Unveiling the axonal connectivity between the precuneus and temporal pole: Structural evidence from the cingulum pathways.

Neuroimaging studies have consistently demonstrated concurrent activation of the human precuneus and temporal pole (TP), both during resting-state conditions and various higher-order cognitive functions. However, the precise underlying structural connectivity between these brain regions remains uncertain despite significant advancements in neuroscience research. In this study, we investigated the connectivity of the precuneus and TP by employing parcellation-based fiber micro-dissections in human brains and fiber tractography techniques in a sample of 1065 human subjects and a sample of 41 rhesus macaques. Our results demonstrate the connectivity between the posterior precuneus area POS2 and the areas 35, 36, and TG of the TP via the fifth subcomponent of the cingulum (CB-V) also known as parahippocampal cingulum. This finding contributes to our understanding of the connections within the posteromedial cortices, facilitating a more comprehensive integration of anatomy and function in both normal and pathological brain processes. PRACTITIONER POINTS: Our investigation delves into the intricate architecture and connectivity patterns of subregions within the precuneus and temporal pole, filling a crucial gap in our knowledge. We revealed a direct axonal connection between the posterior precuneus (POS2) and specific areas (35, 35, and TG) of the temporal pole. The direct connections are part of the CB-V pathway and exhibit a significant association with the cingulum, SRF, forceps major, and ILF. Population-based human tractography and rhesus macaque fiber tractography showed consistent results that support micro-dissection outcomes.

Microstructural abnormalities of white matter in the cingulum bundle of adolescents with major depression and non-suicidal self-injury.

BACKGROUND: Non-suicidal self-injury (NSSI) is prevalent in major depressive disorder (MDD) during adolescence, but the underlying neural mechanisms are unclear. This study aimed to investigate microstructural abnormalities in the cingulum bundle associated with NSSI and its clinical characteristics. METHODS: 130 individuals completed the study, including 35 healthy controls, 47 MDD patients with NSSI, and 48 MDD patients without NSSI. We used tract-based spatial statistics (TBSS) with a region of interest (ROI) analysis to compare the fractional anisotropy (FA) of the cingulum bundle across the three groups. receiver-operating characteristics (ROC) analysis was employed to evaluate the ability of the difficulties with emotion regulation (DERS) score and mean FA of the cingulum to differentiate between the groups. RESULTS: MDD patients with NSSI showed reduced cingulum integrity in the left dorsal cingulum compared to MDD patients without NSSI and healthy controls. The severity of NSSI was negatively associated with cingulum integrity (r = -0.344, p = 0.005). Combining cingulum integrity and DERS scores allowed for successful differentiation between MDD patients with and without NSSI, achieving a sensitivity of 70% and specificity of 83%. CONCLUSIONS: Our study highlights the role of the cingulum bundle in the development of NSSI in adolescents with MDD. The findings support a frontolimbic theory of emotion regulation and suggest that cingulum integrity and DERS scores may serve as potential early diagnostic tools for identifying MDD patients with NSSI.

Identification and Functional Analysis of Adipokinetic Hormone Receptor in Ostrinia furnacalis Guenée Larvae Parasitized by Macrocentrus cingulum.

As a typical G protein-coupled receptor, the adipokinetic hormone receptor (AKHR) has seven transmembrane domains (TMDs), and its structure and function are similar to the gonadotropin-releasing hormone receptor (GnRHR) in vertebrates. However, there is a dearth of information on other components of the AKHR signaling pathway and how it functions in the interaction between insect hosts and parasitoids. In this study, we cloned and analyzed the multifunctional Ostrinia furnacalis AKHR (OfAKHR) cDNA (GenBank accession number MF797868). OfAKHR has a 2206 bp full-length cDNA, which includes an open reading frame containing 1194 bp. OfAKHR contains the typical seven TMDs, and a "DRY" motif. OfAKHR has the highest relative expression in the fat body and the fifth instar larvae. The results revealed that ApoLpⅢ, PPO2, GS, TPS, Cecropin, and Moricin decreased the transcription levels from 48 to 72 h after the knockdown of OfAKHR expression by dsOfAKHR injection in the fourth instar O. furnacalis larvae. The parasitization of Macrocentrus cingulum selectively upregulated the expression levels of nutrition metabolism and immune-related genes in parasitized O. furnacalis larvae, stimulated lysozyme activity, and obviously raised the concentrations of triglyceride and trehalose in the hemolymph of O. furnacalis larvae. However, they inhibited the activities of PO and trehalase. This study is conducive to a deeper cognition of the roles of OfAKHR in nutrition and immune homeostasis, coevolution, and coexistence between parasitic wasps and hosts. It also sheds light on the potential as the target of pest control reagents.

