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The consistently observed age-accompanied diminution in mind-wandering stands seemingly opposed to accounts that present mind-wandering as a failure of executive control. This study examined the impact of aging on the frequency and phenomenology of mind-wandering and investigated distinct variables mediating age-related differences in unintentional and intentional mind-wandering. Thirty-four younger and 34 healthy older adults completed a neuropsychological test battery and contrast change detection task embedded with experience sampling probes asking participants to discriminate the nature of their thoughts. Results revealed age-related decreases in unintentional and intentional mind-wandering, but equivalent task accuracy. Parallel mediations demonstrated that older adults reduced their unintentional mind-wandering through having less anxiety and greater task engagement than younger adults. Despite the evidence of age-related decline on cognitive function tests, neither executive function nor task demand variables further contributed to the model. Our results adjudicate between competing theories, highlighting the roles of affective and motivational factors in unintentional mind-wandering. Intentional mind-wandering showed no significant associations with the neuropsychological measures; however, intentional mind-wandering was associated with more false alarms, which was mediated by greater reaction time variability (RTV). In the context of the exploitation/exploration framework, we suggest that younger adults were more inclined to intentionally mind-wander, indexed by increased RTV, while preserving comparable performance accuracy to older adults. Conversely, older adults exploited greater task focus, marked by reduced RTV, with less bias toward, or resources for, exploration of the mind-wandering space. Therefore, dispositional and strategic factors should be considered in future investigations of mind-wandering across the lifespan. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The location, extent and progression of longitudinal morphometric changes after first-episode of psychosis (FEP) remains unclear. We investigated ventricular and cortico-subcortical regions over a 3-year period in FEP patients compared with healthy controls. High resolution 1.5T T1-weighted MR images were obtained at baseline from 28 FEP patients at presentation and 28 controls, and again after 3-years. The longitudinal FreeSurfer pipeline (v.5.3.0) was used for regional volumetric and cortical reconstruction image analyses. Repeated-measures ANCOVA and vertex-wise linear regression analyses compared progressive changes between groups in subcortical structures and cortical thickness respectively. Compared with controls, patients displayed progressively reduced volume of the caudate [F (1,51)=5.86, p=0.02, Hedges’ g=0.66], putamen [F (1,51)=6.06, p=0.02, g=0.67], thalamus [F (1,51)=6.99, p=0.01, g=0.72] and increased right lateral ventricular volume [F (1, 51)=4.03, p=0.05], and significantly increased rate of cortical thinning [F (1,52)=5.11, p=0.028)] at a mean difference of 0.84% [95% CI (0.10, 1.59)] in the left lateral orbitofrontal region over the 3-year period. In patients, greater reduction in putamen volume over time was associated with lower cumulative antipsychotic medication dose (r=0.49, p=0.01), and increasing lateral ventricular volume over time was associated with worsening negative symptoms (r=0.41, p=0.04) and poorer global functioning (r= −0.41, p=0.04). This study demonstrates localised progressive structural abnormalities in the cortico-striato-thalamo-cortical circuit after the onset of psychosis, with increasing ventricular volume noted as a neuroanatomical marker of poorer clinical and functional outcome.

Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium. We attempted to differentiate BD from control participants, investigated different data handling strategies and studied the neuroimaging/clinical features most important for classification. Individual site accuracies ranged from 45.23% to 81.07%. Aggregate subject-level analyses yielded the highest accuracy (65.23%, 95% CI = 63.47–67.00, ROC-AUC = 71.49%, 95% CI = 69.39–73.59), followed by leave-one-site-out cross-validation (accuracy = 58.67%, 95% CI = 56.70–60.63). Meta-analysis of individual site accuracies did not provide above chance results. There was substantial agreement between the regions that contributed to identification of BD participants in the best performing site and in the aggregate dataset (Cohen’s Kappa = 0.83, 95% CI = 0.829–0.831). Treatment with anticonvulsants and age were associated with greater odds of correct classification. Although short of the 80% clinically relevant accuracy threshold, the results are promising and provide a fair and realistic estimate of classification performance, which can be achieved in a large, ecologically valid, multi-site sample of BD participants based on regional neurostructural measures. Furthermore, the significant classification in different samples was based on plausible and similar neuroanatomical features. Future multi-site studies should move towards sharing of raw/voxelwise neuroimaging data.

