Prefrontal cortical activation associated with prospective memory while walking around a real-world street environment
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ABSTRACT:
SUBMITTER: Burgess P
PROVIDER: S-EPMC10509823 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
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Project description:BackgroundProspective memory (PM) denotes the ability to remember to perform actions in the future. It has been argued that standard laboratory paradigms fail to capture core aspects of PM.Methodology/principal findingsWe combined functional MRI, virtual reality, eye-tracking and verbal reports to explore the dynamic allocation of neurocognitive processes during a naturalistic PM task where individuals performed errands in a realistic model of their residential town. Based on eye movement data and verbal reports, we modeled PM as an iterative loop of five sustained and transient phases: intention maintenance before target detection (TD), TD, intention maintenance after TD, action, and switching, the latter representing the activation of a new intention in mind. The fMRI analyses revealed continuous engagement of a top-down fronto-parietal network throughout the entire task, likely subserving goal maintenance in mind. In addition, a shift was observed from a perceptual (occipital) system while searching for places to go, to a mnemonic (temporo-parietal, fronto-hippocampal) system for remembering what actions to perform after TD. Updating of the top-down fronto-parietal network occurred at both TD and switching, the latter likely also being characterized by frontopolar activity.Conclusion/significanceTaken together, these findings show how brain systems complementary interact during real-world PM, and support a more complete model of PM that can be applied to naturalistic PM tasks and that we named PROspective MEmory DYnamic (PROMEDY) model because of its dynamics on both multi-phase iteration and the interactions of distinct neurocognitive networks.
| S-EPMC2951914 | biostudies-literature
Project description:IntroductionProspective memory (PM) is a marker of independent living in Alzheimer's disease. PM requires cue identification (prospective component) and remembering what should happen in response to the cue (retrospective component). We assessed neuroanatomical basis and functional relevance of PM.Methods84 older participants (53-94 years old, 58% male) with or without Mild Cognitive Impairment (MCI) performed PM tests, Activities of Daily Living (ADL) scale and had a structural MRI of the brain to estimate for cortical thickness and hippocampal subfield volumes. A General Linear Model cluster analysis was carried out using FreeSurfer to determine which cortical regions were correlated with PM scores.ResultsBoth components of PM are impaired in MCI (p < .001). The retrospective component of PM correlates strongly with ADL (p = .005). Prospective component performance correlates positively with cortical thickness of bilateral frontal-temporal-parietal cortex and volume of CA1 of hippocampus. In contrast, the retrospective component performance correlates positively with cortical thickness of a right-lateralised fronto-temporal-parietal network and volumes of subiculum and CA3 hippocampal subfields.DiscussionOur neuroimaging findings complement and extend previous research into structural correlates of PM. Here, we show that there are distinct, yet, overlapping brain regions correlating with the two components of PM. PM performance provides a window into real-life functional abilities in people at risk of Alzheimer's disease and could be utilised as a marker of clinically relevant disease.
| S-EPMC7063259 | biostudies-literature
Project description:Urothelial carcinoma (UC) of the urinary bladder has significant challenges in treatment due to its diverse genetic landscape and variable response to systemic therapy. In recent years, patient-derived organoids (PDOs) emerged as a novel tool to model primary tumors with higher resemblance than conventional 2D cell culture approaches. However, the potential of organoids to predict therapy response in a clinical setting remains to be evaluated. This study explores the clinical feasibility of PDOs for pharmacotyping in UC. Initially, we subjected tumor tissue specimens from 50 patients undergoing transurethral resection or radical cystectomy to organoid propagation, of whom 19 (38%) yielded PDOs suitable for drug sensitivity assessment. Notably, whole transcriptome-based analysis indicated that PDOs may show phenotypes distinct from their parental tumor tissue. Pharmacotyping within a clinically relevant timeframe [mean of 35.44 and 55 days for non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC), respectively] was achieved. Drug sensitivity analyses revealed marked differences between NMIBC and MIBC, with MIBC-derived organoids demonstrating higher chemosensitivity toward clinically relevant drugs. A case study correlating organoid response with patient treatment outcome illustrated the complexity of predicting chemotherapy efficacy, especially considering the rapid acquisition of drug resistance. We propose a workflow of prospective organoid-based pharmacotyping in UC, enabling further translational research and integration of this approach into clinical practice.
