White matter (WM) alterations are well documented in individuals at clinical high-risk for psychosis (CHR-P) and with recent-onset psychosis (ROP), yet it remains unclear whether they reflect vulnerability, psychosis-related symptom severity, or general impairments shared with other disorders such as depression. To disentangle these correlates, we analyzed diffusion MRI data from 882 individuals (457 females) of the multisite Personalized Prognostic Tools for Early Psychosis Management (PRONIA) study, including 183 CHR-P, 206 ROP, 298 healthy controls, and 195 individuals with depression who were assessed as a clinical comparison group of observed associations. Fractional anisotropy (FA) was extracted from 25 WM regions. Analyses of covariance tested group differences across CHR-P, ROP, and healthy controls. Canonical correlation analysis then identified multivariate correlation components between FA and a broad set of twelve clinical, two cognitive, and two risk-related measures in CHR-P and ROP, restricted to regions with group effects. To identify if these findings are not specific to psychosis, we additionally tested whether the correlation components were expressed in the depression comparison group. Group differences emerged in 17 of 25 regions. Canonical correlation analysis identified two significant correlation components. Component 1 linked widespread lower FA with impaired cognition and functioning, representing general impairment. Component 2 linked focal lower FA with more severe psychosis-related symptoms and absence of familial risk. Component 1, but not Component 2, showed also a significant association in the depression group emphasizing its relevance for general impairment. Disentangling general impairment from psychosis-related symptom severity suggests potentially different underlying processes. Developing imaging biomarkers accounting for these processes may guide early detection strategies and targeted interventions.

Benzodiazepines act as positive allosteric modulators of the GABAA receptor and affect several motor and cognitive functions. By engaging perceptual-motor as well as inhibitory control processes, the antisaccade task was used in previous studies to investigate effects of benzodiazepines on behavioral performance. Using a randomized, double-blind, placebo-controlled within-subjects design, this study combined eye-tracking with BOLD fMRI in order to examine the neural correlates of these effects for the first time. N = 39 healthy participants completed an antisaccade task after administration of either 1 mg lorazepam or placebo. On a behavioral level, lorazepam led to reduced (anti-)saccadic peak velocity as well as increased (anti-)saccadic latency. On a neural level, drug-induced reduction of BOLD was found in a fronto-parietal-occipital network, including key oculomotor regions. This result was further supported by our finding of increased GABAA receptor density in the affected network. On an individual level, decline in peak velocity under lorazepam was associated with decreased neural activation in several cortical regions, including medial frontal eye fields. No interactions between drug and saccade condition (prosaccade, antisaccade) were found. Our results therefore suggest GABAergic modulation of a more general saccade-related network rather than of specific components for inhibitory control processes. Future studies may rely on BOLD signal as a sensitive marker for benzodiazepine activity during saccadic eye movements.

Positive and negative schizotypy reflect distinct patterns of subclinical traits in the general population associated with neurodevelopmental and schizophrenia-spectrum pathologies. Yet, a comprehensive characterization of the unique and shared neuroanatomical signatures of these schizotypy dimensions is lacking. Leveraging 3D brain MRI data from 2730 unmedicated healthy individuals, we identified neuroanatomical profiles of positive and negative schizotypy and systematically compared them with disorder-specific, microarchitectural, neurotransmitter-level, and connectome measures. Positive and negative schizotypy were associated with distinct cortical signatures, of predominantly thinner frontal and thicker paralimbic cortical areas, respectively. These cortical signatures of positive and negative schizotypy were differentially linked to brain-wide cortical patterns of schizophrenia-spectrum (clinical high-risk for psychosis, schizophrenia) and neurodevelopmental conditions (ADHD, autism spectrum disorder and 22q11.2 deletion syndrome). Additionally, the positive and negative schizotypy-related cortical profiles mapped onto different local attributes of gene expression, cortical myelination, D1, and histamine receptor distributions. Network models further showed that positive and negative schizotypy cortical signatures were spatially associated with cortical hubs, suggesting that highly interconnected regions are more vulnerable to the morphological differences associated with both schizotypy dimensions. Finally, predominantly sensorimotor-to-association and paralimbic areas emerged as epicenters with connectivity profiles significantly linked to the schizotypy-related cortical patterns. Collectively, this study identified cortical signatures of positive and negative schizotypy traits that are embedded along multiple scales of cortical organization and neuropsychiatric pathologies. Our work yields novel insights into how neurobiology and brain architecture may guide neuroanatomical vulnerability and resilience to psychopathology in the general population.

