Voxel-based Analysis Research Articles

Voxel-based analyses for paediatric outcomes research

Voxel-based analyses for paediatric outcomes research

Insights from simultaneous EEG-fMRI and patient data illuminate the role of the anterior medial temporal lobe in N400 generation

The N400, a negative event-related potential (ERP) peaking approximately 400 ms after stimulus onset, is known to reflect the processing of semantic information. While scalp recordings have contributed to understanding the psychological processes underlying the N400, they have been limited in identifying its neural basis. However, recent intracranial ERP recordings and fMRI studies have shed light on the crucial role of the anterior medial temporal lobe (AMTL) in semantic information processing. These findings suggest that the N400 partially represents activity in the AMTL structures. To investigate the neural underpinnings of the N400 effect, we simultaneously recorded ERPs and event-related fMRI during a semantic priming paradigm in a sample of 12 young, healthy subjects. Additionally, we collected ERPs and structural brain data from older healthy adults and patients with amnestic mild cognitive impairment (aMCI), a population characterized by neurodegenerative changes in the AMTL. In our fMRI results, we identified bilateral loci in the AMTL as the global maxima. Employing an EEG-informed fMRI analysis, we explored trial-to-trial fluctuations in semantic processing by linking single-trial N400 amplitudes to the Blood Oxygen Level Dependent (BOLD) signal. This approach provided the first direct evidence linking the N400 recorded at the scalp level to the corresponding BOLD signal in the AMTL. Consistent with these findings, patients with aMCI exhibited a diminished N400 effect compared to healthy older adults. Furthermore, voxel-based morphometry analysis revealed a correlation between the magnitude of the N400 effect and the integrity of the AMTL. By integrating data from simultaneous EEG-fMRI, and patient studies, our research advances our understanding of the neural substrate of the N400 and highlights the critical involvement of the AMTL in semantic processing.

Newborn Brain Function and Early Emerging Callous-Unemotional Traits

Children with high callous-unemotional traits are more likely to develop severe and persistent conduct problems; however, the newborn neurobiology underlying early callous-unemotional traits remains unknown. Understanding the neural mechanisms that precede the development of callous-unemotional traits could help identify at-risk children and encourage development of novel treatments. To determine whether newborn brain function is associated with early-emerging empathy, prosociality, and callous-unemotional traits. In this prospective, longitudinal cohort study, pregnant women were recruited from obstetric clinics in St Louis, Missouri, from September 1, 2017, to February 28, 2020, with longitudinal data collected until March 20, 2023. Mothers were recruited during pregnancy. Newborns underwent brain magnetic resonance imaging shortly after birth. Mothers completed longitudinal follow-up when the children were aged 1, 2, and 3 years. The sample was enriched for exposure to socioeconomic disadvantage. Functional connectivity between hypothesized brain regions was assessed using newborn-specific networks and voxel-based connectivity analyses. Children's callous-unemotional traits were measured using the Inventory of Callous-Unemotional Traits. Empathy and prosociality were assessed using the Infant and Toddler Socio-Emotional Assessment. A total of 283 children (mean [SD] gestational age, 38 [2] weeks; 159 male [56.2%]; 2 Asian [0.7%], 171 Black [60%], 7 Hispanic or Latino [2.5%], 106 White [38%], 4 other racial or ethnic group [1.4%]) were included in the analysis. Stronger newborn functional connectivity between the cingulo-opercular network (CO) and medial prefrontal cortex (mPFC) was associated with higher callous-unemotional traits at age 3 years (β = 0.31; 95% CI, 0.17-0.41; P < .001). Results persisted when accounting for parental callous-unemotional traits and child externalizing symptoms. Stronger newborn CO-mPFC connectivity was also associated with lower empathy and lower prosociality at ages 1, 2, and 3 years using multilevel models (β = -0.12; 95% CI, -0.21 to -0.04; P = .004 and β = -0.20; 95% CI, -0.30 to -0.10; P < .001, respectively). Newborn functional connectivity was associated with early-emerging empathy, prosociality, and callous-unemotional traits, even when accounting for parental callous-unemotional traits and child externalizing symptoms. Understanding the neurobiological underpinnings of empathy, prosociality, and callous-unemotional traits at the earliest developmental point may help early risk stratification and novel intervention development.