Stability of associations between neuroticism and microstructural asymmetry of the cingulum during late childhood and adolescence: Insights from a longitudinal study with up to 11 waves.

Adolescence is characterized by significant brain development and marks a period of the life span with an increased incidence of mood disorders, especially in females. The risk of developing mood disorders is also higher in individuals scoring high on neuroticism, a personality trait characterized by a tendency to experience negative and anxious emotions. We previously found in a cross-sectional study that neuroticism is associated with microstructural left-right asymmetry of the fronto-limbic white matter involved in emotional processing, with opposite effects in female and male adolescents. We now have extended this work collecting longitudinal data in 76 typically developing children and adolescents aged 7-18 years, including repeated MRI sampling up to 11 times. This enabled us, for the first time, to address the critical question, whether the association between neuroticism and frontal-limbic white matter asymmetry changes or remains stable across late childhood and adolescence. Neuroticism was assessed up to four times and showed good intraindividual stability and did not significantly change with age. Conforming our cross-sectional results, females scoring high on neuroticism displayed increased left-right cingulum fractional anisotropy (FA), while males showed decreased left-right cingulum FA asymmetry. Despite ongoing age-related increases in FA in cingulum, the association between neuroticism and cingulum FA asymmetry was already expressed in females in late childhood and remained stable across adolescence. In males, the association appeared to become more prominent during adolescence. Future longitudinal studies need to cover an earlier age span to elucidate the time point at which the relationship between neuroticism and cingulum FA asymmetry arises.

The microstructural abnormalities of cingulum was related to patients with mild cognitive impairment: a diffusion kurtosis imaging study.

OBJECTIVE: Our study aimed to investigate the correlations between microstructural changes of cingulum and patients with mild cognitive impairment (MCI) by diffusion kurtosis imaging (DKI) technique. METHOD: A total of 104 patients with cerebral small vessel diseases (cSVD) were retrospectively enrolled in this study. According to Montreal Cognitive Assessment Scale (MoCA) scores, these patients were divided into MCI group (n = 59) and non-MCI group (n = 45). The general clinical data was collected and analyzed. The regions of interests (ROIs) were selected for investigation in cingulum. The values of DKI parameters were measured in each ROI and compared between the two groups, the correlations between DKI parameters and MoCA scores were examined. RESULTS: Compared to non-MCI group, MCI patients had more severe white matter hyperintensities (WMHs) (P = 0.038) and lower MoCA scores (P < 0.01). MCI patients showed significantly decreased fractional anisotropy (FA), axial kurtosis (AK), mean kurtosis (MK), radial kurtosis (RK), and kurtosis fractional anisotropy (KFA) in the left cingulum in the cingulated cortex (CgC) region (all P < 0.0125). In the left CgC region, FA, AK, MK, RK, and KFA were positively correlated with MoCA scores (r = 0.348, 0.409, 0.310, 0.441, 0.422, all P < 0.001). Meanwhile, FA, AK, MK, RK, and KFA were also positively correlated with MoCA scores (r = 0.338, 0.352, 0.289, 0.380, 0.370, all P < 0.001) in the right CgC region. CONCLUSION: DKI technique could be used to explore the microstructural changes of cingulum in MCI patients and DKI-derived parameters might be feasible to evaluate MCI patients.

