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.

White matter integrity is associated with cognition and amyloid burden in older adult Koreans along the Alzheimer's disease continuum.

BACKGROUND: White matter (WM) microstructural changes in the hippocampal cingulum bundle (CBH) in Alzheimer's disease (AD) have been described in cohorts of largely European ancestry but are lacking in other populations. METHODS: We assessed the relationship between CBH WM integrity and cognition or amyloid burden in 505 Korean older adults aged ≥ 55 years, including 276 cognitively normal older adults (CN), 142 with mild cognitive impairment (MCI), and 87 AD patients, recruited as part of the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) at Seoul National University. RESULTS: Compared to CN, AD and MCI subjects showed significantly higher RD, MD, and AxD values (all p-values < 0.001) and significantly lower FA values (left p ≤ 0.002, right p ≤ 0.015) after Bonferroni adjustment for multiple comparisons. Most tests of cognition and mood (p < 0.001) as well as higher medial temporal amyloid burden (p < 0.001) were associated with poorer WM integrity in the CBH after Bonferroni adjustment. CONCLUSION: These findings are consistent with patterns of WM microstructural damage previously reported in non-Hispanic White (NHW) MCI/AD cohorts, reinforcing existing evidence from predominantly NHW cohort studies.

Microstructure abnormalities of the diffusion quantities in children with attention-deficit/hyperactivity disorder: an AFQ and TBSS study.

Objective: To explore the specific alterations of white matter microstructure in children with attention-deficit/hyperactivity disorder (ADHD) by automated fiber quantification (AFQ) and tract-based spatial statistics (TBSS), and to analyze the correlation between white matter abnormality and impairment of executive function. Methods: In this prospective study, a total of twenty-seven patients diagnosed with ADHD (20 males, 7 females; mean age of 8.89 ± 1.67 years) and twenty-two healthy control (HC) individuals (11 males, 11 females, mean age of 9.82 ± 2.13 years) were included. All participants were scanned with diffusion kurtosis imaging (DKI) and assessed for executive functions. AFQ and TBSS analysis methods were used to investigate the white matter fiber impairment of ADHD patients, respectively. Axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA) of 17 fiber properties were calculated using the AFQ. The mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MDDKI), axial diffusivity (ADDKI), radial diffusivity (RDDKI) and fractional anisotropy (FADKI) of DKI and AD, RD, MD, and FA of diffusion tensor imaging (DTI) assessed the integrity of the white matter based on TBSS. Partial correlation analyses were conducted to evaluate the correlation between white matter abnormalities and clinical test scores in ADHD while taking age, gender, and education years into account. The analyses were all family-wise error rate (FWE) corrected. Results: ADHD patients performed worse on the Behavior Rating Inventory of Executive Function (BRIEF) test (p < 0.05). Minor variances existed in gender and age between ADHD and HC, but these variances did not yield statistically significant distinctions. There were no significant differences in TBSS for DKI and DTI parameters (p > 0.05, TFCE-corrected). Compared to HC volunteers, the mean AD value of right cingulum bundle (CB_R) fiber tract showed a significantly higher level in ADHD patients following the correction of FWE. As a result of the point-wise comparison between groups, significant alterations (FWE correction, p < 0.05) were mainly located in AD (nodes 36-38, nodes 83-97) and MD (nodes 92-95) of CB_R. There was no significant correlation between white matter diffusion parameters and clinical test scores in ADHD while taking age, gender, and education years into account. Conclusion: The AFQ method can detect ADHD white matter abnormalities in a specific location with greater sensitivity, and the CB_R played a critical role. Our findings may be helpful in further studying the relationship between focal white matter abnormalities and ADHD.

White matter integrity is associated with cognition and amyloid burden in older adult Koreans along the Alzheimer's disease continuum.

BACKGROUND: White matter (WM) microstructural changes in the hippocampal cingulum bundle (CBH) in Alzheimer's disease (AD) have been described in cohorts of largely European ancestry but are lacking in other populations. METHODS: We assessed the relationship between CBH WM integrity and cognition or amyloid burden in 505 Korean older adults aged ≥55 years, including 276 cognitively normal older adults (CN), 142 mild cognitive impairment (MCI), and 87 AD, recruited as part of the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) at Seoul National University. RESULTS: Compared to CN, AD and MCI subjects showed decreased WM integrity in the bilateral CBH. Cognition, mood, and higher amyloid burden were also associated with poorer WM integrity in the CBH. CONCLUSION: These findings are consistent with patterns of WM microstructural damage previously reported in non-Hispanic White (NHW) MCI/AD cohorts, reinforcing existing evidence from predominantly NHW cohort studies.

