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Highlights • We describe Latent change score modelling as a flexible statistical tool. • Key developmental questions can be readily formalized using LCS models. • We provide accessible open source code and software examples to fit LCS models. • White matter structural change is negatively correlated with processing speed gains. • Frontal lobe thinning in adolescence is more variable in males than females. Abstract Assessing and analysing individual differences in change over time is of central scientific importance to developmental neuroscience. However, the literature is based largely on cross-sectional comparisons, which reflect a variety of influences and cannot directly represent change. We advocate using latent change score (LCS) models in longitudinal samples as a statistical framework to tease apart the complex processes underlying lifespan development in brain and behaviour using longitudinal data. LCS models provide a flexible framework that naturally accommodates key developmental questions as model parameters and can even be used, with some limitations, in cases with only two measurement occasions. We illustrate the use of LCS models with two empirical examples. In a lifespan cognitive training study (COGITO, N = 204 (N = 32 imaging) on two waves) we observe correlated change in brain and behaviour in the context of a high-intensity training intervention. In an adolescent development cohort (NSPN, N = 176, two waves) we find greater variability in cortical thinning in males than in females. To facilitate the adoption of LCS by the developmental community, we provide analysis code that can be adapted by other researchers and basic primers in two freely available SEM software packages (lavaan and Ωnyx). [ABSTRACT FROM AUTHOR]

Highlights: [•] We evaluate the conceptual foundations of pathoconnectomics. [•] We overview the construction and analysis of empirical models of brain networks or connectomes. [•] We summarize recent reports of large-scale whole-brain connectome abnormalities of two candidate brain-network disorders, schizophrenia and autism. [ABSTRACT FROM AUTHOR]

During the past 5 years, functional magnetic resonance imaging (MRI) has been used increasingly to map the modulatory effects of psychopharmacological agents on cognitive activation of large-scale networks in the human brain. Such pharmacological MRI (phMRI) studies can be informative about pharmacodynamics, specific neurotransmitter mechanisms that underlie the adaptivity of neurocognitive systems to variation in task difficulty and familiarity, and changes in neurophysiological drug effects associated with genetic variation, neuropsychiatric disorders and normal aging. In this article, we review >50 relevant published articles from this rapidly growing literature and highlight some emerging themes, including: the importance of individual differences in genotype and cognitive phenotype as conditioners of drug effects on brain activation; the formulation of inverted-U models to describe similar effects of agonist and antagonist drugs acting on the same receptors; and the potential utility of this technique for testing transmitter models of disorders, predicting treatment response, and supporting the development of novel compounds in neuropsychiatry. [Copyright &y& Elsevier]

The origins of cerebral abnormalities in psychotic patients remain unknown. Dermatoglyphics are suitable markers of prenatal injury due to their fetal ontogenesis and their susceptibility to some of the factors that also affect cerebral development. In a previous study, positive associations between brain volumetric measures and a dermatoglyphic marker, the ab-ridge count, were reported. The present study is an attempt to replicate that finding in an independent sample. Magnetic resonance imaging (MRI) scans and dermatoglyphic measures were available for 29 schizophrenia patients (Research Diagnostic Criteria [RDC] criteria) and 26 unrelated healthy controls. The images were processed using an automated procedure, yielding volumes of total grey matter, white matter, cerebrospinal fluid (CSF), and total brain volume. The ab-ridge count was not positively associated with brain volumes in either patients or controls. The present findings do not support the hypothesis that the changes in brain volume seen in patients with schizophrenia are of prenatal origin. [ABSTRACT FROM AUTHOR]

Background Schizophrenia is a disorder of brain connectivity and altered neurodevelopmental processes. Cross-sectional case-control studies in different age groups have suggested that deficits in cortical thickness in childhood-onset schizophrenia may normalize over time, suggesting a disorder-related difference in cortical growth trajectories. Methods We acquired magnetic resonance imaging scans repeated over several years for each subject, in a sample of 106 patients with childhood-onset schizophrenia and 102 age-matched healthy volunteers. Using semiparametric regression, we modeled the effect of schizophrenia on the growth curve of cortical thickness in ~80,000 locations across the cortex, in the age range 8 to 30 years. In addition, we derived normative developmental modules composed of cortical regions with similar maturational trajectories for cortical thickness in typical brain development. Results We found abnormal nonlinear growth processes in prefrontal and temporal areas that have previously been implicated in schizophrenia, distinguishing for the first time between cortical areas with age-constant deficits in cortical thickness and areas whose maturational trajectories are altered in schizophrenia. In addition, we showed that when the brain is divided into five normative developmental modules, the areas with abnormal cortical growth overlap significantly only with the cingulo-fronto-temporal module. Conclusions These findings suggest that abnormal cortical development in schizophrenia may be modularized or constrained by the normal community structure of developmental modules of the human brain connectome. [ABSTRACT FROM AUTHOR]

