Prospective Memory Training in Older Adults: A Systematic Review and Meta-Analysis.

Prospective memory (PM), which enables one to remember to carry out delayed intentions, is crucial for everyday functioning. PM commonly deteriorates upon cognitive decline in older adults, but several studies have shown that PM in older adults can be improved by training. The current study aimed to summarise this evidence by conducting a qualitative systematic analysis and quantitative meta-analysis of the effects of PM training in older adults, for which systematic searches were conducted across seven databases (Cochrane Library, Embase, PubMed, PsycInfo, Web of Science, CINAHL and Scopus). Forty-eight studies were included in the qualitative analysis, and 43% of the assessed PM training interventions showed positive gains in enhancing PM. However, the methodological quality varied across the studies, with 41% of the non-randomised control trials (non-RCTs) rated as having either serious or critical risk of bias. Therefore, only 29 RCTs were included in the subsequent quantitative meta-analysis. We found a significant and moderate immediate efficacy (Hedges' g = 0.54) of PM training in enhancing PM performance in older adults, but no significant long-term efficacy (Hedges' g = 0.20). Two subgroup analyses also revealed a robust training efficacy across the study population (i.e., healthy and clinical population) and the number of training sessions (i.e., single session and programme-based). Overall, this study provided positive evidence to support PM training in older adults. Further studies are warranted to explore the mechanisms by which PM training exerts its effects, and better-quality RCTs are needed to provide more robust evidence supporting our findings.

Distinct Causal Influences of Dorsolateral Prefrontal Cortex and Posterior Parietal Cortex in Multiple-Option Decision Making.

Our knowledge about neural mechanisms underlying decision making is largely based on experiments that involved few options. However, it is more common in daily life to choose between many options, in which processing choice information selectively is particularly important. The current study examined whether the dorsolateral prefrontal cortex (dlPFC) and posterior parietal cortex (PPC) are of particular importance to multiple-option decision making. Sixty-eight participants received anodal high definition-transcranial direct current stimulation (HD-tDCS) to focally enhance dlPFC or PPC in a double-blind sham-controlled design. Participants then performed a multiple-option decision making task. We found longer fixations on poorer options were related to less optimal decisions. Interestingly, this negative impact was attenuated after applying anodal HD-tDCS over dlPFC, especially in choices with many options. This suggests that dlPFC has a causal role in filtering choice-irrelevant information. In contrast, these effects were absent after participants received anodal HD-tDCS over PPC. Instead, the choices made by these participants were more biased towards the best options presented on the side contralateral to the stimulation. This suggests PPC has a causal role in value-based spatial selection. To conclude, the dlPFC has a role in filtering undesirable options, whereas the PPC emphasizes the desirable contralateral options.

Fronto-cerebellar connectivity mediating cognitive processing speed.

Processing speed is an important construct in understanding cognition. This study was aimed to control task specificity for understanding the neural mechanisms underlying cognitive processing speed. Forty young adult subjects performed attention tasks of two modalities (auditory and visual) and two levels of task rules (compatible and incompatible). Block-design fMRI captured BOLD signals during the tasks. Thirteen regions of interest were defined with reference to publicly available activation maps for processing speed tasks. Cognitive speed was derived from task reaction times, which yielded six sets of connectivity measures. Mixed-effect LASSO regression revealed six significant paths suggestive of a cerebello-frontal network predicting the cognitive speed. Among them, three are long range (two fronto-cerebellar, one cerebello-frontal), and three are short range (fronto-frontal, cerebello-cerebellar, and cerebello-thalamic). The long-range connections are likely to relate to cognitive control, and the short-range connections relate to rule-based stimulus-response processes. The revealed neural network suggests that automaticity, acting on the task rules and interplaying with effortful top-down attentional control, accounts for cognitive speed.

Common and distinct neural trends of allocentric and egocentric spatial coding: An ALE meta-analysis.

The uniqueness of neural processes between allocentric and egocentric spatial coding has been controversial. The distinctive paradigms used in previous studies for manipulating spatial coding could have attributed for the inconsistent results. This study was aimed to generate converging evidence from previous functional brain imaging experiments for collating neural substrates associated with these two types of spatial coding. An additional aim was to test whether test-taking processes would have influenced the results. We obtained coordinate-based functional neuroimaging data for 447 subjects and performed activation likelihood estimation (ALE) meta-analysis. Among the 28 experiments, the results indicate two common clusters of convergence. They were the right precuneus and the right superior frontal gyrus as parts of the parieto-frontal circuit. Between-type differences were in the parieto-occipital circuit, with allocentric showing convergence in the superior occipital gyrus (SOG) cluster compared with egocentric showing convergence in the middle occipital gyrus (MOG) cluster. Task-specific influences were only found in allocentric spatial coding. Spatial judgment-oriented tasks seem to increase the demands on manipulating spatial relationships among the visual objects, while spatial navigation tasks seem to increase the demands on maintaining object representations. Our findings address the theoretical controversies on spatial coding that both the allocentric and egocentric types are common in their processes mediated by the parieto-frontal network, while unique and additional processes in the allocentric type are mediated by the parieto-occipital network. The positive results on possible task-specific confound offer insights into the future design of spatial tasks for eliciting spatial coding processes.

