Left Cingulum Research Articles

White matter tract-specific alterations in patients with primary restless legs syndrome

Prior diffusion tensor imaging (DTI) studies have investigated white matter (WM) changes in patients with primary restless legs syndrome (RLS), but the results were inconsistent. Here, we proposed using tract-specific statistical analysis (TSSA) to find alterations in specific WM tracts to clarify the pathophysiological mechanisms of RLS. We enrolled 30 patients with RLS and 31 age- and sex- matched controls who underwent brain magnetic resonance imaging, neuropsychological tests, and polysomnography. Fractional anisotropy (FA) maps obtained from whole-brain diffusion tensor imaging and TSSA were used to localize WM changes in patients with RLS. Subsequently, a comparison of FA values for each tract between patients and controls was performed. The associations between FA values and clinical, polysomnographic, and neuropsychological parameters in RLS patients were assessed. RLS patients demonstrated decreased FA values in the left corticospinal tract (CST) and cingulum, and in the right anterior thalamic radiation (ATR) and inferior fronto-occipital fasciculus (IFO). Patients’ attention/executive function and visual memory scores positively correlated with FA values in the right ATR, and anxiety levels negatively correlated with FA values in the right IFO. Additionally, the number of periodic leg movements and movement arousal index were negatively correlated with FA values in the left CST. The TSSA method identified previously unknown tract-specific alterations in patients with RLS and significant associations with distinct clinical manifestations of RLS.

Cortical disconnection in temporal lobe epilepsy

A critical concept in neurology is cortical disconnection, in which seemingly normal gray matter can have reduced function due to loss of white matter (WM) connections. White matter damage has been extensively described in temporal lobe epilepsy (TLE), but the anatomical distribution of cortical disconnection in TLE is not fully characterized. Here, we studied 221 participants (64 left-TLE, 55 right-TLE, 102 controls) from three different epilepsy treatment centers. We employed a group connectometry diffusion imaging tractography approach to identify WM fibers with reduced integrity in TLE. We then assessed the anatomical distribution of the gray matter endpoint projections of abnormal fibers to map the anatomical pattern of disconnections. As expected, left- and right-TLE were associated with multiple WM pathways with reduced integrity, which were associated with extensive cortical disconnection involving predominantly limbic structures. Controlling for medial temporal gray matter atrophy, cortical disconnection of the left cingulum and the thalamus as well as disconnection of the bilateral putamen and the amygdala was associated with lower verbal memory immediate recall.In conclusion, our results support that cortical disconnection is an underappreciated but pervasive phenomenon in TLE, and cortical disconnection of limbic structures beyond the medial temporal regions is related to verbal memory performance.

White Matter Hyperintensities of Bilateral Lenticular Putamen in Patients with Proliferative Diabetic Retinopathy: A Voxel-based Morphometric Study.

ObjectiveTo explore the changes in gray matter volume (GMV) and white matter volume (WMV) in proliferative diabetic retinopathy (PDR) patients using voxel-based morphometry (VBM).Participants and MethodsIn total, 15 patients (10 males, 5 females) with PDR were enrolled to the patient group and 15 healthy controls (10 males, 5 females) to the control group, matched for age, sex, handedness, and education status. All individuals underwent voxel-based morphometry scans. GMV and WMV were compared between the two groups.ResultsGMV in bilateral superior temporal gyrus, sixth area of left cerebellum, left middle temporal gyrus, left orbital inferior frontal gyrus and left middle cingulum gyrus and WMV in left thalamus and left precuneus were significantly lower in patients than controls (P<0.01). Conversely, WMV was significantly higher in bilateral lenticular putamen of patients than controls (P<0.01).ConclusionAbnormal GMV and WMV in many specific areas of the cerebrum provide new insights for exploration of the occurrence and development of DR and its pathophysiology.

Long-term sequelae of herpes simplex virus encephalitis-related white matter injury: correlation of neuropsychological outcome and diffusion tensor imaging.

