Caudal Anterior Cingulate Cortex Research Articles

Deciphering the brain-gut axis: elucidating the link between cerebral cortex structures and functional gastrointestinal disorders via integrated Mendelian randomization.

Observational studies have suggested associations between functional gastrointestinal disorders (FGIDs) and variations in the cerebral cortex. However, the causality of these relationships remains unclear, confounded by anxiety and depression. To clarify these causal relationships and explore the mediating roles of anxiety and depression, we applied univariate, multivariable, and mediation Mendelian randomization (MR) analyses. We utilized genome-wide association study (GWAS) summary data from the FinnGen database and the ENIGMA consortium, identifying genetic variants associated with irritable bowel syndrome (IBS), functional dyspepsia (FD), and cerebral cortex structures. Data on anxiety and depression came from FinnGen and a large meta-analysis. Utilizing a bidirectional univariate MR approach, we explored correlations between FD, IBS, and cortex variations. Then, independent effects were assessed through multivariable MR. A meta-analysis of these results, incorporating data from two cohorts, aimed to increase precision. We also explored the potential mediating roles of anxiety and depression. Our findings indicate a negative causal correlation between FD and the thickness of the rostral anterior cingulate cortex (rACC) across both global and regional adjustments (β = -0.142, 95% confidence interval (CI): -0.209 to-0.074, P.FDR = 0.004; β = -0.112, 95%CI: -0.163 to-0.006, P.FDR = 0.003) and a positive causal correlation with the globally adjusted thickness of the superior frontal gyrus (SFG) (β = 0.107, 95%CI: 0.062 to 0.153, P.FDR = 0.001). The causal correlation with the rACC persisted after multiple variable adjustments (β = -0.137, 95% CI: -0.187 to-0.087, P.FDR = 1.81 × 10-5; β = -0.109, 95%CI: -0.158 to-0.06, P.FDR = 0.002). A significant causal association was found between globally adjusted surface area of the caudal anterior cingulate cortex (cACC) and IBS (odds ratio = 1.267, 95%CI: 1.128 to 1.424, P.FDR = 0.02). The analysis showed that neither anxiety nor depression mediated the relationship between FGIDs and cerebral cortex structures. Our research provides significant MR evidence of a bidirectional causal relationship between FGIDs and the cerebral cortex structures. This evidence not only confirms the two-way communication along the brain-gut axis but also illuminates the underlying pathophysiology, paving the way for identifying potential therapeutic approaches.

Localized alterations in cortical thickness and sulcal depth of the cingulo-opercular network in relation to lower reading fluency skills in children with dyslexia

The traditional models of reading development describe how language processing and word decoding contribute to reading comprehension and how impairments in word decoding, a defining feature of dyslexia, affect reading comprehension outcomes. However, these models do not include word and sentence reading (contextual reading) fluency, both of which engage executive functions, with notably decreased performance in children with dyslexia. In the current study, we compared cortical thickness and sulcal depth (CT/SD) in the cingulo-opercular (CO) executive functions brain network in children with dyslexia and typical readers and examined associations with word vs. contextual reading fluency. Overall, CT was lower in insular regions and higher in parietal and caudal anterior cingulate cortex regions in children with dyslexia. Children with dyslexia showed positive correlations between word reading fluency and CT/SD in insular regions, whereas no significant correlations were observed in typical readers. For sentence reading fluency, negative correlations with CT/SD were found in insular regions in children with dyslexia, while positive correlations with SD were found in insular regions in typical readers. These results demonstrate the differential relations between word and sentence reading fluency and anatomical circuitry supporting executive functions in children with dyslexia vs. typical readers. It also suggests that word and sentence reading fluency, relate to morphology of executive function-related regions in children with dyslexia, whereas in typical readers, only sentence reading fluency relates to morphology of executive function regions. The results also highlight the role of the insula within the CO network in reading fluency. Here we suggest that word and sentence reading fluency are distinct components of reading that should each be included in the Simple View of Reading traditional model.