2024-11-03 | GSE280749 | GEO
Project description:Personalized exoskeleton assistance provides users with the largest improvements in walking speed1 and energy economy2-4 but requires lengthy tests under unnatural laboratory conditions. Here we show that exoskeleton optimization can be performed rapidly and under real-world conditions. We designed a portable ankle exoskeleton based on insights from tests with a versatile laboratory testbed. We developed a data-driven method for optimizing exoskeleton assistance outdoors using wearable sensors and found that it was equally effective as laboratory methods, but identified optimal parameters four times faster. We performed real-world optimization using data collected during many short bouts of walking at varying speeds. Assistance optimized during one hour of naturalistic walking in a public setting increased self-selected speed by 9 ± 4% and reduced the energy used to travel a given distance by 17 ± 5% compared with normal shoes. This assistance reduced metabolic energy consumption by 23 ± 8% when participants walked on a treadmill at a standard speed of 1.5 m s-1. Human movements encode information that can be used to personalize assistive devices and enhance performance.
| S-EPMC9556303 | biostudies-literature
Project description: Not available
| S-EPMC10643567 | biostudies-literature
Project description:BackgroundEcological validity is an important psychometric property when assessing function. How a person with multiple sclerosis (MS) performs in clinical settings and in natural environments can be quite different. Walking is the most frequently assessed and recommended way to maintain health in a progressive disease such as MS. The objective was to estimate the extent to which clinical tests of walking capacity differ from real-world walking performance in people with MS.MethodsNinety-eight women and 27 men with MS were assessed using the 6-Minute Walk Test (6MWT) and wore an accelerometer for 7 consecutive days. Mean number of steps, mean number of steps at a brisk cadence or faster, and cumulative time per week spent walking at a brisk cadence or faster were regressed on 6MWT categories using quantile (median) regression. Contiguous steps were grouped into bouts of less than 5 minutes and 5 minutes or longer, and number of bouts 5 minutes or longer was regressed on 6MWT categories using a zero-inflated Poisson model.ResultsA total of 869 patient-days of accelerometer data were available. Mean total number of steps per day was greater for people with higher walking capacity (6MWT distance, ≥600 m). However, this group spent a small proportion of time walking at higher cadence bands. Compared with people with 6MWT distance of at least 600 m, people walking less than 500 m had approximately half the rate of walking bouts of 5 minutes or longer. Positive mood and fewer exercise barriers predicted more walking bouts of at least 5 minutes.ConclusionsStudy participants with MS spent a small proportion of time walking at a health-promoting intensity.
| S-EPMC7307876 | biostudies-literature
Project description:ObjectiveTo investigate cortical microstructural measures from diffusion MRI as "neurodegeneration" markers that could improve prognostic accuracy in mild cognitive impairment (MCI).MethodsThe prognostic power of Amyloid/Tau/Neurodegeneration (ATN) biomarkers to predict progression from MCI to AD or non-AD dementia was investigated. Ninety patients underwent clinical evaluation (follow-up interval 32 ± 18 months), lumbar puncture, and MRI. Participants were grouped by clinical stage and cerebrospinal fluid Amyloid and Tau status. T1-structural and diffusion MRI scans were analyzed to calculate diffusion metrics related to cortical columnar structure (AngleR, ParlPD, PerpPD+), cortical mean diffusivity, and fractional anisotropy. Statistical tests were corrected for multiple comparisons. Prognostic power was assessed using receiver operating characteristic (ROC) analysis and related indices.ResultsA progressive increase of whole-brain cortical diffusion values was observed along the AD continuum, with all A+ groups showing significantly higher AngleR than A-T-. Investigating clinical progression to dementia, the AT biomarkers together showed good positive predictive value (with 90.91% of MCI A+T+ converting to dementia) but poor negative predictive value (with 40% of MCI A-T- progressing to a mix of AD and non-AD dementias). Adding whole-brain AngleR as an N marker, produced good differentiation between stable and converting MCI A-T- patients (0.8 area under ROC curve) and substantially improved negative predictive value (+21.25%).InterpretationResults support the clinical utility of cortical microstructure to aid prognosis, especially in A-T- patients. Further work will investigate other complexities of the real-world clinical setting, including A-T+ groups. Diffusion MRI measures of neurodegeneration may complement fluid AT markers to support clinical decision-making.