Pragmatic language comprehension: Role of theory of mind, executive functions, and the prefrontal cortex

The specific contribution of focal damage of the prefrontal cortex and the cognitive mechanisms accounting for communicative-pragmatic disorders remains unclear. The objective of the current study was to investigate the impact of focal prefrontal cortex damage on the ability to understand indirect speech or hints and to identify the prefrontal neural mechanisms involved. We also examined the underlying cognitive mechanisms of disorders of indirect speech understanding particularly theory of mind and executive functions. Thirty patients with focal prefrontal cortex damage and 30 control subjects were compared on their performances on the Hinting task assessing pragmatic language skills, the "Faux-Pas" task and the Reading the Mind in the Eyes task assessing Theory of Mind and a battery of executive tasks. Patients were significantly impaired compared with control subjects on all these abilities. Both deficits of executive functions and theory of mind were able to predict impaired ability of patients in understanding non-literal meanings on the Hinting task. Finally, using voxel-based lesion analysis we identified a partially shared neural prefrontal network involved in all these abilities centered on the dorsomedial and ventral regions of the prefrontal cortex.

Exploring structural brain changes in children with neonatal brachial plexus palsy: a voxel-based morphometry analysis

BACKGROUND: Obstetric brachial plexus palsy (OBPP) is paralysis of the upper limb resulting from nerve injury during vaginal delivery. Although current treatment approaches frequently lead to complete reinnervation of the limb, some patients show long-term motor deficits. These impairments may result from upper limb disuse that causes structural brain changes. AIM: This study aimed to compare deep gray matter volumes between children with OBPP and healthy controls. METHODS: We analyzed the structural magnetic resonance imaging results of 46 children with OBPP (n=24, mean age — 10.20, of whom 12 were girls) and healthy age-matched controls (n=22, mean age — 9.63, of whom 10 were girls) using a voxel-based morphometry technique in SPM12 package (Statistical Parametric Mapping) in MATLAB R2019b. To minimize false discoveries, we used a stringent procedure to control the family-wise error rate. RESULTS: We found volumetric brain differences between children with OBPP and healthy controls (all FWE-corrected p 0.005). Children with OBPP had significantly lower gray matter volumes in the left amygdala, bilateral hippocampus, and right entorhinal cortex. CONCLUSION: Integrating our findings with previous work, we speculate that the amygdala–hippocampus–entorhinal cortex complex might play a significant role in motor disorders.

Progressive loss of cortical gray matter in first episode psychosis patients with auditory hallucinations

BackgroundPrevious longitudinal magnetic resonance imaging studies have shown progressive gray matter (GM) reduction during the earliest phases of schizophrenia. It is unknown whether these progressive processes are homogeneous in all groups of patients. One way to obtain more valid findings is to focus on the symptoms. Auditory hallucinations (AHs) are frequent and reliable symptoms of psychosis. The present study aims to analyze whether longitudinal changes in structural abnormalities in cortical regions are related to the presence of AHs and the intensity of psychotic symptoms in a large sample. MethodsA Magnetic Resonance (MR) voxel-based morphometry analysis was applied to a group of 128 first episodes psychosis (FEP) patients (63 patients with AHs and 65 patients without AHs) and 78 matched healthy controls at baseline and at a 2-year follow-up. ResultsAt baseline, FEP patients exhibited significant GM volume reductions in the temporal, frontal and precentral regions. At follow-up, FEP patients exhibited GM volume changes in the temporal, Rolandic, frontal, precentral and insula regions. At baseline, no significant differences were found between FEP patients with and without AHs. At follow-up, while FEP patients with AHs showed less GM volume in temporal and frontal lobes, non-AH FEP patients showed reductions in the frontal, precentral and fusiform areas. PANSS scores showed statistically significant correlations with GM volume reductions at baseline and follow-up. ConclusionsBrain cortical loss in the early phases of psychosis is not associated with potentially transitory AHs; however, brain structural changes may emerge as AHs appear in chronic patients.