Tract-specific differences in white matter microstructure between young adult APOE ε4 carriers and non-carriers: A replication and extension study.

The parahippocampal cingulum bundle (PHCB) interconnects regions known to be vulnerable to early Alzheimer's disease (AD) pathology, including posteromedial cortex and medial temporal lobe. While AD-related pathology has been robustly associated with alterations in PHCB microstructure, specifically lower fractional anisotropy (FA) and higher mean diffusivity (MD), emerging evidence indicates that the reverse pattern is evident in younger adults at increased risk of AD. In one such study, Hodgetts et al. (2019) reported that healthy young adult carriers of the apolipoprotein-E (APOE) ε4 allele - the strongest common genetic risk factor for AD - showed higher FA and lower MD in the PHCB but not the inferior longitudinal fasciculus (ILF). These results are consistent with proposals claiming that heightened neural activity and intrinsic connectivity play a significant role in increasing posteromedial cortex vulnerability to amyloid-ß and tau spread beyond the medial temporal lobe. Given the implications for understanding AD risk, here we sought to replicate Hodgetts et al.'s finding in a larger sample (N = 128; 40 APOE ε4 carriers, 88 APOE ε4 non-carriers) of young adults (age range = 19-33). Extending this work, we also conducted an exploratory analysis using a more advanced measure of white matter microstructure: hindrance modulated orientational anisotropy (HMOA). Contrary to the original study, we did not observe higher FA or lower MD in the PHCB of APOE ε4 carriers relative to non-carriers. Bayes factors (BFs) further revealed moderate-to-strong evidence in support of these null findings. In addition, we observed no APOE ε4-related differences in PHCB HMOA. Our findings indicate that young adult APOE ε4 carriers and non-carriers do not differ in PHCB microstructure, casting some doubt on the notion that early-life variation in PHCB tract microstructure might enhance vulnerability to amyloid-ß accumulation and/or tau spread.

Serum Inflammatory Markers and Their Associations with the Integrity of the Cingulum Bundle in Schizophrenia, from Prodromal Stages to Chronic Psychosis.

Peripheral cytokines may affect the brain through chronic activation of microglia and, as a result, can potentially lead to decreased integrity of white matter of cingulum bundle (CB). Therefore, the aim of the study was to analyze the relationships between peripheral inflammatory markers and the integrity of the CB in various states: from healthy controls, through prodromal states and first-episode psychosis, to long-term schizophrenia. The integrity of the CB was measured using diffusion tensor imaging. We analyzed six parameters: CRP, IL-6, IL-8, IL-10, TNF-α, and IFN-γ. We found that levels of IL-6 and IFN-γ differed significantly between groups. Initial analysis showed some correlations between the inflammatory markers and CB integrity, in particular a correlation with IL-6 that was present in several groups. However, none of the analyzed parameters were associated with the integrity of the CB after correction for multiple comparisons. Conclusions: Our results supported our hypothesis that there are increased levels of inflammatory markers in psychotic disorders, but did not allow to confirm our hypothesis that there is a link between increased peripheral inflammatory markers and decreased integrity of the CB. However, we found some interesting trend levels that need to be verified in larger studies.

Conduction velocity along a key white matter tract is associated with autobiographical memory recall ability.

Conduction velocity is the speed at which electrical signals travel along axons and is a crucial determinant of neural communication. Inferences about conduction velocity can now be made in vivo in humans using a measure called the magnetic resonance (MR) g-ratio. This is the ratio of the inner axon diameter relative to that of the axon plus the myelin sheath that encases it. Here, in the first application to cognition, we found that variations in MR g-ratio, and by inference conduction velocity, of the parahippocampal cingulum bundle were associated with autobiographical memory recall ability in 217 healthy adults. This tract connects the hippocampus with a range of other brain areas. We further observed that the association seemed to be with inner axon diameter rather than myelin content. The extent to which neurites were coherently organised within the parahippocampal cingulum bundle was also linked with autobiographical memory recall ability. Moreover, these findings were specific to autobiographical memory recall and were not apparent for laboratory-based memory tests. Our results offer a new perspective on individual differences in autobiographical memory recall ability, highlighting the possible influence of specific white matter microstructure features on conduction velocity when recalling detailed memories of real-life past experiences.