| S-EPMC11330221 | biostudies-literature
Project description:Autobiographical remembering can depend on two forms of memory: episodic (event) memory and autobiographical semantic memory (remembering personally relevant semantic knowledge, independent of recalling a specific experience). There is debate about the degree to which the neural signals that support episodic recollection relate to or build upon autobiographical semantic remembering. Pooling data from two fMRI studies of memory for real-world personal events, we investigated whether medial temporal lobe (MTL) and parietal subregions contribute to autobiographical episodic and semantic remembering. During scanning, participants made memory judgments about photograph sequences depicting past events from their life or from others' lives, and indicated whether memory was based on episodic or semantic knowledge. Results revealed several distinct functional patterns: activity in most MTL subregions was selectively associated with autobiographical episodic memory; the hippocampal tail, superior parietal lobule, and intraparietal sulcus were similarly engaged when memory was based on retrieval of an autobiographical episode or autobiographical semantic knowledge; and angular gyrus demonstrated a graded pattern, with activity declining from autobiographical recollection to autobiographical semantic remembering to correct rejections of novel events. Collectively, our data offer insights into MTL and parietal cortex functional organization, and elucidate circuitry that supports different forms of real-world autobiographical memory.
| S-EPMC5906442 | biostudies-literature
Project description:Previous research has revealed an age-related shift in how individuals recall events from their personal past, with older adults reporting events that are more positive than young adults. We recently showed that age-by-valence interactions may be partially driven by a prefrontally mediated control mechanism recruited by older adults during retrieval of negative laboratory events to reduce phenomenological richness. Specifically, age was associated with greater increases in prefrontal recruitment during retrieval of negative relative to positive events, with this recruitment linked to decreases in hippocampal activity and subjective vividness ratings. In the current study, we examined whether older adults may rely on a similar mechanism during retrieval of a complex, highly emotional real-world event. Participants (n=58, age: 18-87 years) were presented with images related to the 2013 Boston Marathon Bombings and were asked to retrieve a memory associated with each image. Images cued participants with either negative (associated with fear, destruction, and sadness) or positive (images of hope, resilience, support) features. This study replicated previous episodic memory tasks: age was associated with more negative hippocampal connectivity with dorsomedial prefrontal regions during retrieval of memories triggered by negative relative to positive cues. Such findings suggest that older adults may be recruiting a similar regulatory mechanism during retrieval of both negative laboratory stimuli and highly negative events from their past. These findings are discussed in relation to previous work showing that young and older adults interact differently with the negative details related to a highly negative event.
| S-EPMC6070401 | biostudies-literature
Project description:Dysfunction in prefrontal cortex (PFC) GABA transmission has been proposed to contribute to cognitive dysfunction in schizophrenia, yet how this system regulates different cognitive and mnemonic functions remains unclear. We assessed the effects of pharmacological reduction of GABAA signaling in the medial PFC of rats on spatial reference/working memory using different versions of the radial-arm maze task. We used a massed-trials procedure to probe how PFC GABA regulates susceptibility to proactive interference. Male rats were well-trained to retrieve food from the same 4 arms of an 8-arm maze, receiving 5 trials/day (1-2 min intervals). Infusions of the GABAA receptor antagonist bicuculline (12.5-50 ng) markedly increased working and reference memory errors and response latencies. Similar treatments also impaired short-term memory on an 8-baited arm task. These effects did not appear to be due to increased susceptibility to proactive interference. In contrast, PFC inactivation via infusion of GABA agonists baclofen/muscimol did not affect reference/working memory. In comparison to the pronounced effects on the 8-arm maze tasks, PFC GABAA antagonism only causes a slight and transient decrease in accuracy on a 2-arm spatial discrimination. These findings demonstrate that prefrontal GABA hypofunction severely disrupts spatial reference and short-term memory and that disinhibition of the PFC can, in some instances, perturb memory processes not normally dependent on the frontal lobes. Moreover, these impairments closely resemble those observed in schizophrenic patients, suggesting that perturbation in PFC GABA signaling may contribute to these types of cognitive deficits associated with the disorder.
| S-EPMC4368884 | biostudies-literature