Enhancing skeletal stability and Class III correction through active orthodontist engagement in virtual surgical planning: A voxel-based 3-dimensional analysis

Skeletal stability after bimaxillary surgical correction of Class III malocclusion was investigated through a qualitative and quantitative analysis of the maxilla and the distal and proximal mandibular segments using a 3-dimensional voxel-based superimposition among virtual surgical predictions performed by the orthodontist in close communication with the maxillofacial surgeon and 12-18 months postoperative outcomes. A comprehensive secondary data analysis was conducted on deidentified preoperative (1 month before surgery [T1]) and 12-18 months postoperative (midterm [T2]) cone-beam computed tomography scans, along with virtual surgical planning (VSP) data obtained by Dolphin Imaging software. The sample for the study consisted of 17 patients (mean age, 24.8 ± 3.5 years). Using 3D Slicer software, automated tools based on deep-learning approaches were used for cone-beam computed tomography orientation, registration, bone segmentation, and landmark identification. Colormaps were generated for qualitative analysis, whereas linear and angular differences between the planned (T1-VSP) and observed (T1-T2) outcomes were calculated for quantitative assessments. Statistical analysis was conducted with a significance level of α= 0.05. The midterm surgical outcomes revealed a slight but significantly less maxillary advancement compared with the planned position (mean difference, 1.84 ± 1.50 mm; P= 0.004). The repositioning of the mandibular distal segment was stable, with insignificant differences in linear (T1-VSP, 1.01 ± 3.66 mm; T1-T2, 0.32 ± 4.17 mm) and angular (T1-VSP, 1.53° ± 1.60°; T1-T2, 1.54° ± 1.50°) displacements (P>0.05). The proximal segments exhibited lateral displacement within 1.5° for both the mandibular right and left ramus at T1-VSP and T1-T2 (P>0.05). The analysis of fully digital planned and surgically repositioned maxilla and mandible revealed excellent precision. In the midterm surgical outcomes of maxillary advancement, a minor deviation from the planned anterior movement was observed.

Elevated gonadotropin levels are associated with increased biomarker risk of Alzheimer's disease in midlife women.

In preclinical studies, menopausal elevations in pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), trigger Alzheimer's disease (AD) pathology and synaptic loss in female animals. Herein, we took a translational approach to test whether gonadotropin elevations are linked to AD pathophysiology in women. We examined 191 women ages 40-65 years, carrying risk factors for late-onset AD, including 45 premenopausal, 67 perimenopausal, and 79 postmenopausal participants with clinical, laboratory, cognitive exams, and volumetric MRI scans. Half of the cohort completed 11C-Pittsburgh Compound B (PiB) amyloid-β (Aβ) PET scans. Associations between serum FSH, LH and biomarkers were examined using voxel-based analysis, overall and stratified by menopause status. Associations with region-of-interest (ROI) hippocampal volume, plasma estradiol levels, APOE-4 status, and cognition were assessed in sensitivity analyses. FSH levels were positively associated with Aβ load in frontal cortex (multivariable adjusted P≤0.05, corrected for family wise type error, FWE), an effect that was driven by the postmenopausal group (multivariable adjusted PFWE ≤ 0.044). LH levels were also associated with Aβ load in frontal cortex, which did not survive multivariable adjustment. FSH and LH were negatively associated with gray matter volume (GMV) in frontal cortex, overall and in each menopausal group (multivariable adjusted PFWE ≤ 0.040), and FSH was marginally associated with ROI hippocampal volume (multivariable adjusted P = 0.058). Associations were independent of age, clinical confounders, menopause type, hormone therapy status, history of depression, APOE-4 status, and regional effects of estradiol. There were no significant associations with cognitive scores. Increasing serum gonadotropin levels, especially FSH, are associated with higher Aβ load and lower GMV in some AD-vulnerable regions of midlife women at risk for AD. These findings are consistent with preclinical work and provide exploratory hormonal targets for precision medicine strategies for AD risk reduction.

Changes in Multiparametric Magnetic Resonance Imaging and Plasma Amyloid-Beta Protein in Subjective Cognitive Decline.

