Alterations in Electroencephalography Theta as Candidate Biomarkers of Acute Cannabis Intoxication

The trend toward cannabis legalization in the United States over the past two decades has unsurprisingly been accompanied by an increase in the number of cannabis users and use patterns that potentially pose wider risks to the public like driving under the influence. As such, it is becoming increasingly important to develop methods to accurately quantify cannabis intoxication and its associated impairments on cognitive and motor function. Electroencephalography (EEG) offers a non-invasive method for quantitatively assessing neurophysiological biomarkers of intoxication and impairment with a high degree of temporal resolution. Twelve healthy, young recreational cannabis users completed a series of neurocognitive tasks with concurrent EEG acquisition using the ABM STAT X24 EEG headset in a within-subject counterbalanced design. The 1-h testbed consisted of resting state tasks and tests of attention and memory. Spectral densities were computed for resting state tasks, and event-related potentials (ERPs) were obtained for the attention and memory tasks. Theta band power (3–5 Hz) was decreased during cannabis intoxication compared to placebo during resting state tasks, as were average P400 and late positive potential (LPP) amplitudes during attention and memory tasks. Cannabis intoxication was also associated with elevated frontal coherence and diminished anterior–posterior coherence in the Theta frequency band. This work highlights the utility of EEG to identify and quantify neurophysiological biomarkers from recordings obtained during a short neurocognitive testbed as a method for profiling cannabis intoxication. These biomarkers may prove efficacious in distinguishing intoxicated from non-intoxicated individuals in lab and real-world settings.

Neurocognitive And Dysfunctional Belief Candidate Endophenotypes Of Obsessive-Compulsive And Related Disorders

Background: The current dissertation examined neurocognitive and dysfunctional belief candidate endophenotypes (CEs) across the obsessive compulsive spectrum to elucidate general versus specific factors. This study included CEs from two etiological perspectives well established in the literature. Secondary analyses examined several CEs multidimensionally and examined the relationship between CEs and of QOL. Methods: A total of 77 participants took part in this study, divided into four groups; OCD (n = 21), Hoarding Disorder (HD; n = 16), Grooming Disorders which included both Trichotillomania and Excoriation Disorder (GD; n = 18), and control participants (n = 22). Participants completed a clinical interview and battery of neurocognitive tasks and questionnaires. Results: Those with HD performed worse than controls on measures of response inhibition and set-shifting. OCD continued to predict significant variance in number sequencing. Examination of dysfunctional belief CEs revealed specificity of Responsibility/Threat beliefs and Importance/Control of Thoughts beliefs to OCD. Perfectionism/Intolerance of Uncertainty appear to be broad CEs; however, differing specificity emerged depending on the measure utilized to measure the construct. Self-report indecision revealed specificity to OCD and HD. Differing patterns of QOL impairments emerged across the spectrum. A better understanding of CEs specificity has implications for diagnostic classification, etiology, course, and treatment.

Neurocognitive And Dysfunctional Belief Candidate Endophenotypes Of Obsessive-Compulsive And Related Disorders

Background: The current dissertation examined neurocognitive and dysfunctional belief candidate endophenotypes (CEs) across the obsessive compulsive spectrum to elucidate general versus specific factors. This study included CEs from two etiological perspectives well established in the literature. Secondary analyses examined several CEs multidimensionally and examined the relationship between CEs and of QOL. Methods: A total of 77 participants took part in this study, divided into four groups; OCD (n = 21), Hoarding Disorder (HD; n = 16), Grooming Disorders which included both Trichotillomania and Excoriation Disorder (GD; n = 18), and control participants (n = 22). Participants completed a clinical interview and battery of neurocognitive tasks and questionnaires. Results: Those with HD performed worse than controls on measures of response inhibition and set-shifting. OCD continued to predict significant variance in number sequencing. Examination of dysfunctional belief CEs revealed specificity of Responsibility/Threat beliefs and Importance/Control of Thoughts beliefs to OCD. Perfectionism/Intolerance of Uncertainty appear to be broad CEs; however, differing specificity emerged depending on the measure utilized to measure the construct. Self-report indecision revealed specificity to OCD and HD. Differing patterns of QOL impairments emerged across the spectrum. A better understanding of CEs specificity has implications for diagnostic classification, etiology, course, and treatment.