The pathophysiology of the memory impairment following Herpes Simplex virus encephalitis is not yet established and understood. This study attempts to elucidate the role of white matter injury and its impact on neuropsychological outcome in patients with history of Herpes Simplex virus encephalitis. This is a single-institution prospective study assessing 9 patients and 15 matched controls utilizing a combination of MRI with diffusion tensor imaging and neuropsychological testing. Tract-based spatial statistics analysis was performed and correlated with neuropsychological outcomes. Significantly decreased fractional anisotropy (FA) values were noted in corpus callosum, corona radiata, left posterior thalamic radiation, cingulum, superior longitudinal fasciculus, fornix, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and uncinated fasciculus. Impaired facial recognition significantly correlated with reduction in FA of right uncinate fasciculus, right inferior longitudinal fasciculus, and splenium genu of corpus callosum. FA value of left cingulum significantly correlated with logical memory, auditory verbal learning. FA value of fornix correlated with visual recognition; FA value of left uncinate fasciculus with auditory verbal learning and delayed recall. In conclusion, this study demonstrates microstructural abnormalities involving several white matter tracts corresponding to neuropsychological deficits.

Investigation of endophenotype potential of decreased fractional anisotropy in pediatric bipolar disorder patients and unrelated offspring of bipolar disorder patients.

Bipolar disorder (BD) is a severe psychiatric disorder associated with structural and functional brain abnormalities, some of which have been found in unaffected relatives as well. In this study, we examined the potential role of decreased fractional anisotropy (FA) as a BD endophenotype, in adolescents at high risk for BD. We included 15 offspring of patients with BD, 16 pediatric BD patients, and 16 matched controls. Diffusion weighted scans were obtained on a 3T scanner using an echo-planar sequence. Scans were segmented using FreeSurfer. Our results showed significantly decreased FA in six brain areas of offspring group; left superior temporal gyrus (LSTG; P<.0001), left transverse temporal gyrus (LTTG; P=.002), left banks of the superior temporal sulcus (LBSTS; P=.002), left anterior cingulum (LAC; P=.003), right temporal pole (RTP; P=.004) and left frontal pole (LFP; P=.017). On analysis, LSTG, LAC, and RTP demonstrated a potential to be an endophenotype when comparing all three groups. FA values in three regions, LBSTS, LTTG, and LFP were increased only in controls. Our findings point at decreased FA as a possible endophenotype for BD, as they were found in children of patients with BD. Most of these areas were previously found to have morphological and functional changes in adult and pediatric BD, and are thought to play important roles in affected domains of functioning. Prospective follow up studies should be performed to detect reliability of decreased FA as an endophenotype and effects of treatment on FA.

White matter abnormalities associated with ADHD outcomes in adulthood.

It remains unclear if previously reported structural abnormalities in children with ADHD are present in adulthood regardless of clinical outcome. In this study, we examined the extent to which focal-rather than diffuse-abnormalities in fiber collinearity of 18 major white matter tracts could distinguish 126 adults with rigorously diagnosed childhood ADHD (ADHD; mean age [SD] = 34.3 [3.6] years; F/M = 12/114) from 58 adults without ADHD histories (non-ADHD; mean age [SD] = 33.9 [4.1] years; F/M = 5/53) and if any of these abnormalities were greater for those with persisting ADHD symptomatology. To this end, a tract profile approach was used. After accounting for age, sex, handedness, and comorbidities, a MANCOVA revealed a main effect of group (ADHD < non-ADHD; F[18,155] = 2.1; p = 0.007) on fractional anisotropy (FA, a measure of fiber collinearity and/or integrity), in focal portions of white matter tracts involved in visuospatial processing and memory (i.e., anterior portion of the left inferior longitudinal fasciculus, and middle portion of the left and right cingulum angular bundle). Only abnormalities in the anterior portion of the left inferior longitudinal fasciculus distinguished probands with persisting versus desisting ADHD symptomatology, suggesting that abnormalities in the cingulum angular bundle might reflect "scarring" effects of childhood ADHD. To our knowledge, this is the first study using a tract profile approach to identify focal or widespread structural abnormalities in adults with ADHD rigorously diagnosed in childhood.

