A comparison of rapid rule-learning strategies in humans and monkeys.

Inter-species comparisons are key to deriving an understanding of the behavioral and neural correlates of human cognition from animal models. We perform a detailed comparison of the strategies of female macaque monkeys to male and female humans on a variant of the Wisconsin Card Sort Test (WCST), a widely studied and applied task that provides a multi-attribute measure of cognitive function and depends on the frontal lobe. WCST performance requires the inference of a rule change given ambiguous feedback. We found that well-trained monkeys infer new rules three times more slowly than minimally instructed humans. Input-dependent Hidden Markov Model-Generalized Linear Models were fit to their choices, revealing hidden states akin to feature-based attention in both species. Decision processes resembled a Win-Stay Lose-Shift strategy with inter-species similarities as well as key differences. Monkeys and humans both test multiple rule hypotheses over a series of rule-search trials and perform inference-like computations to exclude candidate choice options. We quantitatively show that perseveration, random exploration and poor sensitivity to negative feedback account for the slower task-switching performance in monkeys.Significance Statement Advances in training and recording from animal models support the study of increasingly complex behaviors in non-humans. Before interpreting their neural computations as human-like, we must first ascertain whether their computational algorithms are human-like. We compared rapid rule-learning strategies of macaque monkeys and humans on a Wisconsin Card Sorting Test variant and found that monkeys are 3-4 times slower than humans at learning new rules. Model fits to choice behavior revealed that both species use qualitatively similar exploration strategies with different decision criteria. These differences produced distinct errors in monkeys that are similar to those observed in humans with prefrontal deficits. Our results generate detailed neural hypotheses and highlight the need for systematic inter-species behavioral and neural comparisons.

Comparing rapid rule-learning strategies in humans and monkeys.

Inter-species comparisons are key to deriving an understanding of the behavioral and neural correlates of human cognition from animal models. We perform a detailed comparison of macaque monkey and human strategies on an analogue of the Wisconsin Card Sort Test, a widely studied and applied multi-attribute measure of cognitive function, wherein performance requires the inference of a changing rule given ambiguous feedback. We found that well-trained monkeys rapidly infer rules but are three times slower than humans. Model fits to their choices revealed hidden states akin to feature-based attention in both species, and decision processes that resembled a Win-stay lose-shift strategy with key differences. Monkeys and humans test multiple rule hypotheses over a series of rule-search trials and perform inference-like computations to exclude candidates. An attention-set based learning stage categorization revealed that perseveration, random exploration and poor sensitivity to negative feedback explain the under-performance in monkeys.

Intra- and inter-regional dynamics in cortical-striatal-tegmental networks.

It is increasingly recognized that networks of brain areas work together to accomplish computational goals. However, functional connectivity networks are not often compared between different behavioral states and across different frequencies of electrical oscillatory signals. In addition, connectivity is always defined as the strength of signal relatedness between two atlas-based anatomical locations. Here, we performed an exploratory analysis using data collected from high-density arrays in the prefrontal cortex (PFC), striatum (STR), and ventral tegmental area (VTA) of male rats. These areas have all been implicated in a wide range of different tasks and computations including various types of memory as well as reward valuation, habit formation and execution, and skill learning. Novel intraregional clustering analyses identified patterns of spatially restricted, temporally coherent, and frequency-specific signals that were reproducible across days and were modulated by behavioral states. Multiple clusters were identified within each anatomical region, indicating a mesoscopic scale of organization. Generalized eigendecomposition (GED) was used to dimension-reduce each cluster to a single component time series. Dense intercluster connectivity was modulated by behavioral state, with connectivity becoming reduced when the animals were exposed to a novel object, compared with a baseline condition. Behavior-modulated connectivity changes were seen across the spectrum, with δ, θ, and γ all being modulated. These results demonstrate the brain's ability to reorganize functionally at both the intra- and inter-regional levels during different behavioral states.NEW & NOTEWORTHY We applied novel clustering techniques to discover functional subregional anatomical patches that changed with behavioral conditions but were frequency specific and stable across days. By taking into account these changes in intraregional signal generator location and extent, we were able to reveal a richer picture of inter-regional functional connectivity than would otherwise have been possible. These findings reveal that the brain's functional organization changes with state at multiple levels of scale.

Effects of home drug delivery on drug-related problems: preliminary evidence for improved patient outcomes during the COVID-19 pandemic in Thailand.

