A Pilot Study of Adolescents with Psychotic Experiences: Potential Cerebellar Circuitry Disruption Early Along the Psychosis Spectrum.

A berrant connectivity in the cerebellum has been found in psychotic conditions such as schizophrenia corresponding with cognitive and motor deficits found in these conditions. Diffusion differences in the superior cerebellar peduncles, the white matter connecting the cerebellar circuitry to the rest of the brain, have also been found in schizophrenia and high-risk states. However, white matter diffusivity in the peduncles in individuals with sub-threshold psychotic experiences (PEs) but not reaching the threshold for a definitive diagnosis remains unstudied. This study investigates the cerebellar peduncles in adolescents with PEs but no formal psychiatric diagnosis.Sixteen adolescents with PEs and 17 age-matched controls recruited from schools underwent High-Angular-Resolution-Diffusion neuroimaging. Following constrained spherical deconvolution whole-brain tractography, the superior, inferior and middle peduncles were isolated and virtually dissected out using ExploreDTI. Differences for macroscopic and microscopic tract metrics were calculated using one-way between-group analyses of covariance controlling for age, sex and estimated Total Intracranial Volume (eTIV). Multiple comparisons were corrected using Bonferroni correction.A decrease in fractional anisotropy was identified in the right (p = 0.045) and left (p = 0.058) superior cerebellar peduncle; however, this did not survive strict Bonferroni multiple comparison correction. There were no differences in volumes or other diffusion metrics in either the middle or inferior peduncles.Our trend level changes in the superior cerebellar peduncle in a non-clinical sample exhibiting psychotic experiences complement similar but more profound changes previously found in ultra-high-risk individuals and those with psychotic disorders. This suggests that superior cerebellar peduncle circuitry perturbations may occur early along in the psychosis spectrum.

Microstructural changes along the cingulum in young adolescents with psychotic experiences: An along-tract analysis.

Psychotic experiences (PEs) such as hallucinations and delusions are common among young people without psychiatric diagnoses and are associated with connectivity and white matter abnormalities, particularly in the limbic system. Using diffusion magnetic resonance imaging (MRI) in adolescents with reported PEs and matched controls, we examined the cingulum white matter tract along its length rather than as the usually reported single indivisible structure. Complex regional differences in diffusion metrics were found along the bundle at key loci following Bonferroni significance adjustment (p < .00013) with moderate to large effect sizes (.11-.76) throughout all significant subsegments. In this prospective community-based cohort of school-age children, these findings suggest that white matter alterations in the limbic system may be more common in the general non-clinical adolescent population than previously thought. Such white matter alternations may only be uncovered using a similar more granular along-tract analysis of white matter tracts.

Abnormal fronto-parietal white matter organisation in the superior longitudinal fasciculus branches in autism spectrum disorders.

Core features of autism spectrum disorder (ASD) may be underpinned by disrupted functional and structural neural connectivity. Abnormal fronto-parietal functional connectivity has been widely reported in the literature; this may be underpinned by disrupted microstructural organisation of white matter. The superior longitudinal fasciculus (SLF) is a major fronto-parietal white matter tract, the structure of which has been little studied in ASD. The fronto-parietal projections of this tract (SLF I, II and III) are thought to play an important role in a number of cognitive functions including attention and visuospatial processing. To date, the isolation of the fronto-parietal branches of the SLF has been hampered by limitations of traditional tractography approaches. Constrained spherical deconvolution (CSD)-based tractography is an advanced approach that allows valid isolation of the fronto-parietal branches of the SLF. Diffusion MRI data were acquired from 45 participants with ASD and 45 age- and IQ-matched controls. The SLF I, II and III branches were isolated using CSD-based tractography in ExploreDTI. Significantly greater fractional anisotropy (FA) was observed in the right SLF II relative to controls. The ASD group also showed greater linear diffusion coefficient in the left SLF I and the right SLF II. In the SLF II, the ASD group had significantly greater right lateralisation of FA in comparison with the control group. The clinical and functional implications of increased FA in white matter are poorly understood; however, it is possible that this increased white matter organisation in the SLF in ASD may contribute to relative processing advantages in the condition.