The association between plasma amyloid-beta protein (Aβ) and subjective cognitive decline (SCD) remains controversial. We aimed to explore the correlation between neuroimaging findings, plasma Aβ, and neuropsychological scales using data from 53 SCD patients and 46 age- and sex-matched healthy controls (HCs). Magnetic resonance imaging (MRI) was used to obtain neuroimaging data for a whole-brain voxel-based morphometry analysis and cortical functional network topological features. The SCD group had slightly lower Montreal Cognitive Assessment (MoCA) scores than the HC group. The Aβ42 levels were significantly higher in the SCD group than in the HC group (p < 0.05). The SCD patients demonstrated reduced volumes in the left hippocampus, right rectal gyrus (REC.R), and right precentral gyrus (PreCG.R); an increased percentage fluctuation in the left thalamus (PerAF); and lower average small-world coefficient (aSigma) and average global efficiency (aEg) values. Correlation analyses with Aβ and neuropsychological scales revealed significant positive correlations between the volumes of the HIP.L, REC.R, PreCG.R, and MoCA scores. The HIP.L volume and Aβ42 were negatively correlated, as were the REC.R volume and Aβ42/40. PerAF and aSigma were negatively and positively correlated with the MoCA scores, respectively. The aEg was positively correlated with Aβ42/40. SCD patients may exhibit alterations in plasma biomarkers and multi-parameter MRI that resemble those observed in Alzheimer's disease, offering a theoretical foundation for early clinical intervention in SCD.

Association of Tooth Loss with Alzheimer's Disease Tau Pathologies Assessed by Positron Emission Tomography.

Deterioration of the oral environment is one of the risk factors for dementia. A previous study of an Alzheimer's disease (AD) model mouse suggests that tooth loss induces denervation of the mesencephalic trigeminal nucleus and neuroinflammation, possibly leading to accelerated tau dissemination from the nearby locus coeruleus (LC). To elucidate the relevance of oral conditions and amyloid-β (Aβ) and tau pathologies in human participants. We examined the number of remaining teeth and the biofilm-gingival interface index in 24 AD-spectrum patients and 19 age-matched healthy controls (HCs). They also underwent positron emission tomography (PET) imaging of Aβ and tau with specific radiotracers, 11C-PiB and 18F-PM-PBB3, respectively. All AD-spectrum patients were Aβ-positive, and all HCs were Aβ-negative. We analyzed the correlation between the oral parameters and radiotracer retention. No differences were found in oral conditions between the AD and HC groups. 11C-PiB retentions did not correlate with the oral indices in either group. In AD-spectrum patients, brain-wide, voxel-based image analysis highlighted several regions, including the LC and associated brainstem substructures, as areas where 18F-PM-PBB3 retentions negatively correlated with the remaining teeth and revealed the correlation of tau deposits in the LC (r = -0.479, p = 0.018) primarily with the hippocampal and neighboring areas. The tau deposition in none of the brain regions was associated with the periodontal status. Our findings with previous preclinical evidence imply that tooth loss may enhance AD tau pathogenesis, promoting tau spreading from LC to the hippocampal formation.

Clinical subtypes in patients with isolated REM sleep behaviour disorder

Patients with Parkinson’s disease (PD) show a broad heterogeneity in clinical presentation, and subtypes may already arise in prodromal disease stages. Isolated REM sleep behaviour disorder (iRBD) is the most specific marker of prodromal PD, but data on clinical subtyping of patients with iRBD remain scarce. Therefore, this study aimed to identify iRBD subtypes. We conducted comprehensive clinical assessments in 66 patients with polysomnography-proven iRBD, including motor and non-motor evaluations, and applied a two-step cluster analysis. Besides, we compared iRBD clusters to matched healthy controls and related the resulting cluster solution to cortical and subcortical grey matter volumes by voxel-based morphometry analysis. We identified two distinct subtypes of patients based on olfactory function, dominant electroencephalography frequency, amount of REM sleep without atonia, depressive symptoms, disease duration, and motor functions. One iRBD cluster (Cluster I, late onset—aggressive) was characterised by higher non-motor symptom burden despite shorter disease duration than the more benign subtype (Cluster II, early onset—benign). Motor functions were comparable between the clusters. Patients from Cluster I were significantly older at iRBD onset and exhibited a widespread reduction of cortical grey matter volume compared to patients from Cluster II. In conclusion, our findings suggest the existence of clinical subtypes already in the prodromal stage of PD. Future longitudinal studies are warranted that replicate these findings and investigate the risk of the more aggressive phenotype for earlier phenoconversion and dementia development.

