing: central executive network (CEN) and default mode network (DMN).
Results
VSOP training led to significantly greater improvements in trained (processing speed and attention: F1,19 = 6.61, partial η2 = 0.26, P = .02) and untrained (working memory: F1,19 = 7.33, partial η2 = 0.28, P = .01; IADLs: F1,19 = 5.16, partial η2 = 0.21, P = .03) cognitive domains than MLA and protective maintenance in DMN (F1, 9 = 14.63, partial η2 = 0.62, P = .004). VSOP training, but not MLA, resulted in a significant improvement in CEN connectivity (Z = −2.37, P = .02).
Conclusion
Target and transfer effects of VSOP training were identified, and links between VSOP training and two neural networks associated with aMCI were found. These findings highlight the potential of VSOP training to slow cognitive decline in individuals with aMCI. Further delineation of mechanisms underlying VSOP‐induced plasticity is necessary to understand in which populations and under what conditions such training may be most effective.
•Cocaine dependence (CD) is a common comorbidity of HIV infection.•The effect of former cocaine dependence on brain integrity in HIV+ individuals was explored.•Higher caudate volume was observed in ...abstinent CD participants.•HIV identified as the primary driver of reduced cognitive performance on neurocognitive testing.•No interactions between HIV and CD history were identified.
Evidence from animal research, postmortem analyses, and magnetic resonance imaging (MRI) investigations indicate substantial morphological alteration in brain structure as a function of human immunodeficiency virus (HIV) or cocaine dependence (CD). Although previous research on HIV+ active cocaine users suggests the presence of deleterious morphological effects in excess of either condition alone, a yet unexplored question is whether there is a similar deleterious interaction in HIV+ individuals with CD who are currently abstinent. To this end, the combinatorial effects of HIV and CD history on regional brain volume, cortical thickness, and neurocognitive performance was examined across four groups of participants in an exploratory study: healthy controls (n = 34), HIV-negative individuals with a history of CD (n = 21), HIV+ individuals with no history of CD (n = 20), HIV+ individuals with a history of CD (n = 15). Our analyses revealed no statistical evidence of an interaction between both conditions on brain morphometry and neurocognitive performance. While descriptively, individuals with comorbid HIV and a history of CD exhibited the lowest neurocognitive performance scores, using Principle Component Analysis of neurocognitive testing data, HIV was identified as the primary driver of neurocognitive impairment. Higher caudate volume was evident in CD+ participants relative to CD− participants. Findings indicate no evidence of compounded differences in neurocognitive function or structural measures of brain integrity in HIV+ individuals in recovery from CD relative to individuals with only one condition.
Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is the first example of a learning health system in multiple sclerosis (MS). This paper describes the initial ...implementation of MS PATHS and initial patient characteristics.
MS PATHS is an ongoing initiative conducted in 10 healthcare institutions in three countries, each contributing standardized information acquired during routine care. Institutional participation required the following: active MS patient census of ≥500, at least one Siemens 3T magnetic resonance imaging scanner, and willingness to standardize patient assessments, share standardized data for research, and offer universal enrolment to capture a representative sample. The eligible participants have diagnosis of MS, including clinically isolated syndrome, and consent for sharing pseudonymized data for research. MS PATHS incorporates a self-administered patient assessment tool, the Multiple Sclerosis Performance Test, to collect a structured history, patient-reported outcomes, and quantitative testing of cognition, vision, dexterity, and walking speed. Brain magnetic resonance imaging is acquired using standardized acquisition sequences on Siemens 3T scanners. Quantitative measures of brain volume and lesion load are obtained. Using a separate consent, the patients contribute DNA, RNA, and serum for future research. The clinicians retain complete autonomy in using MS PATHS data in patient care. A shared governance model ensures transparent data and sample access for research.
As of August 5, 2019, MS PATHS enrolment included participants (
= 16,568) with broad ranges of disease subtypes, duration, and severity. Overall, 14,643 (88.4%) participants contributed data at one or more time points. The average patient contributed 15.6 person-months of follow-up (95% CI: 15.5-15.8); overall, 166,158 person-months of follow-up have been accumulated. Those with relapsing-remitting MS demonstrated more demographic heterogeneity than the participants in six randomized phase 3 MS treatment trials. Across sites, a significant variation was observed in the follow-up frequency and the patterns of disease-modifying therapy use.
