Medial Cortex Research Articles

Prefrontal cortex structural and developmental associations with callous-unemotional traits and aggression.

Youths with high levels of callous-unemotional (CU) traits and aggression are at an increased risk for developing antisocial behaviours into adulthood. In this population, neurostructural grey matter abnormalities have been observed in the prefrontal cortex. However, the directionality of these associations is inconsistent, prompting some to suggest they may vary across development. Although similar neurodevelopmental patterns have been observed for other disorders featuring emotional and behavioural dysregulation, few studies have tested this hypothesis for CU traits, and particularly not for aggression subtypes. The current study sought to examine grey matter correlates of CU traits and aggression (including its subtypes), and then determine whether these associations varied by age. Fifty-four youths (10-19years old) who were characterized for CU traits and aggression underwent MRI. Grey matter volume and surface area within the anterior cingulate cortex was positively associated with CU traits. The correlation between CU traits and medial orbitofrontal cortex (mOFC) volume varied significantly as a function of age, as did the correlation between reactive aggression and mOFC surface area. These associations became more positive with age. There were no significant findings for proactive/total aggression. Results are interpreted considering the potential for delayed cortical maturation in youths with high CU traits/aggression.

EEG-based major depressive disorder recognition by neural oscillation and asymmetry.

Major Depressive Disorder (MDD) is a pervasive mental health issue with significant diagnostic challenges. Electroencephalography (EEG) offers a non-invasive window into the neural dynamics associated with MDD, yet the diagnostic efficacy is contingent upon the appropriate selection of EEG features and brain regions. In this study, resting-state EEG signals from both eyes-closed and eyes-open conditions were analyzed. We examined band power across various brain regions, assessed the asymmetry of band power between the hemispheres, and integrated these features with clinical characteristics of MDD into a diagnostic regression model. Regression analysis found significant predictors of MDD to be beta2 (16-24 Hz) power in the Prefrontal Cortex (PFC) with eyes open (B = 20.092, p = 0.011), beta3 (24-40 Hz) power in the Medial Occipital Cortex (MOC) (B = -12.050, p < 0.001), and beta2 power in the Right Medial Frontal Cortex (RMFC) with eyes closed (B = 24.227, p < 0.001). Asymmetries in beta1 (12-16 Hz) power with eyes open (B = 28.047, p = 0.018), and in alpha (8-12 Hz, B = 9.004, p = 0.013) and theta (4-8 Hz, B = -13.582, p = 0.008) with eyes closed were also significant predictors. The study confirms the potential of multi-region EEG analysis in improving the diagnostic precision for MDD. By including both neurophysiological and clinical data, we present a more robust approach to understanding and identifying this complex disorder. The research is limited by the sample size and the inherent variability in EEG signal interpretation. Future studies with larger cohorts and advanced analytical techniques are warranted to validate and refine these findings.

Sex and pubertal variation in reward-related behavior and neural activation in early adolescents

This study aimed to characterize the role of sex and pubertal markers in reward motivation behavior and neural processing in early adolescence. We used baseline and two-year follow-up data from the Adolescent Brain and Cognitive DevelopmentSM study (15844 observations; 52% from boys; age 9–13). Pubertal development was measured with parent-reported Pubertal Development Scale, and DHEA, testosterone, and estradiol levels. Reward motivation behavior and neural processing at anticipation and feedback stages were assessed with the Monetary Incentive Delay task. Boys had higher reward motivation than girls, demonstrating greater accuracy difference between reward and neutral trials and higher task earnings. Girls had lower neural activation during reward feedback than boys in the nucleus accumbens, caudate, rostral anterior cingulate, medial orbitofrontal cortex, superior frontal gyrus and posterior cingulate. Pubertal stage and testosterone levels were positively associated with reward motivation behavior, although these associations changed when controlling for age. There were no significant associations between pubertal development and neural activation during reward anticipation and feedback. Sex differences in reward-related processing exist in early adolescence, signaling the need to understand their impact on typical and atypical functioning as it unfolds into adulthood.