Older adults display difficulties in encoding and retrieval of information, resulting in poorer memory. This may be due to an inability of older adults to engage elaborative encoding strategies during learning. This study examined behavioural and electrophysiological effects of explicit cues to self-initiate learning during encoding and subsequent recognition of words in younger adults (YA), older control adults (OA) and older adults with relative memory impairment (OD). The task was a variation of the old/new paradigm, some study items were preceded by a cue to learn the word (L) while others by a do not learn cue (X). Behaviourally, YA outperformed OA and OD on the recognition task, with no significant difference between OA and OD. Event-related potentials at encoding revealed enhanced early visual processing (70-140 ms) for L- versus X-words in young and old. Only YA exhibited a greater late posterior positivity (LPP; 200-500 ms) for all words during encoding perhaps reflecting superior encoding strategy. During recognition, only YA differentiated L- versus X-words with enhanced frontal P200 (150-250 ms) suggesting impaired early word selection for retrieval in older groups; however, OD had enhanced P200 activity compared to OA during L-word retrieval. The LPP (250-500 ms) was reduced in amplitude for L-words compared to both X- and new words. However, YA showed greater LPP amplitude for all words compared to OA. For older groups, we observed reduced left parietal hemispheric asymmetry apparent in YA during encoding and recognition, especially for OD. Findings are interpreted in the light of models of compensation and dedifferentiation associated with age-related changes in memory function.

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the Brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD – an objective measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on Reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems.Results supported by bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g. cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

The Noradrenergic Theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the up-regulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test this theory, a study was conducted on a sample of 686 participants (395 Controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC vol-ume, attentional performance and a biological index of brain maintenance (BrainPAD – a measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on reserve indices including education and occupational attainment. Volumetric variation across groups was also explored. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic hypothesis. Results showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on upregulation of the noradrenergic system (e.g. attention training, physical exercise and pharmacological intervention) may yield important clin-ical benefits to mitigate cognitive impairment with age and disease.

The study presented here aims at bringing a global perspective to the phenomenon of unequal representation of females in science by offering empirical data of female representation in neuroscience/schizophrenia academic or clinical departments in several institutions around the world. We took advantage of a budding network of scientists and colleagues from different countries to bring the data together. The data presented are related to sex, that is the biological distinction between males and females, based on genetics and reproductive anatomy, while gender, considered a cultural concept was harder to determine. We report data from two clinical/academic departments in Nigeria, Africa; 2 clinical/academic departments from Sudan, Africa; 1 clinical/academic department from South Africa, Africa; 3 academic institutions from Ireland, Europe; 1 clinical/academic institution from Spain, Europe; 2 academic institutions from Buenos Aires University, Argentina; and the Psychiatry Departments at Harvard Medical School, Boston, USA.

Manual tracing of magnetic resonance imaging (MRI) represents the gold standard for segmentation in clinical neuropsychiatric research studies, however automated approaches are increasingly used due to its time limitations. The accuracy of segmentation techniques for subcortical structures has not been systematically investigated in large samples. We compared the accuracy of fully automated [(i) model-based: FSL-FIRST; (ii) patch-based: volBrain], semi-automated (FreeSurfer) and stereological (Measure®) segmentation techniques with manual tracing (ITK-SNAP) for delineating volumes of the caudate (easy-to-segment) and the hippocampus (difficult-to-segment). High resolution 1.5 T T1-weighted MR images were obtained from 177 patients with major psychiatric disorders and 104 healthy participants. The relative consistency (partial correlation), absolute agreement (intraclass correlation coefficient, ICC) and potential technique bias (Bland-Altman plots) of each technique was compared with manual segmentation. Each technique yielded high correlations (0.77-0.87, p