Abnormal white matter along fibers by automated fiber quantification in patients undergoing hemodialysis.

BACKGROUND: Abnormal white matter has been reported in patients with end-stage renal disease (ESRD). However, few studies have investigated the relationship between specific damage segments and cognition in ESRD. This study aimed to delineate white matter alterations in ESRD and its relationship with cognition. METHODS: A total of 36 patients undergoing hemodialysis and 25 healthy controls underwent diffusion tensor imaging (DTI) and a series of neuropsychiatric tests. Automated fiber quantification was used to extract distinct DTI indices, and the relationship between the specific segment of the white matter and clinical properties was investigated. Furthermore, a support vector machine was applied to differentiate patients with ESRD from healthy controls. RESULTS: Fractional anisotropy values decreased in multiple fiber bundles, including bilateral thalamic radiata, cingulum cingulate, inferior fronto-occipital fasciculus (IFOF), uncinate, Callosum_Forceps_Major/Callosum_Forceps_Minor (CFMaj/CFMin), and left uncinate from the tract level in patients with ESRD. Specific damaged segments were detected in 8 fiber bundles, including bilateral thalamic radiation, cingulum cingulate, IFOF, CFMin, and left corticospinal tract. Few alterations in these fiber bundles were correlated with cognition impairment and hemoglobin levels. The tract profiles of the left thalamic radiata and left cingulum cingulate could be used to differentiate hemodialysis patients from healthy controls, with an accuracy of 76.9% and 67.6%, respectively. CONCLUSIONS: This study revealed white matter damage in hemodialysis patients. This damage occurred in specific segments of the tract, especially in the left thalamic radiata and left cingulum cingulate, which might become a new biomarker for patients with ESRD and cognition impairment.

Microsurgical anatomy of the isthmic cingulum: a new white matter crossroad and neurosurgical implications in the posteromedial interhemispheric approaches and the glioma invasion patterns.

ABTRACT: The dichotomy of the cingulum bundle into the dorsal supracallosal and ventral parahippocampal parts is widely accepted; however, the retrosplenial component with its multiple alternative connections has not been revealed. The aim of this study was to delineate the microsurgical anatomy of a connectionally transition zone, the isthmic cingulum, in relation to the posteromedial interhemispheric access to the atrium and discuss the relevant patterns of glioma invasion on the basis of its fiber connections. White matter (WM) fibers were dissected layer by layer in a medial-to-lateral, lateral-to-medial, and posterior-to-anterior fashion. All related tracts and their connections were generated using deterministic tractography. The magnetic resonance imaging (MRI) tractography findings were correlated with those of fiber dissection. A medial parieto-occipital approach to reach the atrium was performed with special emphasis on the cingulate isthmus and underlying WM connections. The isthmic cingulum, introduced as a retrosplenial connectional crossroad for the first time, displayed multiple connections to the splenium and the superior thalamic radiations. Another new finding was the demonstration of lateral hemispheric extension of the isthmic cingulum fibers through the base of the posterior part of the precuneus at the base of the parieto-occipital sulcus. The laterally crossing cingulum fibers were interconnected with three distinct association tracts: the middle longitudinal (MdLF), the inferior frontooccipital fasciculi (IFOF), and the claustro-cortical fibers (CCF). In the process of entry to the atrium during posterior interhemispheric approaches, the splenial and thalamic connections, as well as the laterally crossing fibers of the isthmic cingulum, were all in jeopardy. The connectional anatomy of the retrosplenial area is much more complicated than previously known. The isthmic cingulum connections may explain the concept of interhemispheric and medial to lateral cerebral hemisphere invasion patterns in medial parieto-occipital and posteromesial temporal gliomas. The isthmic cingulum is of key importance in posteromedial interhemispheric approaches to both: the atrium and the posterior mesial temporal lobe.

A novel cognitive neurosurgery approach for supramaximal resection of non-dominant precuneal gliomas: a case report.