Learning Cognitive Flexibility: Neural Substrates of Adapting Switch-Readiness to Time-varying Demands.

An individual's readiness to switch tasks (cognitive flexibility) varies over time, in part, as the result of reinforcement learning based on the statistical structure of the world around them. Consequently, the behavioral cost associated with task-switching is smaller in contexts where switching is frequent than where it is rare, but the underlying brain mechanisms of this adaptation in cognitive flexibility are not well understood. Here, we manipulated the likelihood of switches across blocks of trials in a classic cued task-switching paradigm while participants underwent fMRI. As anticipated, behavioral switch costs decreased as the probability of switching increased, and neural switch costs were observed in lateral and medial frontoparietal cortex. To study moment-by-moment adjustments in cognitive flexibility at the neural level, we first fitted the behavioral RT data with reinforcement learning algorithms and then used the resulting trial-wise prediction error estimate as a regressor in a model-based fMRI analysis. The results revealed that lateral frontal and parietal cortex activity scaled positively with unsigned switch prediction error and that there were no brain regions encoding signed (i.e., switch- or repeat-specific) prediction error. Taken together, this study documents that adjustments in cognitive flexibility to time-varying switch demands are mediated by frontoparietal cortex tracking the likelihood of forthcoming task switches.

Longitudinal Brain Perfusion and Symptom Presentation Following Pediatric Concussion: A Pediatric Concussion Assessment of Rest and Exertion+MRI (PedCARE+MRI) Substudy.

Emerging evidence suggests that advanced neuroimaging modalities such as arterial spin labelling (ASL) might have prognostic utility for pediatric concussion. This study aimed to: 1) examine group differences in global and regional brain perfusion in youth with concussion or orthopedic injury (OI) at 72 h and 4 weeks post-injury; 2) examine patterns of abnormal brain perfusion within both groups and their recovery; 3) investigate the association between perfusion and symptom burden within concussed and OI youths at both time-points; and 4) explore perfusion between symptomatic and asymptomatic concussed and OI youths. Youths ages 10.00-17.99 years presenting to the emergency department with an acute concussion or OI were enrolled. ASL-magnetic resonance imaging scans were conducted at 72 h and 4 weeks post-injury to measure brain perfusion, along with completion of the Health Behavior Inventory (HBI) to measure symptoms. Abnormal perfusion clusters were identified using voxel-based z-score analysis at each visit. First, mixed analyses of covariance (ANCOVAs) investigated the Group*Time interaction on global and regional perfusion. Post hoc region of interest (ROI) analyses were performed on significant regions. Second, within-group generalized estimating equations investigated the recovery of abnormal perfusion at an individual level. Third, multiple regressions at each time-point examined the association between HBI and regional perfusion, and between HBI and abnormal perfusion volumes within the concussion group. Fourth, whole-brain one-way ANCOVAs explored differences in regional and abnormal perfusion based on symptomatic status (symptomatic vs. asymptomatic) and OIs at each time-point. A total of 70 youths with a concussion [median age (interquartile range; IQR) = 12.70 (11.67-14.35), 47.1% female] and 29 with an OI [median age (IQR) = 12.05 (11.18-13.89), 41.4% female] were included. Although no Group effect was found in global perfusion, the concussion group showed greater adjusted perfusion within the anterior cingulate cortex/middle frontal gyrus (MFG) and right MFG compared with the OI group across time-points (ps ≤ 0.004). The concussion group showed lower perfusion within the right superior temporal gyrus at both time-points and bilateral occipital gyrus at 4 weeks, (ps ≤ 0.006). The number of hypoperfused clusters was increased at 72 h compared with 4 weeks in the concussion youths (p < 0.001), but not in the OIs. Moreover, Group moderated the HBI-perfusion association within the left precuneus and superior frontal gyrus at both time-points, (ps ≤ 0.001). No association was found between HBI and abnormal perfusion volume within the concussion group at any visits. At 4 weeks, the symptomatic sub-group (n = 10) showed lower adjusted perfusion within the right cerebellum and lingual gyrus, while the asymptomatic sub-group (n = 59) showed lower adjusted perfusion within the left calcarine, but greater perfusion within the left medial orbitofrontal cortex, right middle frontal gyrus, and bilateral caudate compared with OIs. Yet, no group differences were observed in the number of abnormal perfusion clusters or volumes at any visit. The present study suggests that symptoms may be associated with changes in regional perfusion, but not abnormal perfusion levels.

