Changes in Brain Functional and Effective Connectivity After Treatment for Breast Cancer and Implications for Intervention Targets.

Background: Patients with breast cancer frequently report cognitive impairment both during and after completion of therapy. Evidence suggests that cancer-related cognitive impairments are related to widespread neural network dysfunction. The default mode network (DMN) is a large conserved network that plays a critical role in integrating the functions of various neural systems. Disruption of the network may play a key role in the development of cognitive impairment. Methods: We compared neuroimaging and neurocognitive data from 43 newly diagnosed primary breast cancer patients (mean age = 48, standard deviation [SD] = 8.9 years) and 50 frequency-matched healthy female controls (mean age = 50, SD = 10 years) before treatment and 1 year after treatment completion. Functional and effective connectivity measures of the DMN were obtained using graph theory and Bayesian network analysis methods, respectively. Results: Compared with healthy females, the breast cancer group displayed higher global efficiency and path length post-treatment (p < 0.03, corrected). Breast cancer survivors showed significantly lower performance on measures of verbal memory, attention, and verbal fluency (p < 0.05) at both time points. Within the DMN, local brain network organization, as measured by edge-betweenness centralities, was significantly altered in the breast cancer group compared with controls at both time points (p < 0.0001, corrected), with several connections showing a significant group-by-time effect (p < 0.003, corrected). Effective connectivity demonstrated significantly altered patterns of neuronal coupling in patients with breast cancer (p < 0.05). Significant correlations were seen between hormone blockade therapy, radiation therapy, chemotherapy cycles, memory, and verbal fluency test and edge-betweenness centralities. Discussion: This pattern of altered network organization in the default mode is believed to result in reduced network efficiency and disrupted communication. Subregions of the DMN, the orbital prefrontal cortex and posterior memory network, appear to be at the center of this disruption and this could inform future interventions. Impact statement This prospective study is the first to investigate how post-treatment changes in functional and effective connectivity in the regions of default mode network are related to cancer therapy and measures of memory and verbal learning in breast cancer patients. We demonstrate that the interactions between treatment, brain connectivity, and neurocognitive outcomes coalesce around a subgroup of brain structures in the orbital frontal and parietal lobe. This would suggest that interventions that target these regions may improve neurocognitive outcomes in breast cancer survivors.

Describing cognitive function and psychosocial outcomes of COVID-19 survivors: A cross-sectional analysis.

BACKGROUND: Neurological and psychological symptoms are increasingly realized in the post-acute phase of COVID-19. PURPOSE: To examine and characterize cognitive and related psychosocial symptoms in adults (21-75 years) who tested positive for or were treated as positive for COVID-19. METHODS: In this cross-sectional study, data collection included a cognitive testing battery (Trails B; Digit Symbol; Stroop; Immediate and Delayed Verbal Learning) and surveys (demographic/clinical history; self-reported cognitive functioning depressive symptoms, fatigue, anxiety, sleep disturbance, social role performance, and stress). Results were compared with published norms, rates of deficits (more than 1 standard deviation (SD) from the norm) were described, and correlations were explored. RESULTS: We enrolled 52 participants (mean age 37.33 years; 78.85% female) who were, on average, 4 months post illness. The majority had a history of mild or moderate COVID-19 severity. Forty percent of participants demonstrated scores that were 1 SD or more below the population norm on one or more of the cognitive tests. A subset had greater anxiety (21.15%), depressive symptoms (23.07%), and sleep disturbance (19.23%) than population norms. Age differences were identified in Stroop, Digit Symbol, and Trails B scores by quartile ( p < .01), with worse performance in those 28-33 years old. CONCLUSIONS: Cognitive dysfunction and psychological symptoms may be present in the weeks or months after COVID-19 diagnosis, even in those with mild to moderate illness severity. IMPLICATIONS FOR PRACTICE: Clinicians need to be aware and educate patients about the potential late/long-term cognitive and psychological effects of COVID-19, even in mild to moderate disease.

Count me in: using a patient portal to minimize implicit bias in clinical research recruitment.

OBJECTIVE: Determine whether women and men differ in volunteering to join a Research Recruitment Registry when invited to participate via an electronic patient portal without human bias. MATERIALS AND METHODS: Under-representation of women and other demographic groups in clinical research studies could be due either to invitation bias (explicit or implicit) during screening and recruitment or by lower rates of deciding to participate when offered. By making an invitation to participate in a Research Recruitment Registry available to all patients accessing our patient portal, regardless of demographics, we sought to remove implicit bias in offering participation and thus independently assess agreement rates. RESULTS: Women were represented in the Research Recruitment Registry slightly more than their proportion of all portal users (n = 194 775). Controlling for age, race, ethnicity, portal use, chronic disease burden, and other questionnaire use, women were statistically more likely to agree to join the Registry than men (odds ratio 1.17, 95% CI, 1.12-1.21). In contrast, Black males, Hispanics (of both sexes), and particularly Asians (both sexes) had low participation-to-population ratios; this under-representation persisted in the multivariable regression model. DISCUSSION: This supports the view that historical under-representation of women in clinical studies is likely due, at least in part, to implicit bias in offering participation. Distinguishing the mechanism for under-representation could help in designing strategies to improve study representation, leading to more effective evidence-based recommendations. CONCLUSION: Patient portals offer an attractive option for minimizing bias and encouraging broader, more representative participation in clinical research.