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.

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.

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.

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.].

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.

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.

The macaque anterior cingulate cortex translates counterfactual choice value into actual behavioral change.

The neural mechanisms mediating sensory-guided decision-making have received considerable attention, but animals often pursue behaviors for which there is currently no sensory evidence. Such behaviors are guided by internal representations of choice values that have to be maintained even when these choices are unavailable. We investigated how four macaque monkeys maintained representations of the value of counterfactual choices-choices that could not be taken at the current moment but which could be taken in the future. Using functional magnetic resonance imaging, we found two different patterns of activity co-varying with values of counterfactual choices in a circuit spanning the hippocampus, the anterior lateral prefrontal cortex and the anterior cingulate cortex. Anterior cingulate cortex activity also reflected whether the internal value representations would be translated into actual behavioral change. To establish the causal importance of the anterior cingulate cortex for this translation process, we used a novel technique, transcranial focused ultrasound stimulation, to reversibly disrupt anterior cingulate cortex activity.

Meditation-induced neuroplastic changes of the prefrontal network are associated with reduced valence perception in older people.

BACKGROUND: Neuroplastic underpinnings of meditation-induced changes in affective processing are largely unclear. METHODS: We included healthy older participants in an active-controlled experiment. They were involved a meditation training or a control relaxation training of eight weeks. Associations between behavioral and neural morphometric changes induced by the training were examined. RESULTS: The meditation group demonstrated a change in valence perception indexed by more neutral valence ratings of positive and negative affective images. These behavioral changes were associated with synchronous structural enlargements in a prefrontal network involving the ventromedial prefrontal cortex and the inferior frontal sulcus. In addition, these neuroplastic effects were modulated by the enlargement in the inferior frontal junction. In contrast, these prefrontal enlargements were absent in the active control group, which completed a relaxation training. Supported by a path analysis, we propose a model that describes how meditation may induce a series of prefrontal neuroplastic changes related to valence perception. These brain areas showing meditation-induced structural enlargements are reduced in older people with affective dysregulations. CONCLUSION: We demonstrated that a prefrontal network was enlarged after eight weeks of meditation training. Our findings yield translational insights in the endeavor to promote healthy aging by means of meditation.

Aging Effect on Audiovisual Integrative Processing in Spatial Discrimination Task.

Multisensory integration is an essential process that people employ daily, from conversing in social gatherings to navigating the nearby environment. The aim of this study was to investigate the impact of aging on modulating multisensory integrative processes using event-related potential (ERP), and the validity of the study was improved by including "noise" in the contrast conditions. Older and younger participants were involved in perceiving visual and/or auditory stimuli that contained spatial information. The participants responded by indicating the spatial direction (far vs. near and left vs. right) conveyed in the stimuli using different wrist movements. electroencephalograms (EEGs) were captured in each task trial, along with the accuracy and reaction time of the participants' motor responses. Older participants showed a greater extent of behavioral improvements in the multisensory (as opposed to unisensory) condition compared to their younger counterparts. Older participants were found to have fronto-centrally distributed super-additive P2, which was not the case for the younger participants. The P2 amplitude difference between the multisensory condition and the sum of the unisensory conditions was found to correlate significantly with performance on spatial discrimination. The results indicated that the age-related effect modulated the integrative process in the perceptual and feedback stages, particularly the evaluation of auditory stimuli. Audiovisual (AV) integration may also serve a functional role during spatial-discrimination processes to compensate for the compromised attention function caused by aging.

Salience of Somatosensory Stimulus Modulating External-to-Internal Orienting Attention.

Shifting between one's external and internal environments involves orienting attention. Studies on differentiating subprocesses associated with external-to-internal orienting attention are limited. This study aimed to reveal the characteristics of the disengagement, shifting and reengagement subprocesses by using somatosensory external stimuli and internally generated images. Study participants were to perceive nociceptive external stimuli (External Low (EL) or External High (EH)) induced by electrical stimulations (50 ms) followed by mentally rehearsing learned subnociceptive images (Internal Low (IL) and Internal High (IH)). Behavioral responses and EEG signals of the participants were recorded. The three significant components elicited were: fronto-central negativity (FCN; 128-180 ms), fronto-central P2 (200-260 ms), and central P3 (320-380 ms), which reflected the three subprocesses, respectively. Differences in the FCN and P2 amplitudes during the orienting to the subnociceptive images revealed only in the EH but not EL stimulus condition that are new findings. The results indicated that modulations of the disengagement and shifting processes only happened if the external nociceptive stimuli were of high salience and the external-to-internal incongruence was large. The reengaging process reflected from the amplitude of P3 correlated significantly with attenuation of the pain intensity felt from the external nociceptive stimuli. These findings suggested that the subprocesses underlying external-to-internal orienting attention serve different roles. Disengagement subprocess tends to be stimulus dependent, which is bottom-up in nature. Shifting and reengagement tend to be top-down subprocesses, which taps on cognitive control. This subprocess may account for the attenuation effects on perceived pain intensity after orienting attention.

Inverted activity patterns in ventromedial prefrontal cortex during value-guided decision-making in a less-is-more task.

Ventromedial prefrontal cortex has been linked to choice evaluation and decision-making in humans but understanding the role it plays is complicated by the fact that little is known about the corresponding area of the macaque brain. We recorded activity in macaques using functional magnetic resonance imaging during two very different value-guided decision-making tasks. In both cases ventromedial prefrontal cortex activity reflected subjective choice values during decision-making just as in humans but the relationship between the blood oxygen level-dependent signal and both decision-making and choice value was inverted and opposite to the relationship seen in humans. In order to test whether the ventromedial prefrontal cortex activity related to choice values is important for decision-making we conducted an additional lesion experiment; lesions that included the same ventromedial prefrontal cortex region disrupted normal subjective evaluation of choices during decision-making.