Future directions in psychiatric neurosurgery: Proceedings of the 2022 American Society for Stereotactic and Functional Neurosurgery meeting on surgical neuromodulation for psychiatric disorders.

OBJECTIVE: Despite advances in the treatment of psychiatric diseases, currently available therapies do not provide sufficient and durable relief for as many as 30-40% of patients. Neuromodulation, including deep brain stimulation (DBS), has emerged as a potential therapy for persistent disabling disease, however it has not yet gained widespread adoption. In 2016, the American Society for Stereotactic and Functional Neurosurgery (ASSFN) convened a meeting with leaders in the field to discuss a roadmap for the path forward. A follow-up meeting in 2022 aimed to review the current state of the field and to identify critical barriers and milestones for progress. DESIGN: The ASSFN convened a meeting on June 3, 2022 in Atlanta, Georgia and included leaders from the fields of neurology, neurosurgery, and psychiatry along with colleagues from industry, government, ethics, and law. The goal was to review the current state of the field, assess for advances or setbacks in the interim six years, and suggest a future path forward. The participants focused on five areas of interest: interdisciplinary engagement, regulatory pathways and trial design, disease biomarkers, ethics of psychiatric surgery, and resource allocation/prioritization. The proceedings are summarized here. CONCLUSION: The field of surgical psychiatry has made significant progress since our last expert meeting. Although weakness and threats to the development of novel surgical therapies exist, the identified strengths and opportunities promise to move the field through methodically rigorous and biologically-based approaches. The experts agree that ethics, law, patient engagement, and multidisciplinary teams will be critical to any potential growth in this area.

Age- and Episodic Memory-related Differences in Task-based Functional Connectivity in Women and Men.

Aging is associated with episodic memory decline and changes in functional brain connectivity. Understanding whether and how biological sex influences age- and memory performance-related functional connectivity has important theoretical implications for the cognitive neuroscience of memory and aging. Here, we scanned 161 healthy adults between 19 and 76 years of age in an event-related fMRI study of face-location spatial context memory. Adults were scanned while performing easy and difficult versions of the task at both encoding and retrieval. We used multivariate whole-brain partial least squares connectivity to test the hypothesis that there are sex differences in age- and episodic memory performance-related functional connectivity. We examined how individual differences in age and retrieval accuracy correlated with task-related connectivity. We then repeated this analysis after disaggregating the data by self-reported sex. We found that increased encoding and retrieval-related connectivity within the dorsal attention network (DAN), and between DAN and frontoparietal network and visual networks, were positively correlated to retrieval accuracy and negatively correlated with age in both sexes. We also observed sex differences in age- and performance-related functional connectivity: (a) Greater between-networks integration was apparent at both levels of task difficulty in women only, and (b) increased DAN-default mode network connectivity with age was observed in men and was correlated with poorer memory performance. Therefore, the neural correlates of age-related episodic memory decline differ in women and men and have important theoretical and clinical implications for the cognitive neuroscience of memory, aging, and dementia prevention.

The association between cognitive reserve and performance-related brain activity during episodic encoding and retrieval across the adult lifespan.

Remembering associations between encoded items and their contextual setting is a feature of episodic memory. Although this ability generally deteriorates with age, there is substantial variability in how older individuals perform on episodic memory tasks. A current topic of debate in the cognitive neuroscience of aging literature revolves around whether this variability may stem from genetic and/or environmental factors related to reserve, allowing some individuals to compensate for age-related decline through differential recruitment of brain regions. In this fMRI study spanning a large adult lifespan sample (N = 154), we tested whether higher cognitive reserve was associated with better task-fMRI context memory performance, and functional compensatory activity patterns in the aging brain. We used multivariate Behaviour Partial Least Squares (B-PLS) analysis to examine how age, retrieval accuracy, and a proxy measure of cognitive reserve [i.e., a composite score consisting of years of education (EDU) and crystallized IQ], impacted brain activity during the encoding and retrieval of spatial and temporal contextual details. The results indicated that age-related increases in encoding activity within anterior and lateral frontal, inferior parietal, occipito-temporal and medial temporal cortices, was correlated with better subsequent memory performance; and may be indicative of age-related functional compensation at encoding. Interestingly this compensatory pattern was not correlated with our proxy measure of cognitive reserve but was associated with total brain volume (a measure of brain reserve). However, cognitive reserve was associated with age-invariant and task-general activity in superior temporal, occipital, and left inferior frontal regions. We conclude that the relationship between cognitive reserve, brain reserve and age-related functional compensation is complex, and that EDU and IQ may not fully account for individual differences in cognitive reserve when studying well educated, healthy aging cohorts.

