A perspective on epigenomic aging processes in the human brain and their plasticity in patients with mental disorders - a systematic review.

The debate surrounding nature versus nurture remains a central question in neuroscience, psychology, and in psychiatry, holding implications for both aging processes and the etiology of mental illness. Epigenetics can serve as a bridge between genetic predisposition and environmental influences, thus offering a potential avenue for addressing these questions. Epigenetic clocks, in particular, offer a theoretical framework for measuring biological age based on DNA methylation signatures, enabling the identification of disparities between biological and chronological age. This structured review seeks to consolidate current knowledge regarding the relationship between mental disorders and epigenetic age within the brain. Through a comprehensive literature search encompassing databases such as EBSCO, PubMed, and ClinicalTrials.gov, relevant studies were identified and analyzed. Studies that met inclusion criteria were scrutinized, focusing on those with large sample sizes, analyses of both brain tissue and blood samples, investigation of frontal cortex markers, and a specific emphasis on schizophrenia and depressive disorders. Our review revealed a paucity of significant findings, yet notable insights emerged from studies meeting specific criteria. Studies characterized by extensive sample sizes, analysis of brain tissue and blood samples, assessment of frontal cortex markers, and a focus on schizophrenia and depressive disorders yielded particularly noteworthy results. Despite the limited number of significant findings, these studies shed light on the complex interplay between epigenetic aging and mental illness. While the current body of literature on epigenetic aging in mental disorders presents limited significant findings, it underscores the importance of further research in this area. Future studies should prioritize large sample sizes, comprehensive analyses of brain tissue and blood samples, exploration of specific brain regions such as the frontal cortex, and a focus on key mental disorders. Such endeavors will contribute to a deeper understanding of the relationship between epigenetic aging and mental illness, potentially informing novel diagnostic and therapeutic approaches.

A double-blind randomized clinical trial on the suggestive effect of anxiety management questionnaires in dental emergencies.

Objective: Dental anxiety is widespread among both children and adults. To diagnose dental anxiety, standardized anxiety questionnaires are recommended. Based on the suggestive nature of the questionnaires, the study aimed to find out whether asking respondents about personal coping strategies before dental treatment influences their anxiety. Methods: This prospective, double-blind, randomized controlled clinical trial included a total of 158 patients of a university dental clinic on emergency service. The intervention group (n = 82) received the Coping with Anxiety Questionnaire (CAQ) and the control group (n = 76) the Hierarchical Anxiety Questionnaire (HAF). State anxiety scores were assessed by using the State-Trait Anxiety Inventory (STAI) before and after the completion of each questionnaire. Results: Anxiety decreased in the intervention group (CAQ) (p < 0.001) and increased in the control group (HAF) (p < 0.001). Conclusion: Within the limitations of the current study, a diagnostic tool of a standardized questionnaire for the assessment to assess personal coping strategies decreased state anxiety in comparison to a questionnaire assessing anxiety. Clinical trial registration: https://www.drks.de, German Trials Register (DRKS00032450).

Mental health during the COVID-19 pandemic: Stress and strain profiles in the German population.

Clinical observations indicate that people frequently display stress-related behavior during the COVID-19 pandemic. Although numerous studies have been published concerning pandemic-related psychological distress, systematic data on the interrelationships between stress sensitivity, personality, and behavioral characteristics of people are still lacking. In the present cross-sectional online survey study, we applied a German version of the COVID Stress Scales (CSS) and standard psychological questionnaires to systematically identify the complex interplay between stress sensitivity, gender, and personality in the modulation of quality of life and mental health in the German population (N = 1774; age ≥ 16 years). A CSS-based cluster analysis revealed two clusters characterized by higher and lower stress levels. Study participants in each cluster differed significantly with respect to neuroticism, extraversion, agreeableness, quality of life, depression, and anxiety. Females were significantly overrepresented in the higher stress cluster, while there was an overrepresentation of males in the lower stress cluster. Neuroticism was identified as a risk factor and extraversion as a protective factor for enhanced pandemic-related stress responses. For the first time our data show a taxonomy of factors, which modulate pandemic-related stress sensitivity and warrant consideration as key indicators of quality of life and psychological distress during the COVID-19 pandemic. We suggest that our data may advise governmental regulation of pandemic-related public health measures, to optimize quality of life and psychological health in different groups of the population.

COVID-19 stress syndrome in the German general population: Validation of a German version of the COVID Stress Scales.