Roles of the medial and lateral orbitofrontal cortex in major depression and its treatment.

We describe evidence for dissociable roles of the medial and lateral orbitofrontal cortex (OFC) in major depressive disorder (MDD) from structure, functional activation, functional connectivity, metabolism, and neurochemical systems. The reward-related medial orbitofrontal cortex has lower connectivity and less reward sensitivity in MDD associated with anhedonia symptoms; and the non-reward related lateral OFC has higher functional connectivity and more sensitivity to non-reward/aversive stimuli in MDD associated with negative bias symptoms. Importantly, we propose that conventional antidepressants act to normalize the hyperactive lateral (but not medial) OFC to reduce negative bias in MDD; while other treatments are needed to operate on the medial OFC to reduce anhedonia, with emerging evidence suggesting that ketamine may act in this way. The orbitofrontal cortex is the key cortical region in emotion and reward, and the current review presents much new evidence about the different ways that the medial and lateral OFC are involved in MDD.

Facing emotions: real-time fMRI-based neurofeedback using dynamic emotional faces to modulate amygdala activity.

Maladaptive functioning of the amygdala has been associated with impaired emotion regulation in affective disorders. Recent advances in real-time fMRI neurofeedback have successfully demonstrated the modulation of amygdala activity in healthy and psychiatric populations. In contrast to an abstract feedback representation applied in standard neurofeedback designs, we proposed a novel neurofeedback paradigm using naturalistic stimuli like human emotional faces as the feedback display where change in the facial expression intensity (from neutral to happy or from fearful to neutral) was coupled with the participant's ongoing bilateral amygdala activity. The feasibility of this experimental approach was tested on 64 healthy participants who completed a single training session with four neurofeedback runs. Participants were assigned to one of the four experimental groups (n = 16 per group), i.e., happy-up, happy-down, fear-up, fear-down. Depending on the group assignment, they were either instructed to "try to make the face happier" by upregulating (happy-up) or downregulating (happy-down) the amygdala or to "try to make the face less fearful" by upregulating (fear-up) or downregulating (fear-down) the amygdala feedback signal. Linear mixed effect analyses revealed significant amygdala activity changes in the fear condition, specifically in the fear-down group with significant amygdala downregulation in the last two neurofeedback runs as compared to the first run. The happy-up and happy-down groups did not show significant amygdala activity changes over four runs. We did not observe significant improvement in the questionnaire scores and subsequent behavior. Furthermore, task-dependent effective connectivity changes between the amygdala, fusiform face area (FFA), and the medial orbitofrontal cortex (mOFC) were examined using dynamic causal modeling. The effective connectivity between FFA and the amygdala was significantly increased in the happy-up group (facilitatory effect) and decreased in the fear-down group. Notably, the amygdala was downregulated through an inhibitory mechanism mediated by mOFC during the first training run. In this feasibility study, we intended to address key neurofeedback processes like naturalistic facial stimuli, participant engagement in the task, bidirectional regulation, task congruence, and their influence on learning success. It demonstrated that such a versatile emotional face feedback paradigm can be tailored to target biased emotion processing in affective disorders.

