Superior Frontal Cortex Research Articles

Involuntary Orienting and Conflict Resolution during Auditory Attention: The Role of Ventral and Dorsal Streams.

Selective attention to sound object features such as pitch and location is associated with enhanced brain activity in ventral and dorsal streams, respectively. We examined the role of these pathways in involuntary orienting and conflict resolution using fMRI. Participants were presented with two tones that may, or may not, share the same nonspatial (frequency) or spatial (location) auditory features. In separate blocks of trials, participants were asked to attend to sound frequency or sound location and ignore the change in the task-irrelevant feature. In both attend-frequency and attend-location tasks, RTs were slower when the task-irrelevant feature changed than when it stayed the same (involuntary orienting). This behavioral cost coincided with enhanced activity in the pFC and superior temporal gyrus. Conflict resolution was examined by comparing situations where the change in stimulus features was congruent (both features changed) and incongruent (only one feature changed). Participants were slower and less accurate for incongruent than congruent sound features. This congruency effect was associated with enhanced activity in the pFC and was greater in the right superior temporal gyrus and medial frontal cortex during the attend-location task than during the attend-frequency task. Together, these findings do not support a strict division of "labor" into ventral and dorsal streams but rather suggest interactions between these pathways in situations involving changes in task-irrelevant sound feature and conflict resolution. These findings also validate the Test of Attention in Listening task by revealing distinct neural correlates for involuntary orienting and conflict resolution.

A Practical Approach to Differentiate the Frontotemporal Tauopathy Subtypes.

This study proposes a practical approach, using the minimum number of brain regions and stains, to consolidate previously published neuropathological criteria into one operationalized schema to differentiate subtypes of frontotemporal lobar degeneration with tau-immunopositive inclusions (FTLD-tau). This approach uses the superior frontal and precentral cortices and hippocampus stained for phosphorylated-tau, p62 and modified Bielschowsky silver, and the midbrain stained only for modified Bielschowsky silver. Accuracy of interrater reliability was determined by 10 raters in 24 FTLD-tau cases (Pick disease = 4, corticobasal degeneration = 9, progressive supranuclear palsy = 5, globular glial tauopathy = 6) including 4 with a mutation in MAPT collected with consent by Sydney Brain Bank. All brain regions and stains assessed proved informative for accurate pathological subtyping, and many neuropathological features were identified as common across the FTLD-tau subtypes. By identifying subtype-specific neuropathological features in the sections selected, 10 independent observers assigned the cases to a FTLD-tau subtype with almost perfect agreement between raters, emphasizing the requirement for the assessment of subtype-specific features for the accurate subtyping of FTLD-tau. This study consolidates current consensus diagnostic criteria for classifying FTLD-tau subtypes with an efficient, simple and accurate approach that can be implemented in future clinicopathological studies.

A distributed frontotemporal network underlies gamma-band synchronization impairments in schizophrenia patients.

Synaptic interactions between parvalbumin-positive γ-aminobutyric acid (GABA)-ergic interneurons and pyramidal neurons evoke cortical gamma oscillations, which are known to be abnormal in schizophrenia. These cortical gamma oscillations can be indexed by the gamma-band auditory steady-state response (ASSR), a robust electroencephalographic (EEG) biomarker that is increasingly used to advance the development of novel therapeutics for schizophrenia, and other related brain disorders. Despite promise of ASSR, the neural substrates of ASSR have not yet been characterized. This study investigated the sources underlying ASSR in healthy subjects and schizophrenia patients. In this study, a novel method for noninvasively characterizing source locations was developed and applied to EEG recordings obtained from 293 healthy subjects and 427 schizophrenia patients who underwent ASSR testing. Results revealed a distributed network of temporal and frontal sources in both healthy subjects and schizophrenia patients. In both groups, primary contributing ASSR sources were identified in the right superior temporal cortex and the orbitofrontal cortex. In conjunction with normal activity in these areas, schizophrenia patients showed significantly reduced source dipole density of gamma-band ASSR (ITC > 0.25) in the left superior temporal cortex, orbitofrontal cortex, and left superior frontal cortex. In conclusion, a distributed network of temporal and frontal brain regions supports gamma phase synchronization. We demonstrated that failure to mount a coherent physiologic response to simple 40-Hz stimulation reflects disorganized network function in schizophrenia patients. Future translational studies are needed to more fully understand the neural mechanisms underlying gamma-band ASSR network abnormalities in schizophrenia.