Acute conceptual disorganization in untreated first-episode psychosis: a combined magnetic resonance spectroscopy and diffusion imaging study of the cingulum

Background:Disorganized thinking is a core feature of acute psychotic episodes that is linked to social and vocational functioning. Several lines of evidence implicate disrupted cognitive control, excitatory overdrive and oxidative stress relating to the anterior cingulate cortex as mechanisms of conceptual disorganization (CD). We examined 3 candidate mechanistic markers related to CD in first-episode psychosis: glutamate excess, cortical antioxidant (glutathione) status and the integrity of the cingulum bundle that connects regions implicated in cognitive control.Methods:We used fractional anisotropy maps from 7 T diffusion-weighted imaging to investigate the bilateral cingulum based on a probabilistic white matter atlas. We compared high CD, low CD and healthy control groups and performed probabilistic fibre tracking from the identified clusters (regions of interest within the cingulum) to the rest of the brain. We quantified glutamate and glutathione using magnetic resonance spectroscopy (MRS) in the dorsal anterior cingulate cortex.Results:We found a significant fractional anisotropy reduction in a cluster in the left cingulum in the high CD group compared to the low CD group (Cohen’s d = 1.39; p < 0.001) and controls (Cohen’s d = 0.86; p = 0.009). Glutamate levels did not vary among groups, but glutathione levels were higher in the high CD group than in the low CD group. We also found higher glutathione related to lower fractional anisotropy in the cingulum cluster in the high CD group.Limitations:The MRS measures of glutamine were highly uncertain, and MRS was acquired from a single voxel only.Conclusion:Acute CD relates to indicators of oxidative stress, as well as reduced white matter integrity of the cingulum, but not to MRI-based glutamatergic excess. We propose that both oxidative imbalance and structural dysconnectivity underlie acute disorganization.

Correlation between DTI effect and white matter structural integrity, working memory in leukoaraiosis patients

Our objective was to study the correlation between Diffusion tensor MR imaging (DTI) effect and white matter structural integrity, working memory in leukoaraiosis patients. 100 leukoaraiosis patients referring to the First Affiliated Hospital of Beijing Medical University from December 2018 to December 2019, were selected as study subjects and divided into four groups according to disease severity: lesion-free group, mild lesion group, moderate lesion group, and severe lesion group. All patients underwent magnetic resonance diffusion tensor imaging to collect DWI images and analyze Fractional anisotropy (FA), mean diffusivity (MD), ReHo values of white matter area under different grading. The patients’ working memory was tested via auditory verb learning test and Stroop color word test, so that correlation between white matter structural integrity and working memory can be analyzed. Results: There are statistically significant differences in FA values of the right posterior thalamic radiation, the right sagittal layer and the right superior longitudinal fasciculus, MD values of the right sagittal layer, the right cingulum bundle, the left cingulum bundle, the right inferior fasciculus fronto-occipitalis and the left inferior fasciculus frontooccipitalis, as well as instant recall, delayed recall, delayed recognition, card A (dot), card B (character), card C (color word) and SIE value (P&lt;0.01). Correlation is shown between white matter structural integrity and working memory, gender, age, grading, disease course, recurrence interval, white matter area, and testing methods. There was a correlation between DTI effect and white matter structural integrity, working memory in leukoaraiosis patients, and leukoaraiosis patients have memory impairment.

Lateralization effects in brain white matter reorganization in patients with unilateral idiopathic tinnitus: a preliminary study.

Idiopathic tinnitus can cause significant auditory-related brain structural and functional changes in patients. However, changes in patterns of the lateralization effects in idiopathic tinnitus have yet to be established, especially on white matter (WM) reorganization. In this study, we studied 19 left-sided and 19 right-sided idiopathic tinnitus (LSIT, RSIT) patients and 19 healthy controls (HCs). We combined applied voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analyses to investigate altered features of the auditory-related brain WM. We also conducted correlation analyses between the clinical variables and WM changes in the patients. Compared with the HCs, both sided tinnitus patients showed significant auditory-related brain WM alterations. More interestingly, the LSIT patients demonstrated a greater decrease in white matter volume (WMV) in the right medial superior frontal gyrus (SFG) than the RSIT; meanwhile, we also found that compared with the RSIT group, the LSIT group showed significantly increased fractional anisotropy (FA) in the body of the corpus callosum (CC), left cingulum, and right superior longitudinal fasciculus (SLF) and decreased mean diffusivity (MD) in the body of CC. Moreover, relative to the RSIT group, the LSIT group also exhibited increases in WM axial diffusivity (AD) in the left SLF, left cingulum, right middle cerebellar peduncle (MCP), left thalamus, and bilateral forceps major (FM) and decreases in radial diffusivity (RD) in the genu of CC. Additionally, the FA value of the right SLF was closely associated with tinnitus severity in the LSIT. Our study suggests that lateralization has a significant effect on WM reorganization in patients with idiopathic tinnitus; in particular, LSIT patients may experience more severe and widespread alterations in WMV and WM microstructure than the RSIT group, and all these changes are indirectly auditory related. These findings provide new useful information that can lead to a better understanding of the tinnitus mechanisms.