Proactive control describes preparatory, anticipatory processes prior to upcoming demands, whereas reactive control is recruited as a late, corrective response to goal interferences. Here, we used fMRI to investigate behavioral and neuronal correlates of proactive and reactive control in major depressive disorder (MDD). Fifty patients and 50 healthy controls performed an antisaccade task with trial-specific central cues informing about the probability of upcoming task demands (antisaccade or prosaccade), thereby manipulating proactive control levels in the cue period. The trial-specific task instruction was contained in the peripheral stimulus, resulting in either congruent or incongruent trials in the saccadic response period to tax reactive control. Saccade stimuli were faces, with differently valenced expressions (negative, positive, neutral) allowing block-wise affective manipulation. Results indicated comparable effects of cue period proactive control in both groups in fronto-parieto-occipital cortex and striatum, including medial frontal and supplementary eye fields. In the response period, incongruent trials evoked enhanced activations in fronto-cingular, parietal and temporal cortex, thalamus and striatum, again without group differences. However, patients with MDD had larger antisaccade amplitudes and lower saccadic peak velocities. Exploratory analysis of a posterior parietal region-of-interest known to be related to non-standard sensorimotor transformations in antisaccades indicated reduced BOLD in patients during the response phase. There were no effects of stimulus valence on any measure. Together, these findings support the role of overlapping fronto-parieto-striatal networks in proactive and reactive control and suggest that in this particular task, such activations may be unaffected by stimulus-induced affective states as well as clinically relevant affective disorder.

Smooth pursuit eye movement (SPEM) performance has previously been shown to have good reliability. While quantifying the relative amounts of reliable trait and state influences on SPEM is relevant to different lines of research including individual differences, clinical and experimental research, this has not yet been done. Here, we apply latent state-trait (LST) theory to SPEM for the first time to examine reliability and to explicitly decompose trait and situational variance. SPEM tasks with sinusoidal and triangular movement patterns were performed by N = 163 healthy participants at three measurement occasions. LST and latent growth curve (LGC) modeling was used to calculate model-based reliability and to distinguish reliable trait variance (consistency) and variance due to influences of the situation and of the person × situation interaction (occasion specificity). We found mostly excellent reliabilities (0.86-0.98), except for the intra-individual standard deviation of root mean square error (RMSE) in both SPEM tasks where reliability was good (0.70-0.74). Consistencies and occasion specificities indicated that a higher proportion of variance was due to trait influences (62% on average) than due to situational influences (26% on average). There were mostly no changes on trait level over time. We conclude that SPEM performance is highly reliable and mainly reflects relatively stable trait components, but is also characterized by substantial state influences. Overall, these findings further support the use of SPEM in individual differences studies. However, potential state influences should be considered more explicitly in future studies examining SPEM.

Proactive control refers to the biasing of information processing toward a task goal during anticipation of a relevant event. This study investigated proactive control of emotional information in adult attention-deficit/hyperactivity disorder (ADHD) using a manual face-word Stroop task. Individuals with ADHD and healthy controls (n = 51 per group) were selected from a large participant pool (n = 1,020) using the Adult ADHD Self-Report-Scale. Images of happy or anxious faces were presented, with the word HAPPY or ANXIOUS written across the faces, congruent or incongruent with facial expressions. Participants had to identify facial expressions while ignoring word meaning. To investigate contextual cue utilization, the proportion of incongruent trials was manipulated (75% vs. 25%) to generate mostly congruent (MC) and mostly incongruent (MI) contexts. Individuals with ADHD showed larger error rate and longer reaction time (RT) than controls. Context effects were reflected by a greater difference in error rate and RT between congruent and incongruent trials within the MC than the MI context. These effects were independent of the presence of ADHD. The findings suggest that the ability to use contextual cues to facilitate proactive cognitive control is preserved in adult ADHD, despite marked impairments in attention and processing speed.