Evidence for a causal role of superior frontal cortex theta oscillations during the processing of joint subliminal and conscious conflicts

Consciously and subliminally processed information can both lead to conflicts that hinder goal-directed behaviour. Conflict monitoring processes are required to cope with situations where one or multiple conflicts occur. It has been suggested, that medial-frontal theta oscillations are associated with the implementation of cognitive control and that conflicts increase theta band activity. Still, a causal mechanistic understanding of theta oscillations during the resolution of combined subliminal and conscious conflicts is missing. To investigate this, we combined EEG signal decomposition methods with EEG beamforming approaches and used the obtained information to modulate theta oscillations with tACS in a second experiment. This showed that theta oscillations in the superior frontal cortex (BA6) and the left paracentral lobule encoded stimulus-related processes during the resolution of conflicts arising from both conscious and subliminal information processing. Response selection and motor-related processes encoded by theta oscillations were not similarly modulated. Thus, the joint modulation of conflicts by conscious and subliminal information affects very specific aspects of the information coded in theta oscillations. Results indicate, that entraining theta-oscillations using tACS modulates conflict resolution depending on the already existing theta activity level. In summary, the study provides further evidence that frontal theta oscillations play a crucial role in conflict monitoring and control.

Cardiac cycle gated cognitive-emotional control in superior frontal cortices

Accumulating evidence suggests that peripheral physiological processes, such as the cardiac cycle, impact the individual's ability to appropriately exert control over behavior and emotional responses. We examine, whether response selection processes during cognitive-emotional control and its neurophysiological correlates, can be experimentally controlled in a cardiac-cycle dependent manner. To this end, we designed an experimental setup in which the EEG experiment, an emotional Stroop task, was controlled by the individual's electrocardiogram (ECG). Since theoretical considerations suggest that the effects of the cardiac cycle may affect only specific aspects during information processing, we apply EEG signal decomposition before examining functional neuroanatomical regions associated with cardiac-cycle dependent effects with EEG-beamforming approaches. Analyzing N = 27 healthy participants, we show that the cardiac-cycle specifically affects response selection processes, when demands on cognitive-emotional control are low. Response execution processes are sped up when trials are presented shortly after the ECG R peak. These effects were confined to conditions were response selection is not modulated by cognitive-emotional conflicts, which is in line with theoretical concepts on response selection. Corroborating the behavioural data, the EEG data show that particularly motor response-related processes encoded in the theta frequency band in middle and superior frontal regions (BA6) are differentially modulated by cardiac phase and difficulty to select a response. The presented work has an essential methodological focus in cognitive neuroscience for investigating brain-body interaction. It shows how peripheral-physiological parameters can be used to control EEG experiments and that the cardiac cycle has very specific effects in neurophysiological processes and associated functional neuroanatomical structures.

Improvement on perception of welding noise by fountain sound masking: Insights from fMRI

Sound masking has been applied to improve subjective perception of noise in recent years. This noise control technology could gain better perceptual effects on certain noises with lower cost compared with the traditional noise control technologies. However, the neural mechanisms underlying sound masking are rarely studied. In this study, 19 healthy subjects were recruited to take fMRI scanning and subjective annoyance assessments with the welding noise and the masked welding noise. The fMRI data were collected with block design paradigm for the welding noise and the masked welding noise in two different sessions respectively. Both contrast analysis of the brain activations and seed-based connectivity analysis were performed. The results showed that the noise annoyance was associated with significant brain activation in putamen and ACC but deficient functional connectivity between anterior cingulate cortex (ACC) and prefrontal cortex (PFC). The sound masking led to significantly strong activations in the left superior medial frontal cortex (SMFC), left supplementary motor area (SMA), and increased functional connectivity between the SMFC and parietal lobe, which were associated with positive emotion and improved the perception of the welding noise. This study offered new insights on the underlying neural mechanisms of sound masking effects.

Functional Dysconnectivity of Frontal Cortex to Striatum Predicts Ketamine Infusion Response in Treatment-Resistant Depression.