Cerebral Cortical Surface Structure and Neural Activation Pattern Among Adolescent Football Players

Recurring exposure to head impacts in American football has garnered public and scientific attention, yet neurobiological associations in adolescent football players remain unclear. To examine cortical structure and neurophysiological characteristics in adolescent football players. This cohort study included adolescent football players and control athletes (swimming, cross country, and tennis) from 5 high school athletic programs, who were matched with age, sex (male), and school. Neuroimaging assessments were conducted May to July of the 2021 and 2022 seasons. Data were analyzed from February to November 2023. Playing tackle football or noncontact sports. Structural magnetic resonance imaging (MRI) data were analyzed for cortical thickness, sulcal depth, and gyrification, and cortical surface-based resting state (RS)-functional MRI analyses examined the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and RS-functional connectivity (RS-FC). Two-hundred seventy-five male participants (205 football players; mean [SD] age, 15.8 [1.2] years; 5 Asian [2.4%], 8 Black or African American [3.9%], and 189 White [92.2%]; 70 control participants; mean [SD] age 15.8 [1.2] years, 4 Asian [5.7], 1 Black or African American [1.4%], and 64 White [91.5%]) were included in this study. Relative to the control group, the football group showed significant cortical thinning, especially in fronto-occipital regions (eg, right precentral gyrus: t = -2.24; P = .01; left superior frontal gyrus: -2.42; P = .002). Elevated cortical thickness in football players was observed in the anterior and posterior cingulate cortex (eg, left posterior cingulate cortex: t = 2.28; P = .01; right caudal anterior cingulate cortex 3.01; P = .001). The football group had greater and deeper sulcal depth than the control groups in the cingulate cortex, precuneus, and precentral gyrus (eg, right inferior parietal lobule: t = 2.20; P = .004; right caudal anterior cingulate cortex: 4.30; P < .001). Significantly lower ALFF was detected in the frontal lobe and cingulate cortex of the football group (t = -3.66 to -4.92; P < .01), whereas elevated ALFF was observed in the occipital regions (calcarine and lingual gyrus, t = 3.20; P < .01). Similar to ALFF, football players exhibited lower ReHo in the precentral gyrus and medial aspects of the brain, such as precuneus, insula, and cingulum, whereas elevated ReHo was clustered in the occipitotemporal regions (t = 3.17; P < .001; to 4.32; P < .01). There was no group difference in RS-FC measures. In this study of adolescent athletes, there was evidence of discernible structural and physiological differences in the brains of adolescent football players compared with their noncontact controls. Many of the affected brain regions were associated with mental health well-being.

Associations between low-moderate prenatal alcohol exposure and brain development in childhood

BackgroundThe effects of low-moderate prenatal alcohol exposure (PAE) on brain development have been infrequently studied. AimTo compare cortical and white matter structure between children aged 6 to 8 years with low-moderate PAE in trimester 1 only, low-moderate PAE throughout gestation, or no PAE. MethodsWomen reported quantity and frequency of alcohol consumption before and during pregnancy. Magnetic resonance imaging was undertaken for 143 children aged 6 to 8 years with PAE during trimester 1 only (n = 44), PAE throughout gestation (n = 58), and no PAE (n = 41). T1-weighted images were processed using FreeSurfer, obtaining brain volume, area, and thickness of 34 cortical regions per hemisphere. Fibre density (FD), fibre cross-section (FC) and fibre density and cross-section (FDC) metrics were computed for diffusion images. Brain measures were compared between PAE groups adjusted for age and sex, then additionally for intracranial volume. ResultsAfter adjustments, the right caudal anterior cingulate cortex volume (pFDR = 0.045) and area (pFDR = 0.008), and right cingulum tract cross-sectional area (pFWE < 0.05) were smaller in children exposed to alcohol throughout gestation compared with no PAE. ConclusionThis study reports a relationship between low-moderate PAE throughout gestation and cingulate cortex and cingulum tract alterations, suggesting a teratogenic vulnerability. Further investigation is warranted.

Exploring the Interplay of Age and Pedagogy in the Maturation of Error‐Monitoring

ABSTRACTError‐monitoring is a crucial cognitive process that enables us to adapt to the constantly changing environment. The anterior cingulate cortex (ACC) plays a vital role in error‐monitoring, and its prolonged maturation suggests that it can be influenced by experience‐dependent plasticity. To explore this possibility, we collected morphometric magnetic resonance imaging (MRI) measures of the ACC and error‐related response‐locked event‐related potentials (ERPs) in 26 schoolchildren, aged 6–12 years, enrolled in either a Montessori or a traditional curriculum in Switzerland. We show that the caudal ACC undergoes significant morphometric changes during this developmental age range that seem related to error detection ERP activity. Furthermore, we observed differences in source localization activity related to error detection within the caudal ACC between Montessori and traditionally‐schooled children, indicating a potential difference in the development of error‐monitoring in these groups. Our study provides preliminary evidence for a potential window of opportunity to influence error‐monitoring during development and calls for more work in that direction.