Background: It is well established that schizophrenia is associated with structural brain abnormalities, but whether these are static or progress over time remains controversial. Methods: A systematic review of longitudinal volumetric studies using region-of-interest structural magnetic resonance imaging in patients with schizophrenia and healthy control subjects. The percentage change in volume between scans for each brain region of interest was obtained, and data were combined using random effects meta-analysis. Results: Twenty-seven studies were included in the meta-analysis, with 928 patients and 867 control subjects, and 32 different brain regions of interest. Subjects with schizophrenia showed significantly greater decreases over time in whole brain volume, whole brain gray matter, frontal gray and white matter, parietal white matter, and temporal white matter volume, as well as larger increases in lateral ventricular volume, than healthy control subjects. The time between baseline and follow-up magnetic resonance imaging scans ranged from 1 to 10 years. The differences between patients and control subjects in annualized percentage volume change were −.07% for whole brain volume, −.59% for whole brain gray matter, −.32% for frontal white matter, −.32% for parietal white matter, −.39% for temporal white matter, and +.36% for bilateral lateral ventricles. Conclusions: These findings suggest that schizophrenia is associated with progressive structural brain abnormalities, affecting both gray and white matter. We found no evidence to suggest progressive medial temporal lobe involvement but did find evidence that this may be partly explained by heterogeneity between studies in patient age and illness duration. The causes and clinical correlates of these progressive brain changes should now be the focus of investigation. [Copyright &y& Elsevier]

This overview describes the generation and development of the ideas that led to the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. It also describes the organization, process, and products of the first meeting. The CNTRICS initiative involves a series of three conferences that will systematically address barriers to translating paradigms developed in the basic animal and human cognitive neuroscience fields for use in translational research aimed at developing novel treatments for cognitive impairments in schizophrenia. The articles in this special section report on the results of the first conference, which used a criterion-based consensus-building process to develop a set of cognitive constructs to be targeted for translation efforts. [Copyright &y& Elsevier]

Abstract: Obsessive-compulsive disorder (OCD) is a common, heritable and disabling neuropsychiatric disorder. Theoretical models suggest that OCD is underpinned by functional and structural abnormalities in orbitofronto-striatal circuits. Evidence from cognitive and neuroimaging studies (functional and structural magnetic resonance imaging (MRI) and positron emission tomography (PET)) have generally been taken to be supportive of these theoretical models; however, results from these studies have not been entirely congruent with each other. With the advent of whole brain-based structural imaging techniques, such as voxel-based morphometry and multivoxel analyses, we consider it timely to assess neuroimaging findings to date, and to examine their compatibility with cognitive studies and orbitofronto-striatal models. As part of this assessment, we performed a quantitative, voxel-level meta-analysis of functional MRI findings, which revealed consistent abnormalities in orbitofronto-striatal and other additional areas in OCD. This review also considers the evidence for involvement of other brain areas outside orbitofronto-striatal regions in OCD, the limitations of current imaging techniques, and how future developments in imaging may aid our understanding of OCD. [Copyright &y& Elsevier]

Background: It would be therapeutically useful to predict clinical response to antidepressant drugs. We evaluated structural magnetic resonance imaging (MRI) and functional MRI (fMRI) data as predictors of symptom change in people with depression. Methods: Brain structure and function were measured with MRI in 17 patients with major depression immediately before 8 weeks treatment with fluoxetine 20 mg/day. For fMRI, patients were scanned during visual presentation of faces representing different intensities of sadness. Clinical response was measured by change in serial scores on the Hamilton Rating Scale for Depression. Symptom change scores (and baseline symptom severity) were regressed on structural and functional MRI data to map brain regions where grey matter volume, or activation by sad facial affect processing, was significantly associated with symptom change (or baseline severity). Results: Faster rates of symptom improvement were strongly associated with greater grey matter volume in anterior cingulate cortex, insula, and right temporo-parietal cortex. Patients with greater than median grey matter volume in this system had faster rates of improvement and significantly lower residual symptom scores after 8 weeks’ treatment. Faster improvement was also predicted by greater functional activation of anterior cingulate cortex. Baseline symptom severity was negatively correlated with greater grey matter volume in dorsal prefrontal and anterior midcingulate regions anatomically distinct from the pregenual and subgenual cingulate regions predicting treatment response. Conclusions: Structural MRI measurements of anterior cingulate cortex could provide a useful predictor of antidepressant treatment response. [Copyright &y& Elsevier]

