Structural Morphometry Research Articles

Testing whether the relations between sex and psychopathology are accounted for by structural morphometry in ABCD.

Sex differences in psychopathology are well-established, with females demonstrating higher rates of internalizing (INT) psychopathology and males demonstrating higher rates of externalizing (EXT) psychopathology. Using two waves of data from the Adolescent Brain Cognitive Development Study (N = 6,778 at each wave), the current study tested whether the relations between sex and psychopathology might be accounted for by structural brain differences. In general, we found robust, relatively consistent relations between sex and structural morphometry across waves. Relatively few morphometric brain variables were significantly related to INT or EXT across waves, however, with very small effect sizes when present. Next, we tested the extent to which each morphometric brain variable could account for the associations of sex with INT and EXT psychopathology. We found a total of 26 brain regions that accounted for significant portions of the associations between sex and psychopathology across both waves (almost all related to EXT), although the effects present were very small. The current evidence suggests that in children aged 9-12, multiple whole-brain and regional brain variables appear to statistically account for small portions of the sex-psychopathology links, especially for externalizing. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Supplemental Material for Testing Whether the Relations Between Sex and Psychopathology Are Accounted for by Structural Morphometry in ABCD

Supplemental Material for Testing Whether the Relations Between Sex and Psychopathology Are Accounted for by Structural Morphometry in ABCD

A comparison of structural morphometry in children and adults with persistent developmental stuttering.

This cross-sectional study aimed to differentiate earlier occurring neuroanatomical differences that may reflect core deficits in stuttering versus changes associated with a longer duration of stuttering by analysing structural morphometry in a large sample of children and adults who stutter and age-matched controls. Whole-brain T1-weighted structural scans were obtained from 166 individuals who stutter (74 children, 92 adults; ages 3-58) and 191 controls (92 children, 99 adults; ages 3-53) from eight prior studies in our laboratories. Mean size and gyrification measures were extracted using FreeSurfer software for each cortical region of interest. FreeSurfer software was also used to generate subcortical volumes for regions in the automatic subcortical segmentation. For cortical analyses, separate ANOVA analyses of size (surface area, cortical thickness) and gyrification (local gyrification index) measures were conducted to test for a main effect of diagnosis (stuttering, control) and the interaction of diagnosis-group with age-group (children, adults) across cortical regions. Cortical analyses were first conducted across a set of regions that comprise the speech network and then in a second whole-brain analysis. Next, separate ANOVA analyses of volume were conducted across subcortical regions in each hemisphere. False discovery rate corrections were applied for all analyses. Additionally, we tested for correlations between structural morphometry and stuttering severity. Analyses revealed thinner cortex in children who stutter compared with controls in several key speech-planning regions, with significant correlations between cortical thickness and stuttering severity. These differences in cortical size were not present in adults who stutter, who instead showed reduced gyrification in the right inferior frontal gyrus. Findings suggest that early cortical anomalies in key speech planning regions may be associated with stuttering onset. Persistent stuttering into adulthood may result from network-level dysfunction instead of focal differences in cortical morphometry. Adults who stutter may also have a more heterogeneous neural presentation than children who stutter due to their unique lived experiences.

Neuroprotective influence of macular xanthophylls and retinal integrity on cognitive function among persons with multiple sclerosis

BackgroundNo studies to date have examined if macular xanthophyll accumulation and retinal integrity are independently associated with cognitive function in individuals with multiple sclerosis (MS). This study explored whether macular xanthophyll accumulation and structural morphometry in the retina were associated with behavioral performance and neuroelectric function during a computerized cognitive task among persons with MS and healthy controls (HCs). Methods42 HCs and 42 individuals with MS aged 18–64 years were enrolled. Macular pigment optical density (MPOD) was measured using heterochromatic flicker photometry. Optic disc retinal nerve fiber layer (odRNFL), macular retinal nerve fiber layer, and total macular volume were assessed via optical coherence tomography. Attentional inhibition was assessed using an Eriksen flanker task while underlying neuroelectric function was recorded using event-related potentials. ResultsPersons with MS had a slower reaction time, lower accuracy, and delayed P3 peak latency time during both congruent and incongruent trials compared with HCs. Within the MS group, MPOD explained variance in incongruent P3 peak latency, and odRNFL explained variance in congruent reaction time and congruent P3 peak latency. ConclusionsPersons with MS exhibited poorer attentional inhibition and slower processing speed, yet higher MPOD and odRNFL levels were independently associated with greater attentional inhibition and faster processing speed among persons with MS. Future interventions are necessary to determine if improvements in these metrics may promote cognitive function among persons with MS.