Resting-State Functional Connectivity of the Anterior Cingulate Cortex Among Persons With Mood Disorders and Suicidal Behaviors.

To assess whether anterior cingulate cortex (ACC) abnormalities contribute to suicide risk in major depressive disorder and bipolar disorder, the investigators compared resting-state functional connectivity (rsFC) of ACC subdivisions between individuals with major depressive or bipolar disorder with and without a lifetime history of suicidal behavior. Forty-two inpatients with and 26 inpatients without a history of suicidal behavior (SB+ and SB-, respectively) associated with major depressive or bipolar disorder and 40 healthy control (HC) participants underwent rsFC neuroimaging. RsFC of the subgenual, perigenual, rostral, dorsal, and caudal subdivisions of the ACC was calculated. Possible confounders, such as psychosis and severity of depression, were controlled for, seed-to-voxel and post hoc region of interest (ROI)-to-ROI analyses were performed, and the accuracy of rsFC in classifying suicidal behavior was studied. Compared with individuals in the SB- and HC groups, patients in the SB+ group had higher rsFC between the left rostral and right dorsal ACC seeds and visual cortex clusters. Conversely, rsFC between the left rostral and right dorsal ACC seeds and cingulate and frontal clusters was lower in the SB+ group than in the HC group. Left rostral ACC to left Brodmann's area 18 connectivity showed up to 75% discriminative accuracy in distinguishing SB+ from SB- patients. A history of suicidal behavior among individuals with major depressive disorder or bipolar disorder was associated with altered rsFC of the rostral and caudal ACC, regions involved in conflict detection and error monitoring. Replication of these findings is needed to further explore the involvement of the ACC in the neurobiology of suicidal behavior and suicidal ideation.

RADT-50. EVIDENCE-BASED MULTIVARIATE NORMAL TISSUE COMPLICATION PROBABILITY (NTCP) STUDY OF DOMAIN-SPECIFIC COGNITIVE DECLINE AFTER PARTIAL BRAIN RADIATION (RT)

Abstract Beyond the hippocampus, there are no evidence-based dose constraints for eloquent brain structures which subserve cognitive domains. We performed a multivariate NTCP analysis of post-RT neurocognitive decline, examining dosimetric predictors of eloquent brain regions in a prospective longitudinal clinical trial. 83 patients with primary brain tumors receiving fractionated RT completed comprehensive neurocognitive evaluation and high-resolution volumetric and diffusion MRI at baseline and 6 months post-RT. Image processing using robust, validated automated segmentation parcellated individual white matter (WM) tracts, cortical regions, and hippocampi. Well-validated neurocognitive tests evaluating multiple cognitive domains were assessed with negative reliable change indices adjusted for practice effects between timepoints scored as decline. Univariate logistic regression and multivariate model building were performed examining dose to eloquent structures and clinical variables. Univariate analysis showed mean dose to the bilateral caudal anterior cingulate cortex and WM were correlated with decline in executive function. Attention/processing speed decline was correlated with mean/max dose to the posterior corpus callosum (CC), volume getting &amp;gt;20 Gy in the combined CC, as well as anti-epileptic use and chemotherapy. On multivariate analysis for attention automated bootstrapped logistic regression performance at nested cross-validation by AUC was 0.59 (0.54-0.65); LASSO model performance by AUC was 0.60 (0.54-0.66) with mean dose to combined CC being the most frequent variable in both. The top three most important variables in Random Forest by mean decrease in Gini coefficient were max dose to posterior and combined CC and mean dose to anterior CC. Model performance by AUC was 0.70 (0.64-0.75). Here we present the first, to our knowledge, NTCP model for decline in attention/processing speed, along with dosimetric predictors of executive function decline. We found that after partial brain RT, dose to several ROIs significantly correlated with post-RT impairment. These data can guide future cognitive-sparing strategies for brain RT.