Cortical Hemodynamic Response Associated with Spatial Coding: A Near-Infrared Spectroscopy Study.

Allocentric and egocentric are two types of spatial coding. Previous studies reported the dorsal attention network's involvement in both types. To eliminate possible paradigm-specific confounds in the results, this study employed fine-grained cue-to-target paradigm to dissociate allocentric (aSC) and egocentric (eSC) spatial coding. Twenty-two participants completed a custom visuospatial task, and changes in the concentration of oxygenated hemoglobin (O2-Hb) were recorded using functional near-infrared spectroscopy (fNIRS). The least absolute shrinkage and selection operator-regularized principal component (LASSO-RPC) algorithm was used to identify cortical sites that predicted the aSC and eSC conditions' reaction times. Significant changes in O2-Hb concentration in the right inferior parietal lobule (IPL) and post-central gyrus regions were common in both aSC and eSC. Results of inter-channel correlations further substantiate cortical activities in both conditions were predominantly over the right parieto-frontal areas. Together with right superior frontal gyrus areas be the reaction time neural correlates, the results suggest top-down attention and response-mapping processes are common to both spatial coding types. Changes unique to aSC were in clusters over the right intraparietal sulcus, right temporo-parietal junction, and left IPL. With the left pre-central gyrus region, be the reaction time neural correlate, aSC is likely to involve more orienting attention, updating of spatial information, and object-based response selection and inhibition than eSC. Future studies will use other visuospatial task designs for testing the robustness of the findings on spatial coding processes.

Contrasting Effects of Medial and Lateral Orbitofrontal Cortex Lesions on Credit Assignment and Decision-Making in Humans.

The orbitofrontal cortex is critical for goal-directed behavior. Recent work in macaques has suggested the lateral orbitofrontal cortex (lOFC) is relatively more concerned with assignment of credit for rewards to particular choices during value-guided learning, whereas the medial orbitofrontal cortex (often referred to as ventromedial prefrontal cortex in humans; vmPFC/mOFC) is involved in constraining the decision to the relevant options. We examined whether people with damage restricted to subregions of prefrontal cortex showed the patterns of impairment observed in prior investigations of the effects of lesions to homologous regions in macaques. Groups of patients with either lOFC (predominantly right hemisphere), mOFC/vmPFC, or dorsomedial prefrontal (DMF), and a comparison group of healthy age- and education-matched controls performed a probabilistic 3-choice decision-making task. We report anatomically specific patterns of impairment. We found that credit assignment, as indexed by the normal influence of contingent relationships between choice and reward, is reduced in lOFC patients compared with Controls and mOFC/vmPFC patients. Moreover, the effects of reward contingency on choice were similar for patients with lesions in DMF or mOFC/vmPFC, compared with Controls. By contrast, mOFC/vmPFC-lesioned patients made more stochastic choices than Controls when the decision was framed by valuable distracting alternatives, suggesting that value comparisons were no longer independent of irrelevant options. Once again, there was evidence of regional specialization: patients with lOFC lesions were unimpaired relative to Controls. As in macaques, human lOFC and mOFC/vmPFC are necessary for contingent learning and value-guided decision-making, respectively.SIGNIFICANCE STATEMENT The lateral and medial regions of the orbitofrontal cortex are cytoarchitectonically distinct and have different anatomical connections. Previous investigations in macaques have shown these anatomical differences are accompanied by functional specialization for learning and decision-making. Here, for the first time, we test the predictions made by macaque studies in an experiment with humans with frontal lobe lesions, asking whether behavioral impairments can be linked to lateral or medial orbitofrontal cortex. Using equivalent tasks and computational analyses, our findings broadly replicate the pattern reported after selective lesions in monkeys. Patients with lateral orbitofrontal damage had impaired credit assignment, whereas damage to medial orbitofrontal cortex meant that patients were more likely to be distracted by irrelevant options.

Dopamine and reward: a view from the prefrontal cortex.