Scene Construction and Spatial Processing in Post-traumatic Stress Disorder.

Introduction: Post-traumatic stress disorder (PTSD) is associated with hippocampal system structural and functional impairments. Neurobiological models of PTSD posit that contextual memory for traumatic events is impaired due to hippocampal system dysfunction whilst memory of sensory details is enhanced due to amygdalar impact on sensory cortices. If hippocampal system dysfunction is a core feature of PTSD, then non-traumatic hippocampal-dependent cognitive functions such as scene construction, spatial processing, and memory should also be impaired in individuals with PTSD. Methods: Forty-six trauma survivors, half diagnosed with PTSD, performed two tasks that involved spatial processing. The first was a scene construction task which requires conjuring-up spatially coherent multimodal scenarios, completed by all participants. Twenty-six participants (PTSD: n = 13) also completed a navigation task in a virtual environment, and underwent structural T1, T2 and diffusion-tensor MRI to quantify gray and white matter integrity. We examined the relationship between spatial processing, neural integrity, and symptom severity in a multiple factor analysis. Results: Overall, patients with PTSD showed impaired performance in both tasks compared to controls. Scenes imagined by patients were less vivid, less detailed, and generated less sense of presence; importantly they had disproportionally reduced spatial coherence between details. Patients also made more errors during virtual navigation. Two components of the multiple factor analysis captured group differences. The first component explained 25% of the shared variance: participants that constructed less spatially coherent scenes also made more navigation errors and had reduced white matter integrity to long association tracts and tracts connecting the hippocampus, thalamus, and cingulate. The second component explained 20% of the variance: participants who generated fewer scene details, with less spatial coherence between them, had smaller hippocampal, parahippocampal and isthmus cingulate volumes. These participants also had increased white matter integrity to the right hippocampal cingulum bundle. Conclusion: Our results suggest that patients with PTSD are impaired at imagining even neutral spatially coherent scenes and navigating through a complex spatial environment. Patients that showed reduced spatial processing more broadly had reduced hippocampal systems volumes and abnormal white matter integrity to tracts implicated in multisensory integration.

Stereotactic cingulotomy and capsulotomy for obsessive-compulsive disorders: Indications and comparative results.

Stereotactic cingulotomy and capsulotomy have been used to treat obsessive-compulsive disorders (OCD) and treatment-resistant depression since the 1950s-60s. To date, these surgical procedures have gained a number of advancements due to progress of neuroimaging and upgrading of stereotactic technique. The effectiveness of operations is related to the restoration of the normal level of limbic regulation in treated patients. In cases of OCD, capsulotomy is somewhat more effective, while cingulotomy has a more favorable safety profile. Moreover, clinical experience shows that these procedures may be efficient for management not only OCD itself, but for obsessive-compulsive symptoms in cases of other mental diseases, such as Tourette syndrome and schizophrenia, thus may be considered in carefully selected patients. An individualized treatment strategy, including staged stereotactic interventions, seems most promising for attainment of the best possible outcomes, and may allow to achieve socialization of 75% of the operated patients with minimal pharmacological support. Other potential stereotactic targets for management of OCD, which selection may depend on detail of clinical manifestation of disease, include thalamic nuclei, nucleus accumbens, globus pallidus, the amygdala, etc., and are currently under active evaluation, and their use is tremendously facilitated by the development of deep brain stimulation techniques. Nevertheless, cingulotomy and capsulotomy still remain highly relevant for treatment of patients with therapy-resistant mental disorders.

Stereotactic surgeries for abuse syndromes: Patient selection and results.

It is known that in present time heroin addiction is the most widespread and difficult to treat. It includes two factors: physical and psychological addiction. The vast majority of patients remained mentally addicted to drugs after physical drug addiction has been eliminated and the organism has been completely detoxed. It is an indomitable desire to take drugs. Neurophysiological mechanisms are in base of psychological dependence. It is similar to those that implement obsessive states (obsessive-compulsive disorders). The central role in these neurophysiological mechanisms is played by limbic system of the brain that provides emotional and motivational behavior of humans (and animals). It was shown that the treatment of medical-resistant forms of obsessive-compulsive disorders requires stereotactic impacts on various structures of the limbic system, including cingulate gyrus. According to literature data, there was several hundred stereotactic effects on the cingulate gyrus in the world. About 1000 stereotactic operations have been performed in our country as a mental addiction of heroin dependent patients' treatment. The efficiency was of about 70%.