Exploratory analysis of cortical thickness in low- and high-fit young adults.

Studies have shown changes in the human brain associated with physical activity and cardiorespiratory fitness (CRF). The effects of CRF on cortical thickness have been well-described in older adults, where a positive association between CRF and cortical thickness has been reported, but the impact of sustained aerobic activity in young adults remains poorly described. Here, exploratory analysis was performed on cortical thickness data that was collected in groups of fit and sedentary young adults. Twenty healthy sedentary individuals (<2 h/week physical activity) were compared to 20 active individuals (>6 h/week physical activity) and cortical thickness was measured in 34 cortical areas. Cortical thickness values were compared between groups, and correlations between cortical thickness and VO2 max were tested. Cardiorespiratory fitness was significantly higher in active individuals compared to sedentary individuals. Cortical thickness was lower in regions of the left (lateral and medial orbitofrontal cortex, pars orbitalis, pars triangularis, rostral anterior cingulate cortex, superior temporal cortex and frontal pole) and right (lateral and medial orbitofrontal cortex and pars opercularis) hemispheres. Only the left frontal pole and right lateral orbitofrontal cortical thickness remained significant after false discovery rate correction. Negative correlations were observed between VO2 max and cortical thickness in the left (frontal pole) and right (caudal anterior cingulate and medial orbitofrontal cortex) hemispheres. The present exploratory analysis supports previous findings suggesting that neuroplastic effects of cardiorespiratory fitness may be attenuated in young compared with older individuals, underscoring a moderating effect of age on the relationship between fitness and cortical thickness.

Functional brain connectivity in young adults with post-stroke epilepsy.

Approximately 1 in 10 young stroke patients (18-50 years) will develop post-stroke epilepsy, which is associated with cognitive impairment. While previous studies have shown altered brain connectivity in patients with epilepsy, little is however known about the changes in functional brain connectivity in young stroke patients with post-stroke epilepsy and their relationship with cognitive impairment. Therefore, we aimed to investigate whether young ischaemic stroke patients have altered functional networks and whether this alteration is related to cognitive impairment. We included 164 participants with a first-ever cerebral infarction at young age (18-50 years), along with 77 age- and sex-matched controls, from the Follow-Up of Transient Ischemic Attack and Stroke patients and Unelucidated Risk Factor Evaluation study. All participants underwent neuropsychological testing and resting-state functional MRI to generate functional connectivity networks. At follow-up (10.5 years after the index event), 23 participants developed post-stroke epilepsy. Graph theoretical analysis revealed functional network reorganization in participants with post-stroke epilepsy, in whom a weaker (i.e. network strength), less-integrated (i.e. global efficiency) and less-segregated (i.e. clustering coefficient and local efficiency) functional network was observed compared with the participants without post-stroke epilepsy group and the controls (P < 0.05). Regional analysis showed a trend towards decreased clustering coefficient, local efficiency and nodal efficiency in contralesional brain regions, including the caudal anterior cingulate cortex, posterior cingulate cortex, precuneus, superior frontal gyrus and insula in participants with post-stroke epilepsy compared with those without post-stroke epilepsy. Furthermore, participants with post-stroke epilepsy more often had impairment in the processing speed domain than the group without post-stroke epilepsy, in whom the network properties of the precuneus were positively associated with processing speed performance. Our findings suggest that post-stroke epilepsy is associated with functional reorganization of the brain network after stroke that is characterized by a weaker, less-integrated and less-segregated brain network in young ischaemic stroke patients compared with patients without post-stroke epilepsy. The contralesional brain regions, which are mostly considered as hub regions, might be particularly involved in the altered functional network and may contribute to cognitive impairment in post-stroke epilepsy patients. Overall, our findings provide additional evidence for a potential role of disrupted functional network as underlying pathophysiological mechanism for cognitive impairment in patients with post-stroke epilepsy.

