Effects of computerized cognitive training on biomarker responses in older adults with mild cognitive impairment: A scoping review.

Background and Aims: Mild cognitive impairment (MCI) is a widespread condition in older individuals, posing significant risk of dementia. However, limited research has been conducted to explore effective interventions and clarify their impact at the neural level. Therefore, this study aimed to investigate the effects of computerized cognitive training (CCT) and explore the associated neural mechanisms in preventing dementia in older individuals with MCI, with a view to inform future intervention efforts. Methods: We reviewed the effects of CCT on biomarker outcomes in older adults with MCI. The search was conducted for studies published between 2010 and May 10, 2023, using three search engines: PubMed, Scopus, and Cumulative Index to Nursing and Allied Health Literature. The inclusion criteria were as follows: studies that involved participants diagnosed with MCI, included CCT, included quantitative assessment of biomarker results, and conducted randomized controlled trials. Results: Sixteen studies that used biomarkers, including magnetic resonance imaging, electroencephalography (EEG), functional near-infrared spectroscopy (fNIRS), and blood or salivary biomarkers, were extracted. The results showed that CCT caused changes in structure and function within the main brain network, including the default mode network, and decreased both theta rhythm activity on EEG and prefrontal activity on fNIRS, with improvement in cognitive function. Furthermore, CCT combined with physical exercise showed more significant structural and functional changes in extensive brain regions compared with CCT alone. Virtual reality-based cognitive training improved not only executive function but also instrumental activities of daily living. Conclusion: CCT causes functional and structural changes in extensive brain regions and improves cognitive function in older adults with MCI. Our findings highlight the potential of individualized intervention methods and biomarker assessment according to the specific causes of MCI. Future research should aim to optimize these personalized therapeutic strategies to maximize the benefits of CCT in older adults with MCI.

Plasma sphingolipid abnormalities in neurodegenerative diseases.

BACKGROUND: In recent years, there has been increasing evidence that several lipid metabolism abnormalities play an important role in the pathogenesis of neurodegenerative diseases. However, it is still unclear which lipid metabolism abnormalities play the most important role in neurodegenerative diseases. Plasma lipid metabolomics (lipidomics) has been shown to be an unbiased method that can be used to explore lipid metabolism abnormalities in neurodegenerative diseases. Plasma lipidomics in neurodegenerative diseases has been performed only in idiopathic Parkinson's disease (IPD) and Alzheimer's disease (AD), and comprehensive studies are needed to clarify the pathogenesis. METHODS: In this study, we investigated plasma lipids using lipidomics in individuals with neurodegenerative diseases and healthy controls (CNs). Plasma lipidomics was evaluated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in those with IPD, dementia with Lewy bodies (DLB), multiple system atrophy (MSA), AD, and progressive supranuclear palsy (PSP) and CNs. RESULTS: The results showed that (1) plasma sphingosine-1-phosphate (S1P) was significantly lower in all neurodegenerative disease groups (IPD, DLB, MSA, AD, and PSP) than in the CN group. (2) Plasma monohexylceramide (MonCer) and lactosylceramide (LacCer) were significantly higher in all neurodegenerative disease groups (IPD, DLB, MSA, AD, and PSP) than in the CN group. (3) Plasma MonCer levels were significantly positively correlated with plasma LacCer levels in all enrolled groups. CONCLUSION: S1P, Glucosylceramide (GlcCer), the main component of MonCer, and LacCer are sphingolipids that are biosynthesized from ceramide. Recent studies have suggested that elevated GlcCer and decreased S1P levels in neurons are related to neuronal cell death and that elevated LacCer levels induce neurodegeneration by neuroinflammation. In the present study, we found decreased plasma S1P levels and elevated plasma MonCer and LacCer levels in those with neurodegenerative diseases, which is a new finding indicating the importance of abnormal sphingolipid metabolism in neurodegeneration.

Decreased sensitivity to loss of options in patients with Parkinson's disease.

Humans prefer to have many options when making decisions. When there is a threat of options disappearing, humans invest more to keep these options available, indicating that they are sensitive to the loss of options. This study examined whether patients with Parkinson's disease (PD), a disease characterized by dopamine depletion, try to keep options available when options are disappearing. Twenty-seven PD patients without dementia and 27 healthy controls (HCs) performed the door game, in which participants were presented with multiple alternatives in the form of three doors, each associated with a different point distribution. The participants were asked to maximize their point earnings by finding the best door. The task included two conditions. In the shutter condition, shutters gradually closed on doors that were not chosen; once the shutters completely closed, the door was no longer available. There were no shutters in the control condition. The results revealed that the HCs switched doors more often in the shutter condition than in the control condition, indicating a tendency to keep options available. However, the PD patients did not show such differences between the two conditions. The difference in the number of switches between the shutter and control conditions in the PD patients was significantly positively correlated with the distribution of dopamine transporters in the left striatum, as measured by 123I-ioflupane-SPECT (DaTSCAN) images. These results suggest that PD patients are less sensitive to the loss of options, and this decreased sensitivity may be caused by a decline in dopaminergic neurotransmission.