BackgroundFrontostriatal disconnectivity plays a crucial role in the pathophysiology of major depressive disorder. However, whether the baseline functional connectivity of the frontostriatal network could predict the treatment outcome of low-dose ketamine infusion remains unknown.MethodsIn total, 48 patients with treatment-resistant depression were randomly divided into 3 treatment groups (a single-dose 40-minute i.v. infusion) as follows: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and saline placebo infusion. Patients were subsequently followed-up for 2 weeks. Resting-state functional magnetic resonance imaging was performed for each patient before infusion administration. In addition, the baseline frontostriatal functional connectivity of patients with treatment-resistant depression was also compared with that of healthy controls.ResultsCompared with the healthy controls, patients with treatment-resistant depression had a decreased functional connectivity in the frontostriatal circuits, especially between the right superior frontal cortex and executive region of the striatum and between the right paracingulate cortex and rostral-motor region of the striatum. The baseline hypoconnectivity of the bilateral superior frontal cortex to the executive region of the striatum was associated with a greater reduction of depression symptoms after a single 0.2-mg/kg ketamine infusion.ConclusionReduced connectivity of the superior frontal cortex to the striatum predicted the response to ketamine infusion among patients with treatment-resistant depression.

The effect of bilingualism on brain development from early childhood to young adulthood

Bilingualism affects the structure of the brain in adults, as evidenced by experience-dependent grey and white matter changes in brain structures implicated in language learning, processing, and control. However, limited evidence exists on how bilingualism may influence brain development. We examined the developmental patterns of both grey and white matter structures in a cross-sectional study of a large sample (n = 711 for grey matter, n = 637 for white matter) of bilingual and monolingual participants, aged 3–21 years. Metrics of grey matter (thickness, volume, and surface area) and white matter (fractional anisotropy and mean diffusivity) were examined across 41 cortical and subcortical brain structures and 20 tracts, respectively. We used generalized additive modelling to analyze whether, how, and where the developmental trajectories of bilinguals and monolinguals might differ. Bilingual and monolingual participants manifested distinct developmental trajectories in both grey and white matter structures. As compared to monolinguals, bilinguals showed: (a) more grey matter (less developmental loss) starting during late childhood and adolescence, mainly in frontal and parietal regions (particularly in the inferior frontal gyrus pars opercularis, superior frontal cortex, inferior and superior parietal cortex, and precuneus); and (b) higher white matter integrity (greater developmental increase) starting during mid-late adolescence, specifically in striatal–inferior frontal fibers. The data suggest that there may be a developmental basis to the well-documented structural differences in the brain between bilingual and monolingual adults.

Fractional amplitude of low-frequency fluctuation (fALFF) alterations in young depressed patients with suicide attempts after cognitive behavioral therapy and antidepressant medication cotherapy: A resting-state fMRI study

BackgroundFractional amplitude of low-frequency fluctuation (fALFF) alterations in young depressed patients with suicide attempts after cognitive behavioral therapy (CBT) and antidepressant medication cotherapy were evaluated. MethodsSeventy-eight subjects (age: 18–28) were recruited from April 2017 to March 2019. Forty young depressed patients who attempted suicide were divided into CBT (8 weeks of structured CBT sessions and antidepressant medication cotherapy) and monotherapy (MG: antidepressant therapy alone) groups, and 38 healthy volunteers constituted a healthy control (HC) group. Resting-state functional magnetic resonance imaging (rs-fMRI) was conducted before and after treatment. ResultsBefore treatment, spontaneous brain activity in the left posterior cerebellar lobe (L-PCL), right anterior cingulate cortex, left caudate nucleus and left superior frontal cortex was higher in untreated patients than in HCs. After treatment, fALFF in the left middle occipital cortex and left precuneus was significantly increased in the CBT compared with the HC group. fALFF in the right middle frontal cortex, right inferior frontal cortex, l-PCL, and left anterior cerebellar lobe (L-ACL) were increased, while fALFF in the l-mPFC and l-SgACC were reduced, in the CBT compared with the MG group. Pearson correlation analyses provided information about clinical scale scores and mean fALFF relationships. LimitationsThere was insufficient evidence to confirm that these spontaneous brain activity alterations were the result of CBT or spontaneous recovery. ConclusionCBT and medication cotherapy can significantly change spontaneous activity in the left cerebellum and default-mode network, thereby regulating and reshaping emotional and cognitive processing.