The role of cognitive estimation in understanding the mental states of others

ABSTRACT Previous studies have emphasized the critical role of the prefrontal cortex in cognitive estimation and theory of mind, however, none of them has questioned the possible role of cognitive estimation processes in understanding the mental states of others. In this study, we compared 30 patients with focal prefrontal cortex damage and 30 control subjects matched by gender, age, and education level on their performances on a cognitive estimation task and two tasks assessing theory of mind: the “Faux-Pas” task and the Reading the Mind in the Eyes task. The results showed that patients were significantly impaired compared with control subjects on both abilities of cognitive estimation and theory of mind. Moreover, regression analyses showed that performance on theory of mind was predicted by the scores on cognitive estimation. Finally, using voxel-based lesion analysis, we identified a partially common bilaterally distributed prefrontal network involved in both these domains centred within the ventral and dorsomedial areas with extension to the dorsolateral prefrontal cortex.

Increased brain iron in patients with thyroid-associated ophthalmopathy: a whole-brain analysis.

To investigate the whole-brain iron deposition alternations in patients with thyroid-associated ophthalmopathy (TAO) using quantitative susceptibility mapping (QSM). Forty-eight patients with TAO and 33 healthy controls (HCs) were enrolled. All participants underwent brain magnetic resonance imaging scans and clinical scale assessments. QSM values were calculated and compared between TAO and HCs groups using a voxel-based analysis. A support vector machine (SVM) analysis was performed to evaluate the performance of QSM values in differentiating patients with TAO from HCs. Compared with HCs, patients with TAO showed significantly increased QSM values in the bilateral caudate nucleus (CN), left thalamus (TH), left cuneus, left precuneus, right insula and right middle frontal gyrus. In TAO group, QSM values in left TH were positively correlated with Hamilton Depression Rating Scale (HDRS) scores (r = 0.414, p = 0.005). The QSM values in right CN were negatively correlated with Montreal Cognitive Assessment (MoCA) scores (r = -0.342, p = 0.021). Besides that, a nearly negative correlation was found between QSM values in left CN and MoCA scores (r = -0.286, p = 0.057). The SVM model showed a good performance in distinguishing patients with TAO from the HCs (area under the curve, 0.958; average accuracy, 90.1%). Patients with TAO had significantly increased iron deposition in brain regions corresponding to known visual, emotional and cognitive deficits. QSM values could serve as potential neuroimaging markers of TAO.

The Association of Incidental Radiation Dose to the Heart Base with Overall Survival and Cardiac Events after Curative-intent Radiotherapy for Non-small Cell Lung Cancer: Results from the NI-HEART Study

AimsCardiac disease is a dose-limiting toxicity in non-small cell lung cancer radiotherapy. The dose to the heart base has been associated with poor survival in multiple institutional and clinical trial datasets using unsupervised, voxel-based analysis. Validation has not been undertaken in a cohort with individual patient delineations of the cardiac base or for the endpoint of cardiac events. The purpose of this study was to assess the association of heart base radiation dose with overall survival and the risk of cardiac events with individual heart base contours. Materials and methodsPatients treated between 2015 and 2020 were reviewed for baseline patient, tumour and cardiac details and both cancer and cardiac outcomes as part of the NI-HEART study. Three cardiologists verified cardiac events including atrial fibrillation, heart failure and acute coronary syndrome. Cardiac substructure delineations were completed using a validated deep learning-based autosegmentation tool and a composite cardiac base structure was generated. Cox and Fine–Gray regressions were undertaken for the risk of death and cardiac events. ResultsOf 478 eligible patients, most received 55 Gy/20 fractions (96%) without chemotherapy (58%), planned with intensity-modulated radiotherapy (71%). Pre-existing cardiovascular morbidity was common (78% two or more risk factors, 46% one or more established disease). The median follow-up was 21.1 months. Dichotomised at the median, a higher heart base Dmax was associated with poorer survival on Kaplan–Meier analysis (20.2 months versus 28.3 months; hazard ratio 1.40, 95% confidence interval 1.14–1.75, P = 0.0017) and statistical significance was retained in multivariate analyses. Furthermore, heart base Dmax was associated with pooled cardiac events in a multivariate analysis (hazard ratio 1.75, 95% confidence interval 1.03–2.97, P = 0.04). ConclusionsHeart base Dmax was associated with the rate of death and cardiac events after adjusting for patient, tumour and cardiovascular factors in the NI-HEART study. This validates the findings from previous unsupervised analytical approaches. The heart base could be considered as a potential sub-organ at risk towards reducing radiation cardiotoxicity.