Convergent and divergent gray matter volume abnormalities in unaffected first-degree relatives and ultra-high risk individuals of schizophrenia

High-risk populations of schizophrenia can be mainly identified as genetic high-risk based on putative endophenotypes or ultra-high-risk (UHR) based on clinically manifested symptoms. Previous studies have consistently shown brain structural abnormalities in both genetic high-risk and UHR individuals. In this study, we aimed to disentangle the convergent and divergent pattern of gray matter alterations between UHR and unaffected first-degree relatives from genetic high-risk individuals. We used structural MRI scans and voxel-based morphometry method to examine gray matter volume (GMV) differences among 23 UHR subjects meeting the Structured Interview for Prodromal Syndromes (SIPS) criteria, 18 unaffected first-degree relatives (UFDR), 26 first-episode schizophrenia patients (FES) and 54 healthy controls (CN). We found that a number of brain regions exhibited a monotonically decreasing trend of GMV from CN to UFDR to UHR to FES. Compared with CN, the UHR subjects showed significant decreases of GMV similar to the patients in the inferior temporal gyrus, fusiform gyrus, middle occipital gyrus, insula, and limbic regions. Moreover, the UHR transformed subgroup had significantly lower GMV than UHR non-transformed subgroup in the right inferior temporal/fusiform gyrus. On the other hand, the UFDR subjects only showed significant GMV decreases in the inferior temporal gyrus and fusiform. Moreover, we found GMV in the occipital lobe was negatively correlated with the UHR subjects’ composite positive symptom of SIPS, and GMV in the cerebellum was positively correlated with FES subjects’ symptom severity. Our results suggest that GMV deficits and regional dysfunction are evident prior to the onset of psychosis and are more prominent in the UHR than the UFDR individuals.

Impact of the Endocannabinoid System on Bone Formation and Remodeling in p62 KO Mice.

Several studies have shown that the G-protein coupled cannabinoid receptor CB2 and its interaction partner p62 are molecularly involved in bone remodeling processes. Pharmacological activation of the CB2 receptor enhanced bone volume in postmenopausal osteoporosis and arthritis models in rodents, whereas knockout or mutation of the p62 protein in aged mice led to Paget’s disease of bone-like conditions. Studies of pharmacological CB2 agonist effects on bone metabolism in p62 KO mice have not been performed to date. Here, we assessed the effect of the CB2-specific agonist JWH133 after a short-term (5 days in 3-month-old mice) or long-term (4 weeks in 6-month-old mice) treatment on structural, dynamic, and cellular bone morphometry obtained by μCT of the femur and histomorphometry of the vertebral bodies in p62 KO mice and their WT littermates in vivo. A genotype-independent stimulatory effect of CB2 on bone formation, trabecular number, and trabecular thickness after short-term treatment and on tissue mineral density after long-term treatment was detected, indicating a weak osteoanabolic function of this CB2 agonist. Moreover, after short-term systemic CB2 receptor activation, we found significant differences at the cellular level in the number of osteoblasts and osteoclasts only in p62 KO mice, together with a weak increase in trabecular number and a decrease in trabecular separation. Long-term treatment showed an opposite JWH133 effect on osteoclasts in WT versus p62 KO animals and decreased cortical thickness only in treated p62 KO mice. Our results provide new insights into CB2 receptor signaling in vivo and suggest that CB2 agonist activity may be regulated by the presence of its macromolecular binding partner p62.

Petabyte-Scale Multi-Morphometry of Single Neurons for Whole Brains.

Recent advances in brain imaging allow producing large amounts of 3-D volumetric data from which morphometry data is reconstructed and measured. Fine detailed structural morphometry of individual neurons, including somata, dendrites, axons, and synaptic connectivity based on digitally reconstructed neurons, is essential for cataloging neuron types and their connectivity. To produce quality morphometry at large scale, it is highly desirable but extremely challenging to efficiently handle petabyte-scale high-resolution whole brain imaging database. Here, we developed a multi-level method to produce high quality somatic, dendritic, axonal, and potential synaptic morphometry, which was made possible by utilizing necessary petabyte hardware and software platform to optimize both the data and workflow management. Our method also boosts data sharing and remote collaborative validation. We highlight a petabyte application dataset involving 62 whole mouse brains, from which we identified 50,233 somata of individual neurons, profiled the dendrites of 11,322 neurons, reconstructed the full 3-D morphology of 1,050 neurons including their dendrites and full axons, and detected 1.9 million putative synaptic sites derived from axonal boutons. Analysis and simulation of these data indicate the promise of this approach for modern large-scale morphology applications.