Sex Differences in the Neural Correlates of Spatial Context Memory Decline in Healthy Aging.

Aging is associated with episodic memory decline and alterations in memory-related brain function. However, it remains unclear if age-related memory decline is associated with similar patterns of brain aging in women and men. In the current task fMRI study, we tested the hypothesis that there are sex differences in the effect of age and memory performance on brain activity during episodic encoding and retrieval of face-location associations (spatial context memory). Forty-one women and 41 men between the ages of 21 and 76 years participated in this study. Between-group multivariate partial least squares analysis of the fMRI data was conducted to directly test for sex differences and similarities in age-related and performance-related patterns of brain activity. Our behavioral analysis indicated no significant sex differences in retrieval accuracy on the fMRI tasks. In relation to performance effects, we observed similarities and differences in how retrieval accuracy related to brain activity in women and men. Both sexes activated dorsal and lateral PFC, inferior parietal cortex, and left parahippocampal gyrus at encoding, and this supported subsequent memory performance. However, there were sex differences in retrieval activity in these same regions and in lateral occipital-temporal and ventrolateral PFC. In relation to age effects, we observed sex differences in the effect of age on memory-related activity within PFC, inferior parietal cortex, parahippocampal gyrus, and lateral occipital-temporal cortices. Overall, our findings suggest that the neural correlates of age-related spatial context memory decline differ in women compared with men.

Age-related differences in prefrontal-hippocampal connectivity are associated with reduced spatial context memory.

Altered functional connectivity between dorsolateral prefrontal cortex (DLPFC), posterior hippocampus (HC) and other brain regions with advanced age may contribute to age-related differences in episodic memory. In the current fMRI study of spatial context memory, we used seed connectivity analysis to test for age-related differences in the correlations between activity in DLPFC and HC seeds, and the rest of the brain, in an adult life span sample. In young adults, we found that connectivity between right DLPFC and other prefrontal cortex regions, parietal cortex, precuneus, and ventral visual cortices during encoding was positively related to performance. Positive seed connectivity among these regions, and negative connectivity with posterior HC at retrieval was also positively correlated with retrieval accuracy in young adults. In older adults, activity in right DLPFC was positively correlated with activity in this same set of brain regions, and with posterior HC during encoding and retrieval. Interestingly, this pattern of seed connectivity in older adults was negatively correlated with retrieval accuracy. Thus, age-related differences in context memory may be related to altered frontal-parietal and visual cortical interactions with posterior HC. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Greater perceived similarity between self and own-age others in older than young adults.

As people age, they increasingly incorporate age-stereotypes into their self-view. Based on this evidence we propose that older compared to young adults identify to a greater extent with their own-age group on personality traits, an effect that may be particularly pronounced for positive traits. Two studies tested these hypotheses by examining associations in young and older adults between evaluations of self and own-age others on personality traits that varied on valence. In both studies, young and older participants rated personality trait adjectives on age typicality, valence, and self-typicality. Converging results across both studies showed that older compared to young participants were more likely to endorse personality traits as self-typical when those traits were also perceived as more typical for their own-age group, independent of whether age was made salient to participants prior to evaluation. In addition, there was evidence that the association between evaluations of self and own-age others in older participants was greater for more positive personality traits. This age-differential pattern is discussed in the context of increased age salience in aging and its effect on the similarity between evaluations of self and own-age others in older compared to young adults. (PsycINFO Database Record

Context Memory Decline in Middle Aged Adults is Related to Changes in Prefrontal Cortex Function.