Benzodiazepines are commonly prescribed psychotropic drugs with anxiolytic, sedating, hypnotic, and anticonvulsant effects. They impair saccadic eye movements in prosaccade tasks, particularly peak velocity, but the extent of the effects on different saccadic parameters remains unclear. Therefore, we conducted a systematic review and meta-analyses on the effects of different benzodiazepines on peak velocity (k (number of included studies) = 30, kES (number of included effect sizes) = 45, N (number of participants) = 444), latency (k = 12, kES = 17, N = 221) and amplitude gain (k = 5, kES = 8, N = 113). Furthermore, we performed meta-analyses and dose-dependent meta-regressions of lorazepam effects on peak velocity (k = 13, kES = 19, N = 257) and latency (k = 8, kES = 12, N = 187). We found a robust and large effect on peak velocity (standardised mean change (SMCC)) = -1.064, 95% CI (confidence intervals) [-1.287, -0.84]), a less consistent, medium sized effect on latency (SMCC = 0.706, 95% CI [0.285, 1.127]), and a medium sized, but non-significant, effect on gain (SMCC = -0.581, 95% CI [-1.226, 0.064]). These findings confirm the sensitivity of saccadic eye movements to modulation of gamma-aminobutyric acid (GABA) through benzodiazepines and point to the peak velocity in particular as a biomarker for sedative effects in pharmacological research in healthy adults.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising tool to modulate motivation and affect, with prior studies showing greater pupil dilation compared to sham. However, sensory differences between conditions may confound results. In a randomized crossover study with 94 participants, we applied right-sided pulsed taVNS (1 s, 20 Hz, and 400 μs) and calibrated stimulation amplitude to match subjective sensation. Contrary to expectations, taVNS did not significantly increase pupil dilation versus sham. However, when participants perceived sham as less intense, taVNS effects were stronger. Differences in perceived sensation between taVNS and sham were mainly linked to sham-induced pupil dilation. Our findings suggest that right-sided pulsed taVNS only leads to greater pupil dilation when a sensory mismatch occurs, underscoring the difficulty of creating an effective sham.

OBJECTIVES:Eye movements (EMs) are considered biomarkers for age-related neurological or psychological deficits, and oculomotor control has been shown to strongly decline with age. This study aimed to understand the neural pathways of these age-related changes. METHODS:The analysis was based on 5,400 participants (aged 30-95 years) from the population-based Rhineland Study. EMs were recorded using video-based infrared oculography at 1,000 Hz. Brain structure measures were obtained from T1-weighted MR images using FreeSurfer. Relations of brain structure with EM outcomes were quantified using multivariable linear regression models while adjusting for age, sex, educational level, and best-corrected visual acuity. Brain structure measures were further analyzed as potential mediators in the relation between age and EM outcomes. RESULTS:Larger volumes of the globus pallidus and thalamus were associated with shorter saccadic latencies. Thicker cortex in frontal and parietal brain regions was associated with fewer direction errors in the antisaccade task in female but not in male participants. Thicker cortex in the calcarine sulcus was associated with better smooth pursuit performance. Cerebellar gray and white matter volumes were associated with better performance on the antisaccade and smooth pursuit tasks. Mediation analyses suggested that age-related differences in brain structures explain up to 18% of age-related differences in oculomotor performance. DISCUSSION:Our findings extend previous studies by identifying novel brain structural correlates of EM performance and quantifying the extent to which they explain age-related differences in EM performance. Our results show that differences in brain structure partly account for age-related differences in EM performance.

This EEG and eye-tracking study investigated affective influences on cognitive preparation using a precued pro-/antisaccade task with emotional faces as cues. Negative information interfered with preparatory processes with high but not low executive function load.

Clinical assessment and scientific research in psychiatry are largely based on questionnaires that are used to assess psychopathology. The development of large language models (LLMs) offers a new perspective for analysis of the language and terminology on which these questionnaires are based. We used state-of-the-art LLMs to derive numerical representations (‘text embeddings’) of the semantic and sentiment content of items from established questionnaires for the assessment of psychopathology. We compared the pairwise associations between empirical data from cross-sectional studies and text embeddings to test whether the empirical structure of psychopathology can be reconstructed by LLMs. Across four large-scale datasets ( n = 1,555, n = 1,099, n = 11,807 and n = 39,755), we found a range of significant correlations between empirical item-pair associations and associations derived from text embeddings ( r = 0.18 to r = 0.57, all P < 0.05). Random forest regression models based on semantic or sentiment embeddings predicted empirical item-pair associations with moderate to high accuracy ( r = 0.33 to r = 0.81, all P < 0.05). Similarly, empirical clustering of items and grouping to established subdomain scores could be partly reconstructed by text embeddings. Our results demonstrate that LLMs are able to represent substantial components of the empirical structure of psychopathology. Consequently, the integration of LLMs into mental health research has the potential to unlock numerous promising avenues. These may encompass improving the process of developing questionnaires, optimizing generalizability and reducing the redundancy of existing questionnaires or facilitating the development of new conceptualizations of mental disorders.