Cortical and Subcortical Structural Morphometric Profiles in Individuals with Nonaffective and Affective Early Illness Psychosis.

Research has found strong evidence for common and distinct morphometric brain abnormality profiles in nonaffective psychosis (NAff-P) and affective psychosis (Aff-P). Due to chronicity and prolonged medication exposure confounds, it is crucial to examine structural morphometry early in the course of psychosis. Using Human Connectome Project-Early Psychosis data, multivariate profile analyses were implemented to examine regional profiles for cortical thickness, cortical surface area, subcortical volume, and ventricular volume in healthy control (HC; n = 56), early illness NAff-P (n = 83), and Aff-P (n = 30) groups after accounting for normal aging. Associations with symptom severity, functioning, and cognition were also examined. Group regional profiles were significantly nonparallel and differed in level for cortical thickness (P < .001), with NAff-P having widespread cortical thinning relative to HC and Aff-P and some regions showing greater deficits than others. Significant nonparallelism of group regional profiles was also evident for cortical surface area (P < .006), with Aff-P and N-Aff-P differing from HC and from each other (P < .001). For subcortical volume, there was significant profile nonparallelism with NAff-P having an enlarged left pallidum and smaller accumbens and hippocampus (P < .028), and Aff-P having a smaller accumbens and amygdala (P < .006), relative to HC. NAff-P also had larger basal ganglia compared to Aff-P. Furthermore, NAff-P had enlarged ventricles (P < .055) compared to HC and Aff-P. Additionally, greater ventricular volume was associated with increased manic symptoms in NAff-P and Aff-P. Overall, this study found common and distinct regional morphometric profile abnormalities in early illness NAff-P and Aff-P, providing evidence for both shared and disease-specific pathophysiological processes.

Person-Based Similarity Index for Cognition and Its Neural Correlates in Late Adulthood: Implications for Cognitive Reserve.

Healthy aging is typically associated with some level of cognitive decline, but there is substantial variation in such decline among older adults. The mechanisms behind such heterogeneity remain unclear but some have suggested a role for cognitive reserve. In this work, we propose the "person-based similarity index" for cognition (PBSI-Cog) as a proxy for cognitive reserve in older adults, and use the metric to quantify similarity between the cognitive profiles of healthy older and younger participants. In the current study, we computed this metric in 237 healthy older adults (55-88years) using a reference group of 156 younger adults (18-39years) taken from the Cambridge Center for Ageing and Neuroscience dataset. Our key findings revealed that PBSI-Cog scores in older adults were: 1) negatively associated with age (rho = -0.25, P = 10-4) and positively associated with higher education (t = 2.4, P = 0.02), 2) largely explained by fluid intelligence and executive function, and 3) predicted more by functional connectivity between lower- and higher-order resting-state networks than brain structural morphometry or education. Particularly, we found that higher segregation between the sensorimotor and executive networks predicted higher PBSI-Cog scores. Our results support the notion that brain network functional organization may underly variability in cognitive reserve in late adulthood.

Structural MRI substrate of long-duration response to levodopa in Parkinson\u2019s disease: an exploratory study

ObjectiveThe long-duration response (LDR) to L-dopa is a sustained benefit deriving from chronic administration of therapy to patients with Parkinson’s disease (PD). Almost all patients with early PD may develop the LDR to L-dopa, even if some patients could not at given dosages of the drug. Aim of this exploratory study is to investigate whether a neuroanatomical substrate may underlie the development of the of LDR using structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) analysis.MethodsTwenty-four drug-naïve PD patients were enrolled and underwent a baseline 3D T1-weighted structural brain MRI. Then, a treatment with 250/25 mg of L-dopa/carbidopa every 24 h was started and, after 2 weeks, LDR was evaluated by movement time recordings.ResultsAfter 2 weeks of continuative therapy, 15 patients (62.5%) showed a sustained LDR (LDR +), while nine patients (37.5%) did not develop a sustained LDR (LDR −). VBM analysis on MRI executed before treatment showed changes of gray matter in precentral and middle frontal gyri in patients subsequently developing a sustained LDR with respect to those patients who will not achieve LDR.ConclusionsParkinsonian patients who will develop a LDR to L-dopa may present, before starting treatment, peculiar structural conditions in cortical areas involved in motor control. Our exploratory study suggests that some cortical structural changes may predispose individual patients for developing the LDR to L-dopa.