Application of diffusion tensor imaging in Alzheimer\u2019s disease: quantification of white matter microstructural changes

BackgroundAlzheimer’s disease (AD) is the most common cause of dementia in the aging population, responsible for 60–70% of all demented cases. Diffusion tensor imaging (DTI) is a very recent technique that allows the mapping of white matter (WM) microstructure changes in neurological disorders. The current study was conducted to compare DTI parameters between AD patients and healthy elderly subjects and to determine whether DTI can act as a potential biomarker for AD.ResultsThere were significant differences in Modified Mini-Mental State Examination (MMMSE) and Clinical Dementia Rating (CDR) between the two groups. As regards the DTI parameters, significant differences were found between AD patients versus healthy subjects, in the mean diffusivity (MD) of the splenium [(1.05 ± 0.19) vs. (0.92 ± 0.22) , P=0.03], the MD of the right uncinate fasciculus [(0.92 ± 0.04) vs. (0.87 ± 0.05), P= 0.01], and MD of the right arcuate fasciculus (AF) [(0.83 ± 0.04) vs. (0.79 ± 0.04) P =0.01], as well as the MD of the right and left inferior fronto-occipital fasiculus (IFOF) [(0.89 ± 0.06) vs. (0.83 ± 0.04), P=0.01]. In addition, there were significant differences in the fractional anisotropy (FA) of the right and left cingulum between both groups [(0.45 ± 0.02) vs. (0.47 ± 0.03), P=0.01 and (0.45 ± 0.03) vs. 0.49± 0.04), P=0.01, respectively]. The overall accuracy of the aforementioned parameters ranged between 73 and 81% with the MD of the left cingulum revealing the highest accuracy.ConclusionDTI proofed to be a useful tool in differentiating AD patients from healthy subjects. In our study, we found that the splenium, cingulum, IFOF, and the right UF and right AF are the main tracts involved in AD. The left cingulum provided the highest accuracy in differentiating AD from normal subjects.

White Matter Correlates of Theory of Mind in Patients With First-Episode Psychosis.

Deficits in theory of mind (ToM) are considered as a distinctive feature of schizophrenia. Functional magnetic resonance imaging (fMRI) studies have suggested that aberrant activity among the regions comprising the mentalizing network is related to observed ToM deficits. However, the white matter structures underlying the ToM functional network in schizophrenia remain unclear. To investigate the relationship between white matter integrity and ToM impairment, 35 patients with first-episode psychosis (FEP) and 29 matched healthy controls (HCs) underwent diffusion tensor imaging (DTI). Using tract-based spatial statistics (TBSS), fractional anisotropy (FA) values of the two regions of interest (ROI)–the cingulum and superior longitudinal fasciculus (SLF)–were acquired, and correlational analysis with ToM task scores was performed. Among the patients with FEP, ToM strange story scores were positively correlated with the FA values of the left cingulum and left SLF. There was no significant correlation between FA and ToM task scores in HCs. These results suggest that the left cingulum and SLF constitute a possible neural basis for ToM deficits in schizophrenia. Our study is the first to demonstrate the white matter connectivity underlying the mentalizing network, as well as its relation to ToM ability in patients with FEP.

Abstract P349: Neuroprotective Effects of L-Carnitine on Vascular Dementia in Hemodialysis Patients