Multimodal MRI reveals structural connectivity differences in 22q11 deletion syndrome related to impaired spatial working memory.

INTRODUCTION: Impaired spatial working memory is a core cognitive deficit observed in people with 22q11 Deletion syndrome (22q11DS) and has been suggested as a candidate endophenotype for schizophrenia. However, to date, the neuroanatomical mechanisms describing its structural and functional underpinnings in 22q11DS remain unclear. We quantitatively investigate the cognitive processes and associated neuroanatomy of spatial working memory in people with 22q11DS compared to matched controls. We examine whether there are significant between-group differences in spatial working memory using task related fMRI, Voxel based morphometry and white matter fiber tractography. MATERIALS AND METHODS: Multimodal magnetic resonance imaging employing functional, diffusion and volumetric techniques were used to quantitatively assess the cognitive and neuroanatomical features of spatial working memory processes in 22q11DS. Twenty-six participants with genetically confirmed 22q11DS aged between 9 and 52 years and 26 controls aged between 8 and 46 years, matched for age, gender, and handedness were recruited. RESULTS: People with 22q11DS have significant differences in spatial working memory functioning accompanied by a gray matter volume reduction in the right precuneus. Gray matter volume was significantly correlated with task performance scores in these areas. Tractography revealed extensive differences along fibers between task-related cortical activations with pronounced differences localized to interhemispheric commissural fibers within the parietal section of the corpus callosum. CONCLUSIONS: Abnormal spatial working memory in 22q11DS is associated with aberrant functional activity in conjunction with gray and white matter structural abnormalities. These anomalies in discrete brain regions may increase susceptibility to the development of psychiatric disorders such as schizophrenia. Hum Brain Mapp 37:4689-4705, 2016. © 2016 Wiley Periodicals, Inc.

White matter alterations in patients with MRI-negative temporal lobe epilepsy and their asymptomatic siblings.

OBJECTIVE: The identification of "endophenotypes"-measurable variations along the pathways between genes and distal disease state-may help deconstruct focal epilepsies into more sensitive phenomena and improve future efforts to map the genetic underpinnings of the disorder. In this study, we set out to determine if diffusion tensor imaging (DTI)-inferred white matter (WM) alterations represent a suitable structural endophenotype for focal epilepsy. METHODS: We recruited 25 patients with sporadic mesial temporal lobe epilepsy (MTLE) with normal magnetic resonance imaging (MRI) findings, 25 of their gender-matched, asymptomatic siblings, and 60 control subjects. Whole-brain, voxelwise statistics were conducted to identify regions of microstructural degeneration in patients with MTLE and/or their asymptomatic siblings. WM tracts exhibiting evidence of microstructural disruption were then reconstructed using deterministic tractography. Diffusion metrics including fractional anisotropy (FA) and mean diffusivity (MD) were compared across groups using a series of one-way multivariate analyses of covariance (MANCOVAs). RESULTS: Voxelwise statistics revealed significant FA reductions in the corpus callosum (CC), bilateral superior longitudinal fasciculi (SLF), bilateral inferior longitudinal fasciculi (ILF), and left corticospinal tract (CST) in MTLE patients only. MD increases were observed in MTLE patients and their asymptomatic siblings in the left SLF and left CST. Deterministic tractography supported the voxelwise results, revealing significant FA alterations in the left SLF and CST in patients only and significant MD alterations in MTLE patients and their unaffected siblings. The diffusion scalars of MTLE patients and their asymptomatic siblings were highly correlated in the SLF and CST ipsilateral to patients' sides of seizure onset. SIGNIFICANCE: These findings confirm the presence of microstructural WM alterations in patients with MRI-negative MTLE and provide preliminary support for a diffusion-based endophenotype in the disorder. Further studies of narrow-sense heritability in larger cohorts of first-degree relatives of MTLE patients are required to confirm these results.

Psychiatric and neuropsychological profiles of people with psychogenic nonepileptic seizures.