Brain Oscillatory Activity during Tactile Stimulation Correlates with Cortical Thickness of Intact Areas and Predicts Outcome in Post-Traumatic Comatose Patients.

In this study, we have reported a correlation between structural brain changes and electroencephalography (EEG) in response to tactile stimulation in ten comatose patients after severe traumatic brain injury (TBI). Structural morphometry showed a decrease in whole-brain cortical thickness, cortical gray matter volume, and subcortical structures in ten comatose patients compared to fifteen healthy controls. The observed decrease in gray matter volume indicated brain atrophy in coma patients induced by TBI. In resting-state EEG, the power of slow-wave activity was significantly higher (2–6 Hz), and the power of alpha and beta rhythms was lower in coma patients than in controls. During tactile stimulation, coma patients’ theta rhythm power significantly decreased compared to that in the resting state. This decrease was not observed in the control group and correlated positively with better coma outcome and the volume of whole-brain gray matter, the right putamen, and the insula. It correlated negatively with the volume of damaged brain tissue. During tactile stimulation, an increase in beta rhythm power correlated with the thickness of patients’ somatosensory cortex. Our results showed that slow-wave desynchronization, as a nonspecific response to tactile stimulation, may serve as a sensitive index of coma outcome and morphometric changes after brain injury.

Daily-Life Negative Affect in Emotional Distress Disorders Associated with Altered Frontoinsular Emotion Regulation Activation and Cortical Gyrification

Emotional distress disorders are characterized by high daily-life negative affect and impaired positive reappraisal emotion regulation ability. These disorders have been associated with altered frontoinsular functioning in important emotion regulation regions, especially medial prefrontal cortex (PFC) and insula, and with structural abnormalities that could be indicative of aberrant underlying connectivity. However, the relationship between frontoinsular activation and structural morphometry with daily-life negative affect is unclear. Using multimodal neuroimaging and ambulatory assessment, individuals with emotional distress disorders (n = 27) completed a positive reappraisal emotion regulation task during scanning and subsequently reported on their daily-life negative affect repeatedly for two weeks. Increased daily-life negative affect was associated with increased medial PFC positive reappraisal activation. In contrast, increased daily-life negative affect was associated with decreased positive reappraisal activation in the left insula and cognitive flexibility regions (putamen and cerebellum). Additionally, increased daily-life negative affect was associated with left insula hypergyria and right posterior/inferior parietal hypogyria. Follow-up psychophysiological interactions analyses found increased daily-life negative affect associated with increased medial PFC-insula functional connectivity during positive reappraisal. Results suggest frontoinsular emotion regulation activation and gyrification abnormalities could be markers of increased daily-life negative affect and important treatment targets for emotional distress disorders.

Limited capacity for ipsilateral secondary motor areas to support hand function post-stroke.