Topographical similarity of cortical thickness represents generalized anxiety symptoms in adolescence

Generalized anxiety disorder (GAD) is a common condition characterized by excessive and uncontrollable worry, along with its high comorbidity rates. Despite increasing efforts to identify the neural underpinnings of GAD, neuroimaging research using cortical thickness have yielded largely inconsistent results. To address this, we adopted an inter-subject representational similarity analysis framework to explore a potential nonlinear relationship between vertex-wise cortical thickness and generalized anxiety symptom severity. We utilized a sample of 120 adolescents (13–18 years of age) from the Healthy Brain Network dataset. Here, we found greater topographical resemblance among participants with heightened generalized anxiety symptoms in the left caudal anterior cingulate and pericalcarine cortex. These results were not driven by the effects of age, sex, ADHD diagnosis, and GAD diagnosis. Such associations were not observed when including a group of younger participants (11–12 years of age) for analyses, highlighting the importance of age range selection when considering the link between cortical thickness and anxiety. Our findings reveal a novel cortical thickness topography that represents generalized anxiety in adolescents, which is embedded within the shared geometries between generalized anxiety symptoms and cortical thickness.

Physical symptoms and brain morphology: a population neuroimaging study in 12,286 pre-adolescents

Physical symptoms, also known as somatic symptoms, are those for which medical examinations do not reveal a sufficient underlying root cause (e.g., pain and fatigue). The extant literature of the neurobiological underpinnings of physical symptoms is largely inconsistent and primarily comprises of (clinical) case-control studies with small sample sizes. In this cross-sectional study, we studied the association between dimensionally measured physical symptoms and brain morphology in pre-adolescents from two population-based cohorts; the Generation R Study (n = 2649, 10.1 ± 0.6 years old) and ABCD Study (n = 9637, 9.9 ± 0.6 years old). Physical symptoms were evaluated using continuous scores from the somatic complaints syndrome scale from the parent-reported Child Behavior Checklist (CBCL). High‐resolution structural magnetic resonance imaging (MRI) was collected using 3-Tesla MRI systems. Linear regression models were fitted for global brain metrics (cortical and subcortical grey matter and total white matter volume) and surface-based vertex-wise measures (surface area and cortical thickness). Results were meta-analysed. Symptoms of anxiety/depression were studied as a contrasting comorbidity. In the meta-analyses across cohorts, we found negative associations between physical symptoms and surface area in the (i) left hemisphere; in the lateral orbitofrontal cortex and pars triangularis and (ii) right hemisphere; in the pars triangularis, the pars orbitalis, insula, middle temporal gyrus and caudal anterior cingulate cortex. However, only a subset of regions (left lateral orbitofrontal cortex and right pars triangularis) were specifically associated with physical symptoms, while others were also related to symptoms of anxiety/depression. No significant associations were observed for cortical thickness. This study in preadolescents, the most representative and well-powered to date, showed that more physical symptoms are modestly related to less surface area of the prefrontal cortex mostly. While these effects are subtle, future prospective research is warranted to understand the longitudinal relationship of physical symptoms and brain changes over time. Particularly, to elucidate whether physical symptoms are a potential cause or consequence of distinct neurodevelopmental trajectories.

Plasticity of Cortico-striatal Neurons of the Caudal Anterior Cingulate Cortex During Experimental Neuropathic Pain

Maladaptive neuronal plasticity is a main mechanism for the development and maintenance of pathological pain. Affective, motivational and cognitive deficits that are comorbid with pain involve cellular and synaptic modifications in the anterior cingulate cortex (ACC), a major brain mediator of pain perception. Here we use a model of neuropathic pain (NP) in male mice and ex-vivo electrophysiology to investigate whether layer 5 caudal ACC (cACC) neurons projecting to the dorsomedial striatum (DMS), a critical region for motivational regulation of behavior, are involved in aberrant neuronal plasticity. We found that while the intrinsic excitability of cortico-striatal cACC neurons (cACC-CS) was preserved in NP animals, excitatory postsynaptic potentials (EPSP) induced after stimulation of distal inputs were enlarged. The highest synaptic responses were evident both after single stimuli and in each of the EPSP that compose responses to trains of stimuli, and were accompanied by increased synaptically-driven action potentials. EPSP temporal summation was intact in ACC-CS neurons from NP mice, suggesting that the plastic changes were not due to alterations in dendritic integration but rather through synaptic mechanisms. These results demonstrate for the first time that NP affects cACC neurons that project to the DMS and reinforce the notion that maladaptive plasticity of the cortico-striatal pathway may be a key factor in sustaining pathological pain.

A longitudinal study of childhood maltreatment, subcortical development, and subcortico-cortical structural maturational coupling from early to late adolescence.