Assessing Forest Traversability for Autonomous Mobile Systems Using Close-Range Airborne Laser Scanning

Advances in sensor technology and computing performance has brought us into an era of digital forestry where a forest environment can be digitally replicated. At the same time, an increasing interest in the use of unmanned vehicles and other autonomous mobile systems (AMSs) in forest mapping and operations has emerged. However, a forest is an unstructured and rather complex environment for AMSs to operate in, and usually some kind of a priori information of traversability is required. The aim of this study was to assess forest traversability for AMSs using high-density airborne laser scanning (ALS) point clouds. It was assumed that such point clouds acquired from a helicopter flying at a low altitude can be used to characterise vegetation obstacles affecting forest traversability. A voxel-based vegetation occupancy analysis was carried out with the aim to detect open space to define traversable three-dimensional space. The experimental setup included seven sample plots (32×32 m) representing diverse boreal forest structures. Terrestrial laser scanning (TLS) was used for obtaining reference for vegetation occupancy. Comparison between ALS and TLS revealed an overall accuracy of 0.85–0.94 with a recall of 0.78–0.91 and a precision of 0.62–0.74 for ALS-based voxel classification for vegetation occupancy depending on forest structure. This implies that up to 91% of voxels assigned a classification »occupied« based on the TLS could be correctly classified using the ALS, while up to 74% of voxels assigned a classification »occupied« using the ALS were occupied based on the TLS. Density of low vegetation accounted for 83% of the variation in accuracy and precision. The feasibility of vegetation occupancy information to be used by an AMS for navigation was also demonstrated. It was assumed that the ALS data convey as sufficient information of AMS path planning as does the TLS data. The experiments showed that out of 1393 randomly generated paths based on empty space detected by the ALS, 72% were considered feasible when validated with the TLS data. The success rate in path planning varied from 0.54 to 0.92 between the sample plots and was seemingly affected by vegetation density that accounted for 53% of variation in success rate. Altogether, the demonstrated possibility to predefine forest traversability using remote sensing will support the use of AMSs in forestry.

NIMG-45. EXTERNAL EVALUATION OF A MACHINE LEARNING MODEL EMPLOYING RADIOMICS TO IDENTIFY REGIONS OF LOCAL RECURRENCE IN GLIOBLASTOMA FROM POSTOPERATIVE MRI

Abstract The standard surgical goal for operable glioblastomas worldwide is the complete excision of the enhancing tumor. Nevertheless, the peritumoral region harbors infiltrating cells leading to recurrence. Our study aims to evaluate a predictive model designed to predict potential regions of recurrence using voxel-based radiomics analysis on postoperative magnetic resonance imaging (MRI). This retrospective, multi-institutional study involved glioblastoma patients who had undergone complete resection. The training cohort comprised 49 patients from two Spanish institutions, with model evaluation using an external dataset of 27 patients from a Norwegian institution and the public Ivy-Gap dataset. We used follow-up MRI scans for ground truth definition of recurrence, while postoperative multiparametric MRI scans provided the data for extracting voxel-based radiomic features. Our method employed an unsupervised, hybrid approach, which combined a deep neural network and instance optimization, to align the MRI sequences for each patient, registering the follow-up with the postoperative scans. To generate ground truth labels, we segmented the peritumoral region in the postoperative scans, identified as the area showing T2/FLAIR signal alterations, in addition to the enhancing tumor visible in the registered follow-up scan. Overlapping voxels between the peritumoral and enhancing tumor regions were classified as recurrence, while non-overlapping voxels were labeled as nonrecurrence. Radiomic features were subsequently extracted from the postoperative peritumoral region. We trained four machine learning classifiers to predict recurrence. Among these, the Categorical Boosting (CatBoost) classifier demonstrated excellent performance on the test dataset, achieving an average area under the curve (AUC) of 0.83 ± 0.07, and an accuracy of 0.80 ± 0.12, based on voxel-wise comparison with the ground truth. Our study resulted in a method that accurately predicts the area of future tumor recurrence in glioblastoma patients' MRI scans. This innovation could potentially tailor surgical and radiotherapy treatment strategies to these specific areas, possibly extending patient survival.