BackgroundVerbal learning (VL) and fluency (VF) are prominent cognitive deficits in psychosis, of which the precise neuroanatomical contributions are not fully understood. We investigated the arcuate fasciculus (AF) and its associated cortical regions to identify structural abnormalities contributing to these verbal impairments in early stages of psychotic illness.MethodsTwenty-six individuals with recent-onset psychosis and 27 healthy controls underwent cognitive testing (MATRICS Consensus Cognitive Battery) and structural/diffusion-weighted MRI. Bilaterally, AF anisotropy and cortical thickness, surface area and volume of seven cortical regions were investigated in relation to VL and VF performance in both groups.ResultsReduced right superior temporal gyrus surface area and volume related to better VF in controls. In psychosis, greater right pars opercularis volume and reduced left lateralization of this region related to better VL, while greater right long AF fractional anisotropy and right pars orbitalis volume related to better VF, these findings not present in controls. Psychosis had reduced right pars orbitalis thickness compared to controls.ConclusionAnatomical substrates for normal processing of VL and VF appear altered in recent-onset psychosis. A possible aberrant role of the right hemisphere arcuate fasciculus and fronto-temporal cortical regions in psychosis may contribute to deficits in VL and VF.

Background The extent and location of longitudinal morphometric changes after first-episode of psychosis (FEP) remains unclear. We investigated the progressive profile of ventricular and cortico-subcortical regions over a 3-year period in FEP patients compared with healthy controls (HC), and whether any progressive neuroanatomical changes were related to clinical factors. Methods High resolution 1.5T T1-weighted MR images were obtained from 28 FEP patients and 28 HCs shortly after presentation to services and again after 3-year follow-up. The longitudinal FreeSurfer pipeline (v.5.3.0) was used for regional volumetric and cortical reconstruction image analyses. Repeated-measures ANCOVA and vertex-wise linear regression analyses were used to compare progressive changes in relation to subcortical structures/ventricles and thickness across the cortical mantle, respectively, between groups. Partial correlations were used to determine associations of progressive neuroanatomical change with clinical and functional characteristics. Results Compared with controls, patients displayed progressively reduced volume of the caudate [F(1,51)=5.86, p=0.02, Hedges’ g=0.66], putamen [F(1,51)=6.06, p=0.02, g=0.67] and thalamus [F(1,51)=6.99, p=0.01, g=0.72], with a trend for increased lateral ventricular volume [F(1,51)=3.37, p=0.07, g=0.50] more prominent on the right [F(1, 51)=4.03, p=0.05], and significantly increased rate of cortical thinning [F(1,52)=5.11, p=0.028)] at a mean difference of 0.844% [95% CI (0.095, 1.593)] in the left lateral orbitofrontal region (LLOFR) over the 3-year period. In FEP individuals, greater reduction in putamen volume over time was associated with low cumulative antipsychotic medication dose (r=0.49, p=0.01), and increasing lateral ventricular volume over time was associated with worsening negative symptoms (r=0.41, p=0.04) and poorer global assessment of functioning (r=-0.41, p=0.04). Discussion Our results demonstrate existence of localised progressive structural disturbance in the subnetwork of the cortico-striato-thalamo-cortical circuitry after the onset of psychosis. Furthermore, increasing ventricular volume is a neuroanatomical marker of poorer clinical and functional outcome. These findings lend weight to the evidence of early progressive brain changes in psychotic disorders and thus, this knowledge could potentially contribute to the identification of imaging biomarkers for timely intervention.

The noradrenergic theory of Cognitive Reserve (Robertson, 2013–2014) postulates that the upregulation of the locus coeruleus—noradrenergic system (LC–NA) originating in the brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 mild cognitive impairment, 135 Alzheimer’s disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD—an objective measure, which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the serotoninergic (5-HT), dopaminergic (DA) and cholinergic (Ach) systems were contrasted with the noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems. Results supported by Bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g., cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