The prefrontal cortex (PFC) is a heterogeneous area that is critical to reward-based decision-making. In particular, the dorsal anterior cingulate cortex, ventromedial PFC and orbitofrontal cortex are frequently implicated in different aspects of choice behaviour. These regions receive projections from midbrain dopamine (DA) neurons and, in turn, project to other key dopaminergic regions such as the striatum. However, our current understanding of the role of DA in reward-based processes is based mainly on studies of midbrain dopaminergic neurons and striatal DA release from nonhuman animal models. An important gap in the literature surrounds the precise functions of DA release in the PFC, particularly in humans. A priority for future research will be to integrate, both computationally and biologically, the seemingly disparate value representations across different nodes within the reward-processing network. Such models should aim to define the functional interactions between the PFC and basal ganglia, through which dopaminergic neurotransmission guides reward-based behaviour.

Phosphorylation of Sox9 is required for neural crest delamination and is regulated downstream of BMP and canonical Wnt signaling.

Coordination of neural crest cell (NCC) induction and delamination is orchestrated by several transcription factors. Among these, Sry-related HMG box-9 (Sox9) and Snail2 have been implicated in both the induction of NCC identity and, together with phoshorylation, NCC delamination. How phosphorylation effects this function has not been clear. Here we show, in the developing chick neural tube, that phosphorylation of Sox9 on S64 and S181 facilitates its SUMOylation, and the phosphorylated forms of Sox9 are essential for trunk neural crest delamination. Both phosphorylation and to a lesser extent SUMOylation, of Sox9 are required to cooperate with Snail2 to promote delamination. Moreover, bone morphogenetic protein and canonical Wnt signaling induce phosphorylation of Sox9, thereby connecting extracellular signals with the delamination of NCCs. Together the data suggest a model in which extracellular signals initiate phosphorylation of Sox9 and its cooperation with Snail2 to induce NCC delamination.

Association between fear of falling and falls following acute and chronic stroke: a systematic review with meta-analysis.

OBJECTIVES: To examine the association between falls and fear of falling in people with stroke and to evaluate the differences between patients with acute stroke and those with chronic stroke with regard to any such association. METHODS: Articles were searched in Medline, CINAHL, AMED, Embase, PsycINFO, Cochrane Library of Reviews and PEDro from inception until March 2023. Experimental, observational or explorative studies investigating the association between fear of falling and falls in people with stroke were included. Articles were screened by 2 independent reviewers. Data were extracted by an independent reviewer. RESULTS: A total of 26 reports were included in this review (n = 2863). Fear of falling, assessed by a single-question survey, was significantly associated with falls (relative risk = 1.44; 95% confidence interval (95% CI) = 1.22, 1.70; I2 = 0%) in people with acute stroke. Significant mean differences in fear of falling, based on the Falls Efficacy Scale (mean difference = 12.80; 95% CI = 1.81, 23.78; I² = 28%) and Activities-specific Balance Confidence Scale (mean difference = -9.99; 95% CI = -15.36, -4.62; I² = 57%), were also reported between fallers and non-fallers in people with chronic stroke. CONCLUSION: A small, but significant, association exists between falls and fear of falling in both acute and chronic stroke patients.

Efficacy and safety of transcranial pulse stimulation in young adolescents with attention-deficit/hyperactivity disorder: a pilot, randomized, double-blind, sham-controlled trial.

Background: This is the first study to evaluate the efficacy and safety of transcranial pulse stimulation (TPS) for the treatment of attention-deficit/hyperactivity disorder (ADHD) among young adolescents in Hong Kong. Methods: This double-blind, randomized, sham-controlled trial included a TPS group and a sham TPS group, encompassing a total of 30 subjects aged 12-17 years who were diagnosed with ADHD. Baseline measurements SNAP-IV, ADHD RS-IV, CGI and executive functions (Stroop tests, Digit Span) and post-TPS evaluation were collected. Both groups were assessed at baseline, immediately after intervention, and at 1-month and 3-month follow-ups. Repeated-measures ANOVAs were used to analyze data. Results: The TPS group exhibited a 30% reduction in the mean SNAP-IV score at postintervention that was maintained at 1- and 3-month follow-ups. Conclusion: TPS is an effective and safe adjunct treatment for the clinical management of ADHD. Clinical trial registration: ClinicalTrials.Gov, identifier NCT05422274.

Frontopolar cortex represents complex features and decision value during choice between environments.