Brain Abnormalities in Becker Muscular Dystrophy: Evaluation by Voxel-Based DTI and Morphometric Analysis.

Although various neuropsychological problems in Becker muscular dystrophy have attracted attention, there have been few related neuroimaging studies. We investigated brain abnormalities in patients with Becker muscular dystrophy using 3D T1WI and DTI. MR images were obtained for 30 male patients and 30 age-matched healthy male controls. We classified patients into Dp140+ and Dp140- subgroups based on their predicted dystrophin Dp140 isoform expression and performed voxel-based comparisons of gray and white matter volumes and DTI metrics among the patients, patient subgroups, and controls. ROI-based DTI analyses were also performed. Significantly decreased fractional anisotropy was observed in the left planum temporale and right superior parietal lobule compared between the Becker muscular dystrophy and control groups. In the Dp140- subgroup, decreased fractional anisotropy was observed in the left planum temporale, but no significant changes were seen in the Dp140+ subgroup. The ROI-based analysis obtained the same results. No significant differences were evident in the gray or white matter volumes or the DTI metrics other than fractional anisotropy between the groups. A DTI metric analysis is useful to detect white-matter microstructural abnormalities in Becker muscular dystrophy that may be affected by the Dp140 isoform expression.

Abstract 296: Comparison of Prognostic Performance Using Quantitative Analysis of Head Computed Tomography and Apparent Diffusion Coefficient Imaging Before Target Temperature Management in Out-of-Hospital Cardiac Arrest Survivors

Aim: We compared head computed tomography (HCT) and diffusion-weighted magnetic resonance imaging (DW-MRI) findings before target temperature management (TTM) to predict neurological outcomes in out-of-hospital cardiac arrest survivors. Methods: Using prospectively collected data from a TTM registry, we included patients who underwent HCT and DW-MRI within 6 h of return of spontaneous circulation (ROSC). We examined the gray-to-white matter ratio (GWR) on HCT and apparent diffusion coefficient (ADC) values obtained through voxel-based analysis of DW-MRI. We analyzed the mean ADC value and the % voxels of ADC thresholds (percentage of voxels below ADC thresholds per total voxel) at 50-step intervals ranging from 200 to 1200 х 10 -6 mm/s, identifying thresholds that differentiate between good and poor neurological outcomes. Additionally, we analyzed the combination of pupillary light reflex (PLR) and neuron-specific enolase (NSE) values acquired at the same time points to predict the neurological outcomes. The primary outcome measure was the dichotomized cerebral performance category (CPC) at six months, defined as good (CPC 1-2) or poor (CPC 3-5). Results: Of 131 patients (26% female), 74 (57%) had poor outcomes. The time from ROSC to HCT and DW-MRI scans was 1.7h and 3.2h, respectively. The group with a good outcome had higher GWR (1.26 vs. 1.20) and mean ADC (787.10 vs. 697.49) values, but lower values in all ranges (250-1150) of ADC values (all P&lt;0.001). Mean ADC and ADC values in the range of 350-650 demonstrated better predictive performance for poor outcomes than the GWR (P &lt; 0.05). The mean ADC value had the highest sensitivity of 51.3% (95% CI 39.4-63.1; cutoff value ≤ 739.2 х 10 –6 mm 2 /s) when the false positive rate (FPR) was 0%. Furthermore, when combined with PLR and NSE values, the prognostic performance was significantly improved compared to using Mean ADC alone (0.83 vs 0.92; P&lt;0.01). Conclusions: In this cohort study, early voxel-based quantitative ADC analysis after ROSC (i.e., before TTM) was associated with poor neurological outcomes 6 months after cardiac arrest. We found that the Mean ADC value showed the highest sensitivity when the FPR was 0% and that combining the NSE and PLR values resulted in an even better prognostic performance.