Brain connectivity patterns associated with individual differences in the access to experience-near personal semantics: a resting-state fMRI study

It has been proposed that a continuum of specificity exists between episodic and semantic autobiographical memory. Personal semantics have been theorized to situate intermediately on this continuum, with more “experience-near” personal semantics (enPS) closer to the episodic end. We used individual differences in behavior as a model to investigate brain networks associated with the access to episodic autobiographical (EAM) and enPS information, assessing the relation between performance in the EAM and enPS conditions of the Autobiographical Fluency Task (AFT) and intrinsic brain connectivity. Results of an intrinsic connectivity contrast analysis showed that the global connectivity of two clusters in the left and right posterior cingulate cortex (PCC) was predicted by performance in the enPS conditions. Moreover, enPS scores predicted the connectivity strength of the right PCC with the bilateral anterior hippocampus (aHC), anterior middle temporal gyrus (aMTG) and medial orbitofrontal cortex, and the left aMTG and PCC. enPS scores also predicted the connectivity strength of the left PCC with the bilateral HC and MTG. The network highlighted involves parts of the core and of the dorsal medial subsystems of the Default Mode Network, in line with the proposal that enPS represents an intermediate entity between episodic and semantic memory.

Genetic risk score for Alzheimer's disease predicts brain volume differences in mid and late life in UK biobank participants.

We estimated the ages when associations between Alzheimer's disease (AD) genes and brain volumes begin among middle-aged and older adults. Among 45,616 dementia-free participants aged 45-80, linear regressions tested whether genetic risk score for AD (AD-GRS) had age-dependent associations with 38 regional brain magnetic resonance imaging volumes. Models were adjusted for sex, assessment center, genetic ancestry, and intracranial volume. AD-GRS modified the estimated effect of age (per decade) on the amygdala (-0.41 mm3 [-0.42, -0.40]); hippocampus (-0.45 mm3 [-0.45, -0.44]), nucleus accumbens (-0.55 mm3 [-0.56, -0.54]), thalamus (-0.38 mm3 [-0.39, -0.37]), and medial orbitofrontal cortex (-0.23 mm3 [-0.24, -0.22]). Trends began by age 45 for the nucleus accumbens and thalamus, 48 for the hippocampus, 51 for the amygdala, and 53 for the medial orbitofrontal cortex. An AD-GRS excluding apolipoprotein E (APOE) was additionally associated with entorhinal and middle temporal cortices. APOE and other genes that increase AD risk predict lower hippocampal and other brain volumes by middle age.

Grey matter structure within the visual networks in migraine with aura: multivariate and univariate analyses.

The visual cortex is involved in the generation of migraine aura. Voxel-based multivariate analyses applied to this region may provide complementary information about aura mechanisms relative to the commonly used mass-univariate analyses. Structural images constrained within the functional resting-state visual networks were obtained in migraine patients with (n = 50) and without (n = 50) visual aura and healthy controls (n = 50). The masked images entered a multivariate analysis in which Gaussian process classification was used to generate pairwise models. Generalizability was assessed by five-fold cross-validation and non-parametric permutation tests were used to estimate significance levels. A univariate voxel-based morphometry analysis was also performed. A multivariate pattern of grey matter voxels within the ventral medial visual network contained significant information related to the diagnosis of migraine with visual aura (aura vs. healthy controls: classification accuracy = 78%, p < 0.001; area under the curve = 0.84, p < 0.001; migraine with aura vs. without aura: classification accuracy = 71%, p < 0.001; area under the curve = 0.73, p < 0.003). Furthermore, patients with visual aura exhibited increased grey matter volume in the medial occipital cortex compared to the two other groups. Migraine with visual aura is characterized by multivariate and univariate patterns of grey matter changes within the medial occipital cortex that have discriminative power and may reflect pathological mechanisms.

From Individual to Population: Circuit Organization of Pyramidal Tract and Intratelencephalic Neurons in Mouse Sensorimotor Cortex.