Functional neural substrates of football fanaticism: Different pattern of brain responses and connectivity in fanatics.

Sports activities provide social interaction for humans. Commitment to a given team is a salient feature of being a sports fan and becomes a prominent part of self-identification for fanatics. Emotion, subjective hedonic experience, and non-romantic love are related to fan behaviors. Few studies have evaluated the neural basis of sports fanaticism. Thirty men, including 16 football fanatics and 14 non-fanatics, with a mean age of 27.4 ± 6.4 years (range, 20-48 years) were enrolled. Subjects underwent functional MRI while watching a set of goals scored by favorite, rival, and neutral teams. The analysis of variance in a general linear model revealed a significant Group × Condition interaction effect in the bilateral dorsal anterior cingulate cortex (dACC) that was more prominent in the left hemisphere. In the post-hoc comparisons, fanatics showed increased activation in bilateral dACC, supplementary motor area, superior frontal cortex, right dorsolateral prefrontal cortex, and right insula for Favorite > Neutral contrast and an increased activation in bilateral dACC and supplementary motor area for Rival > Neutral contrast. Seed-based connectivity analyses using the areas with significant activation differences revealed increased connectivity between dACC and several regions, including the left posterior lateral temporal area, insula, bilateral medial temporal area, and medial superior frontal area as well as the basal ganglia in fanatics compared to non-fanatics. Our results suggest that football fanatics exhibit a different brain activation and connectivity pattern from non-fanatics, both under favorable and unfavorable conditions. This brain activity and connectivity pattern under emotionally laden conditions may represent higher responses to rewards, higher emotional valence attribution, and stronger motivational state of football fanatics, which might underlie their unusual behavioral responses.

Proteomic Profiling of Plasma and Brain Tissue from Alzheimer's Disease Patients Reveals Candidate Network of Plasma Biomarkers.

Alzheimer's disease (AD) is the most prevalent form of dementia with two pathological hallmarks of tau-containing neurofibrillary tangles and amyloid-β protein (Aβ)-containing neuritic plaques. Although Aβ and tau have been explored as potential biomarkers, levels of these pathological proteins in blood fail to distinguish AD from healthy control subjects. We aim to discover potential plasma proteins associated with AD pathology by performing tandem mass tag (TMT)-based quantitative proteomic analysis of proteins from peripheral and central nervous system compartments. We performed comparative proteomic analyses of plasma collected from AD patients and cognitively normal subjects. In addition, proteomic profiles from the inferior frontal cortex, superior frontal cortex, and cerebellum of postmortem brain tissue from five AD patients and five non-AD controls were compared with plasma proteomic profiles to search for common biomarkers. Liquid chromatography-mass spectrometry was used to analyze plasma and brain tissue labeled with isobaric TMT for relative protein quantification. Our results showed that the proteins in complement coagulation cascade and interleukin-6 signaling were significantly altered in both plasma and brains of AD patients. Our results demonstrate the relevance in immune responses between the peripheral and central nervous systems. Those differentially regulated plasma proteins are explored as candidate biomarker profiles that illustrate chronic neuroinflammation in brains of AD patients.

Precision weighting of cortical unsigned prediction error signals benefits learning, is mediated by dopamine, and is impaired in psychosis

Recent theories of cortical function construe the brain as performing hierarchical Bayesian inference. According to these theories, the precision of prediction errors plays a key role in learning and decision-making, is controlled by dopamine and contributes to the pathogenesis of psychosis. To test these hypotheses, we studied learning with variable outcome-precision in healthy individuals after dopaminergic modulation with a placebo, a dopamine receptor agonist bromocriptine or a dopamine receptor antagonist sulpiride (dopamine study n = 59) and in patients with early psychosis (psychosis study n = 74: 20 participants with first-episode psychosis, 30 healthy controls and 24 participants with at-risk mental state attenuated psychotic symptoms). Behavioural computational modelling indicated that precision weighting of prediction errors benefits learning in health and is impaired in psychosis. FMRI revealed coding of unsigned prediction errors, which signal surprise, relative to their precision in superior frontal cortex (replicated across studies, combined n = 133), which was perturbed by dopaminergic modulation, impaired in psychosis and associated with task performance and schizotypy (schizotypy correlation in 86 healthy volunteers). In contrast to our previous work, we did not observe significant precision-weighting of signed prediction errors, which signal valence, in the midbrain and ventral striatum in the healthy controls (or patients) in the psychosis study. We conclude that healthy people, but not patients with first-episode psychosis, take into account the precision of the environment when updating beliefs. Precision weighting of cortical prediction error signals is a key mechanism through which dopamine modulates inference and contributes to the pathogenesis of psychosis.