Background and purpose: L-carnitine alleviated oxidative stress and white matter lesions in an experimental study. Cognitive decline is not uncommon in hemodialysis patients, the pathogenesis of which has not been elucidated. Methods: Using novel diffusion magnetic resonance imaging techniques, white matter microstructural changes and cognitive decline in hemodialysis patients, and the effects of l-carnitine on such disorders were investigated. Fourteen hemodialysis patients underwent diffusion tensor imaging, diffusion kurtosis imaging, neurite orientation dispersion and density imaging, and laboratory and neuropsychological tests, which were compared between two groups based on the duration of l-carnitine treatment: (1) no or short-term l-carnitine treatment; and (2) long-term l-carnitine treatment. Ten age and sex-matched controls were enrolled. Results: On neuropsychological testing, the majority of hemodialysis patients were categorized as having mild cognitive impairment. Seven patients were classified into the no or short-term l-carnitine treatment and long-term l-carnitine treatment groups. Compared to controls, microstructural disorders of white matter were widely detected in no or short-term l-carnitine treatment on diffusion magnetic resonance imaging. An autopsy study from the no or short-term l-carnitine treatment group showed rarefaction of myelinated fibers in white matter. In long-term l-carnitine treatment, microstructural damage on diffusion magnetic resonance imaging was alleviated along with lower levels of high-sensitivity C-reactive protein ( P &lt;0.001) and substantial increases of carnitine levels ( P &lt;0.001). The long-term l-carnitine treatment group showed better achievement in Trail Making Test-A ( P =0.017), which was correlated with amelioration of disorders in bilateral anterior thalamic radiations, the left cingulum in the cingulate gyrus, the right superior longitudinal fasciculus, and the forceps major ( P &lt;0.05). Conclusion: Novel diffusion magnetic resonance imaging tractography detected abnormalities of white matter tracts in hemodialysis patients. Long-term treatment with l-carnitine alleviated white matter microstructural damage and cognitive impairment.

Reduced white matter microstructure in bipolar disorder with and without psychosis.

Affective and psychotic features overlap considerably in bipolar I disorder, complicating efforts to determine its etiology and develop targeted treatments. In order to clarify whether mechanisms are similar or divergent for bipolar disorder with psychosis (BDP) and bipolar disorder with no psychosis (BDNP), neurobiological profiles for both the groups must first be established. This study examines white matter structure in the BDP and BDNP groups, in an effort to identify portions of white matter that may differ between the bipolar and healthy groups or between the bipolar subgroups themselves. Diffusion-weighted imaging data were acquired from participants with BDP (n=45), BDNP (n=40), and healthy comparisons (HC) (n=66). Fractional anisotropy (FA), radial diffusivity (RD), and spin distribution function (SDF) values indexing white matter diffusivity or spin density were calculated and compared between the groups. In comparisons between both the bipolar groups and HC, FA (FDR<0.00001) and RD (FDR=0.0037) differed minimally, in localized portions of the left cingulum and corpus callosum, while reductions in SDF (FDR=0.0002) were more widespread. The bipolar subgroups did not differ from each other on FA, RD, or SDF metrics. Together, these results demonstrate a novel profile of white matter differences in bipolar disorder and suggest that this white matter pathology is associated with the affective disturbance common to those with bipolar disorder rather than the psychotic features unique to some. The white matter alterations identified in this study may provide substrates for future studies examining specific mechanisms that target affective domains of illness.

Associations between different white matter properties and reward-based performance modulation.

Humans can be motivated by the prospect of gaining a reward. However, the extent to which we are affected by reward information differs from person to person. A possible mechanism underlying these inter-individual differences may be alterations in white matter (WM) microstructure; however, the relationship between WM properties and reward-based behaviour in healthy participants has not yet been explored. Here, we used a fixel-based approach to investigate potential associations between WM tracts and performance in a reward-cuing task. We found that WM properties in the corpus callosum, right uncinate fasciculus, left ventral cingulum, and accumbofrontal tracts were inversely related to reward-triggered performance benefits (indexed by faster reaction times). Moreover, smaller WM property values in the corpus callosum, uncinate fasciculus, and accumbofrontal tracts were associated with higher scores on the Behavioral Inhibition System scale, reflecting greater sensitivity to potential punishment. Finally, we also observed associations between functional hemodynamic activity in the ventral striatum and WM microstructure. The finding that reward-based behavioural benefits are related to lower measures of WM tracts is in contrast to studies linking higher WM metrics to superior cognitive performance. We interpret the current pattern in terms of higher susceptibility to motivationally relevant stimuli, which is in line with the current and previous studies reporting inverse relationships between WM properties and motivational traits. Taking a broader perspective, such propensities may only be beneficial up to a certain point, at which thesemay become detrimental to performance and even manifest as impulsive and addictive behaviour.

