Left Caudate Research Articles

Mapping individual aspects of bilingual experience to adaptations in brain structure.

Individual differences in using multiple languages are thought to differentially affect brain structure and function. The present study assessed the neuroanatomical predictions of an emerging theory, the Unifying the Bilingual Experience Trajectories framework, which provides the most comprehensive set of predictions of how individual differences in bilingual experiences lead to specific neural and cognitive adaptations. A total of 140 young adults with variable language experiences were scanned using magnetic resonance imaging and completed demographic questionnaires. Brain structure measures implicated in predictions of the Unifying the Bilingual Experience Trajectories model were extracted and regressed against the model's experiential factors. Consistent with the model's predictions, greater intensity and diversity of bilingual language use resulted in changes in gray matter volume in cortical regions involved in executive control (including inferior frontal gyrus, middle temporal gyrus, angular gyrus, and medial frontal gyrus), indicating adaptations toward handling increased executive control demands. Conversely, duration of bilingual engagement resulted in changes within white matter microstructure (bilateral superior longitudinal fasciculus) and increases in subcortical gray matter (left caudate), indicative of adaptations toward increased efficiency of control. Overall, this research enhances our understanding of how bilingual experiences influence brain structure and provides the first direct empirical evidence for the predictions made by the Unifying the Bilingual Experience Trajectories framework.

Bilingual Spatial Cognition: Spatial Cue Use in Bilinguals and Monolinguals.

Structural plasticity changes and functional differences in executive control tasks have been reported in bilinguals compared to monolinguals, supporting a proposed bilingual 'advantage' in executive control functions (e.g., task switching) due to continual usage of control mechanisms that inhibit one of the coexisting languages. However, it remains unknown whether these differences are also apparent in the spatial domain. The present fMRI study explores the use of spatial cues in 15 bilinguals and 14 monolinguals while navigating in an open-field virtual environment. In each trial, participants had to navigate towards a target object that was visible during encoding but hidden in retrieval. An extensive network was activated in bilinguals compared to monolinguals in the encoding and retrieval phase. During encoding, bilinguals activated the right temporal and left parietal regions (object trials) and left inferior frontal, precentral, and lingual regions more than monolinguals. During retrieval, the same contrasts activated the left caudate nucleus and the right dorsolateral prefrontal cortex (DLPFC), the left parahippocampal gyrus, as well as caudate regions. These results suggest that bilinguals may recruit neural networks known to subserve not only executive control processes but also spatial strategies.

Morphometric alterations of the mesocorticolimbic network in Parkinson's disease with impulse control disorders.

Impulse control disorders (ICDs) are a group of non-motor symptoms of Parkinson disease (PD) leading to significant psychosocial detrimental outcome. The mesocorticolimbic network plays a distinctive role in reward learning and executive decision making and has been suggested to be involved in ICDs in PD. To study morphometric changes of the mesocorticolimbic network in PD with ICD. A total of 18 patients of PD with ICD (PD + ICD), 19 patients of PD without ICD (PD - ICD) and 19 healthy controls (HC) were included in the study. ICDs were diagnosed using Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS). MRI was done using a 3T scanner and assessment of cortical thickness and subcortical volumes were done using FreeSurfer. Brain regions known to be part of the mesocorticolimbic network were extracted and included for statistical analysis. There was no difference between PD + ICD and PD - ICD with regard to duration of illness or total dopaminergic medication. In comparison to HC, patients with PD + ICD demonstrated atrophy of the left frontal pole, and this atrophy neared significance in comparison to PD - ICD. The QUIP-RS had a negative correlation with left caudate volume in PD + ICD. The PD + ICD group showed distinct morphometric changes in regions involved in the mesocorticolimbic system which may contribute to the presence of ICD.

Alterations of spontaneous brain activity in type 2 diabetes mellitus without mild cognitive impairment: a resting-state functional magnetic resonance study.