Negative Effects of COVID-19 Stay-at-Home Mandates on Physical Intervention Outcomes: A Preliminary Study

Background: Due to the COVID-19 pandemic, beneficial physical intervention classes for individuals with Parkinson’s disease (PD) were cancelled. Objective: To understand effects of the COVID-19 stay-at-home mandate and the inability to participate in recommended and structured physical interventions as a consequence of these mandates, specifically designed mobile assessments were used that collected both self-reporting information and objective task-based metrics of neurocognitive functions to assess symptom changes for individuals with PD. Methods: Self-reporting questionnaires focusing on overall quality of life (e.g., when individuals typically feel at their best, changes in activity levels, and symptom progression) were given to all individuals (n = 28). In addition, mobile-based neurocognitive assessments were administered to a subset of the population (n = 8) to quantitatively assess changes due to COVID-19 restrictions. Results: The highest self-reported factors in which individuals denoted feeling their best were after exercise (67.86%) and being in a comfortable and supportive environment (60.71%). Objective measures found overall duration of physical activity during the stay-at-home mandate decreased significantly (p = 0.022). With the lack of overall activity, 82.14%of individuals self-reported having at least one symptom that worsened moderately or higher. Further testing, using mobile-based assessments, showed average completion times of functional tasks increased, taking about 2.1 times longer, while accuracy metrics showed overall degradation. Conclusion: Although the COVID-19 stay-at-home mandate was intended to help protect individuals at high risk from coming into contact with the virus, it also prevented individuals from receiving recommended supervised exercise interventions resulting in significant negative effects in social well-being and across motor and speech neurocognitive tasks for individuals with PD.

A Neurosurgeon's Guide to Cognitive Dysfunction in Adult Glioma

Cognitive decline is common among patients with low- and high-grade glioma and can significantly impact quality of life. Although cognitive outcomes have been studied after therapeutic interventions such as surgery and radiation, it is important to understand the impact of the disease process itself prior to any interventions. Neurocognitive domains of interest in this disease context include intellectual function and premorbid ability, executive function, learning and memory, attention, language function, processing speed, visuospatial function, motor function, and emotional function. Here, we review oncologic factors associated with more neurocognitive impairment, key neurocognitive tasks relevant to glioma patient assessment, as well as the relevance of the human neural connectome in understanding cognitive dysfunction in glioma patients. A contextual understanding of glioma-functional network disruption and its impact on cognition is critical in the surgical management of eloquent area tumors.

Biliverdin reductase bridges focal adhesion kinase to Src to modulate synaptic signaling

ABSTRACTSynapses are complex bridges that connect discrete neurons into vast networks that send, receive, and encode diverse forms of information. However, they must remain dynamic in order to adapt to changing inputs. Here, we report that the enzyme biliverdin reductase (BVR) physically links together key molecules in focal adhesion signaling at the synapse. In challenging mice with a battery of neurocognitive tasks, we first discover that BVR null (BVR-/-) mice exhibit profound deficits in learning and memory. We uncover that these deficits may be explained by a loss of focal adhesion signaling that is both transcriptionally and biochemically disrupted in BVR-/- hippocampi. We learn that BVR mediates focal adhesion signaling by physically bridging the key initiatory kinases FAK/Pyk2 to the effector kinase Src. Activated Src normally promotes synaptic plasticity by phosphorylating the N-methyl-D-aspartate (NMDA) receptor, but FAK/Pyk2 are unable to bind and stimulate Src without BVR. Src itself is a molecular hub upon which many signaling pathways converge in order to stimulate NMDA neurotransmission, positioning BVR at a prominent intersection of synaptic signaling.

Testing a Novel Web-Based Neurocognitive Battery in the General Community: Validation in a Normative Sample (Preprint)

BACKGROUND In recent years, there has been an increased interest in the development of remote psychological assessment. These platforms increase accessibility and allow clinicians to monitor important health metrics thereby informing patient-centered treatment. OBJECTIVE Here we report on the properties and usability of a new web-based neurocognitive assessment battery and present a normative dataset for future use. METHODS Seven hundred eighty-one participants completed a portion of 8 tasks which captured performance in auditory processing, visual-spatial working memory, visual-spatial learning, cognitive flexibility, and emotional processing. A subset of individuals (n=195) completed a five-question survey measuring the acceptability of the tasks. RESULTS Between 252 and 426 participants completed each task. Younger individuals outperformed their older counterparts on 6 of the 8 tasks. Therefore, central tendency data metrics were presented by seven different age bins. The broad majority of participants found the tasks interesting, enjoyable and endorsed some interest in playing them at home. Less than one percent of individuals endorsed not at all for the statement: I understood the instructions. Older individuals were more likely to understand the instructions to a lower extent; however, 72 percent of individuals over the age of 60 still felt that they understood the instructions at the level of mostly or very much. CONCLUSIONS Overall, the tasks were found to be widely acceptable to participants. Use of web-based neurocognitive tasks such as these may increase the ability to deploy precise data informed interventions to a wider population.