OBJECTIVE: This study examined the psychiatric and neuropsychological profiles of people with psychogenic nonepileptic seizures (PNES). METHODS: Twenty-people who had been diagnosed with psychogenic nonepileptic seizures (PNES), but not epilepsy, were recruited into this study. A healthy control group was also recruited and was matched for age and gender. All participants underwent structured psychiatric assessment and psychometric assessment. Neuropsychological assessment was carried out using the Cambridge Neuropsychological Test Battery (CANTAB) after participants passed the Medical Symptom Validity Test (MSVT) of effort. RESULTS: One patient failed the MSVT and was excluded from the analysis. Therefore, data from 19 people with PNES and their matched healthy controls were analyzed. Compared with controls, people with PNES had significantly higher levels of depressive symptoms, anxiety symptoms, dissociative experiences, and alexithymic traits. In addition, people with PNES had impairments in spatial working memory and attention when compared with healthy controls. CONCLUSION: To our knowledge, this is the first study to report that, compared with controls, people with PNES have abnormal cognitive functioning after controlling for effects of effort and FSIQ. People with PNES also have high levels of anxiety, depressive, and dissociative symptoms. In addition, they appear to particularly focus on health problems and show evidence of chronic emotional dysregulation. Further studies are required to replicate our results and to help clarify the pathogenic mechanisms underlying PNES.

The Limbic System in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: A Longitudinal Structural Magnetic Resonance Imaging Analysis.

Background: During childhood and adolescence, attention-deficit/hyperactivity disorder (ADHD) is associated with changes in symptoms and brain structures, but the link between brain structure and function remains unclear. The limbic system, often termed the "emotional network," plays an important role in a number of neurodevelopmental disorders, yet this brain network remains largely unexplored in ADHD. Investigating the developmental trajectories of key limbic system structures during childhood and adolescence will provide novel insights into the neurobiological underpinnings of ADHD. Methods: Structural magnetic resonance imaging data (380 scans), emotional regulation (Affective Reactivity Index), and ADHD symptom severity (Conners 3 ADHD Index) were measured at up to 3 time points between 9 and 14 years of age in a sample of children and adolescents with ADHD (n = 57) and control children (n = 109). Results: Compared with the control group, the ADHD group had lower volume of the amygdala (left: ß standardized [ß_std] = -0.38; right: ß_std = -0.34), hippocampus (left: ß_std = -0.44; right: ß_std = -0.34), cingulate gyrus (left: ß_std = -0.42; right: ß_std = -0.32), and orbitofrontal cortex (right: ß_std = -0.33) across development (9-14 years). There were no significant group-by-age interactions in any of the limbic system structures. Exploratory analysis found a significant Conners 3 ADHD Index-by-age interaction effect on the volume of the left mammillary body (ß_std = 0.17) in the ADHD group across the 3 study time points. Conclusions: Children and adolescents with ADHD displayed lower volume and atypical development in limbic system structures. Furthermore, atypical limbic system development was associated with increased symptom severity, highlighting a potential neurobiological correlate of ADHD severity.

Longitudinal hippocampal subfield development associated with psychotic experiences in young people.

Hippocampal volumetric reductions are observed across the psychosis spectrum, with interest in the localisation of these reductions within the hippocampal subfields increasing. Deficits of the CA1 subfield in particular have been implicated in the neuropathophysiology of psychotic disorders. Investigating the trajectory of these abnormalities in healthy adolescents reporting sub-threshold psychotic experiences (PE) can provide insight into the neural mechanisms underlying psychotic symptoms without the potentially confounding effects of a formal disorder, or antipsychotic medication. In this novel investigation, a sample of 211 young people aged 11-13 participated initially in the Adolescent Brain Development study. PE classification was determined by expert consensus at each timepoint. Participants underwent neuroimaging at 3 timepoints, over 6 years. 78 participants with at least one scan were included in the final sample; 33 who met criteria for a definite PE at least once across all the timepoints (PE group), and 45 controls. Data from bilateral subfields of interest (CA1, CA2/3, CA4/DG, presubiculum and subiculum) were extracted for Linear Mixed Effects analyses. Before correction, subfield volumes were found to increase in the control group and decrease in the PE group for the right CA2 and CA2/3 subfields, with moderate to large effect sizes (d = -0.61, and d = -0.79, respectively). Before correction, right subiculum and left presubiculum volumes were reduced in the PE group compared to controls, regardless of time, with moderate effect sizes (d = -0.52, and d = -0.59, respectively). However, none of these effects survived correction. Severity of symptoms were not associated with any of the noted subfields. These findings provide novel insight to the discussion of the role of hippocampal subfield abnormalities in the pathophysiology underlying psychotic experiences.