Ipsilateral-projecting corticobulbar pathways, originating primarily from secondary motor areas, innervate the proximal and even distal portions, although they branch more extensively at the spinal cord. It is currently unclear to what extent these ipsilateral secondary motor areas and subsequent cortical projections may contribute to hand function following stroke-induced damage to one hemisphere. In the present study, we provide both structural and functional evidence indicating that individuals increasingly rely on ipsilateral secondary motor areas, although at the detriment of hand function. Increased activity in ipsilateral secondary motor areas was associated with increased involuntary coupling between shoulder abduction and finger flexion, most probably as a result of the low resolution of these pathways, making it increasingly difficult to open the hand. These findings suggest that, although ipsilateral secondary motor areas may support proximal movements, they do not have the capacity to support distal hand function, particularly for hand opening. Recent findings have shown connections of ipsilateral cortico-reticulospinal tract (CRST), predominantly originating from secondary motor areas to not only proximal, but also distal muscles of the arm. Following a unilateral stroke, CRST from the ipsilateral side remains intact and thus has been proposed as a possible backup system for post-stroke rehabilitation even for the hand. We argue that, although CRST from ipsilateral secondary motor areas can provide control for proximal joints, it is insufficient to control either hand or coordinated shoulder and hand movements as a result of its extensive spinal branching compared to contralateral corticospinal tract. To address this issue, we combined magnetic resonance imaging, high-density EEG, and robotics in 17 individuals with severe chronic hemiparetic stroke and 12 age-matched controls. We tested for changes in structural morphometry of the sensorimotor cortex and found that individuals with stroke demonstrated higher grey matter density in secondary motor areas ipsilateral to the paretic arm compared to controls. We then measured cortical activity when participants were attempting to generate hand opening either supported on a table or when lifting against a shoulder abduction load. The addition of shoulder abduction during hand opening increased reliance on ipsilateral secondary motor areas in stroke, but not controls. Crucially, the increased use of ipsilateral secondary motor areas was associated with decreased hand opening ability when lifting the arm as a result of involuntary coupling between the shoulder and wrist/finger flexors. Taken together, this evidence implicates a compensatory role for ipsilateral (i.e. contralesional) secondary motor areas post-stroke, although with no apparent capacity to support hand function.

DEEP MULTIMODAL BRAIN NETWORK LEARNING FOR JOINT ANALYSIS OF STRUCTURAL MORPHOMETRY AND FUNCTIONAL CONNECTIVITY.

Learning from the multimodal brain imaging data attracts a large amount of attention in medical image analysis due to the proliferation of multimodal data collection. It is widely accepted that multimodal data can provide complementary information than mining from a single modality. However, unifying the image-based knowledge from the multimodal data is very challenging due to different image signals, resolution, data structure, etc.. In this study, we design a supervised deep model to jointly analyze brain morphometry and functional connectivity on the cortical surface and we name it deep multimodal brain network learning (DMBNL). Two graph-based kernels, i.e., geometry-aware surface kernel (GSK) and topology-aware network kernel (TNK), are proposed for processing the cortical surface morphometry and brain functional network. The vertex features on the cortical surface from GSK is pooled and feed into TNK as its initial regional features. In the end, the graph-level feature is computed for each individual and thus can be applied for classification tasks. We test our model on a large autism imaging dataset. The experimental results prove the effectiveness of our model.

