Post-COVID fatigue: Reduced quality-of-life associated with clinically relevant fatigue in mild disease courses.

Fatigue is a pervasive symptom experienced by many individuals after COVID-19. Despite its widespread occurrence, fatigue remains a poorly understood and complex phenomenon. Our aim is to evaluate the subjective experience of mental fatigue after COVID-19 and to assess its significance for daily life functioning. In this online questionnaire study (N = 220), the Fatigue Severity Scale (FSS), World Health Organization Quality-of-Life assessment (WHOQoL) and a subjective severity rating of the COVID-19 disease progression were used. For our statistical analyses we utilized independent samples t-tests, one-way ANOVA with post-hoc analyses, and a multiple regression. As expected our findings revealed the COVID group reported significantly higher levels of subjective fatigue compared to the control group. Moreover, there was a significant difference between experienced fatigue across the four severity groups. Participants who had a milder course of disease also experienced severe subjective fatigue. Subjective fatigue explained 40% variance in quality-of-life. In conclusion, severe subjective fatigue appears to be associated with increased self-reported COVID-19 symptom severity and lower quality-of-life but is already observable in milder cases. This underscores, firstly, the importance of considering also less severe cases and, secondly, the need to develop rehabilitation and psychological interventions for fatigue.

Heartbeat-Evoked Potential in Major Depressive Disorder: A Biomarker for Differential Treatment Prediction between Venlafaxine and rTMS?

INTRODUCTION: Currently, major depressive disorder (MDD) treatment plans are based on trial-and-error, and remission rates remain low. A strategy to replace trial-and-error and increase remission rates could be treatment stratification. We explored the heartbeat-evoked potential (HEP) as a biomarker for treatment stratification to either antidepressant medication or rTMS treatment. METHODS: Two datasets were analyzed: (1) the International Study to Predict Optimized Treatment in Depression (iSPOT-D; n = 1,008 MDD patients, randomized to escitalopram, sertraline, or venlafaxine, and n = 336 healthy controls) and (2) a multi-site, open-label rTMS study (n = 196). The primary outcome measure was remission. Cardiac field artifacts were removed from the baseline EEG using independent component analysis (ICA). The HEP-peak was detected in a bandwidth of 20 ms around 8 ms and 270 ms (N8, N270) after the R-peak of the electrocardiogram signal. Differences between remitters and non-remitters were statistically assessed by repeated-measures ANOVAs for electrodes Fp1, Cz, and Oz. RESULTS: In the venlafaxine subgroup, remitters showed a lower HEP around the N8 peak than non-remitters on electrode site Cz (p = 0.004; d = 0.497). The rTMS group showed a non-significant difference in the opposite direction (d = -0.051). Retrospective stratification to one of the treatments based on the HEP resulted in enhanced treatment outcome prediction for venlafaxine (+22.98%) and rTMS (+10.66%). CONCLUSION: These data suggest that the HEP could be used as a stratification biomarker between venlafaxine and rTMS; however, future out-of-sample replication is warranted.

Consensus on the reporting and experimental design of clinical and cognitive-behavioural neurofeedback studies (CRED-nf checklist).

Neurofeedback has begun to attract the attention and scrutiny of the scientific and medical mainstream. Here, neurofeedback researchers present a consensus-derived checklist that aims to improve the reporting and experimental design standards in the field.

Neurofeedback as a Treatment Intervention in ADHD: Current Evidence and Practice.

PURPOSE OF REVIEW: Current traditional treatments for ADHD present serious limitations in terms of long-term maintenance of symptom remission and side effects. Here, we provide an overview of the rationale and scientific evidence of the efficacy of neurofeedback in regulating the brain functions in ADHD. We also review the institutional and professional regulation of clinical neurofeedback implementations. RECENT FINDINGS: Based on meta-analyses and (large multicenter) randomized controlled trials, three standard neurofeedback training protocols, namely theta/beta (TBR), sensori-motor rhythm (SMR), and slow cortical potential (SCP), turn out to be efficacious and specific. However, the practical implementation of neurofeedback as a clinical treatment is currently not regulated. We conclude that neurofeedback based on standard protocols in ADHD should be considered as a viable treatment alternative and suggest that further research is needed to understand how specific neurofeedback protocols work. Eventually, we emphasize the need for standard neurofeedback training for practitioners and binding standards for use in clinical practice.