Pretreatment abnormalities in white matter integrity predict one-year clinical outcome in first episode schizophrenia

Schizophrenia is a serious mental illness for which the mainstay of treatment is antipsychotics. Up to 30% of schizophrenia patients show limited response to antipsychotics. Identifying these patients before treatment could guide individualized treatment for improving outcomes in those not likely to show robust benefit from antipsychotics. Diffusion tensor imaging was performed with 56 drug-naïve first-episode schizophrenia patients and 69 matched healthy controls. Patients were followed clinically after one-year of antipsychotic treatment and classified at that point into groups of 17 poor outcome and 39 good outcome patients based on whether they showed at least a 50% reduction of Positive and Negative Syndrome Scale (PANSS) scores from baseline. Tract-based spatial statistics were applied to assess white matter microstructure in the two patient subgroups and healthy controls. Poor outcome patients showed reduced pretreatment fractional anisotropy (FA) in left cingulum and anterior thalamic radiation and increased FA in right superior and inferior longitudinal fasciculus compared with good outcome patients. FA in each of these four tracts was decreased in both patient subgroups relative to healthy controls. Considered together, the four altered tracts showed promising ability to differentiate poor from good outcome patients (sensitivity = 74.4%, specificity = 95.2%, AUC = 0.90, p < 0.001), and superior prediction of clinical outcome to baseline PANSS scores (p < 0.015). Prediction of outcomes using DTI features was not related to duration of untreated psychosis. Baseline alterations in white matter integrity may identify schizophrenia patients less likely to respond to treatment, which could be useful information for stratification in clinical trials and for individualized treatment planning.

Microstructural properties of major white matter tracts in constant exotropia before and after strabismus surgery

AimsThe purpose of this study was to explore the microstructural properties of the major white matter (WM) tracts in constant exotropia (XT) before and after strabismus surgery, and further investigate...

Disruption of Rich-Club Connectivity in Cushing Disease

Cushing disease (CD) is a rare clinical disease in which brain structural and function are impaired as the result of excessive cortisol. However, little is known whether rich-club organization changes in patients with CD, as visualized on resting-state magnetic resonance imaging (fMRI), can reverse to normal conditions after transsphenoidal surgery (TSS). In this study, we aimed to investigate whether the functional connectivity of rich-club organization is affected and whether any abnormal changes may reverse after TSS. In this study, 38 patients with active CD, 33 with patients with CD in remission, and 41 age-, sex-, and education-matched healthy control participants underwent resting-state fMRI. Brain functional connectivity was constructed based on fMRI and rich club was calculated with graph theory approach. We constructed the functional brain networks for all participants and calculated rich-club connectivity based on fMRI. We identified left precuneus, right precuneus, left middle cingulum, right middle cingulum, right inferior temporal, right middle temporal, right lingual, right postcentral, right middle occipital, and right precentral regions as rich club nodes. Compared with healthy control participants, rich-club connectivity was significantly lower in patients with active CD (P < 0.001). Moreover, abnormal rich-club connectivity improved to normal after TSS. Our results show rich-club organization was disrupted in patients with active CD with excessive cortisol production. TSS can reverse abnormal rich-club connectivity. Rich club may be a new indicator to investigate the outcomes of TSS and to increase our understanding of the effect of excessive cortisol on brain functional connectivity in patients with CD.

Motor function and white matter connectivity in children cooled for neonatal encephalopathy

Therapeutic hypothermia reduces the incidence of severe motor disability, such as cerebral palsy, following neonatal hypoxic-ischaemic encephalopathy. However, cooled children without cerebral palsy at school-age demonstrate motor deficits and altered white matter connectivity. In this study, we used diffusion-weighted imaging to investigate the relationship between white matter connectivity and motor performance, measured using the Movement Assessment Battery for Children-2, in children aged 6–8 years treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy at birth, who did not develop cerebral palsy (cases), and matched typically developing controls. Correlations between total motor scores and diffusion properties in major white matter tracts were assessed in 33 cases and 36 controls. In cases, significant correlations (FDR-corrected P < 0.05) were found in the anterior thalamic radiation bilaterally (left: r = 0.513; right: r = 0.488), the cingulate gyrus part of the left cingulum (r = 0.588), the hippocampal part of the left cingulum (r = 0.541), and the inferior fronto-occipital fasciculus bilaterally (left: r = 0.445; right: r = 0.494). No significant correlations were found in controls. We then constructed structural connectivity networks, for 22 cases and 32 controls, in which nodes represent brain regions and edges were determined by probabilistic tractography and weighted by fractional anisotropy. Analysis of whole-brain network metrics revealed correlations (FDR-corrected P < 0.05), in cases, between total motor scores and average node strength (r = 0.571), local efficiency (r = 0.664), global efficiency (r = 0.677), clustering coefficient (r = 0.608), and characteristic path length (r = -0.652). No significant correlations were found in controls. We then investigated edge-level association with motor function using the network-based statistic. This revealed subnetworks which exhibited group differences in the association between motor outcome and edge weights, for total motor scores (P = 0.0109) as well as for balance (P = 0.0245) and manual dexterity (P = 0.0233) domain scores. All three of these subnetworks comprised numerous frontal lobe regions known to be associated with motor function, including the superior frontal gyrus and middle frontal gyrus. The subnetwork associated with total motor scores was highly left-lateralised. These findings demonstrate an association between impaired motor function and brain organisation in school-age children treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy.