Despite mounting evidence pointing to the contrary, classical neurosurgery presumes many cerebral regions are non-eloquent, and therefore, their excision is possible and safe. This is the case of the precuneus and posterior cingulate, two interacting hubs engaged during various cognitive functions, including reflective self-awareness; visuospatial and sensorimotor processing; and processing social cues. This inseparable duo ensures the cortico-subcortical connectivity that underlies these processes. An adult presenting a right precuneal low-grade glioma invading the posterior cingulum underwent awake craniotomy with direct electrical stimulation (DES). A supramaximal resection was achieved after locating the superior longitudinal fasciculus II. During surgery, we found sites of positive stimulation for line bisection and mentalizing tests that enabled the identification of surgical corridors and boundaries for lesion resection. When post-processing the intraoperative recordings, we further identified areas that positively responded to DES during the trail-making and mentalizing tests. In addition, a clear worsening of the patient's self-assessment ability was observed throughout the surgery. An awake cognitive neurosurgery approach allowed supramaximal resection by reaching the cortico-subcortical functional limits. The mapping of complex functions such as social cognition and self-awareness is key to preserving patients' postoperative cognitive health by maximizing the ability to resect the lesion and surrounding areas.

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

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

White matter alterations associated with lifetime and current depression in adolescents: Evidence for cingulum disruptions.

INTRODUCTION: Compared to research on adults with depression, relatively little work has examined white matter microstructure differences in depression arising earlier in life. Here we tested hypotheses about disruptions to white matter structure in adolescents with current and past depression, with an a priori focus on the cingulum bundles, uncinate fasciculi, corpus collosum, and superior longitudinal fasciculus. METHODS: One hundred thirty-one children from the Preschool Depression Study were assessed using a Human Connectome Project style diffusion imaging sequence which was processed with HCP pipelines and TRACULA to generate estimates of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). RESULTS: We found that reduced FA, reduced AD, and increased RD in the dorsal cingulum bundle were associated with a lifetime diagnosis of major depression and greater cumulative and current depression severity. Reduced FA, reduced AD, and increased RD in the ventral cingulum were associated with greater cumulative depression severity. CONCLUSION: These findings support the emergence of white matter differences detected in adolescence associated with earlier life and concurrent depression. They also highlight the importance of connections of the cingulate to other brain regions in association with depression, potentially relevant to understanding emotion dysregulation and functional connectivity differences in depression.

Volumetric development of hippocampal subfields and hippocampal white matter connectivity: Relationship with episodic memory.

The hippocampus is a complex structure composed of distinct subfields. It has been central to understanding neural foundations of episodic memory. In the current cross-sectional study, using a large sample of 830, 3- to 21-year-olds from a unique, publicly available dataset we examined the following questions: (1) Is there elevated grey matter volume of the hippocampus and subfields in late compared to early development? (2) How does hippocampal volume compare with the rest of the cerebral cortex at different developmental stages? and (3) What is the relation between hippocampal volume and connectivity with episodic memory performance? We found hippocampal subfield volumes exhibited a nonlinear relation with age and showed a lag in volumetric change with age when compared to adjacent cortical regions (e.g., entorhinal cortex). We also observed a significant reduction in cortical volume across older cohorts, while hippocampal volume showed the opposite pattern. In addition to age-related differences in gray matter volume, dentate gyrus/cornu ammonis 3 volume was significantly related to episodic memory. We did not, however, find any associations with episodic memory performance and connectivity through the uncinate fasciculus, fornix, or cingulum. The results are discussed in the context of current research and theories of hippocampal development and its relation to episodic memory.

A stepwise laboratory manual for the dissection and illustration of limbic and paralimbic structures: lessons learned from the Klingler's technique.