Multisubject Decomposition of Event-related Positivities in Cognitive Control: Tackling Age-related Changes in Reactive Control.

Age-related neurocognitive effects have been observed at different levels ranging from reduced amplitudes of even-related potentials and brain oscillations, to topography changes of brain activity. However, their association remains incompletely understood. We investigated time-frequency and time-course effects in functional networks underlying the P300 and their involvement in reactive control. Electroencephalographic (EEG) data of three different age groups (30 young: 18-26 years, 30 mid-aged: 49-58 years, 30 elderly: 65-75 years) was measured while they performed a cued colour/thickness switching task. Neural data was analysed concerning the targets. To consider restart, mixing, and switching processes, the targets´ position after a cue (first or third target) as well as their context in the single-task (distractor cue) or the mixed-task block (switch- or repeat cue) was analysed. P300 EEG data was decomposed by means of group-independent component and time-frequency analyses focusing on theta and beta oscillations. RTs generally slowed down with age (main effect group), and effects were specifically strong in targets after a switching cue (larger Cohens d). Peaking at around 300 ms, we detected five functionally independent networks reflecting the multicomponent process underlying task-switching. These networks differed in terms of their topography (parietal and frontal), their involvement in task processes (switch-specific, mixing-, restart-, and single-task processes) and in terms of frequency effects. All were affected by age, as indicated by amplitude changes of the target-P300 and power reductions most consistently shown in beta oscillations. Most extensive age-related changes were observed in one parietal network sensitive to mixing and restart processes. Changes included a topography shift, P300 and beta amplitudes, and were ongoing in the elderly group.

Filling the void-enriching the feature space of successful stopping.

The ability to inhibit behavior is crucial for adaptation in a fast changing environment and is commonly studied with the stop signal task. Current EEG research mainly focuses on the N200 and P300 ERPs and corresponding activity in the theta and delta frequency range, thereby leaving us with a limited understanding of the mechanisms of response inhibition. Here, 15 functional networks were estimated from time-frequency transformed EEG recorded during processing of a visual stop signal task. Cortical sources underlying these functional networks were reconstructed, and a total of 45 features, each representing spectrally and temporally coherent activity, were extracted to train a classifier to differentiate between go and stop trials. A classification accuracy of 85.55% for go and 83.85% for stop trials was achieved. Features capturing fronto-central delta- and theta activity, parieto-occipital alpha, fronto-central as well as right frontal beta activity were highly discriminating between trial-types. However, only a single network, comprising a feature defined by oscillatory activity below 12 Hz, was associated with a generator in the opercular region of the right inferior frontal cortex and showed the expected associations with behavioral inhibition performance. This study pioneers by providing a detailed ranking of neural features regarding their information content for stop and go differentiation at the single-trial level, and may further be the first to identify a scalp EEG marker of the inhibitory control network. This analysis allows for the characterization of the temporal dynamics of response inhibition by matching electrophysiological phenomena to cortical generators and behavioral inhibition performance. Hum Brain Mapp 38:1333-1346, 2017. © 2016 Wiley Periodicals, Inc.

The relationship between depression and executive function and the impact of vascular disease burden in younger and older adults.

Background: depression is associated with worse executive function, but underlying mechanisms might differ by age. Aims: to investigate whether vascular disease burden affects the association between depression and executive dysfunction differentially by age. Method: among 83,613 participants of Lifelines (population-based cohort study), linear regression analyses were applied to examine the association between executive function (Ruff Figural Fluency test, dependent variable) and depression according to DSM-IV criteria (Mini International Neuropsychiatric Interview, independent variable). Results: adjusted for demographic characteristics, major depressive disorder was associated with a lower level of executive function in both younger and older adults. Minor depressive disorder was only associated with worse executive function in younger adults. Adding vascular disease burden to the final model with major depressive disorder, reduced this strength of this association by 5.9% in younger and 5.0% in older adults. Conclusions: major depression was associated with worse executive function across the lifespan, but minor depression only in younger adults. The impact of vascular burden on the association did not differ between younger and older adults. Therefore, vascular risk reduction is important in both age groups.

Functional parcellation of the inferior frontal and midcingulate cortices in a flanker-stop-change paradigm.