Novel Imaging Techniques in Detection of Progressive Multiple Sclerosis

Conventional brain imaging is increasingly used to support clinicians in diagnosing and monitoring the progression of multiple sclerosis (MS). Nevertheless, the correlation between a patient's clinical manifestation and conventional magnetic resonance imaging (MRI) measures is often weak, especially in patients with progressive MS (PMS). Imaging markers for monitoring disease progression in progressive multiple sclerosis (PMS) are scarce, thereby limiting the possibility to monitor disease evolution and to test effective treatments in clinical trials. Advanced imaging techniques that have the advantage of metrics with increased sensitivity to short-term tissue changes and increased specificity to the structural abnormalities characteristic of PMS have recently been applied in clinical trials of PMS. This study conducted on 200 Egyptian patients coming to MS clinic at Al-azhar university hospitals (120 female and 80 male) diagnosed as clinically definite multiple sclerosis according to 2017McDonald criteria for Multiple Sclerosis.The survey was conducted from May 2017 till May 2019. MS patients underwent baseline and 2-year follow-up scans. All patients underwent an examination by MS specialist neurologist including evaluation of the Expanded Disability Status Scale (EDSS) score and timed 25-foot walk (T25FW). All patients received disease-modifying immunotherapy during the observation period, as was selected and prescribed by their treating physician according to routine clinical care. The data came from the combination of computational tools of image processing and neuroimaging acquired in a 1.5 Tesla scanner using different techniques: Diffusion, T2,T1, FLAIR and Structural Morphometry. Data from more than 25 brain regions of 25 healthy individuals and 200 MS patients were collected. This study assessed MRI lesions from 200 clinically well-documented MS with a mean disease duration of 5 years, of whom 10 patients were diagnosed with primary progressive MS (PPMS), 15 with secondary progressive MS (SPMS), and175 with relapsing–remitting MS (RRMS). Twelve of them had an undetermined clinical course. We analysed the heterogeneity of lesion activity and its relationship to the disease course and severity. Compared with patients who had RRMS, those with progressive MS had a higher lesion load and a higher proportion of mixed active–inactive lesions, which helped to explain their greater disease severity (a shorter time to reach an EDSS score of 6). The study demonstrated that extensive cortical damage at disease onset and during the first 2 years of disease monitoring, as assessed by the number and volume of cortical lesions and cortical atrophy, was associated with a higher relapse rate during the study and more rapid onset of a progressive phase. Most importantly, a high cortical lesion count at disease onset predicted conversion to SPMS, and the number of lesions correlated with the speed of conversion (on average 4 years earlier in patients with ≥7 cortical lesions than in those with 1–3 lesions). None of the patients without cortical lesions at baseline evolved to SPMS. Combined with data from patients with clinically isolated syndrome, which suggest that cortical lesions are specific to MS and are associated with the accrual of more severe disability, these findings support the development of standardized MRI sequences for the assessment of cortical lesions in clinical practice. The importance of grey matter involvement for long-term prognosis was also confirmed by follow-up study of 49 patients with RRMS. An MRI model that included diffusion tensor measures of grey matter damage at baseline and measures of neurodegeneration — namely, formation of new T1-hypointense lesions and changes in brain volume — during the first 15 months of follow-up allowed the prediction of long-term disability in 77.6% of the patients. In contrast to previous studies of PPMS with a shorter follow-up (2 years), spinal cord atrophy was not associated with clinical deterioration, suggesting that the processes leading to accrual of disability evolve over time. Conventional and modern magnetic-resonance-based techniques to the study of MS has improved our ability to diagnose and monitor MS, as well as our understanding of disease pathophysiology. New techniques need to be refined and validated before they can be properly integrated into clinical research and practice. New schemes and analysis procedures require standardisation and optimisation so that they can be used in multi-site settings, both in natural history studies and treatment trials. From the data available, it is evident that the combining of different magnetic resonance methods, which are sensitive to different aspects of MS pathology, is a promising way to increase further our understanding of the mechanisms underlying the accumulation of irreversible disability.

Quantifying individual differences in brain morphometry underlying symptom severity in Autism Spectrum Disorders

The neurobiology of heterogeneous neurodevelopmental disorders such as autism spectrum disorders (ASD) are still unclear. Despite extensive efforts, most findings are difficult to reproduce due to high levels of individual variance in phenotypic expression. To quantify individual differences in brain morphometry in ASD, we implemented a novel subject-level, distance-based method on subject-specific attributes. In a large multi-cohort sample, each subject with ASD (n = 100; n = 84 males; mean age: 11.43 years; mean IQ: 110.58) was strictly matched to a control participant (n = 100; n = 84 males; mean age: 11.43 years; mean IQ: 110.70). Intrapair Euclidean distance of MRI brain morphometry and symptom severity measures (Social Responsiveness Scale) were entered into a regularised machine learning pipeline for feature selection, with rigorous out-of-sample validation and permutation testing. Subject-specific structural morphometry features significantly predicted individual variation in ASD symptom severity (19 cortical thickness features, p = 0.01, n = 5000 permutations; 10 surface area features, p = 0.006, n = 5000 permutations). Findings remained robust across subjects and were replicated in validation samples. Identified cortical regions implicate key hubs of the salience and default mode networks as neuroanatomical features of social impairment in ASD. Present results highlight the importance of subject-level markers in ASD, and offer an important step forward in understanding the neurobiology of heterogeneous disorders.

Stuttering and gray matter morphometry: A population-based neuroimaging study in young children

Stuttering is a developmental speech disorder originating in early childhood. We aimed to replicate the association of stuttering and structural morphometry using a large, population-based prospective cohort, the Generation R Study, and explore the neurobiological mechanism of stuttering in children. Twenty-six children with a history of stuttering and 489 fluent speaking peers (ages 6–9) were included in the MRI sub-study. Cortical and subcortical regions of interest were analyzed using linear regression models. Compared to fluent speakers, children with a history of stuttering had less gray matter volume in the left inferior frontal gyrus and supplementary motor area. Exploratory surface-based brain analysis showed thinner cortex in the left inferior frontal gyrus, and in bilateral frontal and parietal areas. These findings corroborate previous studies that reported aberrant brain morphometry in speech motor and auditory regions in children who stutter. Future research is needed to explore the causal nature of this association.