This ERP study investigated the neural correlates of proactive and reactive control using a novel precued antisaccade paradigm. Proactive control refers to preparatory processes during anticipation of a behaviorally relevant event; reactive control is activated after such an event to ensure goal attainment. A 64-channel EEG was obtained in 35 healthy subjects; video-based eye tracking was applied for ocular recording. In the task, a target (probe) appeared left or right of the fixation point 1800 ms after a central cue; subjects had to look toward the probe (prosaccade) or its mirror image position (antisaccade). Probes were positive, negative or neutral face expressions, with their frame colors instructing task requirements. The cue informed about antisaccade probability (70% vs. 30%) in each trial. High antisaccade probability was associated with larger CNV amplitude than low antisaccade probability. In trials with incongruence between expected and actual task requirements, probe N2 and P3a amplitudes were larger than in congruent trials. In incongruent trials, P3a was smaller for negative than positive and neutral probes. Task accuracy and speed were lower in incongruent trials and varied according to affective probe valence. EEG source imaging suggested the origin of the ERPs to be in orbitofrontal cortex and superior frontal gyrus. The effect on the CNV indicates greater cortical activity during higher proactive control demands. Larger N2 and P3a in incongruent trials reflect greater resource allocation to conflict monitoring and conflict resolution, i.e., reactive control. The influence of probe valence on P3a suggests reduced processing capacity due to negative information.

Traditional neuropsychological tests still have limited diagnostic value for assessing adult attention-deficit hyperactivity disorder (ADHD), as they often fail to fully capture ADHD symptoms in everyday life. Recent studies suggest that virtual reality (VR) has the potential to alleviate this problem by enabling the creation of more naturalistic and symptom-relevant test environments. Following prior research investigating VR as an assessment method for ADHD, the present study reports on a VR scenario that does not only entail a realistic environment but also a more naturalistic task design. Specifically, participants are immersed in a newly developed virtual office, where they conduct a virtual email sorting task (VEST), while simultaneously being exposed to distracting events. Twenty-one individuals with ADHD and 21 healthy controls (HC) underwent our new VR paradigm while we simultaneously recorded their VEST performance, task-related subjective symptom ratings, head actigraphy, gaze behavior, and brain activity, assessed via functional near-infrared spectroscopy (fNIRS) during distraction and non-distraction phases. Data were analyzed in a mixed ANOVA design. Individuals with ADHD showed greater processing time variability compared to HC in the VEST. No group differences were found in mean processing time and error rates. In head position, a significant interaction effect of Phase and Group was found, with the ADHD group showing a significant increase in movement during distraction phases compared to non-distraction phases. Additionally, with respect to gaze behavior, a trend effect of Group indicated higher perceptual off-task gaze in ADHD compared to HC. Individuals with ADHD also reported higher hyperactivity and inattention during task performance than HC. No group differences in fNIRS activity in dorsolateral prefrontal cortex were found. Our study provides a further step towards the application of more realistic task designs compared to classic continuous performance tasks and underlines the utility of actigraphy, eye tracking, and distractors in ADHD assessment. However, further studies are necessary to improve the VEST task design and discriminatory ability.

Background:The hippocampus plays a critical role in psychosis, with reduced volume observed across the psychosis continuum. These structural changes are associated with cognitive deficits, symptom severity, and increased risk of psychosis progression. Elevated hippocampal perfusion and glutamate/GABA (gamma-aminobutyric acid) imbalance further suggest metabolic dysregulation as a key mechanism. Gut microbiota composition can influence hippocampal metabolism, but their interplay remains to be explored. Methods:In this cross-sectional study, we recruited 142 healthy participants from the general population, yielding 69 individuals with high schizotypy (HS) and 72 individuals with low schizotypy. All underwent clinical and cognitive testing, multimodal neuroimaging, and gut microbiota analysis via 16S ribosomal RNA gene sequencing. Hippocampal subfield volumes (structural magnetic resonance imaging), perfusion (arterial spin labeling) and glutamate/GABA levels (proton magnetic resonance spectroscopy), and microbial taxa (abundance, diversity, enterotypes) were assessed. Results:Group comparisons of cognition, multimodal neuroimaging, and gut microbiome composition did not reveal significant differences after correction for multiple comparisons. Within the HS group, glutamate (r = 0.38, p = .003) and GABA (r = -0.36, p = .003) ratios were linked to social withdrawal. Across the entire sample, left hippocampal subfield volumes and glutamate/GABA levels differed significantly between predominant gut microbial enterotypes. Conclusions:Our results suggest a potential relationship between aberrant gut microbial composition and hippocampal alterations in people with positive schizotypy from the general population. Our findings inform future large-scale research that further explores specific mechanisms of gut microbiome-hippocampus interactions in psychosis and the potential of tailored microbial interventions targeting hippocampal-mediated symptoms.