BACKGROUND: Drug-related problems cause severe disabilities, premature deaths, and unnecessary costs. Telepharmacy offer easier access to needed medications, preventing DRPs. Adoption has been slow, and it is unclear what aspects of telepharmacy are most important. The COVID-19 pandemic disrupted health services, forcing the rapid adoption of telepharmacy. In Phayao, Thailand, a program was implemented for home delivery of drugs for patients with chronic disease. OBJECTIVES: This study aimed to explore the prevalence and factors associated with DRPs of patients with chronic disease who received home drug-delivery services. METHODS: A cross-sectional study was undertaken in Phayao Province located in North Thailand. Simple random sampling was used to select patients from 6 public hospitals between July and August 2020. Logistic regression was used to analyze multivariate factors that might be related to DRPs. RESULTS: A total of 246 participants reported at least 1 DRP (49.30%). Most participants were female (58.32%) with elementary education (60.72%). Their mean age was 63.69 (SD = 12.97) years. The 5 most common DRPs were changes of drug packaging or drug brands (18.84%), leftover medications of more than 2 weeks (18.44%), nonadherence (17.43%), having conditions or diseases requiring additional medications (6.81%), and adverse drug reactions (5.21%). Univariate analysis identified number of chronic conditions, diabetes mellitus, dyslipidemia, chronic kidney disease, education level, and drug-delivery channel as predictors of DRPs. In multivariate analysis, predictors of DRPs were the number of drugs used per day (adjusted odds ratio [aOR] 1.11 [95% CI 1.03-1.19], P = 0.004) and dyslipidemia (aOR 1.83 [95% CI 1.18-2.84], P = 0.007). Nonadherence was associated with leftover medicines (aOR 4.22 [95% CI 2.44-7.28], P < 0.001) CONCLUSION: The present results indicate that home delivery caused no increase and may have caused a decrease in DRPs, and patients were highly satisfied. These promising results suggest that home delivery should be continued and further investigated even as the COVID-19-induced emergency subsides.

Community Health Workers Improve Smoking Cessation When They Recruit Patients in Their Home Villages.

INTRODUCTION/OBJECTIVE: Community health workers (CHWs) can play a vital role in many aspects of healthcare, particularly for underserved communities, but it is unclear what factors are most important in determining the success of CHW-based programs. We wanted to assess what factors contribute to the effectiveness of CHWs in a smoking cessation program. METHODS: We trained CHWs in 3 areas regarding smoking cessation: knowledge, attitude, and practice (KAP). The training program utilized the 5A's as approach. CHWs actively sought out people addicted to cigarettes to participate. Patients received support from CHWs and a team of medical professionals for a year. At the conclusion of the program, focus group discussions with a group of CHWs, a group of patients, and a group of medical professionals were conducted. RESULTS: On average, patients reduced their cigarettes/day by 7.2% and 29% of patients were completely cigarette free at a 1-year follow-up. Patients marginally decreased exhalation CO levels and increased lung capacity. CHWs gained a good understanding of health risks associated with smoking and common methods to help quit. Their attitude became more sympathetic and caring. CHWs exhibited patient-specific solutions to help with smoking cessation and actively sought out people to participate in the smoking cessation program. CONCLUSIONS: A smoking cessation program combining CHWs and pharmacists was effective. Key factors were having CHWs that are respected and established in their communities, using CHWs who know their patients and can provide individually tailored solutions, and empowering CHWs with intensive training.

mHealth Technology Translation in a Limited Resources Community-Process, Challenges, and Lessons Learned From a Limited Resources Community of Chiang Mai Province, Thailand.

This report aims to provide practical advice about the implementation of a public health monitoring system using both geographic information system technology and mobile health, a term used for healthcare delivery via mobile devices. application amongst household residents and community stakeholders in the limited resource community. A public health monitoring system was implemented in a semi-rural district in Thailand. The challenges encountered during implementation were documented qualitatively in a series of monthly focus group discussions, several community hearings, and many targeted interviews. In addition, lessons learned from the expansion of the program to 75 other districts throughout Thailand were also considered. All challenges proved solvable yielding several key pieces of advice for future project implementation teams. Specifically, communication between team members, anticipating technological challenges, and involvement of community members are critical. The problems encountered in our project were mainly related to the capabilities of the data collectors and technical issues of mobile devices, internet coverage, and the GIS application itself. During the implementation phase, progressive changes needed to be made to the system promptly, in parallel with community team building in order to get the highest public health impact.

The Functional and Structural Neuroanatomy of Systems Consolidation for Autobiographical and Semantic Memory.

It is well established that patients with memory impairment have more difficulty retrieving memories from the recent past relative to the remote past and that damage to the medial temporal lobe (MTL) plays a key role in this pattern of impairment. The precise role of the MTL and how it may interact with other brain regions remains an area of active research. We investigated the role of structures in a memory network that supports remembering. Our chapter focuses on two types of memory: episodic memory and semantic memory. Findings from studies of patients with brain damage and neuroimaging studies in patients and healthy individuals were considered together to identify the functional and structural neuroanatomy of past remembrance.

Autobiographical memory, future imagining, and the medial temporal lobe.

In two experiments, patients with damage to the medial temporal lobe (MTL) and healthy controls produced detailed autobiographical narratives as they remembered past events (recent and remote) and imagined future events (near and distant). All recent events occurred after the onset of memory impairment. The first experiment aimed to replicate the methods of Race et al. [Race E, Keane MM, Verfaellie M (2011) J Neurosci 31(28):10262-10269]. Transcripts from that study were kindly made available for independent analysis, which largely reproduced the findings from that study. Our patients produced marginally fewer episodic details than controls. Patients from the earlier study were more impaired than our patients. Patients in both groups had difficulty in returning to their narratives after going on tangents, suggesting that anterograde memory impairment may have interfered with narrative construction. In experiment 2, the experimenter used supportive questioning to help keep participants on task and reduce the burden on anterograde memory. This procedure increased the number of details produced by all participants and rescued the performance of our patients for the distant past. Neither of the two patient groups had any special difficulty in producing spatial details. The findings suggest that constructing narratives about the remote past and the future does not depend on MTL structures, except to the extent that anterograde amnesia affects performance. The results further suggest that different findings about the status of autobiographical memory likely depend on differences in the location and extent of brain damage in different patient groups.