Type 2 diabetes mellitus (T2DM) has been demonstrated an increased risk factor of cognitive impairment or even dementia. Kinds of resting-state functional magnetic resonance imaging indices have been proposed and used to investigate the brain mechanism underlying diabetic cognitive impairment. This study aimed to explore the early changes in spontaneous neural activity among T2DM patients without cognitive impairment by means of multiple rs-fMRI indices. T2DM patients without cognitive impairment and age-, sex-, and education matched control subjects were included in this study. Three rs-fMRI indices, namely amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and voxel-mirrored homotopic connectivity (VMHC) were computed after image pre-processing. The Montreal Cognitive Assessment (MoCA) was performed to distinguish normal cognition. Brain volume was also evaluated. Correlation analyses were conducted to explore any relationship among rs-fMRI indices and clinical characteristics. The T2DM patients were detected significantly decreased neural activity in right angular and left prefrontal gyrus including middle and superior frontal gyrus. Increased activities were also observed in left caudate and the supplementary motor area. No correlation between rs-fMRI indices and clinical characteristics was survived after multiple comparison correction. But we observed a significant, but decreased correlation between ALFF and ReHo values in the reported brain areas. The combination of ALFF, ReHo and VMHC analyses demonstrated abnormal spontaneous neural activity in brain regions which were reported in T2DM patients without cognitive impairment. These results may enhance our understanding of the diabetic brain changes at the early stage.

Reduced Gray Matter Volume and Cortical Thickness in Patients With Small-Fiber Neuropathy

Small-fiber neuropathy (SFN) is defined by degeneration or dysfunction of peripheral sensory nerve endings. Central correlates have been identified on the level of gray matter volume (GMV) and cortical thickness (CT) changes. However, across SFN etiologies knowledge about a common structural brain signature is still lacking. Therefore, we recruited 26 SFN patients and 25 age- and sex-matched healthy controls to conduct voxel-based- and surface-based morphometry. Across all patients, we found reduced GMV in widespread frontal regions, left caudate, insula and superior parietal lobule. Surface-based morphometry analysis revealed reduced CT in the right precentral gyrus of SFN patients. In a region-based approach, patients had reduced GMV in the left caudate. Since pathogenic gain-of-function variants in voltage-gated sodium channels (Nav) have been associated with SFN pathophysiology, we explored brain morphological patterns in a homogenous subsample of patients carrying rare heterozygous missense variants. Whole brain- and region-based approaches revealed GMV reductions in the bilateral caudate for Nav variant carriers. Further research is needed to analyze the specific role of Nav variants for structural brain alterations. Together, we conclude that SFN patients have specific GMV and CT alterations, potentially forming potential new central biomarkers for this condition. Our results might help to better understand underlying or compensatory mechanisms of chronic pain perception in the future. PerspectiveThis study reveals structural brain changes in small-fiber neuropathy (SFN) patients, particularly in frontal regions, caudate, insula, and parietal lobule. Notably, individuals with SFN and specific Nav variants exhibit bilateral caudate abnormalities. These findings may serve as potential central biomarkers for SFN and provide insights into chronic pain perception mechanisms.

Cerebral blood flow in the paracentral lobule is associated with poor subjective sleep quality among patients with a history of methadone maintenance treatment.

Sleep disorders are prevalent and significant among individuals receiving methadone maintenance treatment (MMT), adversely affecting their quality of life and treatment adherence. While cerebral blood flow (CBF) plays a crucial role in the development of various diseases, its relationship with sleep disorders remains uncertain. This observational study focuses on possible correlations between CBF and poor subjective sleep quality in MMT patients. A total of 75 participants with a history of MMT were recruited and assessed using pseudo-continuous arterial spin labeling magnetic resonance imaging to determine CBF. A LAASO regression model was employed to identify the region of interest (ROI) most associated with sleep disturbance. The association between the CBF of the ROI and the Pittsburgh Sleep Quality Index (PSQI) was examined using regression analyses. Age, gender, BMI, history of hypertension, diabetes, hyperlipidemia, and methadone withdrawal were included as covariates. Among MMT patients with poor subjective sleep quality, significantly higher CBF was observed in the right paracentral lobule (56.1057 ± 11.1624 ml/100 g/min, p = 0.044), right cerebelum_3 (56.6723 ± 15.3139 ml/100 g/min, p = 0.026), right caudate nucleus (48.9168 ± 6.9910 ml/100 g/min, p = 0.009), and left caudate nucleus (47.6207 ± 6.1374 ml/100 g/min, p = 0.006). Furthermore, a positive correlation was found between CBF in the right paracentral lobule and the total PSQI score (β = 0.1135, p = 0.0323), with the association remaining significant even after adjustment for covariates (β = 0.1276, p = 0.0405). MMT patients with poor subjective sleep quality exhibited significantly altered CBF in multiple brain regions. The association between increased CBF in the right paracentral lobule and subjective sleep quality in MMT patients could be crucial in understanding sleep disorders in individuals undergoing MMT. https://www.chictr.org.cn/, identifier: ChiCTR2100051931.