The Role of the Ventromedial Prefrontal Cortex in Preferential Decisions for Own- and Other-Age Faces.

Own-age bias is a well-known bias reflecting the effects of age, and its role has been demonstrated, particularly, in face recognition. However, it remains unclear whether an own-age bias exists in facial impression formation. In the present study, we used three datasets from two published and one unpublished functional magnetic resonance imaging (fMRI) study that employed the same pleasantness rating task with fMRI scanning and preferential choice task after the fMRI to investigate whether healthy young and older participants showed own-age effects in face preference. Specifically, we employed a drift-diffusion model to elaborate the existence of own-age bias in the processes of preferential choice. The behavioral results showed higher rating scores and higher drift rate for young faces than for older faces, regardless of the ages of participants. We identified a young-age effect, but not an own-age effect. Neuroimaging results from aggregation analysis of the three datasets suggest a possibility that the ventromedial prefrontal cortex (vmPFC) was associated with evidence accumulation of own-age faces; however, no clear evidence was provided. Importantly, we found no age-related decline in the responsiveness of the vmPFC to subjective pleasantness of faces, and both young and older participants showed a contribution of the vmPFC to the parametric representation of the subjective value of face and functional coupling between the vmPFC and ventral visual area, which reflects face preference. These results suggest that the preferential choice of face is less susceptible to the own-age bias across the lifespan of individuals.

Facial memory ability and self-awareness in patients with temporal lobe epilepsy after anterior temporal lobectomy.

Anterior temporal lobectomy (ATL) is the most common surgical treatment for drug-resistant temporal lobe epilepsy (TLE). Right ATL has been reported to reduce facial memory ability in patients with TLE, as indicated by poor performance on the Warrington Recognition Memory Test for Faces (RMF), which is commonly used to evaluate visual memory in these patients. However, little is known about whether patients with TLE exhibit difficulties in identifying faces in daily life after ATL. The aim of this study was to investigate facial memory ability and self-awareness of face identification difficulties in patients with TLE after ATL. Sixteen patients with TLE after right ATL, 14 patients with TLE after left ATL, and 29 healthy controls were enrolled in this study. We developed the multiview face recognition test (MFRT), which comprises a learning phase (one or three frontal face images without external facial feature information) and a recognition phase (frontal, oblique, or noise-masked face images). Facial memory abilities were examined in all participants using the MFRT and RMF, and self-awareness of difficulties in face identification was evaluated using the 20-item prosopagnosia index (PI20), which has been widely used to assess developmental prosopagnosia. The MFRT performance in patients with TLE after ATL was significantly worse than that in healthy controls regardless of the resected side, whereas the RMF scores in patients with TLE were significantly worse than those in healthy controls only after right ATL. The MFRT performance in patients with TLE after both left and right ATL was more influenced by working memory load than that in healthy controls. The PI20 scores revealed that patients with TLE after left ATL were aware of their difficulties in identifying faces. These findings suggest that patients with TLE not only after right ATL but also after left ATL might have difficulties in face identification.

Intrinsic motivation in patients with Parkinson's disease: a neuropsychological investigation of curiosity using dopamine transporter imaging.

Both intrinsic and extrinsic motivation are believed to involve brain regions that are innervated by the dopaminergic pathway. Although dopaminergic neurons in the midbrain deteriorate in Parkinson's disease (PD), it remains unclear whether intrinsic motivation is impaired in PD patients. To address this issue, we investigated intrinsic motivation in PD patients using a task designed to assess the "Pandora effect," which constitutes a curiosity for resolving uncertainty, even if this curiosity is likely to result in negative consequences. Twenty-seven PD patients and 27 age-matched healthy controls (HCs) completed a curiosity task in which they were required to decide either to view or skip negative pictures (e.g., snakes, spiders) and an examination battery that included the Mini-Mental State Examination, a verbal fluency test, the Trail Making Test, 10-word recall tests, and questionnaires for behavioral inhibition/activation and depression. DaTSCAN images to assess the distribution of dopamine transporters in the striatum were acquired only from PD patients. The results revealed that PD patients, relative to the HCs, viewed the pictures less frequently under both the certain and uncertain conditions. However, both the PD patients and HCs viewed the pictures at a higher frequency under the uncertain condition than under the certain condition. In the PD patients, the proportion of pictures viewed under the certain condition was positively correlated with the distribution of dopamine transporters in the striatum. These results suggest that despite the overall decreasing level of interest in viewing negative pictures, the motivation to resolve uncertainty is relatively intact in PD patients.