Learning and remembering real-world events after medial temporal lobe damage.

The hippocampus is important for autobiographical memory, but its role is unclear. In the study, patients with hippocampal damage and controls were taken on a 25-min walk on the University of California, San Diego, campus during which 11 planned events occurred. Memory was tested directly after the walk. In addition, a second group of controls took the same walk and were tested after 1 mo. Patients with hippocampal damage remembered fewer details than controls tested directly after the walk but remembered a similar number of details as controls tested after 1 mo. Notably, the details that were reported by patients had the characteristics of episodic recollection and included references to particular places and events. Patients exhibited no special difficulty remembering spatial details in comparison with nonspatial details. Last, whereas both control groups tended to recall the events of the walk in chronological order, the order in which patients recalled the events was unrelated to the order in which they occurred. The findings illuminate the role of the hippocampus in autobiographical memory and in the spatial and nonspatial aspects of episodic recollection.

Memory, scene construction, and the human hippocampus.

We evaluated two different perspectives about the function of the human hippocampus--one that emphasizes the importance of memory and another that emphasizes the importance of spatial processing and scene construction. We gave tests of boundary extension, scene construction, and memory to patients with lesions limited to the hippocampus or large lesions of the medial temporal lobe. The patients were intact on all of the spatial tasks and impaired on all of the memory tasks. We discuss earlier studies that associated performance on these spatial tasks to hippocampal function. Our results demonstrate the importance of medial temporal lobe structures for memory and raise doubts about the idea that these structures have a prominent role in spatial cognition.

Conscious and unconscious memory systems.

The idea that memory is not a single mental faculty has a long and interesting history but became a topic of experimental and biologic inquiry only in the mid-20th century. It is now clear that there are different kinds of memory, which are supported by different brain systems. One major distinction can be drawn between working memory and long-term memory. Long-term memory can be separated into declarative (explicit) memory and a collection of nondeclarative (implicit) forms of memory that include habits, skills, priming, and simple forms of conditioning. These memory systems depend variously on the hippocampus and related structures in the parahippocampal gyrus, as well as on the amygdala, the striatum, cerebellum, and the neocortex. This work recounts the discovery of declarative and nondeclarative memory and then describes the nature of declarative memory, working memory, nondeclarative memory, and the relationship between memory systems.

A novel approach to an old problem: analysis of systematic errors in two models of recognition memory.

For more than a decade, the high threshold dual process (HTDP) model has served as a guide for studying the functional neuroanatomy of recognition memory. The HTDP model's utility has been that it provides quantitative estimates of recollection and familiarity, two processes thought to support recognition ability. Important support for the model has been the observation that it fits experimental data well. The continuous dual process (CDP) model also fits experimental data well. However, this model does not provide quantitative estimates of recollection and familiarity, making it less immediately useful for illuminating the functional neuroanatomy of recognition memory. These two models are incompatible and cannot both be correct, and an alternative method of model comparison is needed. We tested for systematic errors in each model's ability to fit recognition memory data from four independent data sets from three different laboratories. Across participants and across data sets, the HTDP model (but not the CDP model) exhibited systematic error. In addition, the pattern of errors exhibited by the HTDP model was predicted by the CDP model. We conclude that the CDP model provides a better account of recognition memory than the HTDP model.

Hippocampal damage impairs recognition memory broadly, affecting both parameters in two prominent models of memory.

Declarative memory is thought to rely on two processes: recollection and familiarity. Recollection involves remembering specific details about the episode in which an item was encountered, and familiarity involves simply knowing that an item was presented even when no information can be recalled about the episode itself. There has been debate whether the hippocampus supports only recollection or whether it supports both processes. We approached this issue in a relatively theory-neutral way by fitting two prominent models that have been used to describe recognition memory: dual process signal detection and unequal variance signal detection. Both models yield two parameters of interest when fit to recognition memory data. The dual process signal detection model yields estimates of recollection (r) and familiarity (d'). The unequal variance signal detection model yields estimates of the ratio of the variance of target and foil memory strength distributions (σtarget/σfoil) and the difference in the means of the two distributions (d). We asked how the two parameters of each model were affected by hippocampal damage. We tested five patients with well-characterized bilateral lesions thought to be limited to the hippocampus and age-matched controls. The patients exhibited a broad memory deficit that markedly reduced the value of both parameters in both models. In addition, the pattern of results exhibited by the patients was recapitulated in healthy controls as the delay between learning and testing was extended. Thus, hippocampal damage impairs both component processes of recognition memory.