Conflict monitoring and motor inhibition are engaged in the performance of complex tasks. The midcingulate cortex (MCC) has been suggested to detect conflicts, whereas the right inferior frontal cortex (IFC) seems to be of relevance for the inhibition process. The current experiment investigates the neural underpinnings of their interplay via a modified flanker paradigm. Conflict was manipulated by the congruency of flanking stimuli relative to a target (congruent vs. incongruent) and motor inhibition by a within-trial response change of the initiated response (keep response vs. stop-change). We used event-related functional magnetic resonance imaging, decomposition with high model order ICA, and single trial analysis to derive a functional parcellation of the whole-brain data. Results demonstrate the segmentation of the MCC into anterior and posterior subregions, and of the IFC into the pars opercularis, pars triangularis, and pars orbitalis. The pars opercularis and pars triangularis of the right IFC constituted the foundation of inhibition-related networks. With high conflict on incongruent trials, activity in the posterior MCC network, as well as in one right IFC network was observed. Stop-change trials modulated both the MCC as well as networks covering extended parts of the IFC. Whereas conflict processing and inhibition most often are studied separately, this study provides a synopsis of functionally coupled brain regions acting in concert to enable an optimal performance in situations involving interference and inhibition.

Theta power and functional connectivity as neurophysiological markers of executive functions in individuals with cognitive complaints in daily life.

Impairments in executive functions (EFs) are common across psychological disorders. Research into the neural oscillations underlying EFs has the potential to help understand these impairments and contribute to the development of interventions. The aim of this study is to assess theta power and functional theta connectivity in the sensor space of the regions of the superordinate network for the core EFs: conflict monitoring, response inhibition, set-shifting, and working memory updating. We recruited adults with self-reported everyday EFs complaints and formed two groups: one with attention deficit hyperactivity disorder (ADHD) (n=27) and another without any diagnosis (n=22), and compared them to controls (n=21) on the Stroop, Stop-signal, Switching, and N-back task using EEG. Power and functional connectivity analyses were conducted for four regions of interest: frontal-midline, frontolateral left and right, and parietal region. For all four EFs, the groups showed a dynamical increase in theta power over time in the four regions of interest, as well as in functional theta connectivity between these regions. Group differences were found especially for conflict monitoring, with differences in theta power in the frontal-midline and frontolateral right region. These neural markers are also associated with behavioural performance and complaints in daily life. For set-shifting, group differences were less pronounced and for response inhibition and working memory updating no group differences were observed.

Untreated if unrecognized: A cognitive profile of sustained subjective executive dysfunctions in COVID-19.

& STATEMENT OF IMPACTSARS-COV-2 infection can result in acute and long-lasting cognitive complaints, causing ongoing impairments in daily life which poses a challenge to society. Consequently, the evaluation and characterization of cognitive complaints, specifically in the domain of executive functions (EFs) affecting daily life, is imperative in formulating an effective neuropsychological response.In total 442 participants aged 18-65+ years from the Netherlands, Germany, Mexico, and Spain were included in an online questionnaire. Among others, the questionnaire consisted of demographics, the Behavior Rating Inventory of Executive Functioning for Adults (BRIEF-A), measures of subjective disease progression severity and experienced subjective impairment in daily activities. To assess whether daily life activities are affected by EF impairments, the main BRIEF-A composite score (GEC) was analyzed. To determine whether disease-related COVID-19 factors predict EFs complaints in daily life, a stepwise regression analysis was performed with i) experienced disease severity, ii) time since disease, and iii) health risk factor as predictors.The study revealed noteworthy differences in the occurrence of EFs problems in daily life between both groups, as indicated by the GEC, which exhibited a medium effect size even 6 months post-COVID-19 diagnosis even in mild disease progression. The scores of the BRIEF-A subscales follow a domain-specific profile, and includes clinically relevant impairments in: Working memory, Plan/Organize, Task Monitor, Shift, which are affected by the experienced severity of the disease. This cognitive profile has important implications for targeted cognitive training in rehabilitation and has the potential for an applicability to other viruses as well.

Long-term improvements in executive functions after frontal-midline theta neurofeedback in a (sub)clinical group.