Abstract: Aging is normally associated with increased predictability of neurophysiological processes. To test the related prediction of age-related increase in the Hurst exponent, H, of functional MRI time series, and its possible cholinergic mechanisms, two groups of healthy participants (old [mean age=65 years]; young [mean age=22 years]; N =11 per group) were scanned twice at rest, following placebo and a muscarinic receptor antagonist, scopolamine 0.3mg. Older age was associated with significant increase in H of fMRI time series in bilateral hippocampus. Similarly, scopolamine was associated with increased H in left hippocampus; and there was an age-by-drug interaction in medial temporal lobe whereby older participants specifically had increased H following scopolamine. Scopolamine also enhanced fronto-hippocampal low-frequency coherence, and this could be correlated with its effect on hippocampal H. Thus, increased persistence of hippocampal dynamics in older subjects is demonstrable by resting fMRI; scopolamine mimics these effects, especially in older subjects, implying a cholinergic mechanism for age-related change; and cholinergic effects on hippocampal dynamics are associated with enhanced functional connectivity between frontal cortex and hippocampus. [Copyright &y& Elsevier]

Background: The pathophysiology of abnormal mood states–mania and depression–in patients with bipolar disorder remains unclear. Facial affect processing paradigms are an effective way of studying behavioral and functional magnetic resonance imaging (fMRI) correlates of affective disorders. Methods: We used a factorial design to measure the neural correlates of tasks, tapping explicit and implicit recognition of sad, fearful, and happy facial expressions using event-related fMRI paradigms in three groups of participants: eight bipolar depressed patients, eight bipolar manic patients, and eight control subjects. Results: Depressed and manic patients exhibited overactivated responses to fearful faces, as well as to mood-incongruent facial expressions, with the depressed group exhibiting overactivity in fronto-striato-thalamic systems in response to happy faces and the manic group exhibiting overactivity in the fusiform gyrus in response to sad faces. For manic patients, task type also affected the neural response to sad faces, with the corticolimbic regions showing overactivation for implicit processing and underactivation for explicit processing. Conclusions: Depressed and manic patients exhibited abnormal neural responses to sad, fearful, and happy facial expressions. Additionally, the attentional level of sad facial affect processing has important consequences for abnormalities of amygdala and cingulate activation in manic patients. [Copyright &y& Elsevier]

Background: Autistic spectrum disorders (ASD) are neurodevelopmental conditions that may be caused by abnormal connectivity between brain regions constituting neurocognitive networks for specific aspects of social cognition. Methods: We used three-way multidimensional scaling of regionally parcellated functional magnetic resonance imaging (fMRI) data to explore the hypothesis of abnormal functional connectivity in people with ASD. Thirteen high-functioning individuals with Asperger¿s syndrome and 13 healthy volunteers were scanned during incidental processing of fearful facial expressions. Results: Using permutation tests for inference, we found evidence for significant abnormality of functional integration of amygdala and parahippocampal gyrus (p < .05, false discovery rate [FDR] corrected) in people with Asperger¿s syndrome. There were less salient abnormalities in functional connectivity of anterior cingulate, inferior occipital, and inferior frontal cortex, but there was no significant difference between groups in whole brain functional connectivity. Conclusions: We conclude there is evidence that functional connectivity of medial temporal lobe structures specifically is abnormal in people with Asperger¿s syndrome during fearful face processing. [Copyright &y& Elsevier]

Structural cerebral abnormalities are frequently observed in schizophrenia. These abnormalities may indicate vulnerability for the disorder, as evidenced by reports of familial clustering of measures identified through region-of-interest analyses using manual outlining procedures. We used computational morphometry to detect structural differences within the entire brain to further examine possible structural endophenotypes. Magnetic resonance imaging scans were obtained in 31 psychotic patients, 32 non-psychotic first-degree relatives of psychotic patients and 27 healthy controls. The images were processed using an automated procedure, yielding global grey matter, white matter, CSF and total brain volume. The relative distribution of grey matter was compared between groups on a clustered-voxel basis. Global grey matter and total brain volume did not differ between the groups. White matter volume was significantly higher and CSF volume significantly lower in relatives compared to both cases and controls. The clustered-voxel based group comparison yielded evidence for significant grey matter deficits in fronto-thalamic-cerebellar regions, in psychotic patients, whereas the most prominent deficits in relatives involved the cerebellum. Patients with psychosis and first-degree healthy relatives of patients with psychosis show cerebellar abnormalities, which may constitute a marker of genetic transmission. [Copyright &y& Elsevier]