Biomarkers of Parkinson's disease: Striatal sub-regional structural morphometry and diffusion MRI.

Parkinson's disease (PD) is a progressive neurological disorder that has no reliable biomarkers. The aim of this study was to explore the potential of semi-automated sub-regional analysis of the striatum with magnetic resonance imaging (MRI) to distinguish PD patients from controls (i.e., as a diagnostic biomarker) and to compare PD patients at different stages of disease.With 3 Tesla MRI, diffusion- and T1-weighted scans were obtained on two occasions in 24 PD patients and 18 age-matched, healthy controls. PD patients completed one session on and the other session off dopaminergic medication. The striatum was parcellated into seven functionally disparate sub-regions. The segmentation was guided by reciprocal connections to distinct cortical regions. Volume, surface-based morphometry, and integrity of white matter connections were calculated for each striatal sub-region.Test-retest reliability of our volume, morphometry, and white matter integrity measures across scans was high, with correlations ranging from r = 0.452, p < 0.05 and r = 0.985, p < 0.001. Global measures of striatum such as total striatum, nucleus accumbens, caudate nuclei, and putamen were not significantly different between PD patients and controls, indicating poor sensitivity of these measures, which average across sub-regions that are functionally heterogeneous and differentially affected by PD, to act as diagnostic biomarkers. Further, these measures did not correlate significantly with disease severity, challenging their potential to serve as progression biomarkers. In contrast, a) decreased volume and b) inward surface displacement of caudal-motor striatum—the region first and most dopamine depleted in PD—distinguished PD patients from controls. Integrity of white matter cortico-striatal connections in caudal-motor and adjacent striatal sub-regions (i.e., executive and temporal striatum) was reduced for PD patients relative to controls. Finally, volume of limbic striatum, the only striatal sub-region innervated by the later-degenerating ventral tegmental area in PD, was reduced in later-stage compared to early stage PD patients a potential progression biomarker.Segmenting striatum based on distinct cortical connectivity provided highly sensitive MRI measures for diagnosing and staging PD.

18.2 Longitudinal Frontolimbic Development and Symptom Progression in Pediatric PTSD

At present, little is known about the neurodevelopmental changes over time in youth with PTSD and how such changes relate to symptom progression. Here, we present findings from our longitudinal neuroimaging study of youth with PTSD, incorporating whole-brain structural morphometry and resting-state functional connectivity analyses.

Single scan quantitative gradient recalled echo MRI for evaluation of tissue damage in lesions and normal appearing gray and white matter in multiple sclerosis.

Multiple sclerosis (MS) is a chronic disease affecting the human central nervous system (CNS) and leading to neurologic disability. Although conventional MRI techniques can readily detect focal white matter (WM) lesions, it remains challenging to quantify tissue damage in normal-appearing gray matter (GM) and WM. To demonstrate that a new MRI biomarker, R2t*, can provide quantitative analysis of tissue damage across the brain in MS patients in a single scan. Prospective. Forty-four MS patients and 19 healthy controls (HC). 3T, quantitative gradient-recalled-echo (qGRE), Magnetization-prepared rapid gradient-echo, fluid-attenuated inversion recovery. Severity of tissue damage was assessed by reduced R2t*. Tissue atrophy was assessed by cortical thickness and cervical spinal cord cross-sectional area (CSA). Multiple Sclerosis Functional Composite was used for clinical assessment. R2t* in cortical GM was more sensitive to MS damage than cortical atrophy. Using more than two standard deviations (SD) reduction versus age-matched HC as the cutoff, 48% of MS patients showed lower R2t*, versus only 9% with lower cortical thickness. Significant correlations between severities of tissue injury were identified among 1) upper cervical cord and several cortical regions, including motor cortex (P < 0.001), and 2) adjacent regions of GM and subcortical WM (P < 0.001). R2t*-defined tissue cellular damage in cortical GM was greater relative to adjacent WM. Reductions in cortical R2t* correlated with cognitive impairment (P < 0.01). Motor-related clinical signs correlated most with cervical cord CSA (P < 0.001). Reductions in R2t* within cortical GM was more sensitive to tissue damage than atrophy, potentially allowing a reduced sample size in clinical trials. R2t* together with structural morphometry suggested topographic patterns of regions showing correlated tissue damage throughout the brain and the cervical spinal cord of MS patients. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:487-498.