The effects of gastrointestinal symptoms on structural grey matter volume in youth.

Previous neuroimaging studies have examined the association between changes in brain structure and gastrointestinal symptoms (GIS), seen in disorders such as Irritable Bowel Syndrome and Irritable Bowel Disease. Studies in adults have found changes in white and grey matter volume (GMV) in patients with various gastrointestinal disorders. However, it is unclear whether GIS-related structural changes in the brain are limited to adults or could be present throughout the lifespan. Given that gastrointestinal disorders are typically diagnosed between 4 and 18years old, we investigated GIS-induced morphological changes in pre-adolescents (8-10), adolescents (12-16years) and young adults (17-21years). Using a voxel-based morphometry (VBM) analysis, we compared regional grey matter volume (GMV) between participants with GIS and controls, using structural brain images from the Philadelphia Neurodevelopmental Cohort (PNC) database. A total of 211 participants (107 participants with GISs and 104 control participants) who had undergone structural magnetic resonance imaging were analysed. VBM analysis was used to objectively analyse GMV across the whole brain and compare between participants with GIS and controls. Participants experiencing GIS showed smaller GMV in regions within the limbic system/basal ganglia (bilateral caudate, bilateral ventral hippocampus, bilateral amygdala and bilateral superior orbital frontal cortex), and larger GMV in regions within the pain-matrix (thalamus, bilateral putamen, right mid-frontal gyrus) compared to controls. These differences were most prominent in the adolescent and young adult groups compared to pre-adolescents. In conclusion, the structural differences found in participants with GIS support the need for further research into the neurophysiological impact of these symptoms.

Brain networks underlying vulnerability and resilience to drug addiction

Regular drug use can lead to addiction, but not everyone who takes drugs makes this transition. How exactly drugs of abuse interact with individual vulnerability is not fully understood, nor is it clear how individuals defy the risks associated with drugs or addiction vulnerability. We used resting-state functional MRI (fMRI) in 162 participants to characterize risk- and resilience-related changes in corticostriatal functional circuits in individuals exposed to stimulant drugs both with and without clinically diagnosed drug addiction, siblings of addicted individuals, and control volunteers. The likelihood of developing addiction, whether due to familial vulnerability or drug use, was associated with significant hypoconnectivity in orbitofrontal and ventromedial prefrontal cortical-striatal circuits-pathways critically implicated in goal-directed decision-making. By contrast, resilience against a diagnosis of substance use disorder was associated with hyperconnectivity in two networks involving 1) the lateral prefrontal cortex and medial caudate nucleus and 2) the supplementary motor area, superior medial frontal cortex, and putamen-brain circuits respectively implicated in top-down inhibitory control and the regulation of habits. These findings point toward a predisposing vulnerability in the causation of addiction, related to impaired goal-directed actions, as well as countervailing resilience systems implicated in behavioral regulation, and may inform novel strategies for therapeutic and preventative interventions.

4327 Structural Neural Correlates of Social Functioning in First Episode Psychosis and Malleability in Response to Targeted Cognitive Training