BACKGROUND: Three-dimensional relationships within the limbic and paralimbic areas are often hard to grasp. Relevant anatomical structures exhibit a complicated architecture and connectivity and therefore surgical approaches targeting lesions or functional resections in this area pose a distinct challenge. PURPOSE: To provide an educational, comprehensive, systematic and stepwise manual for the dissection and illustration of major limbic structures since there is a gap in the pertinent literature. Further, we aim to offer a thorough yet simplified roadmap for laboratory and intraoperative dissections. METHODS: Twenty (20) normal adult, formalin-fixed cerebral hemispheres were studied through the fiber dissection technique and under the microscope. Stepwise and in tandem medial to lateral and lateral to medial dissections were performed in all specimens aiming to reveal the morphology and spatial relationships of major limbic and paralimbic areas. RESULTS: Fourteen (14) consecutive, discrete and easily reproducible laboratory anatomical steps are systematically described to reveal the intricate anatomy of the limbic and paralimbic structures and their main connections. CONCLUSION: This study offers for the first time in the pertinent literature a focused, step-by-step laboratory manual for the dissection and illustration of the limbic and paralimbic structures. The overreaching goal is to supplement the novice and experienced anatomist and neurosurgeon with a thorough and systematic reference to facilitate laboratory or intraoperative dissections.

Fronto-thalamic structural and effective connectivity and delusions in schizophrenia: a combined DTI/DCM study.

BACKGROUND: Schizophrenia (SZ) is a complex disorder characterized by a range of behavioral and cognitive symptoms as well as structural and functional alterations in multiple cortical and subcortical structures. SZ is associated with reduced functional network connectivity involving core regions such as the anterior cingulate cortex (ACC) and the thalamus. However, little is known whether effective coupling, the directed influence of one structure over the other, is altered during rest in the ACC-thalamus network. METHODS: We collected resting-state fMRI and diffusion-weighted MRI data from 18 patients and 20 healthy controls. We analyzed fronto-thalamic effective connectivity using dynamic causal modeling for cross-spectral densities in a network consisting of the ACC and the left and right medio-dorsal thalamic regions. We studied structural connectivity using fractional anisotropy (FA). RESULTS: We found decreased coupling strength from the right thalamus to the ACC and from the right thalamus to the left thalamus, as well as increased inhibitory intrinsic connectivity in the right thalamus in patients relative to controls. ACC-to-left thalamus coupling strength correlated with the Positive and Negative Syndrome Scale (PANSS) total positive syndrome score and with delusion score. Whole-brain structural analysis revealed several tracts with reduced FA in patients, with a maximum decrease in white matter tracts containing fronto-thalamic and cingulo-thalamic fibers. CONCLUSIONS: We found altered effective and structural connectivity within the ACC-thalamus network in SZ. Our results indicate that ACC-thalamus network activity at rest is characterized by reduced thalamus-to-ACC coupling. We suggest that positive symptoms may arise as a consequence of compensatory measures to imbalanced fronto-thalamic coupling.

Accelerating Structural Degeneration in Temporal Regions and Their Effects on Cognition in Aging of MCI Patients.

Age is the major risk factor for Alzheimer's disease (AD) and for mild cognitive impairment (MCI). However, there is limited evidence about MCI-specific aging-related simultaneous changes of the brain structure and their impact on cognition. We analyzed the brain imaging data from 269 subjects (97 MCI patients and 172 cognitively normal [CN] elderly) using voxel-based morphometry and tract-based spatial statistics procedures to explore the special structural pattern during aging. We found that the patients with MCI showed accelerated age-related reductions in gray matter volume in the left planum temporale, thalamus, and posterior cingulate gyrus. The similar age×group interaction effect was found in the fractional anisotropy of the bilateral parahippocampal cingulum white matter tract, which connects the temporal regions. Importantly, the age-related temporal gray matter and white matter alterations were more significantly related to performance in memory and attention tasks in MCI patients. The accelerated degeneration patterns in the brain structure provide evidence for different neural mechanisms underlying aging in MCI patients. Temporal structural degeneration may serve as a potential imaging marker for distinguishing the progression of the preclinical AD stage from normal aging.