Adult attention-deficit/hyperactivity disorder (ADHD) is associated with substantial impairments in well-being and quality of life. In addition to cognitive and behavioral symptoms, emotional dysregulation characterizes the disorder. This study investigated habitual worry in the context of cognitive control and heart rate variability (HRV) in adult ADHD. Groups with high and low ADHD symptoms (n = 51 per group) were selected from a large participant pool (n = 1020) using the Adult ADHD Self-Report Scale. HRV was recorded during a breathing focus task assessing cognitive control. The task included two phases during which participants' ability to concentrate on their breathing was recorded before and after an instructed worry phase. While groups did not differ in HRV, participants with high ADHD symptoms reported greater habitual worry, more negative affect, and less positive affect than those with low ADHD symptoms. They exhibited less ability to concentrate on breathing, more frequent positive, neutral, and negative thought intrusions, and greater distress during instructed worry. In the total sample, habitual worry correlated negatively with breathing focus ability and positively with intrusive thoughts. HRV correlated positively with breathing focus ability and negatively with thought intrusions. Moreover, HRV correlated negatively with distress during instructed worry. Impaired cognitive control may contribute to exaggerated worry and negative emotional states related to ADHD symptoms. The lack of association between HRV and ADHD symptoms accords with previous studies. The correlations seen for HRV implicate prefrontal cortex function and vagal cardiac control in emotional regulation and inhibition of intrusive thoughts.

The human brain is a large-scale network, containing multiple segregated, functionally specialized systems. With increasing age, these systems become less segregated, but the reasons and consequences of this age-related reorganization are largely unknown. Thus, after characterizing age- and sex-specific differences in the segregation of global, sensorimotor, and association systems using resting-state functional MRI data, we analyzed how segregation relates to cognitive performance in both classical and eye movement tasks across age strata and whether this is influenced by the degree of neuropathology. Our analyses included 6,455 participants (30-95 years) of the community-based Rhineland Study. System segregation indices were based on functional connectivity within and between 12 brain systems. We assessed cognitive performance with tests for memory, processing speed, executive function, and crystallized intelligence and oculomotor tasks. Multivariable regression models confirmed that brain systems become less segregated with age (e.g., global segregation: standardized regression coefficient (ß) = -0.298; 95% confidence interval [-0.299, -0.297], p < 0.001) and that in older age this effect is stronger in women compared to men. Higher segregation benefited memory (especially in young individuals) and processing speed in individuals with mild neuropathology (not significant after multiple testing correction). Lower segregation benefited crystallized intelligence in 46- to 55-year-olds. Associations between segregation indices and cognition were generally weak (ß ~ 0.01-0.06). This suggests that optimal brain organization may depend on the degree of brain pathology. Age-related brain reorganization could serve as a compensatory mechanism and partly explain improvements in crystallized intelligence and the decline in fluid cognitive domains from adolescence to (late) adulthood.