Longitudinal Gray Matter Development Associated With Psychotic Experiences in Young People.

Background: Gray matter abnormalities are observed across the psychosis spectrum. The trajectory of these abnormalities in healthy adolescents reporting subthreshold psychotic experiences (PEs) may provide insight into the neural mechanisms underlying psychotic symptoms. The risk of psychosis and additional psychopathology is even higher among these individuals who also report childhood adversity/DSM-5 diagnoses. Thus, the aims of this longitudinal study were to investigate PE-related volumetric changes in young people, noting any effects of childhood adversity/DSM-5 diagnosis. Methods: A total of 211 young people 11 to 13 years of age participated in the initial Adolescent Brain Development study. PE classification was determined by expert consensus at each time point. Participants underwent neuroimaging at 3 time points over 6 years. A total of 76 participants with at least one scan were included in the final sample; 34 who met criteria for PEs at least once across all the time points (PE group) and 42 control subjects. Data from 20 bilateral regions of interest were extracted for linear mixed-effects analyses. Results: Right hippocampal volume increased over time in the control group, with no increase in the PE group (p = .00352). DSM-5 diagnosis and childhood adversity were not significantly associated with right hippocampal volume. There was no significant effect of group or interaction in any other region. Conclusions: These findings further implicate right hippocampal volumetric abnormalities in the pathophysiology underlying PEs. Furthermore, as suggested by previous studies in those at clinical high risk for psychosis and those with first-episode psychosis, it is possible that these deficits may be a marker for later clinical outcomes.

White matter microstructure in children and adolescents with ADHD.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Advances in diffusion magnetic resonance imaging (MRI) acquisition sequences and analytic techniques have led to growing body of evidence that abnormal white matter microstructure is a core pathophysiological feature of ADHD. This systematic review provides a qualitative assessment of research investigating microstructural organisation of white matter amongst children and adolescents with ADHD. This review included 46 studies in total, encompassing multiple diffusion MRI imaging techniques and analytic approaches, including whole-brain, region of interest and connectomic analyses. Whole-brain and region of interest analyses described atypical organisation of white matter microstructure in several white matter tracts: most notably in frontostriatal tracts, corpus callosum, superior longitudinal fasciculus, cingulum bundle, thalamic radiations, internal capsule and corona radiata. Connectomic analyses, including graph theory approaches, demonstrated global underconnectivity in connections between functionally specialised networks. Although some studies reported significant correlations between atypical white matter microstructure and ADHD symptoms or other behavioural measures there was no clear pattern of results. Interestingly however, many of the findings of disrupted white matter microstructure were in neural networks associated with key neuropsychological functions that are atypical in ADHD. Limitations to the extant research are outlined in this review and future studies in this area should carefully consider factors such as sample size, sex balance, head motion and medication status.

MRI volumetric changes in hippocampal subfields in psychosis: a protocol for a systematic review and meta-analysis.