Examining neurobiological mechanisms that may transmit the effects of childhood maltreatment on mental health in youth is crucial for understanding vulnerability to psychopathology. This study investigated associations between childhood maltreatment, adolescent structural brain development, and mental health trajectories into young-adulthood. Structural magnetic resonance imaging data was acquired from 144 youth at three time points (age 12, 16, and 18 years). Childhood maltreatment was reported to occur prior to the first scan. Linear mixed models were utilized to examine the association between total childhood maltreatment, neglect, abuse and (i) amygdala and hippocampal volume development, and (ii) maturational coupling between amygdala/hippocampus volume and the thickness of prefrontal regions. We also examined whether brain development mediated the association between maltreatment and depressive and anxiety symptoms trajectories from age 12 to 28. Total maltreatment, and neglect, were associated with positive maturational coupling between the amygdala and caudal anterior cingulate cortex (cACC), whereby at higher and lower levels of amygdala growth, maltreatment was associated with lower and higher PFC thinning, respectively. Neglect was also associated with maturational coupling of the hippocampus with prefrontal regions. While positive amygdala-cACC maturational coupling was associated with greater increases in anxiety symptoms, it did not significantly mediate the association between maltreatment and anxiety symptom trajectories. We found maltreatment to be associated with altered patterns of coupling between subcortical and prefrontal regions during adolescence, suggesting that maltreatment is associated with the development of socio-emotional neural circuitry. The implications of these findings for mental health require further investigation.

Neuroanatomical restoration of salience network links reduced headache impact to cognitive function improvement in mild traumatic brain injury with posttraumatic headache

BackgroundNeuroanatomical alterations have been associated with cognitive deficits in mild traumatic brain injury (MTBI). However, most studies have focused on the abnormal gray matter volume in widespread brain regions using a cross-sectional design in MTBI. This study investigated the neuroanatomical restoration of key regions in salience network and the outcomes in MTBI.MethodsThirty-six MTBI patients with posttraumatic headache (PTH) and 34 matched healthy controls were enrolled in this study. All participants underwent magnetic resonance imaging scans and were assessed with clinical measures during the acute and subacute phases. Surface-based morphometry was conducted to get cortical thickness (CT) and cortical surface area (CSA) of neuroanatomical regions which were defined by the Desikan atlas. Then mixed analysis of variance models were performed to examine CT and CSA restoration in patients from acute to subacute phase related to controls. Finally, mediation effects models were built to explore the relationships between neuroanatomical restoration and symptomatic improvement in patients.ResultsMTBI patients with PTH showed reduced headache impact and improved cognitive function from the acute to subacute phase. Moreover, patients experienced restoration of CT of the left caudal anterior cingulate cortex (ACC) and left insula and cortical surface area of the right superior frontal gyrus from acute to subacute phase. Further mediation analysis found that CT restoration of the ACC and insula mediated the relationship between reduced headache impact and improved cognitive function in patients.ConclusionsThese results showed that neuroanatomical restoration of key regions in salience network correlated reduced headache impact with cognitive function improvement in MTBI with PTH, which further substantiated the vital role of salience network and provided an alternative clinical target for cognitive improvement in MTBI patients with PTH.Graphical

Preliminary findings on the effect of childhood trauma on the functional connectivity of the anterior cingulate cortex subregions in major depressive disorder.

Childhood trauma (CT) is a known risk factor for major depressive disorder (MDD), but the mechanisms linking CT and MDD remain unknown. The purpose of this study was to examine the influence of CT and depression diagnosis on the subregions of the anterior cingulate cortex (ACC) in MDD patients. The functional connectivity (FC) of ACC subregions was evaluated in 60 first-episode, drug-naïve MDD patients (40 with moderate-to-severe and 20 with no or low CT), and 78 healthy controls (HC) (19 with moderate-to-severe and 59 with no or low CT). The correlations between the anomalous FC of ACC subregions and the severity of depressive symptoms and CT were investigated. Individuals with moderate-to severe CT exhibited increased FC between the caudal ACC and the middle frontal gyrus (MFG) than individuals with no or low CT, regardless of MDD diagnosis. MDD patients showed lower FC between the dorsal ACC and the superior frontal gyrus (SFG) and MFG. They also showed lower FC between the subgenual/perigenual ACC and the middle temporal gyrus (MTG) and angular gyrus (ANG) than the HCs, regardless of CT severity. The FC between the left caudal ACC and the left MFG mediated the correlation between the Childhood Trauma Questionnaire (CTQ) total score and HAMD-cognitive factor score in MDD patients. Functional changes of caudal ACC mediated the correlation between CT and MDD. These findings contribute to our understanding of the neuroimaging mechanisms of CT in MDD.