The COVID Stress Scales (CSS) are a new self-report instrument for multidimensional assessment of psychological stress in the context of the pandemic. The CSS have now been translated and validated in over 20 languages, but a validated German version has not yet been available. Therefore, the aim was to develop a German version of the CSS, to test its factor structure, reliability, and validity, and to compare it with international studies. In an online survey (08/2020-06/2021), N = 1774 individuals from the German general population (71.5% female; Mage = 41.2 years, SD = 14.2) completed the CSS as well as questionnaires on related constructs and psychopathology. After eight weeks, participants were asked to participate again for the purpose of calculating retest reliability (N = 806). For the German version, the 6-factor structure with good model fit (Root Mean Square Error of Approximation, RMSEA = 0.06) was confirmed, with the six subscales: Danger, Socio-Economic Consequences, Xenophobia, Contamination, Traumatic Stress, and Compulsive Checking. Internal consistencies ranged from ω = .82-.94 (except Compulsive Checking ω = .70), and retest reliability from rtt = .62-.82. Convergent and discriminant validity were confirmed for the German version. Related constructs such as health anxiety, general xenophobia, obsessive-compulsive behavior, and posttraumatic stress disorder symptoms correlated moderately with the respective subscale and lower with the other scales. With anxiety and depression, Traumatic Stress showed the strongest correlation. Overall, there was a high degree of agreement in an international comparison. The CSS can help to identify pandemic-related psychological stress and to derive appropriate interventions.

Anxiety and depression in patients with breast cancer undergoing radiotherapy: the role of intelligence, life history, and social support-preliminary results from a monocentric analysis.

PURPOSE: It is known that the diagnosis of breast cancer often causes anxiety and depression. Radiotherapy of the breast as an obligatory part of a breast-conserving treatment concept can markedly increase these psychological symptoms in many, but not all patients. In this clinical observational study, we aimed at identifying cognitive, health-related and social factors that may either enhance or reduce the emergence of anxiety and depression. METHODS: Using a longitudinal study design with 25 women (mean age: 52.9 years; SD = 10.6; age range 29-70 years) with a first diagnosis of nonmetastatic breast cancer, measures of anxiety, depression, situational emotional states, intelligence, and aspects of social frameworks were assessed before, during, and after radiotherapy of the breast. At 4 time-points, standard and self-constructed questionnaires were used to assess the course of anxiety and depressive symptoms across the radiotherapy intervention. RESULTS: We found that anxiety is highest immediately before the start of radiation therapy, while the anxiety level was lowest on the day that therapy was completed. Anxiety and depression were enhanced in women with a lifetime history of chronic diseases at all time points of measurement. Moreover, women with high intelligence and low social support had stronger symptoms of depression than women with low intelligence and a stable family background at some time points of measurement. The degree of anxiety was neither related to intelligence nor to social support. CONCLUSION: For the first time, we demonstrate empirical pilot data on cognitive and social modulators of anxiety and depression in women with breast cancer over the course of radiotherapy. Our results may help to optimize clinical procedures and thereby reduce symptoms of anxiety and depression in these patients.

Cognitive training in an everyday-like virtual reality enhances visual-spatial memory capacities in stroke survivors with visual field defects.

OBJECTIVES: Visual field defects due to hemi- or quadrantanopia after stroke represent an under-recognized neurological symptom with inefficient instruments for neurorehabilitation to date. We here examined the effects of training in a virtual reality (VR) supermarket on cognitive functions, depressive symptoms, and subjective cognitive complaints in patients with hemianopia/quadrantanopia and healthy controls. METHODS: During a 14-day rehabilitation program, 20 patients and 20 healthy controls accomplished a real-life-like shopping task in a VR supermarket. A comparison between pre- and post-training standard neuropsychological measures, depressive symptoms, and subjective memory complaints allowed us to assess a putative transfer of rehabilitation effects from the training tasks to specific cognitive functions. RESULTS: The results indicate that VR training may improve performance not only in the trained task but also in specific neuropsychological functions. After the training, both patients and controls showed improved performances in visual scanning, mental rotation, visuoconstruction, and cognitive flexibility. Moreover, depressive symptoms were attenuated in both groups. In the patient group compared to the control group, the training particularly resulted in improved visual memory retrieval and reduced memory complaints. CONCLUSIONS: The results of the current study suggest that VR training can improve particularly visual-spatial skills in patients with hemianopia or quadrantanopia. Our study thus introduces an interesting novel treatment approach to improve cognitive functions relevant to daily life in stroke patients with visual field defects.