The sensorimotor cortex participates in diverse functions with different reciprocally connected subregions and projection-defined pyramidal neuron types therein, while the fundamental organizational logic of its circuit elements at the single-cell level is still largely unclear. Here, using mouse Cre driver lines and high-resolution whole-brain imaging to selectively trace the axons and dendrites of cortical pyramidal tract (PT) and intratelencephalic (IT) neurons, we reconstructed the complete morphology of 1,023 pyramidal neurons and generated a projectome of 6 subregions within the sensorimotor cortex. Our morphological data revealed substantial hierarchical and layer differences in the axonal innervation patterns of pyramidal neurons. We found that neurons located in the medial motor cortex had more diverse projection patterns than those in the lateral motor and sensory cortices. The morphological characteristics of IT neurons in layer 5 were more complex than those in layer 2/3. Furthermore, the soma location and morphological characteristics of individual neurons exhibited topographic correspondence. Different subregions and layers were composed of different proportions of projection subtypes that innervate downstream areas differentially. While the axonal terminals of PT neuronal population in each cortical subregion were distributed in specific subdomains of the superior colliculus (SC) and zona incerta (ZI), single neurons selectively innervated a combination of these projection targets. Overall, our data provide a comprehensive list of projection types of pyramidal neurons in the sensorimotor cortex and begin to unveil the organizational principle of these projection types in different subregions and layers.

Estimating Time and Rhythm byPredicting External Stimuli.

In this chapter, we present recent findings from our group showing that elapsed time, interval timing, and rhythm maintenance might be achieved by the well-known ability of the brain to predict the future states of the world. The difference between predictions and actual sensory evidence is used to generate perceptual and behavioral adjustments that help subjects achieve desired behavioral goals. Concretely, we show that (1) accumulating prediction errors is a plausible strategy humans could use to determine whether a train of consecutive stimuli arrives at regular or irregular intervals. By analyzing the behavior of human and non-human primate subjects performing rhythm perception tasks, we demonstrate that (2) the ability to estimate elapsed time and internally maintain rhythms is shared across primates and humans. Neurophysiological recordings show that (3) the medial premotor cortex engages in rhythm entrainment and maintains oscillatory activity that reveals an internal metronome's spatial and temporal characteristics. Finally, we demonstrate that (4) the amplitude of gamma oscillations within this cortex increases proportionally to the total elapsed time. In conjunction with our most recent experiments, our results suggest that timing might be achieved by an internal simulation of the sensory stimuli and the motor commands that define the timing task that needs to be performed.

Optimizing outcomes in drug-resistant mesial temporal lobe epilepsy patients undergoing stereoelectroencephalography-guided radiofrequency thermocoagulation.

Mesial temporal lobe epilepsy (MTLE) epileptiform discharges have been reported to arise from the hippocampus or the extrahippocampal medial temporal cortex, such as the amygdala, and then propagate to the temporal lobe cortex. The surgical ablation of which of these structures would result in a better postoperative outcome is debatable. To assess the possible factors that might have influenced the postoperative outcome of a group of drug-resistant mesial MTLE patients who underwent stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC). Single-center, retrospective. The present study utilized a pre- and postoperative gray matter voxel-by-voxel ablation mapping comparison approach, along with a white matter mapping of longitudinal changes in the native space technique, to evaluate the association between the post-SEEG implantation signal recordings (obtained from clinically relevant electrode contacts used during RFTC) and the post-RFTC ablation volume of the different selected regions of interest (ROIs). The study included 22 patients (12 men and 10 women, mean age 28.86 ± 14.04 years). Sixteen patients (72.72%) were seizure-free (SF), and six patients (27.27%) were non-SF. Five patients (22.72%) experienced mild side effects following RFTC. The post-RFTC follow-up period varied from 12 to 48 months, with an average of 24.17 ± 9.86 months. The SF group was associated with a higher number of implanted electrode contacts in the amygdala that were used during RFTC, a larger preoperative volume of the amygdala; a larger ablation volume of both the amygdala and rhinal cortex. The ablation volume of the white matter was statistically similar between both groups. This study provides valuable insights into the significance of the amygdala and rhinal cortex as ROIs in the preoperative evaluation of patients with MTLE. Future implantation scheme plans should consider evaluating the preoperative volume of these ROIs. Additionally, increasing the number of electrode contacts implanted within these regions might be beneficial to capture more clinically relevant signals and enhance their ablation volume.

Heart failure causally affects the brain cortical structure: a Mendelian randomization study.