High Angular Resolution Diffusion MRI Reveals Conserved and Deviant Programs in the Paths that Guide Human Cortical Circuitry.

Diffusion magnetic resonance (MR) tractography represents a novel opportunity to investigate conserved and deviant developmental programs between humans and other species such as mice. To that end, we acquired high angular resolution diffusion MR scans of mice [embryonic day (E) 10.5 to postnatal week 4] and human brains [gestational week (GW) 17-30] at successive stages of fetal development to investigate potential evolutionary changes in radial organization and emerging pathways between humans and mice. We compare radial glial development as well as commissural development (e.g., corpus callosum), primarily because our findings can be integrated with previous work. We also compare corpus callosal growth trajectories across primates (i.e., humans and rhesus macaques) and rodents (i.e., mice). One major finding is that the developing cortex of humans is predominated by pathways likely associated with a radial glial organization at GW 17-20, which is not as evident in age-matched mice (E 16.5, 17.5). Another finding is that, early in development, the corpus callosum follows a similar developmental timetable in primates (i.e., macaques and humans) as in mice. However, the corpus callosum grows for an extended period of time in primates compared with rodents. Taken together, these findings highlight deviant developmental programs underlying the emergence of cortical pathways in the human brain.

White matter tract myelin maturation and its association with general psychopathology in adolescence and early adulthood.

Adolescence is a time period associated with marked brain maturation that coincides with an enhanced risk for onset of psychiatric disorder. White matter tract myelination, a process that continues to unfold throughout adolescence, is reported to be abnormal in several psychiatric disorders. Here, we ask whether psychiatric vulnerability is linked to aberrant developmental myelination trajectories. We assessed a marker of myelin maturation, using magnetisation transfer (MT) imaging, in 10 major white matter tracts. We then investigated its relationship to the expression of a general psychopathology "p-factor" in a longitudinal analysis of 293 healthy participants between the ages of 14 and 24. We observed significant longitudinal MT increase across the full age spectrum in anterior thalamic radiation, hippocampal cingulum, dorsal cingulum and superior longitudinal fasciculus. MT increase in the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus and uncinate fasciculus was pronounced in younger participants but levelled off during the transition into young adulthood. Crucially, longitudinal MT increase in dorsal cingulum and uncinate fasciculus decelerated as a function of mean p-factor scores over the study period. This suggests that an increased expression of psychopathology is closely linked to lower rates of myelin maturation in selective brain tracts over time. Impaired myelin growth in limbic association fibres may serve as a neural marker for emerging mental illness during the course of adolescence and early adulthood.

Altered White Matter Organization in the TUBB3 E410K Syndrome.

Seven unrelated individuals (four pediatric, three adults) with the TUBB3 E410K syndrome, harboring identical de novo heterozygous TUBB3 c.1228 G>A mutations, underwent neuropsychological testing and neuroimaging. Despite the absence of cortical malformations, they have intellectual and social disabilities. To search for potential etiologies for these deficits, we compared their brain's structural and white matter organization to 22 controls using structural and diffusion magnetic resonance imaging. Diffusion images were processed to calculate fractional anisotropy (FA) and perform tract reconstructions. Cortical parcellation-based network analysis and gyral topology-based FA analyses were performed. Major interhemispheric, projection and intrahemispheric tracts were manually segmented. Subjects had decreased corpus callosum volume and decreased network efficiency. While only pediatric subjects had diffuse decreases in FA predominantly affecting mid- and long-range tracts, only adult subjects had white matter volume loss associated with decreased cortical surface area. All subjects showed aberrant corticospinal tract trajectory and bilateral absence of the dorsal language network long segment. Furthermore, pediatric subjects had more tracts with decreased FA compared with controls than did adult subjects. These findings define a TUBB3 E410K neuroimaging endophenotype and lead to the hypothesis that the age-related changes are due to microscopic intrahemispheric misguided axons that are pruned during maturation.

White Matter-Based Structural Brain Network of Anxiety.

