PFC-amygdala functional interactions are reciprocal and likely necessary to process socially based emotional signals to generate an emotional response . Additionally, connections between the amygdala and insular cortex have been shown to be involved in the interoceptive processes involved in recognizing intoxication . That finding supports our interpretation that low LR individuals may have an impaired ability to recognize the effects of alcohol at the moderate doses used in our challenge paradigms. It is interesting to note that the findings of low LR-related lower connectivity between the amygdala and cortical region pathways observed with angry faces were not seen in the reaction to fearful faces. While similar in that both are negatively valenced emotions, fearful and angry emotional responses regulate the stress response in specific adaptive ways with different biological profiles. For example, when responding to a psychosocial stressor , angry reactions to stress lead to greater increases in cortisol over time but not to elevations in pro-inflammatory cytokines. In contrast, fear reactions to stressors lead to increases in pro-inflammatory cytokines over time and decreased cortisol . Therefore, our findings of altered functional connectivity needed to process anger in low LR individuals are consistent with the perspective that distinct emotional experiences trigger specific adaptive biological processes. Another finding of interest relates to happy faces. Here,cannabis square pot we also observed an opposite main effect pattern such that low LR participants had greater functional connectivity between the amygdala and anterior cingulate as compared to high LR participants across both placebo and alcohol.
Positive emotions often elicit activation in the brain’s reward circuitry and future studies should examine if the LR group patterns related to happy faces are also related to future problematic drinking and the development of AUD. Regional brain differences, especially in the anterior insula and frontal gyrus, predicted future problems with alcohol 5 years later in this sample . In our post hoc exploratory analyses, lower cingulate-amygdala functional connectivity during the placebo condition among low LR individuals significantly predicted an increase in alcohol problems 5 years later. Given the exploratory nature of these analyses, and that we did not correct for multiple tests, caution should be applied in interpretation of these post hoc findings. Nonetheless, they do suggest that LR-specific functional MRI findings may be predictive of future alcohol problems and additional research is needed in this area. In viewing the current results, it is important to keep some limitations in our research protocol in mind. First, the participants were all relatively stable and functional European American university students, and it is not clear whether the current results generalize to other groups. Second, consistent with the results reported by Paulus et al. and most of our prior papers, in order to place LR into a more useful clinical context LR was evaluated as a dichotomy, and examination of LR-derived scores as a continuous variable may yield additional findings. Third, reflecting the fact that laterality findings are unclear in many fMRI studies of emotion , we analyzed the combination of both the left and right amygdala seeds and their respective connectivity patterns. Thus, future work will need to further evaluate the importance of laterality influencing connectivity patterns associated with the low LR. Fourth, our analyses focused on the whole amygdala and not amygdalar subregions, and future work will be needed to expand upon the analyses presented here . Fifth, there are physiological effects when consuming alcohol that directly impact the BOLD signal, such as cerebral blood flow changes.
With advances in neuroimaging methodologies, future studies can be done isolating mechanisms that drive BOLD signal changes observed in the literature including blood flow, volume, and oxygenation. Sixth, only 18 trials per emotional face were used in the current protocol yielding a task time of 512 s, which may have limited statistical power given concerns for task-based fMRI reliability.Seventh, gPPI analyses are correlational and, therefore, directionally between the amygdala and other regions cannot be inferred. Future studies on dose-dependent effects of alcohol are needed to make causal inferences, and it would be interesting to examine other important brain regions as gPPI seeds. Finally, regarding the post hoc exploratory analyses linking some of the functional connectivity findings with the development of future alcohol problems, these results should be considered tentative until tested more directly in future research. In summary, building upon prior findings of regional brain LR group fMRI differences in frontal and insular cortices , we demonstrate that low LR individuals have amygdala connectivity differences relative to high LR individuals. These findings add to a growing body of fMRI studies that show regional brain characteristics in low LR individuals and demonstrate how amygadla-dependent functional connections may play a role in those characteristics. Attenuated connectivity among low LR individuals may contribute to an impaired ability to recognize developing alcohol intoxication in social situations and impaired ability to make appraisals of angry and happy emotions irrespective of consuming alcohol.In the 1990s, ∼11% of persons experiencing homelessness in San Francisco were 50 years of age and older, and by 2013, this figure had risen to 32% . Similar demographic trends exist in other metropolitan areas of the country, with the number of persons who are homeless and elderly expected to triple nationally by 2030 .