OBJECTIVES/GOALS: Development of interventions that improve social functioning (SF) in first episode psychosis (FEP) is hindered by a poor understanding of the neural mechanisms underlying SF deficits. This research aims to identify neural correlates of social functioning in FEP, and to evaluate whether this substrate is malleable in response to cognitive training. METHODS/STUDY POPULATION: This is a secondary data-analysis of participants in an ongoing randomized clinical trial investigating whether 12 weeks of targeted cognitive training is neuroprotective in FEP, versus treatment as usual. Baseline and post-training assessments include a brain MRI, three measures of SF, and a neurocognitive battery. Healthy controls complete MRI only. Differences in cortical thickness (CTh) and gray matter volume (GMV) in regions of interest between FEP and controls will be determined with ANCOVA. Multiple linear regression will be used to determine the relationship between neural substrate and SF in FEP. Linear mixed models will be used to examine the relationship between change in CTh and GMV and change in SF. Data collection is ongoing for this study. RESULTS/ANTICIPATED RESULTS: In preliminary data including 12 FEP and 9 healthy controls, FEP demonstrated cortical loss in the right superior frontal cortex and the right isthmus-posterior cingulate. Greater cortical thickness in the posterior cingulate cortex was associated with better social functioning across multiple measures when controlling for global cognition. Gray matter volume in the parahippocampal gyrus was also associated with better social functioning. Preliminary results evaluating whether targeted cognitive training is neuroprotective in these regions of interest in a manner that is associated with improved social functioning will also be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: Preliminary results link the posterior cingulate and parahippocampal gyrus to SF in FEP. Further research will investigate the contribution of changes in these brain regions to improved SF. The identification of biological treatment targets for SF may lead to development and optimization of novel interventions to alleviate SF deficits in FEP.

Distinct Regional Oscillatory Connectivity Patterns During Auditory Target and Novelty Processing.

Auditory attention allows us to focus on relevant target sounds in the acoustic environment while maintaining the capability to orient to unpredictable (novel) sound changes. An open question is whether orienting to expected vs. unexpected auditory events are governed by anatomically distinct attention pathways, respectively, or by differing communication patterns within a common system. To address this question, we applied a recently developed PeSCAR analysis method to evaluate spectrotemporal functional connectivity patterns across subregions of broader cortical regions of interest (ROIs) to analyze magnetoencephalography data obtained during a cued auditory attention task. Subjects were instructed to detect a predictable harmonic target sound embedded among standard tones in one ear and to ignore the standard tones and occasional unpredictable novel sounds presented in the opposite ear. Phase coherence of estimated source activity was calculated between subregions of superior temporal, frontal, inferior parietal, and superior parietal cortex ROIs. Functional connectivity was stronger in response to target than novel stimuli between left superior temporal and left parietal ROIs and between left frontal and right parietal ROIs, with the largest effects observed in the beta band (15-35 Hz). In contrast, functional connectivity was stronger in response to novel than target stimuli in inter-hemispheric connections between left and right frontal ROIs, observed in early time windows in the alpha band (8-12 Hz). Our findings suggest that auditory processing of expected target vs. unexpected novel sounds involves different spatially, temporally, and spectrally distributed oscillatory connectivity patterns across temporal, parietal, and frontal areas.

M154. INTRA- AND INTER-SCANNER RELIABILITY OF GRAY MATTER VOLUME AND CORTICAL THICKNESS ESTIMATES: IMPLICATIONS FOR MULTICENTRE IMAGING STUDIES IN PSYCHOSIS