Anxiety disorders are characterized by excessive fear and anxiety and related behavioral disturbances. Because diffusion tensor imaging is sensitive to detect subtle pathology of the brain, it has been used to characterize differences in white matter microstructure for a broad spectrum of psychiatric disorders. The neurobiological underpinnings of a trait anxiety seem to be associated with the uncinate fasciculus, a major pathway between the amygdala and orbitofrontal cortex. Apparent WM micro-alterations in patients with panic disorder are present in diverse and widespread regions, although alterations vary in terms of clinical symptom severity and comorbidities. Social anxiety disorder is associated with structural dysconnectivity in a fronto-limbic network consistent with reduced fractional anisotropy values in uncinate fasciculus and inferior longitudinal fasciculus. The pathogenesis of obsessive-compulsive disorder may include abnormal findings in not only the fronto-striato-thalamic circuit but also the posterior and temporal regions of forceps major and cingulum bundle. Studies of white matter status in anxiety revealed overlapping patterns of front-cortical and fronto-limbic changes with uncinate fasciculus and cingulum alterations a frequent component.

The cingulum and cingulate U-fibers in children and adolescents with autism spectrum disorders.

The cingulum is the major fiber system connecting the cingulate and surrounding medial cortex and medial temporal lobe internally and with other brain areas. It is important for social and emotional functions related to core symptomatology in autism spectrum disorders (ASDs). While the cingulum has been examined in autism, the extensive system of cingulate U-fibers has not been studied. Using probabilistic tractography, we investigated white matter fibers of the cingulate cortex by distinguishing its deep intra-cingulate bundle (cingulum proper) and short rostral anterior, caudal anterior, posterior, and isthmus cingulate U-fibers in 61 ASD and 54 typically developing children and adolescents. Increased mean and radial diffusivity of the left cingulum proper was observed in the ASD group, replicating previous findings on the cingulum. For cingulate U-fibers, an atypical age-related decline in right posterior cingulate U-fiber volume was found in the ASD group, which appeared to be driven by an abnormally large volume in younger children. History of repetitive and restrictive behavior was negatively associated with right caudal anterior cingulate U-fiber volume, linking cingulate motor areas with neighboring gyri. Aberrant development in U-fiber volume of the right posterior cingulate gyrus may underlie functional abnormalities found in this region, such as in the default mode network.

Aberrant myelination of the cingulum and Schneiderian delusions in schizophrenia: a 7T magnetization transfer study.

BACKGROUND: The structural integrity of the anterior cingulum has been repeatedly observed to be abnormal in patients with schizophrenia. More recently, aberrant myelination of frontal fasciculi, especially, cingulum has been proposed to underlie delayed corollary discharges that can affect sense of agency and contribute to delusions of control (Schneiderian delusions). Using the magnetization transfer phenomenon at an ultra-high field 7T MRI, we investigated the putative myelin content of cingulum bundle in patients with schizophrenia. METHODS: Seventeen clinically stable patients with schizophrenia and 20 controls were recruited for this 7T MRI study. We used a region-of-interest method and extracted magnetization transfer ratio (MTR) from left and right dorsal cingulum bundles and estimated patients v. controls differences. We also related the cingulum MTR values to the severity of Schneiderian delusions. RESULTS: Patients had a significant reduction in the MTR, indicating reduced myelin content, in the cingulum bundle (right cingulum Hedges' g = 0.91; left cingulum g = 0.03). The reduced MTR of left cingulum was associated with higher severity of Schneiderian delusions (τ = -0.45, p = 0.026) but no such relationship was seen for the right cingulum MTR (τ = -0.136, p = 0.50) among patients. The association between the left cingulum MTR and Schneiderian delusions was not explained by the presence of other delusions, hallucinations, disorganization or negative symptoms. CONCLUSIONS: Dysmyelination of the cingulum bundle is seen in a subgroup of patients with schizophrenia and may be involved in the mechanism of Schneiderian delusions.