BACKGROUND: The hippocampus has for long been known for its ability to form new, declarative memory. However, emerging findings across conditions in the psychosis spectrum also implicate its role in emotional regulation. Systematic reviews have demonstrated consistent volume atrophic changes in the hippocampus. The aim of the systematic review and metanalysis which will follow from this protocol will be to investigate the volume-based neuroimaging findings across each of the subfields of the hippocampus in psychosis independent of diagnosis. METHODS: Volume changes across subfields of the hippocampus in psychotic illnesses will be assessed by systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). MRI neuroimaging studies of patients with a definitive diagnosis of psychosis (including brief pre-diagnostic states) will be included. Studies lacking adequate controls, illicit drug use, medical psychosis, history of other significant psychiatric comorbidities, or emphasis on age groups above 65 or below 16 will be excluded. Subfields investigated will include the CA1, CA2/3, CA4, subiculum, presubiculum, parasubiculum, dentate gyrus, stratum, molecular layer, granular cell layer, entorhinal cortex, and fimbria. Two people will independently screen abstracts from the output of the search to select suitable studies. This will be followed by the two reviewers performing a full-text review of the studies which were selected based on suitable abstracts. One reviewer will independently perform all the data extraction, and another reviewer will then systemically check all the extracted information using the original articles to ensure accuracy. Statistical analysis will be performed using the metafor and meta-packages in R Studio with the application of the random-effects model. DISCUSSION: This study will provide insight into the volumetric changes in psychosis of the subfields of the hippocampus, independent of diagnosis. This may shed light on the intricate neural pathology which encompasses psychosis and will open avenues for further exploration of the structures identified as potential drivers of volume change. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020199558.

Examining the Role of the Noradrenergic Locus Coeruleus for Predicting Attention and Brain Maintenance in Healthy Old Age and Disease: An MRI Structural Study for the Alzheimer's Disease Neuroimaging Initiative.

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.

Amygdala substructure volumes in Major Depressive Disorder.

The role of the amygdala in the experience of emotional states and stress is well established. Connections from the amygdala to the hypothalamus activate the hypothalamic-pituitaryadrenal (HPA) axis and the cortisol response. Previous studies have failed to find consistent whole amygdala volume changes in Major Depressive Disorder (MDD), but differences may exist at the smaller substructural level of the amygdala nuclei. High-resolution T1 and T2-weighted-fluid-attenuated inversion recovery MRIs were compared between 80 patients with MDD and 83 healthy controls (HC) using the automated amygdala substructure module in FreeSurfer 6.0. Volumetric assessments were performed for individual nuclei and three anatomico-functional composite groups of nuclei. Salivary cortisol awakening response (CAR), as a measure of HPA responsivity, was measured in a subset of patients. The right medial nucleus volume was larger in MDD compared to HC (p = 0.002). Increased right-left volume ratios were found in MDD for the whole amygdala (p = 0.004), the laterobasal composite (p = 0.009) and in the central (p = 0.003) and medial (p = 0.014) nuclei. The CAR was not significantly different between MDD and HC. Within the MDD group the left corticoamygdaloid transition area was inversely correlated with the CAR, as measured by area under the curve (AUCg) (p ≤ 0.0001). In conclusion, our study found larger right medial nuclei volumes in MDD compared to HC and relatively increased right compared to left whole and substructure volume ratios in MDD. The results suggest that amygdala substructure volumes may be involved in the pathophysiology of depression.

Structural and functional brain correlates of subclinical psychotic symptoms in 11-13 year old schoolchildren.

Studying children experiencing psychotic symptoms provides a unique opportunity to examine the vulnerability to psychosis within the context of development. Using neuroimaging techniques this study investigated cognitive control functions, brain volumetrics and white matter integrity in an at-risk cohort of children. Between-subjects assessment of brain function and structure among 11 school-going, non-treatment seeking children aged 11-13 who were at symptomatic risk for psychosis (AR) and 14 healthy control children aged 11-12 without subclinical psychotic symptoms (CON). MRI assessments included functional measures of response inhibition and error-related processes, whole brain voxel-based morphometry (VBM) of gray matter (GM) and diffusion tensor imaging (DTI) utilizing fractional anisotropy to probe white matter (WM) integrity. fMRI results showed reduced activity in the AR group within right frontal and bilateral temporal cortex for response inhibition and reduced activity within the anterior cingulate, insula and middle frontal gyrus for error-related processing (p<.05, corrected). VBM analysis revealed GM increases in the AR group within middle and superior temporal gyri, angular gyrus, orbitofrontal gyrus and GM decrease within the inferior temporal gyrus (p<.05, corrected). DTI analysis identified WM decreases in the AR group along the inferior fronto-occipital fasciculus, cingulum and inferior longitudinal fasciculus (p<.05, corrected). This multimodal investigation revealed aberrant prefrontal-temporal dysfunction in addition to cingulate and insular dysfunctions which provide potential early neurocognitive risk markers related to the susceptibility for developing psychosis and subsequently the neurodevelopmental trajectory leading to schizophrenia.