Altered Brain Functional and Effective Connectivity Induced by Electroacupuncture in Rats Following Anterior Cruciate Ligament Transection.

The chronic pain arising from knee osteoarthritis (KOA) is a prevalent clinical manifestation. As a traditional Chinese approach, electroacupuncture (EA) has a positive influence in relieving chronic pain from KOA. The study aims to explore functional connectivity (FC) and effective connectivity (EC) alterations induced by EA in anterior cruciate ligament transection (ACLT) rat model of KOA using resting-state functional magnetic resonance imaging (fMRI). After the establishment of ACLT, rats were randomly divided into the EA group and the sham-EA group. The EA group received EA intervention while the sham-EA group received sham-intervention for 3 weeks. Mechanical pain threshold (MPT) assessment was performed before and after intervention, and fMRI was conducted after intervention. EA intervention effectively relieved pain in post-ACLT rats. Results of rest-state functional connectivity (rs-FC) analysis revealed that compared with the sham-EA group, the EA group had higher FC between the right raphe and the left auditory cortex, the left caudate_ putamen and the left internal capsule (IC), as well as the right zona incerta (ZI) and the left piriform cortex, but lower FC between the right raphe and the left hippocampus ventral, as well as the right septum and the left septum. Furthermore, Granger causality analysis (GCA) found the altered EC between the right septum and the left septum, as well as the left IC and the right septum. The results confirmed the effect of EA on analgesia in post- ACLT rats. The alterations of FC and EC, mainly involving basal ganglia and limbic system neural connections, might be one of the neural mechanisms underlying the effect of EA, providing novel information about connectomics plasticity of EA following ACLT.

Comparison of spontaneous brain activity in distinguishing parkinsonian variant of multiple system atrophy from Parkinson's disease at an early stage.

The overlapping clinical manifestations in parkinsonian variant of multiple system atrophy (MSA-P) and Parkinson's Disease (PD) can complicate clinical diagnostic accuracy, particularly in the early stage. The study aims to uncover the patterns of brain function in the initial phase of the two conditions. We recruited 24 MSA-P patients, 34 PD patients and 27 healthy controls (HC). Voxel-wise fractional amplitude of low-frequency fluctuation (fALFF) was compared to characterize regional brain function, followed by seed-based functional connectivity (FC) analysis. Receiver operating characteristic (ROC) analyses were used to examine the diagnostic accuracy of fALFF. Compared to HC, decreased fALFF was observed in the bilateral basal ganglia (BG) of MSA-P patients, while decreased fALFF was identified in the left BG of PD patients. Additionally, elevated fALFF was found in the superior cerebellum for MSA-P patients and the temporo-occipital cortex for PD patients. Furthermore, PD patients exhibited increased FC in the cortico-striatal loop compared to MSA-P patients. The fALFF of the left caudate distinguished MSA-P from HC with an area under the curve (AUC) of 0.838 (p < 0.001) and from PD with an AUC of 0.772 (p < 0.001). The fALFF of the left putamen distinguished PD from HC with an AUC of 0.736 (p = 0.002). Our findings indicated common and distinct abnormalities in spontaneous brain activity within BG, cerebellum, and cortices in early-stage MSA-P and PD patients. PD patients employed more compensatory mechanisms than MSA-P patients. Furthermore, fALFF may aid in early differentiation between MSA-P and PD.

Predicting suicidality in late-life depression by 3D convolutional neural network and cross-sample entropy analysis of resting-state fMRI.