Effect of aging on choice-induced cognitive conflict.

When individuals are forced to choose between similarly preferable alternatives, a negatively arousing cognitive conflict occurs, and the preference attitudes toward the chosen and rejected alternatives diverge. This phenomenon, often referred to as "cognitive dissonance", is of interest in psychological and decision neuroscience research. The dorsal anterior cingulate cortex (dACC) is involved in representing the cognitive conflict induced by difficult-choice tasks. Previous studies have shown age-related decline of the dACC function. However, whether the heightened activity of the dACC regarding cognitive conflict, and choice-induced preference change that behaviorally occur in young subjects also occur in the elderly is unclear. Furthermore, recent studies have noted substantial methodological flaw with the free-choice paradigm that often used in studies focusing on cognitive dissonance. Here, we used functional magnetic resonance imaging (fMRI) and a modified free-choice paradigm to formally test the effect of aging on choice-induced cognitive conflict. In the young participants, behavioral data confirmed the existence of cognitive conflict and preference change for the alternatives that they rejected in the difficult-choice trials. The imaging data revealed that the right dACC displayed an interaction effect associated with cognitive conflict. In contrast, we did not observe such effects in the elderly participants. These suggest a possibility that elderly people likely feel less cognitive dissonance.

Do Patients With Parkinson's Disease Exhibit Reduced Cheating Behavior? A Neuropsychological Study.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by loss of dopamine neurons. Since a seminal report was published in the early twentieth century, a growing body of literature has suggested that patients with PD display characteristic personality traits, such as cautiousness and inflexibility. Notably, PD patients have also been described as "honest," indicating that they have a remarkable tendency to avoid behaving dishonestly. In this study, we predicted that PD patients show reduced cheating behavior in opportunities for dishonest gain due to dysfunction of the dopaminergic reward system. Thirty-two PD patients without dementia and 20 healthy controls (HC) completed an incentivized prediction task where participants were rewarded based on their self-reported accuracy, affording them the opportunity to behave dishonestly. Compared with HC, PD patients showed significantly lower accuracy in the prediction task. Furthermore, the mean accuracy of PD patients was virtually equivalent to the chance level. These results indicate that PD patients exhibit reduced cheating behavior when confronted with opportunities for dishonest gain.

Gender differences in ventromedial prefrontal cortex activity associated with valuation of faces.

Psychological studies have indicated that males exhibit stronger preferences for physical attributes in the opposite gender, such as facial attractiveness, than females. However, whether gender differences in mate preference originate from differential brain activity remains unclear. Using functional magnetic resonance imaging (fMRI), we investigated the patterns of brain activity in the ventromedial prefrontal cortex (vmPFC), a region critical for the valuation of faces, in response to elderly male, elderly female, young male, and young female faces. During fMRI, male and female subjects were presented with a face and asked to rate its pleasantness. Following fMRI, the subjects were presented with pairs of faces and asked to select the face that they preferred. We analyzed the vmPFC activity during the pleasantness-rating task according to the gender of the face stimulus (male and female) and the age of the face stimulus (elderly and young). Consistent with the results of previous studies, the vmPFC activity parametrically coded the subjective value of faces. Importantly, the vmPFC activity was sensitive to physical attributes, such as the youthfulness and gender of the faces, only in the male subjects. These findings provide a possible neural explanation for gender differences in mate preference.

Loss of awareness of hyposmia is associated with mild cognitive impairment in Parkinson's disease.

BACKGROUND: Hyposmia is a common non-motor symptom in Parkinson's disease (PD). However, patients with PD are sometimes unaware of their olfactory dysfunction, resulting in an under-diagnosis of this symptom. To determine whether the loss of awareness of hyposmia results from cognitive impairment in patients with PD, we investigated the relationship between the degree of hyposmia self-awareness and the cognitive status of non-demented PD patients. METHODS: Thirty-one non-demented patients with PD and 20 healthy controls (HC) were assessed via a self-reported olfactory questionnaire and an odor identification test. PD patients were sub-classified as having mild cognitive impairment (PD-MCI) or as cognitively normal (PD-CN) (according to the current PD-MCI criteria). We compared the degree of hyposmia self-awareness between the PD-MCI and PD-CN groups. RESULTS: The PD-MCI group scored the lowest on the odor identification test among all groups, whereas PD-MCI patients tended to rate their olfactory function higher on the self-reported olfactory questionnaire than PD-CN patients. Differences in the scores of subjective and objective olfactory measures between the PD-MCI and PD-CN groups were significant (p = 0.0069). CONCLUSIONS: The loss of awareness of hyposmia is closely associated with mild cognitive impairment (MCI) in PD patients.