Impairments in executive functions (EFs) are common across disorders and can greatly affect daily functioning. Frontal-midline (FM) theta neurofeedback (NF) has been shown effective in enhancing EFs in healthy adults, prompting interest in exploring its potential as an alternative treatment for EFs in (sub)clinical samples. This study aims to determine the effects of FM theta NF on EFs in a sample of 58 adults (aged 20-60 years) with pronounced subjective EF complaints in daily life. Using a pre/post/follow-up design with a sham NF group, the present study assessed upregulation of FM theta in an eight-session individualized FM theta NF training and its immediate and long-term transfer effects on objective and subjective measures of EFs. These included behavioral performance on EF tasks assessing working memory updating (N-back task), set-shifting (Switching task), conflict monitoring (Stroop task), and response inhibition (Stop-signal task), as well as FM theta power during these tasks, and subjective EFs in daily life (BRIEF-A). The results indicate that there are only differences in FM theta self-upregulation between the NF group and sham group when non-responders are excluded from the analysis. Regarding behavioral transfer effects, NF-specific improvements are found in working memory updating reaction time (RT) and conflict monitoring RT variability at 6-month follow-up, but not immediately after the NF training. The effects on FM theta power during the EF tasks and subjective changes in EFs in daily life were not specific to the NF training. As a next step, research should identify the best predictors to stratify NF training, as well as explore ways to improve NF responsiveness, for instance by increasing neuroplasticity.

Extended FNAME performance is preserved in subjective cognitive decline but highly affected in amnestic mild cognitive impairment.

OBJECTIVE: The cognitive characterization of Alzheimer's disease risk states, such as amnestic mild cognitive impairment (aMCI) and subjective cognitive decline (SCD), is fundamental for timely diagnosis and interventions. The Face Name Associative Memory Exam (FNAME) is sensitive to early Alzheimer's disease brain changes, and an extended version captures a fuller range of associative memory abilities. We aimed to assess group effects in the extended FNAME in older adults with SCD, aMCI, and older adult controls (CON). METHOD: Two concurrently created versions of the extended FNAME were used to test three groups of older adults (CON = 35, SCD = 37, aMCI = 31) at two sites (Mexico = 59, Netherlands = 44). Extended FNAME memory abilities were analyzed in five analyses of variance. Group and site were considered as independent variables. For the recall ability, subtest levels were entered as a within-subject variable. The remaining abilities (Face Recognition, Name Recognition, Spontaneous Name Recall, and Face-Name Matching) were analyzed in independent models. RESULTS: In all models, the main effect for group was significant with large effect sizes, driven by a worse performance of aMCI participants. No significant differences were found between SCD and CON. The main effect for site was only significant in Face Recognition. CONCLUSIONS: The worse performance of aMCI in the extended FNAME implies an impairment in associative memory abilities beyond recall. The similar performance of CON and SCD might be explained by the recruitment of SCD participants that did not spontaneously seek help for memory decline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Understanding the relationship between apathy, cognition and functional outcome in schizophrenia: The significance of an ecological assessment.

In recent years there has been an increasing interest in understanding the role apathy plays in mediating the relationship between cognitive impairment and functional outcome. In general, most studies measure cognition with traditional cognitive tests that give explicit instructions and guide the participants toward generating a response. However, given that apathy is defined by a decrease in self-initiated behavior, it is crucial to evaluate cognition with ecological tasks that do not explicitly direct the patient´s motivation to generate behaviors to assess the actual effect. This study investigated whether an ecological cognitive assessment (the Jansari Executive Function Assessment, JEF©) would uniquely contribute to the relationship between cognition, apathy, and functional outcome in schizophrenia. The Apathy Evaluation Scale (AES), neuropsychological tests and the JEF© were administered to 20 patients with schizophrenia. Hierarchical multiple regression and mediation analysis were performed to test the associations between the variables of interest. Results showed that JEF© explained a significant portion of the variance in AES (25%). In addition, apathy explained 36% of the variance in functional outcome. However, AES did not mediate between cognition and functional outcome. Our results highlight the importance of assessing cognition with tasks that require integration of cognitive functions needed for real life demands.

Conceptual representation of actions in sign language.

The idea that knowledge of events entails a universal spatial component, that is conceiving agents left of patients, was put to test by investigating native users of German sign language and native users of spoken German. Participants heard or saw event descriptions and had to illustrate the meaning of these events by means of drawing or arranging toys. Two types of verbs were tested, differing in the way they are signed. Verbs with a horizontal transient are typically signed with a left-to-right directionality, from the addressee's point of view. In contrast, verbs with sagittal transients display transitions moving toward or away from speaker. Signers showed a direct mapping preference for verbs with horizontal transients, by putting agents at the same position in space as in the signed message (i.e., mirroring signing space). No such effect was found for verbs with sagittal transients. In all, the data fit with the idea that interpretations of signed or spoken languages are modulated by task and culture as well as language-related factors and constraints.