The ability to encode and retrieve spatial and temporal contextual details of episodic memories (context memory) begins to decline at midlife. In the current study, event-related fMRI was used to investigate the neural correlates of context memory decline in healthy middle aged adults (MA) compared with young adults (YA). Participants were scanned while performing easy and hard versions of spatial and temporal context memory tasks. Scans were obtained at encoding and retrieval. Significant reductions in context memory retrieval accuracy were observed in MA, compared with YA. The fMRI results revealed that overall, both groups exhibited similar patterns of brain activity in parahippocampal cortex, ventral occipito-temporal regions and prefrontal cortex (PFC) during encoding. In contrast, at retrieval, there were group differences in ventral occipito-temporal and PFC activity, due to these regions being more activated in MA, compared with YA. Furthermore, only in YA, increased encoding activity in ventrolateral PFC, and increased retrieval activity in occipital cortex, predicted increased retrieval accuracy. In MA, increased retrieval activity in anterior PFC predicted increased retrieval accuracy. These results suggest that there are changes in PFC contributions to context memory at midlife.

Age-related differences in the neural basis of the subjective vividness of memories: evidence from multivoxel pattern classification.

Although older adults often show reduced episodic memory accuracy, their ratings of the subjective vividness of their memories often equal or even exceed those of young adults. Such findings suggest that young and older adults may differentially access and/or weight different kinds of information in making vividness judgments. We examined this idea using multivoxel pattern classification of fMRI data to measure category representations while participants saw and remembered pictures of objects and scenes. Consistent with our hypothesis, there were age-related differences in how category representations related to the subjective sense of vividness. During remembering, older adults' vividness ratings were more related, relative to young adults', to category representations in prefrontal cortex. In contrast, young adults' vividness ratings were more related, relative to older adults, to category representations in parietal cortex. In addition, category representations were more correlated among posterior regions in young than in older adults, whereas correlations between PFC and posterior regions did not differ between the 2 groups. Together, these results are consistent with the idea that young and older adults differentially weight different types of information in assessing subjective vividness of their memories.

Age-related differences in agenda-driven monitoring of format and task information.

Age-related source memory deficits may arise, in part, from changes in the agenda-driven processes that control what features of events are relevant during remembering. Using fMRI, we compared young and older adults on tests assessing source memory for format (picture, word) or encoding task (self-, other-referential), as well as on old-new recognition. Behaviorally, relative to old-new recognition, older adults showed disproportionate and equivalent deficits on both source tests compared to young adults. At encoding, both age groups showed expected activation associated with format in posterior visual processing areas, and with task in medial prefrontal cortex. At test, the groups showed similar selective, agenda-related activity in these representational areas. There were, however, marked age differences in the activity of control regions in lateral and medial prefrontal cortex and lateral parietal cortex. Results of correlation analyses were consistent with the idea that young adults had greater trial-by-trial agenda-driven modulation of activity (i.e., greater selectivity) than did older adults in representational regions. Thus, under selective remembering conditions where older adults showed clear differential regional activity in representational areas depending on type of test, they also showed evidence of disrupted frontal and parietal function and reduced item-by-item modulation of test-appropriate features. This pattern of results is consistent with an age-related deficit in the engagement of selective reflective attention.

The cognitive neuroscience of true and false memories.

Of central relevance to the recovered/false memory debate is understanding the factors that cause us to believe that a mental experience is a memory of an actual past experience. According to the source monitoring framework (SMF), memories are attributions that we make about our mental experiences based on their subjective qualities, our prior knowledge and beliefs, our motives and goals, and the social context. From this perspective, we discuss cognitive behavioral studies using both objective (e.g., recognition, source memory) and subjective (e.g., ratings of memory characteristics) measures that provide much information about the encoding, revival and monitoring processes that yield both true and false memories. The chapter also considers how neuroimaging findings, especially from functional magnetic resonance imaging studies, are contributing to our understanding of the relation between memory and reality.