Loxapine for Treatment of Patients With Refractory, Chemotherapy-Induced Neuropathic Pain: A Prematurely Terminated Pilot Study Showing Efficacy But Limited Tolerability.

Neuropathic pain is a debilitating and commonly treatment-refractory condition requiring novel therapeutic options. Accumulating preclinical studies indicate that the potassium channel Slack (KNa1.1) contributes to the processing of neuropathic pain, and that Slack activators, when injected into mice, ameliorate pain-related hypersensitivity. However, whether Slack activation might reduce neuropathic pain in humans remains elusive. Here, we evaluated the tolerability and analgesic efficacy of loxapine, a first-generation antipsychotic drug and Slack activator, in neuropathic pain patients. We aimed to treat 12 patients with chronic chemotherapy-induced, treatment-refractory neuropathic pain (pain severity ≥ 4 units on an 11-point numerical rating scale) in a monocentric, open label, proof-of-principle study. Patients received loxapine orally as add-on analgesic in a dose-escalating manner (four treatment episodes for 14 days, daily dose: 20, 30, 40, or 60 mg loxapine) depending on tolerability and analgesic efficacy. Patient-reported outcomes of pain intensity and/or relief were recorded daily. After enrolling four patients, this study was prematurely terminated due to adverse events typically occurring with first-generation antipsychotic drugs that were reported by all patients. In two patients receiving loxapine for at least two treatment episodes, a clinically relevant analgesic effect was found at a daily dose of 20-30 mg of loxapine. Another two patients tolerated loxapine only for a few days. Together, our data further support the hypothesis that Slack activation might be a novel strategy for neuropathic pain therapy. However, loxapine is no valid treatment option for painful polyneuropathy due to profound dopamine and histamine receptor-related side effects. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02820519.

Memory performance of patients with major depression in an everyday life situation.

Although patients with major depressive disorder (MDD) report severe memory impairment in their everyday life, memory tests indicate only moderate deficits. In order to clarify these conflicting observations, the present study aimed at the investigation of MDD patients' memory performance in a real everyday life situation. The study included 20 MDD patients and 20 healthy control subjects. Nonverbal memory was assessed by means of the Rey Complex Figure Test whereas verbal memory was assessed by the recall of a 20-item wordlist with supermarket products. For the assessment of everyday life memory, subjects had to purchase as many products as possible of the 20-item wordlist in a real supermarket. Furthermore, subjects were asked for memory complaints. MDD patients' performance in the supermarket resembled memory test results and was not significantly impaired. MDD patients' self-reports, however, indicated severe memory problems that clearly fell below their performance in the supermarket. This study helped to identify everyday life-related factors that do not impair MDD patients' cognitive performance beyond their performance in standard laboratory testing situations. These factors may not be relevant for remediation programs that are specifically developed for depressed patients.

Acute social stress before the planning phase improves memory performance in a complex real life-related prospective memory task.

Successful execution of intentions, but also the failure to recall are common phenomena in everyday life. The planning, retention, and realization of intentions are often framed as the scientific concept of prospective memory. The current study aimed to examine the influence of acute stress on key dimensions of complex "real life" prospective memory. To this end, we applied a prospective memory task that involved the planning, retention, and performance of intentions during a fictional holiday week. Forty healthy males participated in the study. Half of the subjects were stressed with the Socially Evaluated Cold Pressor Test (SECPT) before the planning of intentions, and the other half of the participants underwent a control procedure at the same time. Salivary cortisol was used to measure the effectiveness of the SECPT stress induction. Stressed participants did not differ from controls in planning accuracy. However, when we compared stressed participants with controls during prospective memory retrieval, we found statistically significant differences in PM across the performance phase. Participants treated with the SECPT procedure before the planning phase showed improved prospective memory retrieval over time, while performance of controls declined. Particularly, there was a significant difference between the stress and control group for the last two days of the holiday week. Interestingly, control participants showed significantly better performance for early than later learned items, which could be an indicator of a primacy effect. This differential effect of stress on performance was also found in time- and event-dependent prospective memory. Our results demonstrate for the first time, that acute stress induced before the planning phase may improve prospective memory over the time course of the performance phase in time- and event-dependent prospective memory. Our data thus indicate that prospective memory can be enhanced by acute stress.

Disturbed spatial cognitive processing of body-related stimuli in a case of a lesion to the right fusiform gyrus.

