Verbal Fluency Is Affected by Altered Brain Lateralization in Adults Who Were Born Very Preterm.

Language difficulties have been reported in children and adolescents who were born very preterm (<32 weeks' gestation) and associated with an atypical lateralization of language processing, i.e., increased right-hemispheric engagement. This study used functional magnetic resonance imaging (fMRI) and spherical deconvolution tractography to study the hemodynamic responses associated with verbal fluency processing (easy and hard letter trials) and verbal fluency-related white matter fiber tracts in 64 very preterm born adults and 36 adult controls (mean age: 30 years). Tractography of the arcuate fasciculus (AF) and frontal aslant tract (FAT) was performed. Tracts were quantified in terms of mean volume, hindrance modulated orientational anisotropy, and lateralization, assessed using a laterality index (LI) to indicate hemispheric dominance. During verbal fluency fMRI, very preterm participants displayed decreased hemodynamic response suppression in both the Easy > Rest and Hard > Rest conditions, compared to controls, in superior temporal gyrus (STG), insula, thalamus, and sensorimotor cortex, particularly in the right hemisphere. At the whole-group level, decreased hemodynamic response suppression in the right sensorimotor cortex was associated with worse on-line performance on the hard letter trials. Increased left-laterality in the AF was present alongside increased right hemispheric hemodynamic response suppression in controls. When only right-handed participants were considered, decreased hemodynamic response suppression in the right STG during hard letter trials was related to weaker left and right FAT white matter integrity in the preterm group only. These results show that verbal fluency is affected by altered functional lateralization in adults who were born very preterm.

A dimensional approach to assessing psychiatric risk in adults born very preterm.

BACKGROUND: Individuals who were born very preterm have higher rates of psychiatric diagnoses compared with term-born controls; however, it remains unclear whether they also display increased sub-clinical psychiatric symptomatology. Hence, our objective was to utilize a dimensional approach to assess psychiatric symptomatology in adult life following very preterm birth. METHODS: We studied 152 adults who were born very preterm (before 33 weeks' gestation; gestational range 24-32 weeks) and 96 term-born controls. Participants' clinical profile was examined using the Comprehensive Assessment of At-Risk Mental States (CAARMS), a measure of sub-clinical symptomatology that yields seven subscales including general psychopathology, positive, negative, cognitive, behavioural, motor and emotional symptoms, in addition to a total psychopathology score. Intellectual abilities were examined using the Wechsler Abbreviated Scale of Intelligence. RESULTS: Between-group differences on the CAARMS showed elevated symptomatology in very preterm participants compared with controls in positive, negative, cognitive and behavioural symptoms. Total psychopathology scores were significantly correlated with IQ in the very preterm group only. In order to examine the characteristics of participants' clinical profile, a principal component analysis was conducted. This revealed two components, one reflecting a non-specific psychopathology dimension, and the other indicating a variance in symptomatology along a positive-to-negative symptom axis. K-means (k = 4) were used to further separate the study sample into clusters. Very preterm adults were more likely to belong to a high non-specific psychopathology cluster compared with controls.Conclusion and RelevanceVery preterm individuals demonstrated elevated psychopathology compared with full-term controls. Their psychiatric risk was characterized by a non-specific clinical profile and was associated with lower IQ.

Volumetric grey matter alterations in adolescents and adults born very preterm suggest accelerated brain maturation.

Previous research investigating structural neurodevelopmental alterations in individuals who were born very preterm demonstrated a complex pattern of grey matter changes that defy straightforward summary. Here we addressed this problem by characterising volumetric brain alterations in individuals who were born very preterm from adolescence to adulthood at three hierarchically related levels - global, modular and regional. We demarcated structural components that were either particularly resilient or vulnerable to the impact of very preterm birth. We showed that individuals who were born very preterm had smaller global grey matter volume compared to controls, with subcortical and medial temporal regions being particularly affected. Conversely, frontal and lateral parieto-temporal cortices were relatively resilient to the effects of very preterm birth, possibly indicating compensatory mechanisms. Exploratory analyses supported this hypothesis by showing a stronger association between lateral parieto-temporal volume and IQ in the very preterm group compared to controls. We then related these alterations to brain maturation processes. Very preterm individuals exhibited a higher maturation index compared to controls, indicating accelerated brain maturation and this was specifically associated with younger gestational age. We discuss how the findings of accelerated maturation might be reconciled with evidence of delayed maturation at earlier stages of development.