Treatment Efficacy and Clinical Effectiveness of EEG Neurofeedback as a Personalized and Multimodal Treatment in ADHD: A Critical Review.

PURPOSE: Recent reviews have proposed that scientifically validated standard EEG neurofeedback (NF) protocols are an efficacious and specific treatment for attention-deficit hyperactivity disorder (ADHD). Here, we review the current evidence for the treatment efficacy and clinical effectiveness of NF in ADHD to investigate whether NF treatment personalization (standard protocols matched to the electrophysiological features of ADHD) and combination with other interventions (psychosocial, sleep hygiene and nutritional advice) might yield superior long-term treatment outcomes relative to non-personalized NF and medication monotreatments. METHODS: The electronic databases PubMed and PsycINFO were systematically searched using our key terms. Of the 38 resulting studies, 11 randomized controlled trials (RCTs) and open-label studies were eligible for inclusion. Studies were analyzed for effect sizes and remission rates at the end of treatment and at follow-up. The effects of personalized and multimodal NF treatments were compared to non-personalized NF monotreatments and with two benchmark medication studies. RESULTS: The analysis of RCTs indicated that the long-term effects of personalized NF interventions were superior to non-personalized NF and comparable to those of medication alone or in combination with behavioral intervention. The analysis of open-label trials further indicates that the interaction of NF with parental interventions, sleep and nutritional advice might yield superior clinical effectiveness relative to NF and medication monotreatments. CONCLUSION: Personalized and multimodal NF interventions seem to yield superior treatment efficacy relative to NF alone and superior clinical effectiveness relative to medication. We propose that treatment outcomes may be further enhanced by adjusting NF non-specific factors (eg, reinforcement contingencies) to specific ADHD characteristics (eg, reward sensitivity). Future NF research should focus on the systematic evaluation of the treatment outcomes of personalized and multimodal treatments.

Anosognosia in Amnestic Mild Cognitive Impairment Is Related to Diminished Hippocampal Volume Comparable to Alzheimer's Disease Dementia: Preliminary MRI Findings.

Although the presence of anosognosia in amnestic mild cognitive impairment (aMCI) may be predictive of conversion to Alzheimer's disease (AD), little is known about its neural correlates in AD and aMCI. Four different groups were compared using volumetric and diffusion magnetic resonance imaging metrics in regions of interest (hippocampus and cingulum cortex gray matter, cingulum bundle white matter): aMCI subjects with anosognosia (n = 6), aMCI subjects without anosognosia (n = 12), AD subjects with anosognosia (n = 6), and AD subjects without anosognosia (n = 9). aMCI subjects with anosognosia displayed a significantly lower gray matter density (GMD) in the bilateral hippocampus than aMCI subjects without anosognosia, which was accounted for by bilateral hippocampal differences. Furthermore, we identified that the mean hippocampal gray matter density of aMCI subjects with anosognosia was not statistically different than that of AD subjects. The groups of aMCI and AD subjects with anosognosia also displayed a lower GMD in the bilateral cingulum cortex compared to subjects without anosognosia, but these differences were not statistically significant. No statistically significant differences were found in the fractional anisotropy or mean diffusivity of the hippocampus or cingulum between subjects with and without anosognosia in aMCI or AD groups. While these findings are derived from a small population of subjects and are in need of replication, they suggest that anosognosia in aMCI might be a useful clinical marker to suspect brain changes associated with AD neuropathology.

Worse associative memory recall in healthy older adults compared to young ones, a face-name study in Spain and Mexico.

INTRODUCTION: The Face Name Associative Memory Exam (FNAME) is sensitive to associative memory changes early in the Alzheimer's disease spectrum, but little is known about how healthy aging affects FNAME performance. We aimed to assess aging effects on an extended version of the test, which captures further associative memory abilities beyond the recall and recognition domains measured in the original version. METHOD: We adapted FNAME versions in Spain and Mexico, adding new subtests (Spontaneous Name Recall, Face-Name Matching). We compared the performance of 21 young adults (YA) and 27 older adults (OA) in Spain, and 34 YA and 36 OA in Mexico. Recall was analyzed using a mixed-model ANOVA including subtest scores as dependent variables, age group as a fixed-factor independent variable, and recall subtest as a three-level repeated-measure independent variable. The rest of the associative memory domains were analyzed through t-tests comparing the performance of YA and OA. RESULTS: In Spain, we found significant effects for age group and recall subtest, with large effect sizes. The recognition subtests (Face Recognition, Name Recognition) displayed ceiling effects in both groups. The new subtests displayed medium-to-large effect sizes when comparing age groups. In Mexico, these results were replicated, additionally controlling for education. In both studies, recall performance improved after repeated exposures and it was sustained after 30 minutes in YA and OA. CONCLUSIONS: We document, in two different countries, a clear aging pattern on the extended FNAME: regardless of education, OA remember fewer stimuli than YA through recall subtests. The new subtests provide evidence on associative memory changes in aging beyond recall.