The fusiform gyrus (FG) is well known as one of the main neural sites of human face and body processing. We report the case of a young male patient with epilepsy and a circumscribed lesion in the right FG who presented with isolated impairments in spatial cognitive processing of body-related stimuli. However, he did not show any clinical signs of prosopagnosia. In particular, handling/processing of body and face stimuli was impaired, when stimuli were presented in unconventional views and orientations, thus requiring additional spatial cognitive operations. In this case study, we discuss the patient's selective impairment from the view of current empirical and theoretical work on the segregation of functions in the FG.

A Bayesian latent group analysis for detecting poor effort in a sample of cognitively impaired patients.

Using a Bayesian latent group analysis in a simulation design, we recently showed a high diagnostic accuracy when assessing effort in the context of malingered memory deficits. We here further evaluate our Bayesian model in a sample of cognitively impaired patients. The main analysis showed both high sensitivity and specificity, thus corroborating a high diagnostic accuracy of the model. Additional analysis showed variations on effort estimates after changes in malingering base rates. Variations affected sensitivity, but not specificity, which is in line with typical findings in malingering research. These data suggest that Bayesian analyses may complement and improve existing effort measures.

Age-dependent changes in the neural substrates of empathy in autism spectrum disorder.

In typical development, empathic abilities continue to refine during adolescence and early adulthood. Children and adolescents with autism spectrum disorders (ASD) show deficits in empathy, whereas adults with ASD may have developed compensatory strategies. We aimed at comparing developmental trajectories in the neural mechanisms underlying empathy in individuals with ASD and typically developing control (TDC) subjects. Using an explicit empathizing paradigm and functional magnetic resonance imaging, 27 participants with ASD and 27 TDC aged 12-31 years were investigated. Participants were asked to empathize with emotional faces and to either infer the face's emotional state (other-task) or to judge their own emotional response (self-task). Differential age-dependent changes were evident during the self-task in the right dorsolateral prefrontal cortex, right medial prefrontal cortex, right inferior parietal cortex, right anterior insula and occipital cortex. Age-dependent decreases in neural activation in TDC were paralleled by either increasing or unchanged age-dependent activation in ASD. These data suggest ASD-associated deviations in the developmental trajectories of self-related processing during empathizing. In TDC, age-dependent modulations of brain areas may reflect the 'fine-tuning' of cortical networks by reduction of task-unspecific brain activity. Increased age-related activation in individuals with ASD may indicate the development of compensatory mechanisms.

The Bergen left-right discrimination test: practice effects, reliable change indices, and strategic performance in the standard and alternate form with inverted stimuli.

Several authors pointed out that left-right discrimination (LRD) tasks may be entangled with differential demands on mental rotation (MR). However, studies considering this interrelationship are rare. To differentially assess LRD of stimuli with varying additional demands on MR, we constructed and evaluated an extended version of the Bergen right-left discrimination (BRLD) test including additional subtests with inverted stickmen stimuli in 174 healthy participants (50♂, 124♀) and measured subjective reports on participants' strategies to accomplish the task. Moreover, we analyzed practice effects and reliable change indices (RCIs) on BRLD performance, as well as gender differences. Performance significantly differed between subtests with high and low demands on MR with best scores on subtests with low demands on MR. Participants' subjective strategies corroborate these results: MR was most frequently reported for subtests with highest MR demands (and lowest test performance). Pronounced practice effects were observed for all subtests. Sex differences were not observed. We conclude that our extended version of the BRLD allows for the differentiation between LRD with high and low demands on MR abilities. The type of stimulus materials is likely to be critical for the differential assessment of MR and LRD. Moreover, RCIs provide a basis for the clinical application of the BRLD.

Diagnostic accuracy of a bayesian latent group analysis for the detection of malingering-related poor effort.

In the last decade, different statistical techniques have been introduced to improve assessment of malingering-related poor effort. In this context, we have recently shown preliminary evidence that a Bayesian latent group model may help to optimize classification accuracy using a simulation research design. In the present study, we conducted two analyses. Firstly, we evaluated how accurately this Bayesian approach can distinguish between participants answering in an honest way (honest response group) and participants feigning cognitive impairment (experimental malingering group). Secondly, we tested the accuracy of our model in the differentiation between patients who had real cognitive deficits (cognitively impaired group) and participants who belonged to the experimental malingering group. All Bayesian analyses were conducted using the raw scores of a visual recognition forced-choice task (2AFC), the Test of Memory Malingering (TOMM, Trial 2), and the Word Memory Test (WMT, primary effort subtests). The first analysis showed 100% accuracy for the Bayesian model in distinguishing participants of both groups with all effort measures. The second analysis showed outstanding overall accuracy of the Bayesian model when estimates were obtained from the 2AFC and the TOMM raw scores. Diagnostic accuracy of the Bayesian model diminished when using the WMT total raw scores. Despite, overall diagnostic accuracy can still be considered excellent. The most plausible explanation for this decrement is the low performance in verbal recognition and fluency tasks of some patients of the cognitively impaired group. Additionally, the Bayesian model provides individual estimates, p(zi |D), of examinees' effort levels. In conclusion, both high classification accuracy levels and Bayesian individual estimates of effort may be very useful for clinicians when assessing for effort in medico-legal settings.