The effects of heart failure (HF) on cortical brain structure remain unclear. Therefore, the present study aimed to investigate the causal effects of heart failure on cortical structures in the brain using Mendelian randomization (MR) analysis. We conducted a two-sample MR analysis utilizing genetically-predicted HF trait, left ventricular ejection fraction (LVEF), and N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels to examine their effects on the cortical surface area (SA) and thickness (TH) across 34 cortical brain regions. Genome-wide association study summary data were extracted from studies by Rasooly (1,266,315 participants) for HF trait, Schmidt (36,548 participants) for LVEF, the SCALLOP consortium (21,758 participants) for NT-proBNP, and the ENIGMA Consortium (51,665 participants) for cortical SA and TH. A series of MR analyses were employed to exclude heterogeneity and pleiotropy, ensuring the stability of the results. Given the exploratory nature of the study, p-values between 1.22E-04 and 0.05 were considered suggestive of association, and p-values below 1.22E-04 were defined as statistically significant. In this study, we found no significant association between HF and cortical TH or SA (all p > 1.22E-04). We found that the HF trait and elevated NT-proBNP levels were not associated with cortical SA, but were suggested to decrease cortical TH in the pars orbitalis, lateral orbitofrontal cortex, temporal pole, lingual gyrus, precuneus, and supramarginal gyrus. Reduced LVEF was primarily suggested to decrease cortical SA in the isthmus cingulate gyrus, frontal pole, postcentral gyrus, cuneus, and rostral middle frontal gyrus, as well as TH in the postcentral gyrus. However, it was suggested to causally increase in the SA of the posterior cingulate gyrus and medial orbitofrontal cortex and the TH of the entorhinal cortex and superior temporal gyrus. We found 15 brain regions potentially affected by HF, which may lead to impairments in cognition, emotion, perception, memory, language, sensory processing, vision, and executive control in HF patients.

Frontal and occipital brain glutathione levels are unchanged in autistic adults.

The neurobiological underpinnings of Autism Spectrum Disorder (ASD) are diverse and likely multifactorial. One possible mechanism is increased oxidative stress leading to altered neurodevelopment and brain function. However, this hypothesis has mostly been tested in post-mortem studies. So far, available in vivo studies in autistic individuals have reported no differences in glutathione (GSH) levels in frontal, occipital, and subcortical regions. However, these studies were limited by the technically challenging quantification of GSH, the main brain antioxidant molecule. This study aimed to overcome previous studies' limitations by using a GSH-tailored spectroscopy sequence and optimised quantification methodology to provide clarity on GSH levels in autistic adults. We used spectral editing proton-magnetic resonance spectroscopy (1H-MRS) combined with linear combination model fitting to quantify GSH in the dorsomedial prefrontal cortex (DMPFC) and medial occipital cortex (mOCC) of autistic and non-autistic adults (male and female). We compared GSH levels between groups. We also examined correlations between GSH and current autism symptoms, measured using the Autism Quotient (AQ). Data were available from 31 adult autistic participants (24 males, 7 females) and 40 non-autistic participants (21 males, 16 females); the largest sample to date. The GSH levels did not differ between groups in either region. No correlations with AQ were observed. GSH levels as measured using 1H-MRS are unaltered in the DMPFC and mOCC regions of autistic adults, suggesting that oxidative stress in these cortical regions is not a marked neurobiological signature of ASD.

Altered connectivity patterns of medial and lateral orbitofrontal cortex underlie the severity of bulimic symptoms