Predicting suicide is a pressing issue among older adults; however, predicting its risk is difficult. Capitalizing on the recent development of machine learning, considerable progress has been made in predicting complex behavior such as suicide. As depression remained the strongest risk for suicide, we aimed to apply deep learning algorithms to identify suicidality in a group with late-life depression (LLD). We enrolled 83 patients with LLD, 35 of which were non-suicidal and 48 were suicidal, including 26 with only suicidal ideation and 22 with past suicide attempts, for resting-state functional magnetic resonance imaging (MRI). Cross-sample entropy (CSE) analysis was conducted to examine the complexity of MRI signals among brain regions. Three-dimensional (3D) convolutional neural networks (CNNs) were used, and the classification accuracy in each brain region was averaged to predict suicidality after sixfold cross-validation. We found brain regions with a mean accuracy above 75% to predict suicidality located mostly in default mode, fronto-parietal, and cingulo-opercular resting-state networks. The models with right amygdala and left caudate provided the most reliable accuracy in all cross-validation folds, indicating their neurobiological importance in late-life suicide. Combining CSE analysis and the 3D CNN, several brain regions were found to be associated with suicidality.

Grey matter structural alterations in anxiety disorders: a voxel-based meta-analysis.

Anxiety disorders (ADs) are a group of prevalent and destructive mental illnesses, but the current understanding of their underlying neuropathology is still unclear. Employing voxel-based morphometry (VBM), previous studies have demonstrated several common brain regions showing grey matter volume (GMV) abnormalities. However, contradictory results have been reported among these studies. Considering that different subtypes of ADs exhibit common core symptoms despite different diagnostic criteria, and previous meta-analyses have found common core GMV-altered brain regions in ADs, the present research aimed to combine the results of individual studies to identify common GMV abnormalities in ADs. Therefore, we first performed a systematic search in PubMed, Embase, and Web of Science on studies investigating GMV differences between patients with ADs and healthy controls (HCs). Then, the anisotropic effect-size signed differential mapping (AES-SDM) was applied in this meta-analysis.A total of 24 studies (including 25 data sets) were included in the current study, and 906 patients with ADs and 1003 HCs were included. Compared with the HCs, the patients with ADs showed increased GMV in the left superior parietal gyrus, right angular gyrus, left precentral gyrus, and right lingual gyrus, and decreased GMV in the bilateral insula, bilateral thalamus, left caudate, and right putamen. In conclusion,the current study has identified some abnormal GMV brain regions that are related to the pathological mechanisms of anxiety disorders. These findings could contribute to a better understanding of the underlying neuropathology of ADs.

Immune-related visual dysfunction in thyroid eye disease: a combined orbital and brain neuroimaging study.

To investigate the pathological interplay between immunity and the visual processing system (VPS) in thyroid eye disease (TED). A total of 24 active patients (AP), 26 inactive patients (IP) of TED, and 27 healthy controls (HCs) were enrolled. Orbital magnetic resonance imaging (MRI) and resting-state functional MRI (rs-fMRI) were conducted for each participant. Multiple MRI parameters of the intraorbital optic nerve (ON) were assessed. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were calculated. Correlation analyses were carried out on the above parameters and clinical characteristics. Visual functioning scores differentiated between the AP and IP groups. The ON subarachnoid space and ON sheath diameter were significantly higher in AP than in IP. Six vision-related brain regions were identified in TED patients compared with HCs, including right calcarine (CAL.R), right cuneus (CUN.R), left postcentral gyrus (PoCG.L), right middle temporal gyrus (MTG.R), left superior frontal gyrus (SFG.L), and left caudate (CAU.L). The brain activity of MTG.R, SFG.L, and CAU.L differentiated between the AP and IP groups. The correlation analysis revealed a close association among the vision-related brain regions, MRI parameters of ON, and clinical characteristics in AP and IP, respectively. Combined orbital and brain neuroimaging revealed abnormalities of the VPS in TED, which had a close correlation with immune statuses. Vision-related brain regions in TED might be possibly altered by peripheral immunity via a direct or indirect approach. The discovery of this study explained the disparity of visual dysfunction in TED patients with different immune statuses. With the uncovered neuroimaging markers, early detection and intervention of visual dysfunction could be achieved and potentially benefit TED patients. • Patients with different immune statuses of thyroid eye disease varied in the presentation of visual dysfunction. • The combined orbital and brain neuroimaging study identified six altered vision-related brain regions, which had a significant correlation with the MRI parameters of the intraorbital optic nerve and immunological characteristics. • Peripheral immunity might possibly give rise to alterations in the central nervous system part of the visual processing system via a direct or indirect approach.