Mental disorders have been linked to an increased risk of developing dementia including Alzheimer’s disease. However, previous studies have typically focused on individuals who meet diagnostic criteria for a given psychiatric disorder. The goal of our study was to examine whether diverse neuropsychiatric symptoms are related to early markers of neurodegeneration in the general population. The analysis was based on 8,318 participants (aged 30-95) from the population-based Rhineland Study. Neuropsychiatric symptoms (perceived stress, depressive symptoms, anxiety symptoms, attention deficit hyperactivity (ADHD) symptoms, obsessive-compulsive disorder (OCD) symptoms) were measured using self-report questionnaires. A general psychopathology factor was generated using principal component analysis (PCA). Cognitive performance was measured across different cognitive domains. Whole-brain and regional brain volumes as well as white matter hyperintensities (WMH) were obtained from magnetic resonance images (3T Siemens MAGNETOM Prisma). Plasma neurofilament light chain (NfL) levels were assessed using Quanterix’s Simoa NF-light™ assay. Relations of symptom scores with markers of neurodegeneration were quantified using multivariable linear regression models. We performed a sensitivity analysis by excluding participants reporting a neurodegenerative or psychiatric disease (n = 1,784). Participants with more severe neuropsychiatric symptoms and higher scores on the psychopathology factor performed significantly worse in all fluid cognitive domains (standardized beta coefficients (β) range between -0.01 and -0.06). The strength of association between neuropsychiatric symptoms and cognitive performance increased with age. Furthermore, neuropsychiatric symptoms (except for ADHD symptoms) and general psychopathology were associated with smaller grey matter volume (β between -0.00 and -0.02). Perceived stress, depressive symptoms, and anxiety were additionally associated with higher WMH load (β between 0.02 and 0.04), while OCD symptoms were associated with thinner cerebral cortex (β = -0.05 [-0.07, -0.02]). Sensitivity analysis showed robustness of the associations. We found no associations between neuropsychiatric symptoms and NfL levels. Various neuropsychiatric symptoms and a generally higher level of psychopathology are associated with poorer cognitive performance, grey matter atrophy, and WMH burden, even in adults without a psychiatric diagnosis. However, we did not find direct evidence of neuroaxonal injury, as indicated by the absence of an association with NfL.

BACKGROUND:Prepulse inhibition (PPI) of the acoustically elicited startle response is a widely used cross-species measure of sensorimotor gating. It is known to be reduced in various psychiatric disorders. Given previous reports of (a) disrupted PPI in young adults following overnight sleep deprivation and (b) disrupted sleep-wake cycles and psychiatric disorders being more common in evening than morning chronotypes, it is possible that there are chronobiological influences on human PPI. AIMS:We investigated chronotype, time of day (ToD) and synchrony effects (i.e. optimal functioning at preferred ToD) in acoustic PPI in young healthy adults. METHODS:Thirty-six adults, selected from a larger pool (N = 213) to represent morning, intermediate or evening chronotypes, were assessed on PPI (prepulse-to-pulse intervals: 30, 60 and 120-ms) on two occasions, 1 week apart: once in the morning (8:00-10:00) and once during the late afternoon (16:00-18:00). RESULTS:There were no chronotype or synchrony effects on PPI. In the late afternoon, compared to the morning session, (i) there was greater startle amplitude on pulse-alone trials in association with higher schizotypy and (ii) greater PPI on 120-ms (but not 30-ms or 60-ms) PPI trials, but this effect became non-significant after covarying for schizotypy. CONCLUSIONS:Our findings showed no chronotype or synchrony effect on PPI, and offer further support for PPI to be a stable biomarker that is not significantly modulated by chronotype or ToD in healthy adults. ToD, however, may influence some startle parameters in association with schizotypy and should be considered in future studies of schizotypy and related populations.

Chronotype is a proxy for various intra-individual rhythms (e.g. sleep-wake cycles) which fluctuate throughout the day. The extent to which chronotype modulates cognitive performance remains unclear. Here, we systematically reviewed studies to determine the influence of chronotype on its own, and/or in interaction with time of day (ToD; optimal/non-optimal), in cognitive function in healthy adults. Following PRISMA guidelines, data searches were conducted in PubMed and Web of Science databases (11 March 2024), yielding 65 studies (53 in adults aged 18-45 y; 11 comparing adults aged 18-32 and 50-95 y; one involving only morning type adults aged 60-76 y). Most of the reviewed studies (>80%) indicated no main effect of chronotype on cognitive function. There was evidence from 29 (45.31%) of 64 studies involving adults aged 18-45 y of a synchrony effect (i.e. superior performance at optimal ToD) in morning and/or evening types, mostly in attention, inhibition, and memory. In older adults, there was evidence of a synchrony effect from 10 (83.33%) of 12 studies, especially on tasks involving fluid abilities. Limited evidence suggested higher activation of inhibition-related brain regions at optimal ToD in both chronotypes, and synchrony effects being impacted by certain exogenous factors known to affect arousal and performance (e.g. task complexity, lighting conditions). Our findings highlight the need to carefully consider age along with endogenous and exogenous sources of intra-individual variations in arousal while determining synchrony effect in cognitive functions. Not acknowledging these synchrony effects may also result in exaggerated cognitive deficits especially in the elderly.