ObjectiveCompared to clinical bulimia nervosa, sub-threshold bulimic symptoms are becoming more prevalent in non-clinical or general population, which is repeatedly linked with the connectivity in orbitofrontal cortex (OFC), including functionally heterogeneous the medial and lateral OFC (mOFC; lOFC). However, the specific connectivity patterns of the mOFC and lOFC in individuals with severe or mild bulimic symptoms (SB; MB) remain poorly understood. MethodsWe first utilized resting-state functional connectivity (FC) and spectral dynamic causal modeling (spDCM) to investigate abnormal functional and effective connectivity (EC) of OFC subregions in adults with different severity of bulimic. The SB group (n = 21), MB group (n = 114), and healthy controls (HC, n = 91) underwent rs-fMRI scans. A generalized linear model was applied to determine the OFC-seeded whole-brain FC across the three groups. Subsequently, spDCM was used to estimate differences in EC among the three groups based on the FC results. ResultsWe observed a shared neural basis for SB and MB groups (i.e., weaker lOFC-superior parietal lobule connectivity), which may support the role of dysfunctional inhibitory control in general bulimic symptomatology. Whereas, SB group displayed greater lOFC-occipital pole connectivity than MB group, suggesting the specificity of the neural correlates of full-threshold/severe bulimia. The directional links from the mOFC to lOFC and amygdala could further explain the aberrant interactions of reward sensitivity with inhibitory control and homeostatic energy in sub-threshold/mild condition. ConclusionThe current study provides novel evidence that divergent connectivity patterns of the lOFC and mOFC may contribute to different severities of bulimia, which will expands our understanding of the neurobiological substrates underlying bulimia across a spectrum from healthy to unhealthy.

Pathoanatomy and pathomechanics of pertrochanteric fractures - an MRI study.

Magnetic resonance imaging (MRI) has been used for more than 20 years in the region of the proximal femur to diagnose occult, or incomplete, fractures of the femoral neck and the trochanteric segment. MRI has also potential to contribute to the understanding of the pathogenesis and pathoanatomy of trochanteric fractures. The group including 13 patients was examined by MRI for a suspected, or incomplete, fracture of the trochanteric segment within 24 hours post-injury. In all cases, this was the first injury to the hip joint, with the other hip joint remaining intact. The coronal scans showed a marked fracture line which, in the region of the intertrochanteric line, extended from the base of the greater trochanter (GT) medially and distally and involved the medial cortex. This inclination, however, was gradually changing posteriorwards and close before the posterior cortex. The fracture line was passing vertically along the lateral trochanteric wall as far as the level of the lesser trochanter (LT). Then the fracture line changed its course and ran horizontally to the cortex of the LT. Sagittal scans showed clearly the primary fracture line originating in the greater trochanter, extending medially and starting to separate the posterior cortex. Analysis of MRI findings has documented that the primary fracture line in pertrochanteric fractures originates in the GT and extends distally, medially and anteriorly towards the anterior cortex, the intertrochanteric line and the LT. Thus, the GT presents a rather vulnerable site and is always broken into more fragments than shown by a radiograph.

A Lateral Fracture Line Affects Femoral Trochanteric Fracture Instability and Swing Motion of the Intramedullary Nail: A Biomechanical Study.

An unstable trochanteric femoral fracture is a serious injury, with a 1-year mortality rate of 5.4% to 24.9%, for which there is currently no standard treatment method. The lag screw insertion site is one of the primary contact areas between the cortical bone and an intramedullary nail. We hypothesized that a posterolateral fracture causes intramedullary nail instability when the posterolateral fracture line interferes with lag screw insertion. The purpose of the present study was to investigate the effect of posterolateral fracture line morphology on intramedullary nail stability by simulating unstable trochanteric femoral fractures with a posterolateral fracture fragment. Eighteen custom-made synthetic osteoporotic bone samples were used in the present study. Nine samples had a posterolateral fracture line interfering with the lag screw insertion hole (Fracture A), and the other 9 had a fracture line 10 mm away from the hole (Fracture B). Cyclic loading (750 N) was applied to the femoral head 1,500 times. Movement of the end cap attached to the intramedullary nail was recorded. The amplitudes of motion in the coronal plane (coronal swing motion), sagittal plane (sagittal swing motion), and axial plane (total swing motion) were evaluated. The change in the neck-shaft angle was evaluated on photographs that were made before and after the test. Medial cortical displacement was measured before and after the test. Two Fracture-A samples were excluded because the amplitude of sagittal swing motion was too large. The mean values for coronal, sagittal, and total swing motion were 1.13 ± 0.28 mm and 0.51 ± 0.09 mm (p < 0.001), 0.50 ± 0.12 mm and 0.46 ± 0.09 mm (p = 0.46), and 1.24 ± 0.24 mm and 0.69 ± 0.11 mm (p < 0.001) for Fractures A and B, respectively. The mean neck-shaft angle change was -8.29° ± 2.69° and -3.56° ± 2.35° for Fractures A and B, respectively (p = 0.002). The mean displacement of the medial cortex was 0.38 ± 1.12 mm and 0.12 ± 0.37 mm for Fractures A and B, respectively (p = 0.57). This study showed that an unstable trochanteric femoral fracture with a posterolateral fracture line that interferes with the lag screw insertion holes is a risk factor for increased intramedullary nail instability.