An increasing number of unhoused adults are becoming homeless for the first time after 50 years of age . Among those 50 and older and homeless, 44% had never experienced homelessness prior to age 50. Studying the brain health of older adults and elderly persons experiencing homelessness is important for two main reasons. First, the incidence and prevalence of different forms of age-related neurodegenerative disease of the brain , such as Alzheimer disease and frontotemporal lobar degeneration , is expected to rise as the general population ages . The early clinical signs and symptoms of some forms of NDDB, especially those that affect the anterior frontal and temporal lobes early in the illness lead to focal deficits in social cognition and socioemotional processing. Persons affected by NDDB often engage in behaviors that are harmful to their personal and social lives, intimate relationships, and work responsibilities . We hypothesize that early changes in cognition caused by NDDB, particularly changes in social cognition, could precipitate homelessness in selected individuals, especially those who live alone, are minimally supported, or are socioeconomically vulnerable . Second,drying cannabis most of the non-communicable health conditions that are disproportionately prevalent in homeless older adults are known risk factors for NDDB . There is a high prevalence of cognitive impairment and accelerated cognitive aging among older adult homeless persons , and at least 48% of homeless individuals with cognitive impairment exhibit signs of functional decline , yet little is known about the role that NDDB play in leading to cognitive impairment and functional decline in homeless older adults. Studies on cognitive impairment in homeless adults generally rely on limited, brief assessments of cognition to evaluate participants without incorporating more comprehensive neuropsychological, neurological, functional, and biomarker examinations that are currently considered gold standard practices in the evaluation of persons with suspected NDDB. Few studies have characterized cognitive impairment in this population using contemporary neurological approaches, including brain health biomarkers . Such approaches are important as they may greatly inform prognosis of these older adults as well as guide the provision of person-centered supportive measures to help them obtain and maintain housing. To study the intersection between NDDB and the experience of homelessness among older adults, we previously investigated relationships between homelessness and NDDB among an existing cohort of adult research participants with different forms of NDDB evaluated in the Memory and Aging Center of the University of California San Francisco.
We found that persons with anterior frontal and temporal neurocognitive deficits were highly represented among our homeless cohort, and most of these participants had become homeless in the setting of a fragile socioeconomic context. In this study, we seek to expand this work by characterizing the neurocognitive health of a community-based cohort of older adults who experienced homelessness for the first time after the age of 50, employing gold standard neurological and neuropsychological examination approaches currently in use at the UCSF MAC. We recruited participants from the HOPE HOME study, which used a venue-based sampling method to enroll 350 participants between 2013 and 2014, 100 additional participants between 2017 and 2018, and followed all participants at 6 months intervals since. At enrollment, participants needed to be age 50 and older , homeless by the HEARTH criteria, and speak English. Participants remained in the study regardless of housing status at followup. HOPE HOME sampled from all overnight homeless shelters serving homeless adults in Oakland, CA, all free and low-cost meal programs serving three or more meals a week, and a random selection of homeless encampments and recycling programs. staf sampled randomly within sites in order to reflect the population of interest . staf obtained consent using a teach-back method and excluded individuals unable to give informed consent . We used multiple modalities to provide consent . We assessed understanding by conducting a post consent quiz that documents the participants’ knowledge of critical elements of the informed consent . We administered a post exam quiz to assess understanding. For subjects who score less than perfect on the initial presentation, educational procedures were employed to raise their understanding to sufficient levels for them to make a meaningful choice about participating. Such procedures may include simple repetition of the relevant information in the consent form or more detailed explanations of items that the subject has difficulty understanding . Participants received gift cards or cash for each check-in and interview . We identified HOPE HOME study participants who remained active in the study between November of 2020 and February of 2021 and who reported that they first became homeless at age 50 and older and had an active phone number . We offered recruitment to the first 35 individuals on a list of participants ordered sequentially by latest followup date. We were able to enroll 27 consecutive participants, 25 of whom completed all components of this study: structured neurocognitive history intake, neurological examination, and neuropsychological examination. Two participants were unable to complete all components due to inability to travel to site for in-person evaluation. We conducted interviews and exams between November 2020 and February 2021. We offered a $30 debit card for neurocognitive history and an additional $30 for the neurological and neuropsychological examinations. Due to research restrictions imposed by the Coronavirus Disease 2019 pandemic, we conducted in person evaluations outdoors in a private setting outside the HOPE-HOME study site in Oakland, California. Whenever possible, we conducted neurocognitive history intakes over the telephone. We used data on functional status from the most recent HOPE HOME semi-annual interview that was conducted prior to each participant’s neurocognitive evaluation for this study. As part of HOPE HOME study procedures, participants reported whether they received support from anyone on a daily basis to help with instrumental and/or non-instrumental activities of daily living . Participants reported whether they had difficulty with everyday activities because of a physical, mental, emotional, or memory problem: dressing, bathing, or showering, eating, getting in or out of bed, using the toilet, and walking across the room . If a participant could not perform an activity because of lack of access to resources, the interviewer determined the participant could otherwise perform said activity. HOPE HOME also used the Brief Instrumental Functioning Scale to determine iADLs as it has been validated in homeless populations staf asked participants if in the past 4 weeks they could perform each activity on their own, with help, with a little help, with a lot of help, or needing someone to do the tasks for them. These activities included: Taking medications as prescribed by a doctor, filling out an application for benefits, keeping up with or budgeting money, using public transportation, setting up a job interview by phone, and finding an attorney to help with a legal problem. We scored BIFS as binary. The mean duration between time of most recent functional assessment and time of neurocognitive evaluation for this study was 3 months prior to our neurological examination.