Abnormal functional connectivity of the reward network is associated with social communication impairments in autism spectrum disorder: A large-scale multi-site resting-state fMRI study

BackgroundThe social motivation hypothesis proposes that the social deficits of autism spectrum disorder (ASD) are related to reward system dysfunction. However, functional connectivity (FC) patterns of the reward network in ASD have not been systematically explored yet. MethodsThe reward network was defined as eight regions of interest (ROIs) per hemisphere, including the nucleus accumbens (NAc), caudate, putamen, anterior cingulate cortex (ACC), ventromedial prefrontal cortex (vmPFC), orbitofrontal cortex (OFC), amygdala, and insula. We computed both the ROI-wise resting-state FC and seed-based whole-brain FC in 298 ASD participants and 348 typically developing (TD) controls from the Autism Brain Imaging Data Exchange I dataset. Two-sample t-tests were applied to obtain the aberrant FCs. Then, the association between aberrant FCs and clinical symptoms was assessed with Pearson's correlation or Spearman's correlation. In addition, Neurosynth Image Decoder was used to generate word clouds verifying the cognitive functions of the aberrant pathways. Furthermore, a three-way multivariate analysis of variance (MANOVA) was conducted to examine the effects of gender, subtype and age on the atypical FCs. ResultsFor the within network analysis, the left ACC showed weaker FCs with both the right amygdala and left NAc in ASD compared with TD, which were negatively correlated with the Autism Diagnostic Observation Schedule (ADOS) total scores and Social Responsiveness Scale (SRS) total scores respectively. For the whole-brain analysis, weaker FC (i.e., FC between the left vmPFC and left calcarine gyrus, and between the right vmPFC and left precuneus) accompanied by stronger FC (i.e., FC between the left caudate and right insula) were exhibited in ASD relative to TD, which were positively associated with the SRS motivation scores. Additionally, we detected the main effect of age on FC between the left vmPFC and left calcarine gyrus, of subtype on FC between the right vmPFC and left precuneus, of age and age-by-gender interaction on FC between the left caudate and right insula. ConclusionsOur findings highlight the crucial role of abnormal FC patterns of the reward network in the core social deficits of ASD, which have the potential to reveal new biomarkers for ASD.

Neurobiological basis of reinforcement-based decision making in adults with ADHD treated with lisdexamfetamine dimesylate: Preliminary findings and implications for mechanisms influencing clinical improvement

BackgroundADHD is often described as a disorder of altered reward sensitivity, yet few studies have examined the extent to which: (i) treatments for ADHD impact reward-related mechanisms; and (ii) changes in the reward system are associated with clinical improvement. This study addresses these issues - examining the extent to which clinical improvement following lisdexamfetamine (LDX) treatment is associated with changes in brain reward system activation. MethodsTwenty adults (M = 11, 55%, F = 9, 45%), ages 19–52 (M = 33.9, SD = 10.0) with ADHD participated in a randomized cross-over study with lisdexamfetamine (LDX) and placebo (PB). Changes in brain activation were assessed during functional magnetic resonance (fMRI) scans: after receiving 3–5 weeks of treatment with LDX and 3–5 weeks of no drug/PB. fMRI contrasts were derived from the passive-avoidance (PA) learning task, which assessed reward-related learning using computational variables. We analyzed the following conditions: the Choice-Phase, modulated by the expected value (EV; i.e., object-choose and object-reject), and the Feedback-Phase, modulated by the prediction error (PE; i.e., reward and punish). Clinical symptom severity was assessed via interview with the ADHD-Rating Scale (ADHD-RS-IV). To address the primary objective, we performed group-level mass-univariate regression analyses between LDX and PB of percent change of the ADHD-RS total scores and the four contrast images under the Choice- and Feedback-conditions. Significance was set at a whole-brain voxel-wise threshold of p < 0.05 with family-wise error (FWE) correction and an extent (cluster) threshold of 50 contiguous voxels. ResultsImprovement in ADHD symptoms with LDX was accompanied by significantly increased activation in a series of brain regions previously implicated in reinforcement processing in the choice and feedback conditions (e.g., left caudate and putamen, right orbitofrontal cortex, left middle frontal, superior frontal, and precentral gyri). ConclusionsThese findings, while preliminary, are the first to show that ADHD symptom improvement with stimulant treatment is associated with increased responsiveness of brain systems engaged in reward processing. Results support the hypothesis that LDX treatment may restore balance to dysfunction (e.g., hypoactivation) within the brain reward circuitry in adults with ADHD.Trial RegistrationClinicaltrials.gov Identifier: NCT01924429.