Hippocampal and Amygdalar Volume Changes in Major Depressive Disorder: A Targeted Review and Focus on Stress.

Medial temporal lobe structures have long been implicated in the pathogenesis of major depressive disorder. Although findings of smaller hippocampal and amygdalar volumes are common, inconsistencies remain in the literature. In this targeted review, we examine recent and significant neuroimaging papers examining the volumes of these structures in major depressive disorder. A targeted PubMed/Google Scholar search was undertaken focusing on volumetric neuroimaging studies of the hippocampus and amygdala in major depressive disorder. Where possible, mean volumes and accompanying standard deviations were extracted allowing computation of Cohen's ds effect sizes. Although not a meta-analysis, this allows a broad comparison of volume changes across studies. Thirty-nine studies in total were assessed. Hippocampal substructures and amygdale substructures were investigated in 11 and 2 studies, respectively. The hippocampus was more consistently smaller than the amygdala across studies, which is reflected in the larger cumulative difference in volume found with the Cohen's ds calculations. The left and right hippocampi were, respectively, 92% and 91.3% of the volume found in controls, and the left and right amygdalae were, respectively, 94.8% and 92.6% of the volume of controls across all included studies. The role of stress in temporal lobe structure volume reduction in major depressive disorder is discussed.

Multiple Network Dysconnectivity in Adolescents with Psychotic Experiences: A Longitudinal Population-Based Study.

Abnormal functional connectivity (FC, the temporal synchronization of activation across distinct brain regions) of the default mode (DMN), salience (SN), central executive (CEN), and motor (MN) networks is well established in psychosis. However, little is known about FC in individuals, particularly adolescents, reporting subthreshold psychotic experiences (PE) and their trajectory over time. Thus, the aim of this study was to investigate the FC of these networks in adolescents with PE. In this population-based case-control study, 24 adolescents (mean age = 13.58) meeting the criteria for PE were drawn from a sample of 211 young people recruited and scanned for a neuroimaging study, with a follow-up scan 2 years later (n = 18, mean age = 15.78) and compared to matched controls drawn from the same sample. We compared FC of DMN, SN, CEN, and MN regions between PE and controls using whole-brain FC analyses. At both timepoints, the PE group displayed significant hypoconnectivity compared to controls. At baseline, FC in the PE group was decreased between MN and DMN regions. At follow-up, dysconnectivity in the PE group was more widespread. Over time, controls displayed greater FC changes than the PE group, with FC generally increasing between MN, DMN, and SN regions. Adolescents with PE exhibit hypoconnectivity across several functional networks also found to be hypoconnected in established psychosis. Our findings highlight the potential for studies of adolescents reporting PE to reveal early neural correlates of psychosis and support further investigation of the role of the MN in PE and psychotic disorders.

Magnetic resonance diffusion weighted imaging using constrained spherical deconvolution-based tractography of the extracranial course of the facial nerve.

OBJECTIVE: To evaluate the accuracy of magnetic resonance diffusion weighted imaging (DWI) featuring constrained spherical deconvolution-based tractography in tracking the extracranial course of the facial nerve to provide a reliable facial nerve map to facilitate well-tolerated and effective tumor resection. STUDY DESIGN: Magnetic resonance DWI was conducted on 2 parotid-healthy cadaveric patients with various protocols to identify the best representation of the extracranial facial nerve tract. This was subsequently correlated to dissection of the facial nerves to ascertain anatomic validation. These protocols were applied to 2 live, parotid-healthy patients to assess feasibility of in vivo facial nerve tract identification. RESULTS: Correlations between imaged tracts and the anatomic course of the extracranial facial nerve were identified to an accuracy of 1 mm. The main trunk and bifurcation tracts were identified on imaging. Fractional anisometry values in cadaveric and live patients were within the range expected for the facial nerve within the parotid gland. CONCLUSIONS: Our results indicated the potential for accurate 3-dimensional visualization of the extracranial course of the facial nerve, which could have diagnostic implications in differentiating benign from malignant tumors and, crucially, neural involvement. Preoperative planning applications of DWI could help in planning surgical approaches and providing focused counseling.