Real-Life Impact of Executive Function Impairments in Adults Who Were Born Very Preterm.

OBJECTIVES: Children and adolescents who were born very preterm (≤32 weeks' gestation) are vulnerable to experiencing cognitive problems, including in executive function. However, it remains to be established whether cognitive deficits are evident in adulthood and whether these exert a significant effect on an individual's real-lifeachievement. METHODS: Using a cross-sectional design, we tested a range of neurocognitive abilities, with a focus on executive function, in a sample of 122 very preterm individuals and 89 term-born controls born between 1979 and 1984. Associations between executive function and a range of achievement measures, indicative of a successful transition to adulthood, were examined. RESULTS: Very preterm adults performed worse compared to controls on measures of intellectual ability and executive function with moderate to large effect sizes. They also demonstrated significantly lower achievement levels in terms of years spent in education, employment status, and on a measure of functioning in work and social domains. Results of regression analysis indicated a stronger positive association between executive function and real-life achievement in the very preterm group compared to controls. CONCLUSIONS: Very preterm born adults demonstrate executive function impairments compared to full-term controls, and these are associated with lower achievement in several real-life domains. (JINS, 2017, 23, 381-389).

A multimodal imaging study of recognition memory in very preterm born adults.

Very preterm (<32 weeks of gestation) birth is associated with structural brain alterations and memory impairments throughout childhood and adolescence. Here, we used functional MRI (fMRI) to study the neuroanatomy of recognition memory in 49 very preterm-born adults and 50 controls (mean age: 30 years) during completion of a task involving visual encoding and recognition of abstract pictures. T1-weighted and diffusion-weighted images were also collected. Bilateral hippocampal volumes were calculated and tractography of the fornix and cingulum was performed and assessed in terms of volume and hindrance modulated orientational anisotropy (HMOA). Online recognition memory task performance, assessed with A scores, was poorer in the very preterm compared with the control group. Analysis of fMRI data focused on differences in neural activity between the recognition and encoding trials. Very preterm born adults showed decreased activation in the right middle frontal gyrus and posterior cingulate cortex/precuneus and increased activation in the left inferior frontal gyrus and bilateral lateral occipital cortex (LOC) compared with controls. Hippocampi, fornix and cingulum volume was significantly smaller and fornix HMOA was lower in very preterm adults. Among all the structural and functional brain metrics that showed statistically significant group differences, LOC activation was the best predictor of online task performance (P = 0.020). In terms of association between brain function and structure, LOC activation was predicted by fornix HMOA in the preterm group only (P = 0.020). These results suggest that neuroanatomical alterations in very preterm born individuals may be underlying their poorer recognition memory performance. Hum Brain Mapp 38:644-655, 2017. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Reinforcement of the Brain's Rich-Club Architecture Following Early Neurodevelopmental Disruption Caused by Very Preterm Birth.

The second half of pregnancy is a crucial period for the development of structural brain connectivity, and an abrupt interruption of the typical processes of development during this phase caused by the very preterm birth (<33 weeks of gestation) is likely to result in long-lasting consequences. We used structural and diffusion imaging data to reconstruct the brain structural connectome in very preterm-born adults. We assessed its rich-club organization and modularity as 2 characteristics reflecting the capacity to support global and local information exchange, respectively. Our results suggest that the establishment of global connectivity patterns is prioritized over peripheral connectivity following early neurodevelopmental disruption. The very preterm brain exhibited a stronger rich-club architecture than the control brain, despite possessing a relative paucity of white matter resources. Using a simulated lesion approach, we also investigated whether putative structural reorganization takes place in the very preterm brain in order to compensate for its anatomical constraints. We found that connections between the basal ganglia and (pre-) motor regions, as well as connections between subcortical regions, assumed an altered role in the structural connectivity of the very preterm brain, and that such alterations had functional implications for information flow, rule learning, and verbal IQ.

Very Early Brain Damage Leads to Remodeling of the Working Memory System in Adulthood: A Combined fMRI/Tractography Study.