Conflict and inhibition differentially affect the N200/P300 complex in a combined go/nogo and stop-signal task.

Conflict and inhibition are considered to exert strong influences on the neurophysiological N200 and P300 brain responses as evoked in go/nogo and stop-signal tasks. In order to separate their underlying neural and functional mechanisms, the current experiment manipulated both conflict and inhibition. To do so, the go/nogo and stop-signal tasks were merged into one paradigm. Conflict was manipulated by varying go-trial frequencies across blocks (75% vs. 25%). Motor inhibition was manipulated by using go, nogo and stop trials each representing a different load of inhibition. Event-related potentials (ERPs) as well as current density reconstructions (CDRs) of fifteen healthy participants were analyzed. Overall, infrequent trials evoked significantly more pronounced N200s than frequent trials. The P300 predominantly revealed significant variations between trial types (go, nogo, stop). Estimated source activations of the MCC and the IFC supported the ERP results; N200-related effects were revealed in both regions, whereas the condition-specific variations of the P300 were only observed in the IFC. The results indicate that the N200 primarily reflects conflict-related effects whereas the P300 predominantly represents motor inhibition.

Expressive deficits and amotivation as mediators of the associations between cognitive problems and functional outcomes: Results from two independent cohorts.

Many individuals with severe mental disorders have difficulties in vocational and social functioning, which are regarded the most important outcomes, together with clinical symptoms. To understand the underlying mechanisms, research is increasingly focused on factors influencing functional outcomes. One established association has been shown between cognition and community functioning with negative symptoms as a possible mediator. Although it has been shown that negative symptoms consist of two subdomains, thus far negative symptoms have been assessed as one unitary construct. This study considers for the first time subdomains of negative symptoms as putative mediators (expressive deficits, amotivation) of the association between cognition (neuro- and social cognition) and functional outcome (living situation, occupation, social functioning). We expected that specific subdomains of negative symptoms (e.g. amotivation) would mediate the effect of cognition on specific functional outcomes (e.g. social functioning) independently from illness duration. To assess this, we included two independent cohorts, consisting of participants with different illness duration. These two independent cohorts consisted of patients with a recent-onset psychotic disorder: PROGR-S (first time treated; N = 1129) and GROUP (illness duration preferably <5 years; N = 1200). Using linear regression, mediation analyses were performed with two cognition domains (neurocognition and social cognition) as predictors, negative symptoms (Expressive deficits and Amotivation as indexed with items from the Positive and Negative Syndrome Scale) as mediators and three measures of functional outcomes (living situation, occupation and social functioning) as outcome measures. The analyses were repeated with the same outcome measures three years later. Three main results were obtained. I) Both in the cross-sectional and longitudinal analyses, the associations of neurocognition (both cohorts) and social cognition (GROUP) with social functioning were mediated by amotivation. II) The association between cognition and living situation was mediated by Expressive deficits in one cohort (GROUP) but not in the cohort assessing first-episode psychosis (PROGR-S). III) The association between cognition and occupation was mediated by Amotivation in PROGR-S and by Expressive deficits in GROUP. CONCLUSION: The current results show a less robust mediating role for specific negative symptom domains regarding the associations of cognition with occupation and living situation that may depend on the duration of psychotic illness. However, Amotivation, mediates the association between cognition and social functioning, which holds true for patients experiencing a first-onset and patients with a longer illness duration alike. The results may have implications for the development of therapeutic approaches focusing on amotivation to improve social functioning. GENERAL SCIENTIFIC SUMMARY: This study stresses the importance of distinguishing subdomains of negative symptoms, cognition and functioning. Our results show that specific negative symptom dimensions mediate the effects of cognition on specific functional outcomes.