Neural substrates of subcortical aphasia in subacute stroke: Voxel-based lesion symptom mapping study

Subcortical aphasia develops as a result of damage to subcortical brain areas without loss of cortical functions. Although earlier voxel-based lesion-symptom mapping (VLSM) studies have shown possible neural correlates for aphasia, it remains to be clarified which brain regions are associated with subcortical aphasia. The aim of this study was to investigate the neural substrates associated with subcortical aphasia in patients with stroke using VLSM and atlas-based analyses to explore the involvement of white matter tracts and subcortical structures. Fifty patients with subacute subcortical stroke without cortical involvement were retrospectively enrolled: 24 with and 26 without aphasia. We performed VLSM and atlas-based analyses of the patients' fluid-attenuated inversion recovery images and found that the left perisylvian white matter, left fronto-occipital fasciculus, uncinate fasciculus, and forceps minor were significantly more greatly affected in the aphasia than in the non-aphasia group. The left anterior thalamic radiation, cingulum (cingulate gyrus), and superior longitudinal fasciculus also showed higher involvement in this group (marginal significance). Among the subcortical regions, the left caudate and putamen were more greatly involved in the aphasia group. Our findings confirm language processing as one of the integrated sensory-motor processes that occur in the region around the left sylvian fissure. Our atlas-based analysis approach can be used to complement VLSM analyses.

The cingulum in very preterm infants relates to language and social-emotional impairment at 2 years of term-equivalent age

BackgroundRelative to full-term infants, very preterm infants exhibit disrupted white matter (WM) maturation and problems related to development, including motor, cognitive, social-emotional, and receptive and expressive language processing. ObjectiveThe present study aimed to determine whether regional abnormalities in the WM microstructure of very preterm infants, as defined relative to those of full-term infants at a near-term age, are associated with neurodevelopmental outcomes at the age of 18–22 months. MethodsWe prospectively enrolled 89 very preterm infants (birth weight < 1500 g) and 43 normal full-term control infants born between 2016 and 2018. All infants underwent a structural brain magnetic resonance imaging scan at near-term age. The diffusion tensor imaging (DTI) metrics of the whole-brain WM tracts were extracted based on the neonatal probabilistic WM pathway. The elastic net logistic regression model was used to identify altered WM tracts in the preterm brain. We evaluated the associations between the altered WM microstructure at near-term age and motor, cognitive, social-emotional, and receptive and expressive language developments at 18–22 months of age, as measured using the Bayley Scales of Infant Development, Third Edition. ResultsWe found that the elastic net logistic regression model could classify preterm and full-term neonates with an accuracy of 87.9% (corrected p < 0.008) using the DTI metrics in the pathway of interest with a 10% threshold level. The fractional anisotropy (FA) values of the body and splenium of the corpus callosum, middle cerebellar peduncle, left and right uncinate fasciculi, and right portion of the pathway between the premotor and primary motor cortices (premotor-PMC), as well as the mean axial diffusivity (AD) values of the left cingulum, were identified as contributive features for classification. Increased adjusted AD values in the left cingulum pathway were significantly correlated with language scores after false discovery rate (FDR) correction (r = 0.217, p = 0.043). The expressive language and social-emotional composite scores showed a significant positive correlation with the AD values in the left cingulum pathway (r = 0.226 [p = 0.036] and r = 0.31 [p = 0.003], respectively) after FDR correction. ConclusionOur approach suggests that the cingulum pathways of very preterm infants differ from those of full-term infants and significantly contribute to the prediction of the subsequent development of the language and social-emotional domains. This finding could improve our understanding of how specific neural substrates influence neurodevelopment at later ages, and individual risk prediction, thus helping to inform early intervention strategies that address developmental delay.