The human brain can adapt to overcome injury even years after an initial insult. One hypothesis states that early brain injury survivors, by taking advantage of critical periods of high plasticity during childhood, should recover more successfully than those who suffer injury later in life. This hypothesis has been challenged by recent studies showing worse cognitive outcome in individuals with early brain injury, compared with individuals with later brain injury, with working memory particularly affected. We invited individuals who suffered perinatal brain injury (PBI) for an fMRI/diffusion MRI tractography study of working memory and hypothesized that, 30 years after the initial injury, working memory deficits in the PBI group would remain, despite compensatory activation in areas outside the typical working memory network. Furthermore we hypothesized that the amount of functional reorganization would be related to the level of injury to the dorsal cingulum tract, which connects medial frontal and parietal working memory structures. We found that adults who suffered PBI did not significantly differ from controls in working memory performance. They exhibited less activation in classic frontoparietal working memory areas and a relative overactivation of bilateral perisylvian cortex compared with controls. Structurally, the dorsal cingulum volume and hindrance-modulated orientational anisotropy was significantly reduced in the PBI group. Furthermore there was uniquely in the PBI group a significant negative correlation between the volume of this tract and activation in the bilateral perisylvian cortex and a positive correlation between this activation and task performance. This provides the first evidence of compensatory plasticity of the working memory network following PBI.

A comparison of mental state examination documentation by junior clinicians in electronic health records before and after the introduction of a semi-structured assessment template (OPCRIT+).

OBJECTIVES: The mental state examination (MSE) provides crucial information for healthcare professionals in the assessment and treatment of psychiatric patients as well as potentially providing valuable data for mental health researchers accessing electronic health records (EHRs). We wished to establish if improvements could be achieved in the documenting of MSEs by junior doctors within a large United Kingdom mental health trust following the introduction of an EHR based semi-structured MSE assessment template (OPCRIT+). METHODS: First, three consultant psychiatrists using a modified version of the Physician Documentation Quality Instrument-9 (PDQI-9) blindly rated fifty MSEs written using OPCRIT+ and fifty normal MSEs written with no template. Second, we conducted an audit to compare the frequency with which individual components of the MSE were documented in the normal MSEs compared with the OPCRIT+MSEs. RESULTS: PDQI-9 ratings indicated that the OPCRIT+MSEs were more 'Thorough', 'Organized', 'Useful' and 'Comprehensible' as well as being of an overall higher quality than the normal MSEs. The audit identified that the normal MSEs contained fewer mentions of the individual components of 'Thought content', 'Anxiety' and 'Cognition & Insight'. CONCLUSIONS: These results indicate that a semi-structured assessment template significantly improves the quality of MSE recording by junior doctors within EHRs. Future work should focus on whether such improvements translate into better patient outcomes and have the ability to improve the quality of information available on EHRs to researchers.

Neural compensation in adulthood following very preterm birth demonstrated during a visual paired associates learning task.

Very preterm birth (VPT; < 33 weeks of gestation) is associated with an increased risk of learning disability, which contributes to more VPT-born children repeating grades and underachieving in school. Learning problems associated with VPT birth may be caused by pathophysiological alterations in neurodevelopment resulting from perinatal brain insult; however, adaptive neuroplastic processes may subsequently occur in the developing preterm brain which ameliorate, to an extent, the potential sequelae of altered neurophysiology. Here, we used functional magnetic resonance imaging (fMRI) to compare neuronal activation in 24 VPT individuals and 22 controls (CT) in young adulthood during a learning task consisting of the encoding and subsequent recognition of repeated visual paired associates. Structural MRI data were also collected and analysed in order to explore possible structure-function associations. Whilst the two groups did not differ in their learning ability, as demonstrated by their capacity to recognize previously-seen and previously-unseen visual pairs, between-group differences in linear patterns of Blood Oxygenation Level Dependant (BOLD) activity were observed across the four repeated blocks of the task for both the encoding and recognition conditions, suggesting that the way learning takes place differs between the two groups. During encoding, significant between-group differences in patterns of BOLD activity were seen in clusters centred on the cerebellum, the anterior cingulate gyrus, the midbrain/substantia nigra, medial temporal (including parahippocampal) gyrus and inferior and superior frontal gyri. During the recognition condition, significant between-group differences in patterns of BOLD activity were seen in clusters centred on the claustrum and the posterior cerebellum. Structural analysis revealed smaller grey matter volume in right middle temporal gyrus in VPT individuals compared to controls, however volume in this region was not significantly associated with functional activation. These results demonstrate that although cognitive task performance between VPT individuals and controls may be comparable on certain measures, differences in BOLD signal may also be evident, some of which could represent compensatory neural processes following VPT-related brain insult.

Dysconnectivity of neurocognitive networks at rest in very-preterm born adults.