Assessment of quantitative susceptibility mapping (QSM) and oxygen extraction fraction (OEF) in the spectrum of Alzheimer’s disease clinical presentations

AbstractBackgroundDifferent methods have been proposed to assess vascular dysfunction in Alzheimer’s disease (AD), mild cognitive impairment (MCI), and cognitively unimpaired (CU) subjects including quantitative susceptibility mapping (QSM), and recently oxygen extraction fraction (OEF). QSM is sensitive to the presence of iron and is a non‐invasive MR approach to measure local tissue susceptibility with high spatial resolution. OEF is a measure of the percentage of oxygen taken from the brain’s blood supply and relates directly to brain oxygen metabolism. Here, we aimed to examine QSM (Figure1) and OEF (Figure1) potential in differentiating AD, MCI, and CU.MethodA cohort of 310 subjects with AD (n = 48), MCI (n = 80), and CU (n = 182) were recruited. All the patients received 3D gradient‐recalled echo sequence MRI. All QSM images were constructed by MEDI+0 and OEF images were constructed by QSM+qBOLD model with CCTV (Temporal clustering, tissue composition, and total variation). Eighty‐two various brain regions of interest (ROI) and 6 Braak ROI were investigated in the current study. ANOVA and Posthoc least significant difference (LSD) tests were implemented for each ROI over AD, MCI, and CU.ResultOver Braak ROI analysis, the ANOVA test showed that the average susceptibility of QSM with Braak 4 ROI is significantly different (p&lt;0.001). LSD test showed that Braak 4 ROI of QSM is significantly different between AD vs. MCI and AD vs. CU (p&lt;0.001). Braak 2 ROI of OEF was significantly different between AD vs. MCI and AD vs. CU (p = 0.21 and p = 0.32, respectively). Over brain ROI, the ANOVA test showed QSM right and left posterior cingulate and right Caudate were significantly different (p&lt;0.001). Besides, these ROIs were significantly different between AD vs. MCI and AD vs. CU, according to the LSD test. Over brain ROI, OEF right Caudate was significantly different (p&lt;0.001) followed by left Caudate and Right transverse temporal with p = 0.002 based on the ANOVA test. However, right and left Caudate were just significantly different between AD vs. CU (p&lt;0.001) based on the LSD test (Table 1 and 2).ConclusionQSM and OEF are affordable non‐invasive MR approaches to assess vascular dysfunction in the spectrum of clinical presentations of AD.

Early‐life bilingualism could protect from age‐related gray matter volume loss in the left caudate – preliminary results