BackgroundHigh-resolution structural MRI has been widely used in clinical research to detect and quantify subtle brain changes in patient populations. Findings from prospective, longitudinal studies show structural brain abnormalities as well as progressive gray matter changes over time in individuals at clinical high risk for psychosis compared to healthy subjects. In recent years, research in this field has seen an increase in multicentre neuroimaging projects, such as EU-GEI, PSYSCAN, PRONIA and NAPLS. Additional sources of variance, alongside known technological and biological factors, may be introduced when MRI images are acquired and combined from different sites. It is imperative for longitudinal multicentre studies to determine the accuracy of quantitative MRI measurements and account for systematic differences both between scanners and across scanning sessions. This is particularly true within psychosis research where morphometric changes as small as 3% or less are expected.MethodsSix healthy participants were scanned on four separate occasions over a two-month period at King’s College London; twice on a GE SIGNA HDx 3T scanner used locally in the EU-GEI High Risk Study and twice on a GE MR750 3T scanner used locally in the PSYSCAN study. Both scanners implemented the ADNI-2 T1 protocol which is used globally across the EU-GEI and PSYSCAN consortia. Structural imaging data was segmented using the FreeSurfer 6.0 longitudinal pipeline. Intraclass correlation coefficients (ICCs) with a two-way mixed effects model of absolute agreement were calculated to assess intra- and inter-scanner reliability of brain morphometry. For volumetric studies, ICC values greater than 0.9 indicate ‘excellent’ reliability. Reliability analyses of key regions implicated in psychosis included gray matter volume estimates of the hippocampus, insula, lateral ventricle, orbitofrontal cortex and anterior cingulate cortex, and average cortical thickness measurements of the whole brain, parahippocampus and superior frontal cortex.ResultsGray matter volume estimates of all structures yielded ‘excellent’ reliability for both intra-scanner (ICCs of 0.979 – 0.998) and inter-scanner analyses (ICCs of 0.976 – 0.999). Intra-scanner reliability for mean cortical thickness measurements was ‘excellent’ for right total cortex, resulting in an ICC of 0.901, but otherwise ‘good’ for left and total cortex, parahippocampus, superior frontal cortex (ICCs of 0.754 – 0.875). Inter-scanner reliability for mean cortical thickness estimates were most variable across the brain structures. Here, results demonstrated ‘excellent’ reliability for the parahippocampus and left total cortex (ICCs of 0.907 – 0.965), ‘good’ for total cortex (ICC of 0.835), ‘moderate’ for right total cortex, right and total superior frontal cortex (ICCs of 0.520 – 0.676), and ‘poor’ for the left superior frontal cortex which produced an ICC of 0.470. Overall, mean cortical thickness estimates of the superior frontal cortex from two different MR scanners showed the least reliability.DiscussionResults confirmed highly reliable estimates for gray matter volumes in all brain structures, both from images acquired within the same scanner and across two different scanners. However, the findings indicated increased variability of mean cortical thickness estimates, particularly between scanners, which should be considered when interpreting study findings. Multicentre structural neuroimaging within the field of psychosis is becoming more common and it must be acknowledged that combining MRI data in multicentre studies will contribute additional sources of variance and potential bias with certain brain regions affected more than others.

T60. GENETIC INFLUENCES ON MEMORY FUNCTIONS AND RELATED BRAIN STRUCTURES AND ASSOCIATIONS WITH SCHIZOPHRENIA SPECTRUM DISORDERS: A NATION-WIDE TWIN STUDY

BackgroundImpaired memory is among the most profound cognitive deficits observed in patients with schizophrenia. Evidence from twin studies suggests that memory is mainly influenced by genetics. Moreover, a few twin studies have demonstrated genetic overlap between specific memory functions and schizophrenia. Memory deficits in schizophrenia seem to involve abnormalities in frontal cortical areas and the middle temporal lobe, particularly the hippocampus. In the general population, twin studies have consistently demonstrated genetic influences on brain volumes, however, evidence from twin pairs discordant for schizophrenia suggests that hippocampus volumes may be more susceptible to environmental effects in patients.MethodsTwin pairs concordant or discordant for a diagnosis in the schizophrenia spectrum were recruited nation-wide by linking The Danish Twin Register and The Danish Psychiatric Central Research Register. Both monozygotic (MZ) and dizygotic (DZ) proband pairs as well as healthy control (HC) pairs were identified. A total of 216 twins participated in this study consisting of 32 complete MZ and 24 complete DZ proband pairs, 29 complete MZ and 20 complete DZ HC pairs, and six twins from proband pairs were included without their sibling. Verbal memory was assessed using the list learning task from the Brief Assessment of Cognition in Schizophrenia (BACS), visual memory using the Rey Complex Figure Test (RCFT) and associative memory using 15 word pairs. Structural brain scans were acquired with T1-weighted sequence on a Philips 3.0 T Achieva MRI scanner with a 32-channel SENSE head coil. Images were processed using FreeSurfer (version 5.3) and the Desikan-Killiany atlas was used to extract the volumes of bilateral hippocampi, superior frontal, rostral and caudal middle frontal cortices as well as the whole brain volume. Structural equation modelling was applied to examine the genetic and environmental contributions to the variability in memory and brain measures and to quantify associations with schizophrenia spectrum liability.ResultsSignificant heritability estimates were observed for verbal memory (h2=0.53), visual memory (h2=0.58) and associative memory (immediate h2=0.33, delayed h2=0.54), whereas the copy and recognition task from RCFT were only explained by unique environmental factors. Except for verbal memory, all memory measures were significantly associated with schizophrenia spectrum liability, and these were mainly due to overlapping genetic factors. Genetic factors also significantly contributed to whole brain (h2=0.36), right superior frontal (h2=0.48), left rostral middle frontal (h2=0.40) and hippocampus volumes (right h2=0.29, left h2=0.50). Common environmental factors significantly influenced whole brain (c2=0.51), right hippocampus (c2=0.51) and right rostral middle frontal (c2=0.47) volumes. Hippocampus volumes were significantly associated with schizophrenia spectrum liability, and for the left hippocampus this association was due to overlapping genetic factors.DiscussionSpecific memory measures and related brain areas were heritable, providing further evidence of the importance of genetics in memory functioning. Furthermore, the majority of the applied memory measures and left hippocampal volume were (genetically) associated with schizophrenia spectrum liability, suggesting a partially shared etiology. The heritable memory measures and related brain areas showing associations with disease may represent endophenotypes for schizophrenia spectrum disorders. In future analyses, we plan to examine the covariance between memory, brain volumes and schizophrenia.