An exploratory study of brain temperature and choline abnormalities in temporal lobe epilepsy patients with depressive symptoms.

Epilepsy and depression share neurobiological origins, and evidence suggests a possible bidirectional relationship that remains poorly understood. This exploratory, cross-sectional study aimed to investigate this relationship by employing magnetic resonance spectroscopic imaging (MRSI) and thermometry (MRSI-t) in patients with temporal lobe epilepsy (TLE) with comorbid depressive symptoms and control participants. This is the first study to combine MRSI and MRSI-t to examine brain temperature and choline abnormalities in regions implicated in seizure onset and depression. Twenty-six patients with TLE and 26 controls completed questionnaires and underwent imaging at 3T. Volumetric echo-planar MRSI/MRSI-t data were processed within the Metabolite Imaging and Data Analysis System (MIDAS). Choline (CHO) was quantified as a ratio over creatine (CRE; CHO/CRE). Brain temperature (TCRE ) was calculated based on the chemical shift difference of H2 O relative to CRE's stable location on the ppm spectrum. The Hospital Anxiety and Depression Scale measured anxiety and depressive symptoms. The Chalfont Seizure Severity Scale measured seizure severity in patients with TLE. Two sets of voxelwise independent sample t tests examined group differences in CHO/CRE and TCRE maps. Voxel-based multimodal canonical correlation analysis (mCCA) linked both datasets to investigate if, how, and where CHO/CRE and TCRE abnormalities were correlated in TLE participants and controls. Compared to controls, patients with TLE reported more depressive symptoms (P = 0.04) and showed CHO/CRE and TCRE elevations in left temporal and bilateral frontal regions implicated in seizure onset and depressive disorders (pFWE < 0.05). For the TLE group, CHO/CRE levels in temporal and frontal cortices were associated with elevated TCRE in bilateral frontal and temporal gyri (r = 0.96), and decreased TCRE in bilateral fronto-parietal regions (r = -0.95). Abnormalities in TCRE and CHO/CRE were observed in seizure-producing areas and in regions implicated in depression. These preliminary findings suggest that common metabolic changes may underlie TLE and depression. Our results suggest further investigations into the proposed bidirectional mechanisms underlying this relationship are warranted.

Production of emotions conveyed by voice in Parkinson's disease: Association between variability of fundamental frequency and gray matter volumes of regions involved in emotional prosody.

Parkinson's disease (PD) is associated with impairment in producing emotions conveyed by voice which could depend on motor limitations of the vocal apparatus and/or alterations in emotional processing. This study explores the relationship between the standard deviation of fundamental frequency (F0SD) of emotional speech and the volume of specific gray matter regions. Fifteen PD patients and 15 healthy controls (HC) were asked to produce different emotions vocally elicited by reading short stories. For each vocal track, the F0SD was calculated as index of variability. All subjects underwent a structural magnetic resonance imaging and a voxel-based morphometry analysis. An ad hoc mask of brain regions implicated in emotional prosody was constructed to test the relationship between F0SD and the level of brain atrophy. PD patients showed lower F0SD values than HC in the expression of anger. Neuroimaging results showed brain atrophy in PD patients in a widespread bilateral network, including frontal areas, left cingulate cortex, parietal areas as well as occipital cortices. In the PD group, a positive correlation was observed between F0SD values of anger and volumes of the bilateral supramarginal gyrus, left thalamus, right inferior frontal gyrus, and amygdala. The lower F0SD values observed in PD patients in anger production are consistent with their lower ability to express anger effectively through voice compared to HC. Our data demonstrated the involvement of right-lateralized areas, such as the inferior frontal gyrus and amygdala, which are typically involved in emotional prosody. Disturbances in emotion processing might contribute to speech production deficits in PD, probably in addition to the motor impairment of the articulatory system. (PsycInfo Database Record (c) 2023 APA, all rights reserved).