AbstractBackgroundEarly‐life bilingualism (i.e., second language acquisition before the age of 30) has been shown to confer benefits in separate cognitive domains later in life, possibly contributing to the concept of cognitive reserve. However, the effects of early‐life bilingualism on cognitive performance and gray matter volume (GMV) in the elderly have been studied scarcely. In an ongoing cohort, we examined the influence of early‐life bilingualism on cognitive performance (e.g., phonemic fluency as tested by the Regensburg word fluency test (RWT), among others) as well as age‐related brain gray matter volume in older adults.MethodWe analysed 3‐Tesla T1‐weighted Multi‐Echo MPRAGE and cognitive data from 25 healthy adults (72.8±7.69 years, 10 female) in our new cohort established within the CRC1436 (https://sfb1436.de/). Assessment of bilingualism was conducted using the Lifetime of Experiences Questionnaire (LEQ). MRI data were preprocessed and analysed using FSL‐VBM. We performed a whole‐brain analysis looking for an interaction between age and bilingualism on GMV values, postulating that early bilingualism might contribute to a preservation of gray matter along the age trajectory. We extracted GMV values from significant regions of interest (ROIs) and looked for correlations with cognitive performance. Due to the small cohort and the preliminary nature of these analyses, we chose an exploratory threshold of p&lt;0.001 (uncorrected) for the whole brain analysis. ROIs were defined by a threshold of p&lt;0.1 cluster‐corrected (z&gt;3.1).ResultParticipants with early‐life bilingualism (n = 7) had significantly more years of education (p&lt;0.05) and performed better in the RWT (p&lt;0.05) than monolinguals (n = 18). The age‐bilingualism interaction term across the whole brain (adjusted for education) identified the head of left caudate nucleus as being protected from age‐related GMV loss by early‐life bilingualism (Fig. 1). The age‐GMV‐relationship for both groups is shown in Fig. 2. We observed no significant relationship between GMV in the left caudate and performance in any cognitive tests.ConclusionThese preliminary results hint at a role of early‐life bilingualism in modulating GMV in older adults. How these relate to better cognitive performance remains to be elucidated. Moreover, considering brain areas not typically studied in cognitive aging, such as the basal ganglia, seems worthwhile.

FC21: Loose functional connectivity within the striatum in behavioral variant frontotemporal dementia

Objective:Previous studies have reported that the structure and function of the striatum are important in bvFTD, and the striatum can be divided into more subregions. Changes within brain regions has recently attracted increasing attention, but most studies have explored the relationship between the striatum and other brain regions. Therefore, the aim of this study was to explore the changes in the intra-striatal resting-state functional connectivity (RSFC).Methods:We acquired fMRI data from 26 bvFTD patients and 36 healthy controls. The Human Brainnetome Atlas was used to define the spatial extent of the striatum and delineate its subregions. Intra- and extra-striatal FC values were then calculated for each individual and compared between bvFTD and control groups.Results:Compared to healthy controls, bvFTD showed decreased intra-striatal FC. Both intra-hemispheric and inter-hemispheric functional connectivity were compromised. There was also a gradient reduction in terms of the functional connectivity within striatum: the left dorsolateral putamen showed most decrease and the left ventral caudate exhibited the least (Fig 1). The extra-striatal FC between striatum and the insula was also decreased.Conclusion:The loose intra-striatal functional connectivity may underly the neural substrate of bvFTD.

P23: Suicide Prediction in late-life depression by Machine learning and Complexity analysis in resting-state functional MRI data

Objective:Late-life suicide is the most serious consequences of late-life depression (LLD). Nevertheless, suicidal behavior is complex and hard to predict. With the help of MRI scans and machine learning algorithm, we aim to examine the neural signatures of suicidality in patients of LLD.Methods:We recruited 83 patients of LLD with a mean age of 68.8 years, where 48 were suicidal (26 with suicidal ideation and 22 with past suicide attempts). Cross-sample entropy (CSE) analysis was employed to analyze the resting-state function MRI data. Three-dimensional CSE volume in 90 region-of-interest of the brain in each participant was input into convolutional neural networks (CNN) to test the classification accuracy of suicidality.Results:After six-fold cross-validation, we found several regions in the default mode, fronto-parietal, and cingulo-opercular resting-state networks to have a mean accuracy above 75% to predict suicidality. Moreover, the models with right amygdala and left caudate provided the most reliable accuracy in all cross-validation folds, signifying their unique roles in late-life suicide.Conclusion:Our results provide potential targets for intervention or biomarkers in late-life suicide. More research must be conducted to consolidate our results with scalable implementation in clinical setting.