Retrieval, monitoring, and control processes: a 7 tesla FMRI approach to memory accuracy.

MEMORY RESEARCH HAS BEEN GUIDED BY TWO POWERFUL METAPHORS: the storehouse (computer) and the correspondence metaphor. The latter emphasizes the dependability of retrieved mnemonic information and draws upon ideas about the state dependency and reconstructive character of episodic memory. We used a new movie to unveil the neural correlates connected with retrieval, monitoring, and control processes, and memory accuracy (MAC), according to the paradigm of Koriat and Goldsmith (1996a,b). During functional magnetic resonance imaging, subjects performed a memory task which required (after an initial learning phase) rating true and false statements [retrieval phase (RP)], making confidence judgments in the respective statement [monitoring phase (MP)], and deciding for either venturing (volunteering) the respective answer or withholding the response [control phase (CP)]. Imaging data pointed to common and unique neural correlates. Activations in brain regions related to RP and MAC were observed in the precuneus, middle temporal gyrus, and left hippocampus. MP was associated with activation in the left anterior and posterior cingulate cortex along with bilateral medial temporal regions. If an answer was volunteered (as opposed to being withheld) during the CP, temporal, and frontal as well as middle and posterior cingulate areas and the precuneus revealed activations. Increased bilateral hippocampal activity was found during withholding compared to volunteering answers. The left caudate activation detected during withholding compared to venturing an answer supports the involvement of the left caudate in inhibiting unwanted responses. Contrary to expectations, we did not evidence prefrontal activations during withholding (as opposed to volunteering) answers. This may reflect our design specifications, but alternative interpretations are put forth.

Learning real-life cognitive abilities in a novel 360°-virtual reality supermarket: a neuropsychological study of healthy participants and patients with epilepsy.

BACKGROUND: To increase the ecological validity of neuropsychological instruments the use of virtual reality (VR) applications can be considered as an effective tool in the field of cognitive neurorehabilitation. Despite the growing use of VR programs, only few studies have considered the application of everyday activities like shopping or travelling in VR training devices. METHODS: We developed a novel 360°-VR supermarket, which is displayed on a circular arrangement of 8 touch-screens--the "OctaVis". In this setting, healthy human adults had to memorize an auditorily presented shopping list (list A) and subsequently buy all remembered products of this list in the VR supermarket. This procedure was accomplished on three consecutive days. On day four, a new shopping list (list B) was introduced and participants had to memorize and buy only products of this list. On day five, participants had to buy all remembered items of list A again, but without new presentation of list A. Additionally, we obtained measures of participants' presence, immersion and figural-spatial memory abilities. We also tested a sample of patients with focal epilepsy with an extended version of our shopping task, which consisted of eight days of training. RESULTS: We observed a comprehensive and stable effect of learning for the number of correct products, the required time for shopping, and the length of movement trajectories in the VR supermarket in the course of the training program. Task performance was significantly correlated with participants' figural-spatial memory abilities and subjective level of immersion into the VR. CONCLUSIONS: Learning effects in our paradigm extend beyond mere verbal learning of the shopping list as the data show evidence for multi-layered learning (at least visual-spatial, strategic, and verbal) on concordant measures. Importantly, learning also correlated with measures of figural-spatial memory and the degree of immersion into the VR. We propose that cognitive training with the VR supermarket program in the OctaVis will be efficient for the assessment and training of real-life cognitive abilities in healthy subjects and patients with epilepsy. It is most likely that our findings will also apply for patients with cognitive disabilities resulting from other neurological and psychiatric syndromes.