Advances in neonatal medicine have resulted in a larger proportion of preterm-born individuals reaching adulthood. Their increased liability to psychiatric illness and impairments of cognition and behaviour intimate lasting cerebral consequences; however, the central physiological disturbances remain unclear. Of fundamental importance to efficient brain function is the coordination and contextually-relevant recruitment of neural networks. Large-scale distributed networks emerge perinatally and increase in hierarchical complexity through development. Preterm-born individuals exhibit systematic reductions in correlation strength within these networks during infancy. Here, we investigate resting-state functional connectivity in functional magnetic resonance imaging data from 29 very-preterm (VPT)-born adults and 23 term-born controls. Neurocognitive networks were identified with spatial independent component analysis conducted using the Infomax algorithm and employing Icasso procedures to enhance component robustness. Network spatial focus and spectral power were not generally significantly affected by preterm birth. By contrast, Granger-causality analysis of the time courses of network activity revealed widespread reductions in between-network connectivity in the preterm group, particularly along paths including salience-network features. The potential clinical relevance of these Granger-causal measurements was suggested by linear discriminant analysis of topological representations of connection strength, which classified individuals by group with a maximal accuracy of 86%. Functional connections from the striatal salience network to the posterior default mode network informed this classification most powerfully. In the VPT-born group it was additionally found that perinatal factors significantly moderated the relationship between executive function (which was reduced in the VPT-born as compared with the term-born group) and generalised partial directed coherence. Together these findings show that resting-state functional connectivity of preterm-born individuals remains compromised in adulthood; and present consistent evidence that the striatal salience network is preferentially affected. Therapeutic practices directed at strengthening within-network cohesion and fine-tuning between-network inter-relations may have the potential to mitigate the cognitive, behavioural and psychiatric repercussions of preterm birth.

An asymmetry of translational biological motion perception in schizophrenia.

BACKGROUND: Biological motion perception is served by a network of regions in the occipital, posterior temporal, and parietal lobe, overlapping areas of reduced cortical volume in schizophrenia. The atrophy in these regions is assumed to account for deficits in biological motion perception described in schizophrenia but it is unknown whether the asymmetry of atrophy found in previous studies has a perceptual correlate. Here we look for possible differences in sensitivity to leftward and rightward translation of point-light biological motion in data collected for a previous study and explore its underlying neurobiology using functional imaging. METHODS: n = 64 patients with schizophrenia and n = 64 controls performed a task requiring the detection of leftward or rightward biological motion using a standard psychophysical staircase procedure. six control subjects took part in the functional imaging experiment. RESULTS: We found a deficit of leftward but not rightward biological motion (leftward biological motion % accuracy patients = 57.9% ± 14.3; controls = 63.6% ± 11.3 p = 0.01; rightward biological motion patients = 62.7% ± 12.4; controls = 64.1% ± 11.7; p > 0.05). The deficit reflected differences in distribution of leftward and rightward accuracy bias in the two populations. Directional bias correlated with functional outcome as measured by the Role Functioning Scale in the patient group when co-varying for negative symptoms (r = -0.272, p = 0.016). Cortical regions with preferential activation for leftward or rightward translation were identified in both hemispheres suggesting the psychophysical findings could not be accounted for by selective atrophy or functional change in one hemisphere alone. CONCLUSION: The findings point to translational direction as a novel functional probe to help understand the underlying neural mechanisms of wider cognitive dysfunction in schizophrenia.

A review of the reliability and validity of OPCRIT in relation to its use for the routine clinical assessment of mental health patients.

The OPCRIT program is a symptom checklist with accompanying algorithms producing operationally defined diagnoses. We undertook a review of studies which had used OPCRIT and had reported statistics concerning its reliability and validity, producing summary measures from 44 studies. The first main measure of interest was inter-rater reliability where mean kappa values indicated that agreement between raters was "substantial" with a marginal improvement at the diagnostic (0.76) versus individual item (0.69) level. The second main measure of interest was convergent validity - the agreement between OPCRIT and clinical diagnoses. Most studies reported these figures as concordance rates suggesting mean agreement, unadjusted for chance, of 69%. Very few studies used the chance-adjusted kappa statistic but where this was used agreement was "fair" (0.39). Agreement between OPCRIT and other research diagnoses was "moderate" (0.60). We also considered differences between the way OPCRIT has traditionally been used in research settings and the naturalistic manner in which it will be employed in the hospital ward. This review provides a summary of the reliability and validity of OPCRIT, which will be considered during the preparation for its use in the routine characterization of mental health patients in clinical settings.