Higher impulsivity and lower grey matter volume in the bilateral prefrontal cortex in long-term abstinent individuals with severe methamphetamine use disorder

BackgroundPrevious studies have shown that grey matter volume (GMV) might be lower in individuals with methamphetamine use disorder and that dynamic alterations in selected brain regions might appear in individuals after short-term abstinence. However, the GMV of brains in these individuals after long-term abstinence is poorly understood. Moreover, individuals with severe methamphetamine use disorder have been considered to have high levels of impulsivity, but the biological mechanism is still unclear. MethodsIn this study, the impulsivity of all participants was assessed using the Barratt Impulsiveness Scale (BIS-11). Using voxel-based morphometry (VBM) in conjunction with statistical parametric mapping on structural magnetic resonance images, the GMVs of the whole brain were compared among 32 drug-naïve healthy controls (HC) and 40 individuals with severe methamphetamine use disorder who had been abstinent for at least 20 months (SMUD-A). ResultsWe observed significantly higher BIS-11 impulsivity scores and lower GMV in the bilateral superior frontal cortex of SMUD-A individuals than in those of control subjects. The impulsivity score was negatively correlated with GMV in the right superior frontal cortex. ConclusionsThese findings offer novel evidence with respect to the impulsivity trait and brain GMV feature in long-term abstinent individuals with severe methamphetamine use disorder. Moreover, our findings suggest that lower GMV in the right superior frontal cortex might reflect a trait marker of higher impulsivity in this population.

Leptin predicts cortical and subcortical gray matter volume recovery in alcohol dependent patients: A longitudinal structural magnetic resonance imaging study

The neuroprotective effects of leptin and its role in addictive disorders has been highlighted by several recent studies. However, its potential effects on morphological alterations in alcohol dependence are yet to be investigated.Associations between leptin and the longitudinal courses of gray matter volume (GMV) and cortical thickness (CT) were investigated in N = 62 alcohol-dependent patients that underwent structural magnetic resonance imaging after a mean abstinence of 12 (baseline) and 27 days (follow-up) respectively. Blood samples were collected at baseline to determine leptin levels. A cohort of N = 74 healthy individuals served as a reference sample.At baseline, alcohol-dependent patients compared to healthy controls displayed smaller GMV in the insula, parts of the superior, middle and inferior frontal gyri and hippocampal regions and thinner CT in the insula, parts of the superior and middle frontal cortices, the lateral orbitofrontal cortex and parts of the occipital and lingual cortices that partially recovered during abstinence (pFWE < 0.05). In alcohol-dependent patients, leptin was a significant predictor of GMV and CT recovery in the areas that showed the strongest whole-brain effects, specifically GMV in the right insula (R2 = 0.070, pFDR = 0.040) and left inferior frontal triangular gyrus (R2 = 0.076, pFDR = 0.040), as well as CT in the left insula (R2 = 0.158, pFDR = 0.004) and right superior frontal cortex (R2 = 0.180, pFDR = 0.004). Present results support the role of leptin in predicting GMV and CT recovery during the first month of abstinence in alcohol-dependent patients.