The association of neuroanatomical progression with cognitive and clinical deterioration after first-episode of psychosis remains uncertain. This longitudinal study aims to assess whether i)impaired executive functioning and emotional intelligence at first presentation are associated with progressive prefrontal and orbitofrontal cortical thinning ii)negative symptom severity is linked to progressive prefrontal cortical thinning. 1.5T MRI images were acquired at baseline and after 3.5 years for 20 individuals with first-episode psychosis and 18 controls. The longitudinal pipeline of Freesurfer was employed to parcellate prefrontal cortex at two time points. Baseline cognitive performance was compared between diagnostic groups using MANCOVA. Partial correlations investigated relationships between cognition and negative symptoms at baseline and cortical thickness change over time. Patients displayed poorer performance than controls at baseline in working memory, reasoning/problem solving and emotional intelligence. In patients, loss of prefrontal and orbitofrontal thickness over time was predicted by impaired working memory and emotional intelligence respectively at baseline. Moreover, exploratory analyses revealed that the worsening of negative symptoms over time was significantly related to prefrontal cortical thinning. Results indicate that specific cognitive deficits at the onset of psychotic illness are markers of progressive neuroanatomical deficits and that worsening of negative symptoms occurs with prefrontal thickness reduction as the illness progresses.

Journal article First episode psychosis (FEP) has been associated with structural brain changes, largely identified by volumetric analyses. Advances in neuroimaging processing have made it possible to measure geometric properties that may identify subtle structural changes not appreciated by a measure of volume alone. In this study we adopt complementary methods of assessing the structural integrity of grey matter in FEP patients and assess whether these relate to patient clinical and functional outcome at 3year follow-up. 1.5Tesla T1-weighted Magnetic Resonance (MR) images were acquired for 46 patients experiencing their first episode of psychosis and 46 healthy controls. Cerebral cortical thickness and local gyrification index (LGI) were investigated using FreeSurfer software. Volume and shape of the hippocampus, caudate and lateral ventricles were assessed using manual tracing and spherical harmonics applied for shape description. A cluster of cortical thinning was identified in FEP compared to controls; this was located in the right superior temporal gyrus, sulcus, extended into the middle temporal gyrus (lateral temporal cortex - LTC). Bilateral caudate volumes were significantly lower in FEP relative to controls and the right caudate also displayed regions of shape deflation in the FEP group. No significant structural abnormalities were identified in cortical LGI or hippocampal or lateral ventricle volume/shape. Neither LTC nor caudate abnormalities were related to change in symptom severity or global functioning 3years later. LTC and caudate abnormalities are present at the first episode of psychosis but do not appear to directly affect clinical or functional outcome. peer-reviewed

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10(-7)) and thalamus (d=-0.148; P=4.27 × 10(-3)) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10(-5)) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.Molecular Psychiatry advance online publication, 9 February 2016; doi:10.1038/mp.2015.227. ispartof: Molecular Psychiatry vol:21 issue:12 pages:1710-1716 ispartof: location:England status: published

The current study examines the EEG coherence of young, old, and old declined adults performing a visual paired-associates task. In order to examine the effects of encoding context and stimulus repetition, target pairs were presented on either detailed or white backgrounds and were repeatedly presented during both early and late phases of encoding. Younger adults were found to have lower levels of frontal-temporal and temporal-parietal coherence, but higher levels of frontal-parietal coherence, particularly for the gamma frequency band. A number of differential coherence responses to background context and early- versus late-encoding phases were also observed across the groups, particularly for lower alpha and upper alpha frequencies. Coherence-performance maps were generated to further explore topographical differences in the relationship between coherence and performance across groups. Results revealed a more diffuse pattern of negative coherence-performance relations in older declined adults. Results are discussed in light of the literature on age-related cognitive decline.