Harnessing clinical psychiatric data with an electronic assessment tool (OPCRIT+): the utility of symptom dimensions.

Progress in personalised psychiatry is dependent on researchers having access to systematic and accurately acquired symptom data across clinical diagnoses. We have developed a structured psychiatric assessment tool, OPCRIT+, that is being introduced into the electronic medical records system of the South London and Maudsley NHS Foundation Trust which can help to achieve this. In this report we examine the utility of the symptom data being collected with the tool. Cross-sectional mental state data from a mixed-diagnostic cohort of 876 inpatients was subjected to a principal components analysis (PCA). Six components, explaining 46% of the variance in recorded symptoms, were extracted. The components represented dimensions of mania, depression, positive symptoms, anxiety, negative symptoms and disorganization. As indicated by component scores, different clinical diagnoses demonstrated distinct symptom profiles characterized by wide-ranging levels of severity. When comparing the predictive value of symptoms against diagnosis for a variety of clinical outcome measures (e.g. 'Overactive, aggressive behaviour'), symptoms proved superior in five instances (R(2) range: 0.06-0.28) whereas diagnosis was best just once (R(2):0.25). This report demonstrates that symptom data being routinely gathered in an NHS trust, when documented on the appropriate tool, have considerable potential for onward use in a variety of clinical and research applications via representation as dimensions of psychopathology.

Emotion perception and functional outcome in schizophrenia: the importance of negative valence and fear.

A substantial body of work has demonstrated that persons with schizophrenia have a deficit in the perception of emotional stimuli. More recently this deficit has been linked to poor functional outcomes (FO) in this group. The current research investigated the perception of emotional stimuli in a group of 64 schizophrenia patients and 65 matched healthy controls. In the patient group, across two different emotion perception tasks and a social perception task, small deficits were found in the perception of negative, positive and neutrally valenced stimuli. Only the ability to perceive negative and neutrally valenced stimuli significantly correlated with a set of FO measures in the patients, with one task indicating these associations were strongest for the perception of fear. Subsequent regression modelling, controlling for the effects of symptomatology, demonstrated that for each of the three tasks, the measure of negative valence perception accounted for a similar but small amount (4%) of the variance seen in the functional status of the patients.

OPCRIT+: an electronic system for psychiatric diagnosis and data collection in clinical and research settings.

BACKGROUND: The increasingly large sample size requirements of modern adult mental health research suggests the need for a data collection and diagnostic application that can be used across a broad range of clinical and research populations. Aims To develop a data collection and diagnostic application that can be used across a broad range of clinical and research settings. METHOD: We expanded and redeveloped the OPCRIT system into a broadly applicable diagnostic and data-collection package and carried out an interrater reliability study of this new tool. RESULTS: OPCRIT+ performed well in an interrater reliability study with relatively inexperienced clinicians, giving a combined, weighted kappa of 0.70 for diagnostic reliability. CONCLUSIONS: OPCRIT+ showed good overall interrater reliability scores for diagnoses. It is now incorporated in the electronic patient record of the Maudsley and associated hospitals. OPCRIT+ can be downloaded free of charge at http://sgdp.iop.kcl.ac.uk/opcritplus.

Visual processing, social cognition and functional outcome in schizophrenia.

Visual processing deficits are well recognised in schizophrenia and have potentially important clinical implications. First, the pattern of deficits for different visual tasks may help understand the underlying pathophysiology of the visual dysfunction. Second, several studies report deficits correlating with functional outcomes, suggesting that outcome improvement is possible through visual remediation strategies. We investigated these issues in a group of 64 schizophrenia patients and matched controls with a battery of visual tasks targeting different points along the visual pathways and by examining direct and indirect relationships (via a potential mediator) of such deficits to functional outcome. The schizophrenia group was significantly worse on the visual tasks overall, with the deficit constant for low- and high-level processing. Zero-order correlations suggested minimal association between vision and outcome, however, correlations between three visual tasks and 'social perceptual' ability were found which in turn correlated with functional outcome; path analysis confirmed a significant but small and indirect effect of 'biological motion' processing ability on functional outcome mediated by 'social perception'. In conclusion, the pathophysiology of visual dysfunction affects low- and high-level visual areas similarly and the relationship between deficits and outcome is small and indirect.