Medial temporal lobe activity associated with the successful retrieval of destination memory.

Destination memory is the process of remembering to whom we tell particular things. Although recent behavioral studies have clarified the cognitive nature of destination memory, the neural mechanisms underlying destination memory retrieval remain unclear. We used functional magnetic resonance imaging (fMRI) to determine whether the medial temporal lobe (MTL), a structure that has been implicated in recollection-based memory, is activated during the successful retrieval of destination information. During a study phase before fMRI scanning, the subjects told a series of facts to either a woman or a man. During fMRI scanning, the subjects were asked to judge whether each fact presented was old or new, and if they judged it as old, to indicate, including a confidence rating (high or low), whether the subjects had told that fact to either a man or a woman. We found that successful destination retrieval, when compared to failed destination retrieval, was associated with increased activity in the parahippocampal gyrus. We also found that the confidence level (high vs. low) for destination memory retrieval was associated with increased activity in another (posterior) region of the parahippocampal gyrus. The present study suggests that the successful retrieval of destination information depends highly on MTL-mediated recollection processes.

Differential activation of the ventromedial prefrontal cortex between male and female givers of social reputation.

Accumulating evidence has shown the profound influence of social reputation on human behavior and has implicated the ventromedial prefrontal cortex (vmPFC) in representing subjective values induced by social interaction. However, little is known regarding how the vmPFC encodes subjective pleasantness induced by social reputation received from others. We used functional magnetic resonance imaging (fMRI) to investigate how the vmPFC in males and females encodes the subjective pleasantness of social reputation received from the same gender and from the opposite gender. Behavioral data showed that positive reputation was perceived to be more pleasant than negative reputation. Intriguingly, both male and female subjects showed greater differences in the pleasantness scores between the positive reputation condition and the negative reputation condition from females than between positive and negative reputations from males. Imaging data revealed that the left vmPFC specifically contributed to the processing of positive reputation. The activity patterns of the vmPFC corresponded to the gender differences in behavior during the processing of social reputation. These results indicate that the vmPFC plays a role in representing the subjective value of positive social reputation and that this region might be a final computational site in a stream of value-based decision-making processes.

Distinct neural correlates of the preference-related valuation of supraliminally and subliminally presented faces.

Recent neuroimaging studies have investigated the neural substrates involved in the valuation of supraliminally presented targets and the subsequent preference decisions. However, the neural mechanisms of the valuation of subliminally presented targets, which can guide subsequent preference decisions, remain to be explored. In the present study, we determined whether the neural systems associated with the valuation of supraliminally presented faces are involved in the valuation of subliminally presented faces. The subjects were supraliminally and subliminally presented with faces during functional magnetic resonance imaging (fMRI). Following fMRI, the subjects were presented with pairs of faces and were asked to choose which face they preferred. We analyzed brain activation by back-sorting the fMRI data according to the subjects' choices. The present study yielded two main findings. First, the ventral striatum and the ventromedial prefrontal cortex predict preferences only for supraliminally presented faces. Second, the dorsomedial prefrontal cortex may predict preferences for subliminally presented faces. These findings indicate that neural correlates of the preference-related valuation of faces are dissociable, contingent upon whether the subjects consciously perceive the faces.

Neural activity associated with enhanced facial attractiveness by cosmetics use.

Previous psychological studies have shown that make-up enhances facial attractiveness. Although neuroimaging evidence indicates that the orbitofrontal cortex (OFC) shows greater activity for faces of attractive people than for those of unattractive people, there is no direct evidence that the OFC also shows greater activity for the face of an individual wearing make-up than for the same face without make-up. Using functional magnetic resonance imaging (fMRI), we investigated neural activity while subjects viewed 144 photographs of the same faces with and without make-up (48 with make-up, 48 without make-up, and 48 scrambled photographs) and assigned these faces an attractiveness rating. The behavioral data showed that the faces with make-up were rated as more attractive than those without make-up. The imaging data revealed that the left OFC and the right hippocampus showed greater activity for faces with make-up than for those without make-up. Furthermore, the activities of the right anterior cingulate cortex, left hippocampus, and left OFC increased with increasing facial attractiveness resulting from cosmetics use. These results provide direct evidence of the neural underpinnings of cosmetically enhanced facial attractiveness.