Background Neurocognitive impairments are a prevalent aspect of psychosis which, on average, begin in early adolescents, with particular impairment apparent in speed of processing and nonverbal working memory in early stages (Kelleher et al., 2012). It is important to understand the impact of cognitive impairment on functional ability, particularly in early stages of illness which may assist in the development of targeted therapeutic strategies. Methods A population sample of 212 school going adolescents aged 11–13 years partook in the study, which included community-based adolescents who report experiencing psychotic symptoms but who were not clinically diagnosed. Psychotic symptoms were assessed using the psychosis section of the Schedule for Affective Disorders and Schizophrenia. Six cognitive domains were assessed using the MATRICS consensus cognitive battery. Functioning was assessed using the Children’s Global Assessment Scale. Six separate linear regression analyses were performed to test if each cognitive domain of the MATRICS battery predicted functioning. Results In the entire sample (including those who experienced psychotic experiences and those who did not) (n=211), speed of processing significantly explained 8% of the variance in functioning (F(1, 76) = 6.61, p = .0012, R-squared = 0.08.), (Beta = 0.39, p = 0.012). When the sample was subdivided into those who ever experienced auditory hallucinations (AH) (n=62) versus those that did not (n=149), speed of processing significantly predicted 18% of the variance in functioning in the group experiencing AHs (F(2, 33) = 3.82, p =0.032, R-squared = 0.18), (Beta = 0.43, p = 0.06). However, no effect was found in the group without AVs (F(1,40) = 1.19, p =0.28). No other cognitive domain predicted functioning. Discussion Speed of processing appears to be a core cognitive deficit in psychosis which impacts on functioning in young adolescents particularly in those experiencing psychotic symptoms such as auditory hallucinations, however the variance predicted by processing speed is relatively low. This research highlights the potential of speed of processing as a possible viable target for early intervention in psychotic disorders.

While cognitive impairments are prevalent in first-episode psychosis, the course of these deficits is not fully understood. Most deficits appear to remain stable, however there is uncertainty regarding the trajectory of specific cognitive domains after illness onset. This study investigates the longitudinal course of cognitive deficits four years after a first-episode of psychosis and the relationship of performance with clinical course and response to treatment. Twenty three individuals with psychotic illness, matched with 21 healthy volunteers, were assessed using the MATRICS Consensus Cognitive Battery at illness onset and 4years later. We also investigated the relationship between cognitive deficits and quality of life and clinical indices. Verbal learning and two measures of processing speed had marked poorer trajectory over four years compared to the remaining cognitive domains. Processing speed performance was found to contribute to the cognitive deficits in psychosis. Poorer clinical outcome was associated with greater deficits at illness onset in reasoning and problem solving and social cognition. Cognitive deficits did not predict quality of life at follow-up, nor did diagnosis subtype differentiate cognitive performance. In conclusion, an initial psychotic episode may be associated with an additional cost on verbal learning and two measures of processing speed over a time spanning at least four years. Moreover, processing speed, which has been manipulated through intervention in previous studies, may represent a viable therapeutic target. Finally, cognition at illness onset may have a predictive capability of illness course.. peer-reviewed

The current study examined the EEG of young, old and old declined adults performing a visual paired associate task. In order to examine the effects of encoding context and stimulus repetition, target pairs were presented on either detailed or white backgrounds and were repeatedly presented during both early and late phases of encoding. Results indicated an increase in P300 amplitude in the right parietal cortex from early to late stages of encoding in older declined adults, whereas both younger adults and older controls showed a reduction in P300 amplitude in this same area from early to late phase encoding. In the right hemisphere, stimuli encoded with a white background had larger P300 amplitudes than stimuli presented with a detailed background; however, in the left hemisphere, in the later stages of encoding, stimuli presented with a detailed background had larger amplitudes than stimuli presented with a white background. Behaviourally, there was better memory for congruent stimuli reinstated with a detailed background, but this finding was for older controls only. During recognition, there was a general trend for congruent stimuli to elicit a larger amplitude response than incongruent stimuli, suggesting a distinct effect of context reinstatement on underlying patterns of physiological responding. However, behavioural data suggest that older declined adults showed no memory benefits associated with context reinstatement. When compared with older declined adults, younger adults had larger P100 amplitude responses to stimuli presented during recognition, and overall, younger adults had faster recognition reaction times than older control and older declined adults. Further analysis of repetition effects and context-based hemispheric asymmetry may prove informative in identifying declining memory performance in the elderly, potentially before it becomes manifested behaviourally.