Reduced hippocampal volume in adolescents with psychotic experiences: A longitudinal population-based study.

AIMS: Smaller hippocampal volumes are among the most consistently reported neuroimaging findings in schizophrenia. However, little is known about hippocampal volumes in people who report psychotic experiences. This study investigated differences in hippocampal volume between young people without formal diagnoses who report psychotic experiences (PEs) and those who do not report such experiences. This study also investigated if any differences persisted over two years. METHODS: A nested case-control study of 25 adolescents (mean age 13.5 years) with reported PEs and 25 matched controls (mean age 13.36 years) without PEs were drawn from a sample of 100 local schoolchildren. High-resolution T1-weighted anatomical imaging and subsequent automated cortical segmentation (Freesurfer 6.0) was undertaken to determine total hippocampal volumes. Comprehensive semi-structured clinical interviews were also performed including information on PEs, mental diagnoses and early life stress (bullying). Participants were invited for a second scan at two years. RESULTS: 19 adolescents with PEs and 19 controls completed both scans. Hippocampal volumes were bilaterally lower in the PE group compared to the controls with moderate effects sizes both at baseline [left hippocampus p = 0.024 d = 0.736, right hippocampus p = 0.018, d = 0.738] and at 2 year follow up [left hippocampus p = 0.027 d = 0.702, right = 0.048 d = 0.659] throughout. These differences survived adjustment for co-morbid mental disorders and early life stress. CONCLUSIONS: Psychotic experiences are associated with total hippocampal volume loss in young people and this volume loss appears to be independent of possible confounders such as co-morbid disorders and early life stress.

Untangling the dorsal diencephalic conduction system: a review of structure and function of the stria medullaris, habenula and fasciculus retroflexus.

The often-overlooked dorsal diencephalic conduction system (DDCS) is a highly conserved pathway linking the basal forebrain and the monoaminergic brainstem. It consists of three key structures; the stria medullaris, the habenula and the fasciculus retroflexus. The first component of the DDCS, the stria medullaris, is a discrete bilateral tract composed of fibers from the basal forebrain that terminate in the triangular eminence of the stalk of the pineal gland, known as the habenula. The habenula acts as a relay hub where incoming signals from the stria medullaris are processed and subsequently relayed to the midbrain and hindbrain monoaminergic nuclei through the fasciculus retroflexus. As a result of its wide-ranging connections, the DDCS has recently been implicated in a wide range of behaviors related to reward processing, aversion and motivation. As such, an understanding of the structure and connections of the DDCS may help illuminate the pathophysiology of neuropsychiatric disorders such as depression, addiction and pain. This is the first review of all three components of the DDCS, the stria medullaris, the habenula and the fasciculus retroflexus, with particular focus on their anatomy, function and development.

Psychotic experiences in childhood are associated with increased structural integrity of the left arcuate fasciculus - A population-based case-control study.

Around 1 in 5 children under 13 years old experience sub-clinical psychotic experiences (PEs) like hallucinations and delusions. While PEs in childhood are a significant risk factor for adult psychotic disorders, the majority of those experiencing childhood PEs do not develop a psychotic disorder. Individual differences in regional brain maturation rates may be responsible for this age-related and often transient emergence of PEs. Fronto-temporal association tracts undergo extensive maturation and myelination throughout childhood and adolescence, thus we focus on individual differences in one such tract, the arcuate fasciculus. A normative population-based sample of children (aged 11-13) attended a clinical interview and MRI (n = 100), 25 of whom were identified as reporting strong PEs. This group had reduced mean and radial diffusivity in the arcuate fasciculus compared with a group of matched controls (n = 25) who reported no PEs. The group difference was greater in the left hemisphere than the right. Mediation analyses showed that this group difference was driven predominantly by perceptual disturbances and an along-tract analysis showed that the group difference was greatest approximately halfway between the frontal and temporal termination points of the tract (adjacent to the left lateral ventricle). This study is the first to investigate links between arcuate fasciculus diffusivity and psychotic experiences in a population sample of children.