Prediction of white matter integrity pattern in overweight and obese adults

IntroductionObesity has been associated with lower white matter integrity (WMI) in limbic brain regions, including the fornix. Both early decrease of WMI in the fornix (WMIf) and midlife obesity have been related to dementia incidence with advancing age. No studies have explored early cognitive predictors of WMIf in overweight-obese (OO) adults. Aim of this study was to compare OO and normal-weight (NW) participants with respect to (a) WMIf in adulthood and (b) the relationship between cognitive performance at school-age and in adolescence with WMIf in adulthood.MethodsParticipants were part of a cohort followed since infancy who underwent magnetic resonance imaging studies in adulthood (22.3 ± 1.3 years). Diffusion tensor imaging was performed and Tract Based Spatial Statistics (TBSS) was used to obtain fractional anisotropy (FA) skeleton; increased FA relates to greater WMI. A mask for the fornix was created (JHU-ICBM DTI-81 Atlas) and then used to extract the average FA for each individual. Participants also performed neurocognitive tasks: (a) school-age (10.3 ± 1.0 years): the trail making test comprises two conditions and time difference between conditions reflects cognitive flexibility; (b) adolescence (15.6 ± 0.5 years): incentive task that test the effect of incentives (reward, loss avoidance or neutral) on inhibitory control performance (correct responses latency). In adulthood, BMI was categorized as NW (≥ 18.5 to < 25.0 kg/m2) and OO (≥ 25.0 kg/m2) groups. A t-test and univariate GLM were conducted. Analysis were adjusted by sex and age-specific BMI z-scores.ResultsParticipants were 27 NW (41% female) and 41 OO (49% female). Compared to NW, OO participants showed decreased FA in the fornix (0.585 vs. 0.618, p < 0.05), i.e. lower WMIf. Differences were apparent in the relationship between cognitive flexibility at school-age (F = 2.9, p = 0.06) and loss avoidance latency in adolescence (F = 3.5, p < 0.05) with FA in the fornix in adulthood. Increased cognitive flexibility at school-age (β = 0.335, p < 0.05) and decreased loss avoidance latency in adolescence (β = -0.581, p < 0.001) were related to higher FA in the fornix in OO adults. No relationship resulted significant in NW adults.DiscussionPerformance in neurocognitive tasks at earlier developmental stages were related with WMIf only in OO adults, group characterized by decreased WMIf. Our results provide evidence regarding specific neurocognitive tasks with predictive value for WMIf alterations. Further, they could contribute to the understanding of neural mechanisms underlying obesity and also provide insight relative to neurodegenerative risk with advancing age.SupportFondecyt 11160671 and NIH HD33487.

Using Outliers in Freesurfer Segmentation Statistics to Identify Cortical Reconstruction Errors in Structural Scans

IntroductionQuality assurance (QA) is vital for ensuring the integrity of processed neuroimaging data for use in clinical neurosciences research. Manual QA (visual inspection) of processed brains for cortical surface reconstruction errors is resource-intensive, particularly with large datasets. Several semi-automated QA tools use quantitative detection of subjects for editing based on outlier brain regions. There were two project goals: (1) evaluate the adequacy of a statistical QA method relative to visual inspection, and (2) examine whether error identification and correction significantly impacts estimation of cortical parameters and established brain-behavior relationships.MethodsT1 MPRAGE images (N = 530) of healthy adults were obtained from the NKI-Rockland Sample and reconstructed using Freesurfer 5.3. Visual inspection of T1 images was conducted for: (1) participants (n = 110) with outlier values (z scores ± 3 SD) for subcortical and cortical segmentation volumes (outlier group), and (2) a random sample of remaining participants (n = 110) with segmentation values that did not meet the outlier criterion (nonoutlier group).ResultsThe outlier group had 21% more participants with visual inspection-identified errors than participants in the non-outlier group, with a medium effect size (Φ = 0.22). Nevertheless, a considerable portion of images with errors of cortical extension were found in the non-outlier group (41%). Sex significantly predicted error rate; men were 2.8 times more likely to have errors than women. Although nine brain regions significantly changed size from pre-to postediting (with effect sizes ranging from 0.26 to 0.59), editing did not substantially change the correlations of neurocognitive tasks and brain volumes (ps > 0.05).ConclusionsStatistically-based QA, although less resource intensive, is not accurate enough to supplant visual inspection. We discuss practical implications of our findings to guide resource allocation decisions for image processing.