Neural mechanisms of encoding social and non-social context information in autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) often fail to attach context to their memories and are specifically impaired in processing social aspects of contextual information. The aim of the present study was to investigate the modulatory influence of social vs. non-social context on neural mechanisms during encoding in ASD. Using event-related fMRI, 13 boys with ASD and 13 typically developing boys comparable for age and IQ were investigated during encoding of neutral objects presented either with a social (faces) or a non-social (houses) context. A memory paradigm was then applied to identify brain activation patterns associated with encoding of subsequently recollected versus non-recollected objects. On the behavioural level, no significant between-group differences emerged. In particular, no differential effects of context on memory performance were observed. Neurally, however, context-specific group differences were observed in several brain regions. During encoding of subsequently recollected objects presented with a face, ASD subjects (compared to controls) showed reduced neural activation in the bilateral inferior frontal gyrus, bilateral middle frontal gyrus and right inferior parietal lobule. Neural activation in the right inferior frontal gyrus was positively correlated with memory performance in controls, but negatively in ASD individuals. During encoding of subsequently non-recollected objects presented in the non-social context, ASD subjects showed increased activation in the dorsal MPFC. Our findings suggest that in ASD subjects, fronto-parietal brain regions subserving memory formation and the association of contextual information are activated atypically when a social context is presented at encoding. The data add to findings from related research fields indicating that in ASD, socioemotional impairment extends into domains beyond social cognition. Increased activation in the dorsal MPFC in ASD individuals might reflect supervisory cognitive processes related to the suppression of a distracting non-social context.

Computer-assisted analysis of spontaneous speech: quantification of basic parameters in aphasic and unimpaired language.

Although generally accepted as an important part of aphasia assessment, detailed analysis of spontaneous speech is rarely carried out in clinical practice mostly due to time limitations. The Aachener Sprachanalyse (ASPA; Aachen Speech Analysis) is a computer-assisted method for the quantitative analysis of German spontaneous speech that allows for a detailed assessment by means of linguistic basic parameters in an acceptable amount of time. It has previously been proven sensitive for monitoring changes over time. In this study, we present data of 52 aphasic participants whose spontaneous speech was analyzed retrospectively before and after an intensive therapy program. The measured changes are evaluated with reference to normative data of 60 non-brain-damaged speakers. Results confirm good sensitivity to document changes over time. Clinical relevance of changes is assessed with reference to critical score ranges derived from the normative data. Findings provide further evidence of the clinical applicability and usefulness of ASPA.

A Bayesian latent group analysis for detecting poor effort in the assessment of malingering.

Despite their theoretical appeal, Bayesian methods for the assessment of poor effort and malingering are still rarely used in neuropsychological research and clinical diagnosis. In this article, we outline a novel and easy-to-use Bayesian latent group analysis of malingering whose goal is to identify participants displaying poor effort when tested. Our Bayesian approach also quantifies the confidence with which each participant is classified and estimates the base rates of malingering from the observed data. We implement our Bayesian approach and compare its utility in effort assessment to that of the classic below-chance criterion of symptom validity testing (SVT). In two experiments, we evaluate the accuracy of both a Bayesian latent group analysis and the below-chance criterion of SVT in recovering the membership of participants assigned to the malingering group. Experiment 1 uses a simulation research design, whereas Experiment 2 involves the differentiation of patients with a history of stroke from coached malingerers. In both experiments, sensitivity levels are high for the Bayesian method, but low for the below-chance criterion of SVT. Additionally, the Bayesian approach proves to be resistant to possible effects of coaching. We conclude that Bayesian latent group methods complement existing methods in making more informed choices about malingering.

Aging-related changes of neural mechanisms underlying visual-spatial working memory.

Capacities of the prefrontal cortex (PFC) such as working memory (WM) are known to decline with increasing age. However, it is unclear which neurofunctional mechanisms may underlie this aging-related cognitive decline. The finding that PFC activity tends to be less lateralized in older subjects has led to the assumption of a hemispheric asymmetry reduction in the PFC associated with aging (HAROLD). Using functional magnetic resonance imaging (fMRI), we here investigated aging-related neurofunctional alterations during the performance of a visual-spatial WM task with differential levels of difficulty. Older volunteers activated dorsolateral PFC regions bilaterally while young subjects recruited these areas only in the left hemisphere. These data corroborate the hemispheric asymmetry reduction in the PFC associated with aging (HAROLD) account. However, we also observed functional reorganizations in parieto-occipital areas, and with increasing WM demands, an aging-related reversed hemispheric asymmetry of prefrontal activations. Importantly, neither PFC nor parieto-occipital reorganizations prevented older participants from showing worse WM performance than young volunteers. We conclude that frontal-parietal functional reorganizations may reflect compensational mechanisms related to aging, but do not obviate diminished visual-spatial WM performance in older people.