Important decisions often involve choosing between complex environments that define future item encounters. Despite its importance for adaptive behavior and distinct computational challenges, decision-making research primarily focuses on item choice, ignoring environment choice altogether. Here we contrast previously studied item choice in ventromedial prefrontal cortex with lateral frontopolar cortex (FPl) linked to environment choice. Furthermore, we propose a mechanism for how FPl decomposes and represents complex environments during decision making. Specifically, we trained a choice-optimized, brain-naive convolutional neural network (CNN) and compared predicted CNN activation with actual FPl activity. We showed that the high-dimensional FPl activity decomposes environment features to represent the complexity of an environment to make such choice possible. Moreover, FPl functionally connects with posterior cingulate cortex for guiding environment choice. Further probing FPl's computation revealed a parallel processing mechanism in extracting multiple environment features.

Intraparietal stimulation disrupts negative distractor effects in human multi-alternative decision-making.

There has been debate about whether addition of an irrelevant distractor option to an otherwise binary decision influences which of the two choices is taken. We show that disparate views on this question are reconciled if distractors exert two opposing but not mutually exclusive effects. Each effect predominates in a different part of decision space: (1) a positive distractor effect predicts high-value distractors improve decision-making; (2) a negative distractor effect, of the type associated with divisive normalisation models, entails decreased accuracy with increased distractor values. Here, we demonstrate both distractor effects coexist in human decision making but in different parts of a decision space defined by the choice values. We show disruption of the medial intraparietal area (MIP) by transcranial magnetic stimulation (TMS) increases positive distractor effects at the expense of negative distractor effects. Furthermore, individuals with larger MIP volumes are also less susceptible to the disruption induced by TMS. These findings also demonstrate a causal link between MIP and the impact of distractors on decision-making via divisive normalisation.

Evaluating the efficacy and safety of transcranial pulse stimulation on adolescents with attention deficit hyperactivity disorder: Study protocol of a pilot randomized, double-blind, sham-controlled trial.

Background: Traditional treatment alone might not effectively control the severity of attention deficit hyperactivity disorder (ADHD) symptoms. Transcranial pulse stimulation (TPS) is a non-invasive brain stimulation (NIBS) technology used on older adults with mild neurocognitive disorders and adults with major depressive disorder. However, there has been no study conducted on young adolescents with ADHD. This will be the first nationwide study evaluating the efficacy and safety of TPS in the treatment of ADHD among young adolescents in Hong Kong. Methods: This study proposes a double-blinded, randomized, sham-controlled trial including TPS as an intervention group and a sham TPS group. Both groups will be measured at baseline (T1), immediately after the intervention (T2), and at the 1-month (T3) and 3-month follow-ups (T4). Recruitment: A total of 30 subjects aged between 12 and 17 years, diagnosed with attention deficit hyperactivity disorder (ADHD), will be recruited in this study. All subjects will be computer randomized into either the intervention group or the sham TPS group on a 1:1 ratio. Intervention: All subjects in each group will have to undertake functional MRI (fMRI) before and after six 30-min TPS sessions, which will be completed in 2 weeks' time. Outcomes: Baseline measurements and post-TPS evaluation of the ADHD symptoms and executive functions will also be conducted on all participants. The 1- and 3-month follow-up periods will be used to assess the long-term sustainability of the TPS intervention. For statistical analysis, ANOVA with repeated measures will be used to analyze data. Missing data were managed by multiple imputations. The level of significance will be set to p < 0.05. Significance of the study: Results emerging from this study will generate new knowledge to ascertain whether TPS can be used as a top-on treatment for ADHD. Clinical trial registration: clinicaltrails.gov, identifier: NCT05422274.

Corrigendum: Functional and structural architectures of allocentric and egocentric spatial coding in aging: A combined DTI and fMRI study.

[This corrects the article DOI: 10.3389/fneur.2021.802975.].

Potential mechanisms underlying the accelerated cognitive decline in people with chronic low back pain: A scoping review.

A growing body of evidence has shown that people with chronic low back pain (CLBP) demonstrate significantly greater declines in multiple cognitive domains than people who do not have CLBP. Given the high prevalence of CLBP in the ever-growing aging population that may be more vulnerable to cognitive decline, it is important to understand the mechanisms underlying the accelerated cognitive decline observed in this population, so that proper preventive or treatment approaches can be developed and implemented. The current scoping review summarizes what is known regarding the potential mechanisms underlying suboptimal cognitive performance and cognitive decline in people with CLBP and discusses future research directions. Five potential mechanisms were identified based on the findings from 34 included studies: (1) altered activity in the cortex and neural networks; (2) grey matter atrophy; (3) microglial activation and neuroinflammation; (4) comorbidities associated with CLBP; and (5) gut microbiota dysbiosis. Future studies should deepen the understanding of mechanisms underlying this association so that proper prevention and treatment strategies can be developed.