Functional dysconnectivity of anterior cingulate subregions in schizophrenia and psychotic and nonpsychotic bipolar disorder.

Aberrant resting-state functional connectivity (FC) of anterior cingulate cortex (ACC) has been implicated in the pathophysiology of schizophrenia and bipolar disorder (BP). This study investigated the subregional FC of ACC across schizophrenia and psychotic (PBP) and nonpsychotic BP (NPBP) and the relationship between brain functional alterations and clinical manifestations. A total of 174 first-episode medication-naive patients with schizophrenia (FES), 80 patients with PBP, 77 patients with NPBP and 173 demographically matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Brain-wide FC of ACC subregions was computed for each individual, and compared between the groups. General intelligence was evaluated using the short version of the Wechsler Adult Intelligence Scale. Relationships between FC and various clinical and cognitive variables were estimated using the skipped correlation. The FES, PBP and NPBP groups showed differing connectivity patterns in the left caudal, dorsal and perigenual ACC. Transdiagnostic dysconnectivity was found in the subregional ACC associated with cortical, limbic, striatal and cerebellar regions. Disorder-specific dysconnectivity in FES was identified between the left perigenual ACC and bilateral orbitofrontal cortex, and the left caudal ACC coupling with the default mode network (DMN) and visual processing region was correlated with psychotic symptoms. In the PBP group, FC between the left dorsal ACC and the right caudate was correlated with psychotic symptoms, and FC connected with the DMN was associated with affective symptoms. The current findings confirmed that subregional ACC dysconnectivity could be a key transdiagnostic feature and associated with differing clinical symptomology across schizophrenia and PBP.

Dysgranular retrosplenial cortex modulates histaminergic and nonhistaminergic itch processing

Itch is an unpleasant sensation followed by an intense desire to scratch. Previous researches have advanced our understanding about the role of anterior cingulate cortex and prelimbic cortex in itch modulation, whereas little is known about the effects of retrosplenial cortex (RSC) during this process. Here we firstly confirmed that the neuronal activity of dysgranular RSC (RSCd) is significantly elevated during itch-scratching processing through c-Fos immunohistochemistry and fiber photometry recording. Then with designer receptors exclusively activated by designer drugs approaches, we found that pharmacogenetic inhibition of global RSCd neurons attenuated the number of scratching bouts as well as the cumulative duration of scratching bouts elicited by both 5-HT or compound 48/80 injection into rats’ nape or cheek; selective inhibition of the pyramidal neurons in RSCd, or of the excitatory projections from caudal anterior cingulate cortex (cACC) to RSCd, demonstrated the similar effects of decreasing itch-related scratching induced by both 5-HT or compound 48/80. Pharmacogenetic intervention of the neuronal or circuitry activities did not affect rats’ motor ability. This study presents direct evidence that pyramidal neurons in RSCd, and the excitatory projection from cACC to RSCd are critically involved in central regulation of both histaminergic and nonhistaminergic itch.

Altered anterior cingulate cortex subregional connectivity associated with cognitions for distinguishing the spectrum of pre-clinical Alzheimer's disease.

Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are considered part of the early progression continuum of Alzheimer's disease (AD). The anterior cingulate cortex (ACC), a hub of information processing and regulation in the brain, plays an essential role in AD pathophysiology. In the present study, we aimed to systematically identify changes in the functional connectivity (FC) of ACC subregions in patients with SCD and aMCI and evaluate the association of these changes with cognition. Functional connectivity (FC) analysis of ACC sub-regions was performed among 66 patients with SCD, 71 patients with aMCI, and 78 healthy controls (HCs). Correlation analyses were performed to examine the relationship between FC of altered ACC subnetworks and cognition. Compared to HCs, SCD patients showed increased FC of the bilateral precuneus (PCUN) and caudal ACC, left superior frontal gyrus (SFG) and subgenual ACC, left inferior parietal lobule (IPL) and dorsal ACC, left middle occipital gyrus (MOG) and dorsal ACC, and left middle temporal gyrus (MTG) and subgenual ACC, while aMCI patients showed increased FC of the left inferior frontal gyrus (IFG) and dorsal ACC and left medial frontal gyrus (MFG) and subgenual ACC. Compared to patients with SCD, patients with aMCI showed increased FC of the right MFG and dorsal ACC and left ACC and subgenual ACC, while the left posterior cingulate cortex (PCC) showed decreased FC with the caudal ACC. Moreover, some FC values among the altered ACC subnetworks were significantly correlated with episodic memory and executive function. SCD and aMCI, part of the spectrum of pre-clinical AD, share some convergent and divergent altered intrinsic connectivity of ACC subregions. These results may serve as neuroimaging biomarkers of the preclinical phase of AD and provide new insights into the design of preclinical interventions.

Exploring the heterogeneous morphometric data in essential tremor with probabilistic modelling

Essential tremor (ET) is a prevalent movement disorder characterized by marked clinical heterogeneity. Here, we explored the morphometric underpinnings of this cross-subject variability on a cohort of 34 patients with right-dominant drug-resistant ET and 29 matched healthy controls (HCs). For each brain region, group-wise morphometric data was modelled by a multivariate Gaussian to account for morphometric features’ (co)variance.No group differences were found in terms of mean values, highlighting the limits of more basic group comparison approaches. Variance in surface area was higher in ET in the left lingual and caudal anterior cingulate cortices, while variance in mean curvature was lower in the right superior temporal cortex and pars triangularis, left supramarginal gyrus and bilateral paracentral gyrus. Heterogeneity further extended to the right putamen, for which a mixture of two Gaussians fitted the ET data better than a single one.Partial Least Squares analysis revealed the rich clinical relevance of the ET population’s heterogeneity: first, increased head tremor and longer symptoms’ duration were accompanied by broadly lower cortical gyrification. Second, more severe upper limb tremor and impairments in daily life activities characterized the patients whose morphometric profiles were more atypical compared to the average ET population, irrespective of the exact nature of the alterations.Our results provide candidate morphometric substrates for two different types of clinical variability in ET. They also demonstrate the importance of relying on analytical approaches that can efficiently handle multivariate data and enable to test more sophisticated hypotheses regarding its organization.

Physical Activity Level Moderates the Association Between Response Inhibition and Anterior Cingulate Cortex Volume in Older Adults

AbstractBackgroundAging is generally associated with a decline in executive function, a cognitive domain that is critical to functional independence. Response inhibition is an executive process that contributes to anticipation, planning, and goal setting. The anterior cingulate cortex (ACC) is a key brain structure that supports response inhibition and shows gray matter loss with age. Evidence suggests that both response inhibition performance and the Anterior Cingulate Cortex (ACC) are responsive to exercise training. Whether physical activity moderates the relationship between response inhibition and the ACC in older adults is unknown.MethodA cross‐sectional analysis of a subset of community‐dwelling older adults enrolled in a 3‐arm, 8‐week proof of concept randomized control trial of computerized cognitive training, with or without exercise, who completed T1 magnetic resonance imaging (MRI) at baseline. Of the 68 MRI participants, 11 were removed from this analysis due to poor scan quality. Response inhibition was measured using the Flanker Task from the NIH Toolbox Cognitive Battery. Participants were split into either a high or low physical activity groups determined by their median Physical Activity Scale for the Elderly (PASE) score. Caudal and rostral ACC volumes were segmented and quantified using FreeSurfer. To assess for moderation, we performed linear regressions with age‐adjusted Flanker Task score as the dependent variable, and ACC volume, high/low PASE, and the interaction of ACC volume * high/low PASE as independent variables.ResultPhysical activity level significantly moderated the association between left caudal anterior cingulate cortex (LCACC) volume and age‐adjusted Flanker Task score, (β = –6.428, t(53) = ‐2.075, p &lt; .05). Among those with low physical activity levels (n = 30), greater LCACC volume was associated with better response inhibition (r = 0.44, p = .01) while there was no association among those with high physical activity levels (n = 27; r = ‐0.13; p = .52).ConclusionHigher physical activity may mitigate the negative effects of age‐related gray matter loss in the ACC on response inhibition performance in community‐dwelling older adults.