Cortical and subcortical structural differences in psychostimulant-free ADHD youth with and without a family history of bipolar I disorder: a cross-sectional morphometric comparison

Although attention-deficit/hyperactivity disorder (ADHD) and a family history of bipolar I disorder (BD) are associated with increased risk for developing BD, their neuroanatomical substrates remain poorly understood. This study compared cortical and subcortical gray matter morphology in psychostimulant-free ADHD youth with and without a first-degree relative with BD and typically developing healthy controls. ADHD youth (ages 10-18 years) with (‘high-risk’, HR) or without (‘low-risk’, LR) a first-degree relative with BD and healthy comparison youth (HC) were enrolled. High-resolution 3D T1-weighted images were acquired using a Philips 3.0 T MR scanner. The FreeSurfer image analysis suite was used to measure cortical thickness, surface area, and subcortical volumes. A general linear model evaluated group differences in MRI features with age and sex as covariates, and exploratory correlational analyses evaluated associations with symptom ratings. A total of n = 142 youth (mean age: 14.16 ± 2.54 years, 35.9% female) were included in the analysis (HC, n = 48; LR, n = 49; HR, n = 45). The HR group exhibited a more severe symptom profile, including higher mania and dysregulation scores, compared to the LR group. For subcortical volumes, the HR group exhibited smaller bilateral thalamic, hippocampal, and left caudate nucleus volumes compared to both LR and HC, and smaller right caudate nucleus compared with LR. No differences were found between LR and HC groups. For cortical surface area, the HR group exhibited lower parietal and temporal surface area compared with HC and LR, and lower orbitofrontal and superior frontal surface area compared to LR. The HR group exhibited lower left anterior cingulate surface area compared with HC. LR participants exhibited greater right pars opercularis surface area compared with the HC. Some cortical alterations correlated with symptom severity ratings. These findings suggest that ADHD in youth with a BD family history is associated with a more a severe symptom profile and a neuroanatomical phenotype that distinguishes it from ADHD without a BD family history.

Changes in iron load in specific brain areas lead to neurodegenerative diseases of the central nervous system

The causes of neurodegenerative diseases remain largely elusive, increasing their personal and societal impacts. To reveal the causal effects of iron load on Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis and multiple sclerosis, we used Mendelian randomisation and brain imaging data from a UK Biobank genome-wide association study of 39,691 brain imaging samples (predominantly of European origin). Using susceptibility-weighted images, which reflect iron load, we analysed genetically significant brain regions. Inverse variance weighting was used as the main estimate, while MR Egger and weighted median were used to detect heterogeneity and pleiotropy. Nine clear associations were obtained. For AD and PD, an increased iron load was causative: the right pallidum for AD and the right caudate, left caudate and right accumbens for PD. However, a reduced iron load was identified in the right and left caudate for multiple sclerosis, the bilateral hippocampus for mixed vascular dementia and the left thalamus and bilateral accumbens for subcortical vascular dementia. Thus, changes in iron load in different brain regions have causal effects on neurodegenerative diseases. Our results are crucial for understanding the pathogenesis and investigating the treatment of these diseases.

Hyperconnecitivity between dorsal attention and frontoparietal networks predicts treatment response in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) presented with repetitive obsessions and/or compulsions were associated with disrupted resting-state functional connectivity (rs-FC). To investigate the pharmacological treatment effect on rs-FC changes in OCD patients we conducted the seed-to-voxel FC analyses using dorsal attention network (DAN), default mode network (DMN), salience network (SN) and frontoparietal network (FPN) and basal ganglia seeds. Twenty-two healthy subjects and twenty-four unmedicated OCD patients underwent resting-state functional magnetic resonance imaging. Patients were rescanned after 12 weeks of escitalopram treatment. We found increased FC both within the DAN and between the DAN and the FPN which was ameliorated after medication and correlated significantly with the clinical improvement in obsession scores. We also observed an anticorrelation between the left caudate and the supplementary motor area in unmedicated OCD patients which also normalized with treatment. Results further showed treatment related normalization of orbitofrontal cortex hyperconnectivity with DMN and hypoconnectivity with DAN whereas aberrant FC between the SN and visual areas appears to be a medication effect. We suggest that DAN to FPN hyperconnectivity which is positively correlated with clinical improvement in obsession scores at pre-treatment stage in present study has a potential for being a neuroimaging marker to predict the treatment response in OCD.