Functional and Structural Architectures of Allocentric and Egocentric Spatial Coding in Aging: A Combined DTI and fMRI Study.

BACKGROUND: Aging disrupts the optimal balance between neural nodes underlying orienting and attention control functions. Previous studies have suggested that age-related changes in cognitive process are associated to the changes in the myelinated fiber bundles, which affected the speed and actions of the signal propagation across different neural networks. However, whether the age-related difference in allocentric and egocentric spatial coding is accounted by the difference in white-matter integrity is unclear. In this study, using diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI), we sought to elucidate whether age-related differences in white matter integrity accounts for the difference in nodes to the distributed spatial coding-relevant brain networks. MATERIAL AND METHOD: Older (n = 24) and younger (n = 27) participants completed the structural DTI and fMRI scans during which they engaged in a cue-to-target task to elicit allocentric or egocentric processes. RESULTS AND CONCLUSION: Efficient modulation of both allocentric and egocentric spatial coding in fronto-parietal attention network (FPAN) requires structure-function interaction. Allocentric task-modulated connectivity of the fronto-parietal network (FPN) and dorsal attention network (DAN) with the temporal lobe was influenced by the aging differences of the white-matter tracts of the posterior and superior corona radiata (PCR and SCR), respectively. On the other hand, aging difference of the superior longitudinal fasciculus mainly influenced the egocentric-task-modulated connections of the DAN and FPN with frontal regions and posterior cingulate cortex. This study suggested that functional connections of the FPAN with near and far task-relevant nodes vary significantly with age and conditions.

Global reward state affects learning and activity in raphe nucleus and anterior insula in monkeys.

People and other animals learn the values of choices by observing the contingencies between them and their outcomes. However, decisions are not guided by choice-linked reward associations alone; macaques also maintain a memory of the general, average reward rate - the global reward state - in an environment. Remarkably, global reward state affects the way that each choice outcome is valued and influences future decisions so that the impact of both choice success and failure is different in rich and poor environments. Successful choices are more likely to be repeated but this is especially the case in rich environments. Unsuccessful choices are more likely to be abandoned but this is especially likely in poor environments. Functional magnetic resonance imaging (fMRI) revealed two distinct patterns of activity, one in anterior insula and one in the dorsal raphe nucleus, that track global reward state as well as specific outcome events.

Consistent patterns of distractor effects during decision making.

The value of a third potential option or distractor can alter the way in which decisions are made between two other options. Two hypotheses have received empirical support: that a high value distractor improves the accuracy with which decisions between two other options are made and that it impairs accuracy. Recently, however, it has been argued that neither observation is replicable. Inspired by neuroimaging data showing that high value distractors have different impacts on prefrontal and parietal regions, we designed a dual route decision-making model that mimics the neural signals of these regions. Here we show in the dual route model and empirical data that both enhancement and impairment effects are robust phenomena but predominate in different parts of the decision space defined by the options' and the distractor's values. However, beyond these constraints, both effects co-exist under similar conditions. Moreover, both effects are robust and observable in six experiments.

Neural Processes of Proactive and Reactive Controls Modulated by Motor-Skill Experiences.

This study investigated the experience of open and closed motor skills on modulating proactive and reactive control processes in task switching. Fifty-four participants who were open-skilled (n = 18) or closed-skilled athletes (n = 18) or non-athletic adults (n = 18) completed a cued task-switching paradigm task. This task tapped into proactive or reactive controls of executive functions under different validity conditions. Electroencephalograms of the participants were captured during the task. In the 100% validity condition, the open-skilled participants showed significantly lower switch cost of response time than the closed-skilled and control participants. Results showed that the open-skilled participants had less positive-going parietal cue-locked P3 in the switch than repeat trials. Participants in the control group showed more positive-going cue-locked P3 in the switch than repeat trials, whereas the closed-skilled participants had no significant differences between the two types of trials. In the 50% validity condition, the open- and closed-skilled participants had less switch cost of response time than the control participants. Participants in the open- and closed-skilled groups showed less positive-going parietal stimulus-locked P3 in the switch than repeat trials, which was not the case for those in the control group. Our findings confirm the dissociation between proactive and reactive controls in relation to their modulations by the different motor-skill experiences. Both proactive and reactive controls of executive functions could be strengthened by exposing individuals to anticipatory or non-anticipatory enriched environments, suggesting proactive and reactive controls involved in motor-skill development seem to be transferable to domain-general executive functions.