What is the Optimal Nail Length to Treat Osteoporotic Subtrochanteric Fractures? A Finite Element Analysis.

Operative management with intramedullary nail fixation remains the definitive treatment of choice for osteoporotic subtrochanteric (ST) fractures; however, there remains no consensus regarding the proper nail length. We aimed to use 3-dimensional finite element (FE) analysis to determine the optimal nail length for the safe fixation of osteoporotic ST fractures. Nine modes of FE models were constructed using 9 different lengths of cephalomedullary nails (short nails: 170, 180, and 200 mm; long nails: 280, 300, 320, 340, 360, and 380 mm) from the same company. The interfragmentary motion was analyzed. Additionally, the peak von Mises stress (PVMS) in the cortical bone, cancellous bone of the femoral head, and the nail were measured, and the yielding risk for each subject was investigated. Long nails were associated with less interfragmentary motion. In the cortical bone, the PVMS of short nails was observed at the distal locking screw holes of the femoral medial cortex; however, in long nails, the PVMS was observed at the lag screw holes on the lateral cortex. The mean yielding risk of long nails was 40.1% lower than that of short nails. For the cancellous bone of the femoral head, the PVMS in all 9 FE models was in the same area: at the apex of the femoral head. There was no difference in the yielding risk between short and long nails. For implants, the PVMS was at the distal locking screw hole of the nail body in the short nails and the nail body at the fracture level in the long nails. The mean yielding risk was 74.9% lower for long nails than that for short nails. Compared to short nails, long nails with a length of 320 mm or more showed less interfragmentary motion and lower yielding risk in low-level osteoporotic ST fractures. The FE analysis supports long nails as a safer option than short nails, especially for treating transverse-type low-level osteoporotic ST fractures.

Causal associations between gut microbiota and regional cortical structure: a Mendelian randomization study.

Observational studies have reported associations between gut microbiota composition and central nervous system diseases. However, the potential causal relationships and underlying mechanisms remain unclear. Here, we applied Mendelian randomization (MR) to investigate the causal effects of gut microbiota on cortical surface area (SA) and thickness (TH) in the brain. We used genome-wide association study summary statistics of gut microbiota abundance in 18,340 individuals from the MiBioGen Consortium to identify genetic instruments for 196 gut microbial taxa. We then analyzed data from 56,761 individuals from the ENIGMA Consortium to examine associations of genetically predicted gut microbiota with alterations in cortical SA and TH globally and across 34 functional brain regions. Inverse-variance weighted analysis was used as the primary MR method, with MR Egger regression, MR-PRESSO, Cochran's Q test, and leave-one-out analysis to assess heterogeneity and pleiotropy. At the functional region level, genetically predicted higher abundance of class Mollicutes was associated with greater SA of the medial orbitofrontal cortex (β = 8.39 mm2, 95% CI: 3.08-13.70 mm2, p = 0.002), as was higher abundance of phylum Tenericutes (β = 8.39 mm2, 95% CI: 3.08-13.70 mm2, p = 0.002). Additionally, higher abundance of phylum Tenericutes was associated with greater SA of the lateral orbitofrontal cortex (β = 10.51 mm2, 95% CI: 3.24-17.79 mm2, p = 0.0046). No evidence of heterogeneity or pleiotropy was detected. Specific gut microbiota may causally influence cortical structure in brain regions involved in neuropsychiatric disorders. The findings provide evidence for a gut-brain axis influencing cortical development, particularly in the orbitofrontal cortex during adolescence.