Through digital health technology, it is feasible to collect standardized, quantitative, and interpretable data from each patient in busy MS practices, facilitating the merger of research and patient care. This approach holds promise for data-driven clinical decisions and accelerated systematic learning.
Individuals with a diagnosis of co-morbid HIV infection and cocaine use disorder are at higher risk of poor health outcomes. Active cocaine users, both with and without HIV infection, show clear ...deficits in response inhibition and other measures of executive function that are instrumental in maintaining drug abstinence, factors that may complicate treatment. Neuroimaging and behavioral evidence indicate normalization of executive control processes in former cocaine users as a function of the duration of drug abstinence, but it is unknown to what extent co-morbid diagnosis of HIV affects this process. To this end, we investigate the combinatorial effects of HIV and cocaine dependence on the neural substrates of cognitive control in cocaine-abstinent individuals with a history of cocaine dependence. Blood-oxygen level dependent signal changes were measured as 86 participants performed a Go/NoGo response inhibition task while undergoing functional magnetic resonance imaging (fMRI). Four groups of participants were selected based on HIV and cocaine-dependence status. Participants affected by both conditions demonstrated the lowest response accuracy of all participant groups. In a region of interest analysis, hyperactivation in the left putamen and midline-cingulate hyperactivation was observed in individuals with both HIV and cocaine dependence relative to individuals with only one condition. Results of a whole-brain analysis indicate response inhibition-related hyperactivation in the bilateral supplementary motor area, bilateral hippocampi, bilateral primary somatosensory areas, right dorsal anterior cingulate, and left insula in the CD+/HIV+ group relative to all other groups. These results indicate complex and interactive alterations in neural activation during response inhibition and highlight the importance of examining the neurocognitive effects of co-morbid conditions.
•Drug abuse is a common comorbidity of HIV infection.•Effects of HIV on neural function were assessed using fMRI in former cocaine users.•Participants with both conditions showed poorest response inhibition performance.•Interactive effects of HIV and drug abuse observed in the cingulate and left putamen.•Whole-brain analysis revealed 18 additional regions showing interactive effects.
Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common, sometimes dose-limiting side effect of neurotoxic chemotherapy. Treatment is limited because its pathophysiology is poorly ...understood. Compared to research on peripheral mechanisms, the role of the brain in CIPN is understudied and it may be important to develop better treatments. We propose a novel task that assesses brain activation associated with attention to bodily sensations (interoception), without the use of painful stimulation, to understand how CIPN symptoms may be processed in the brain. The goals of this preliminary study were to assess, 1) feasibility of the task, 2) sensitivity to changes in brain activity, and 3) suitability for assessing relationships between brain activation and CIPN severity. Eleven participants with varying types of cancer completed a brain fMRI scan and rated CIPN severity (CIPN-20) before and/or 12 weeks after starting neurotoxic chemotherapy. The Bodily Attention Task is a 7.5-min long fMRI task involving attentional focus on the left fingertips, the heart, or a flashing word “target” for visual attention (reference condition). Feasibility was confirmed, as 73% of all data collected were usable and participants reported feeling or focus during 75% of the trials. Regarding brain activity, finger attention increased activation in somatosensory regions (primary sensory cortex, insula) and sensory integration regions (precuneus, dorsolateral prefrontal cortex). Exploratory analyses suggested that brain activation may be associated with CIPN severity. A larger sample size and accounting of confounding factors is needed to test for replication and to identify brain and interoceptive biomarkers to help improve the prediction, prevention, and treatment of CIPN.
•Most cancer patients receiving chemotherapy experience CIPN.•Limited treatment options due to poor understanding of CIPN mechanisms.•We present a novel bodily attention task to assess brain correlates of CIPN.•Task is feasible and produces brain activation which may relate to CIPN severity.
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