Hub Regions Research Articles

Reconfiguration of metabolic connectivity in ageing

Information transfer across the brain has a high energetic cost and requires efficient glucose metabolism. Here we use recently developed high temporal resolution functional positron emission tomography (fPET) to create a timecourse of glucose metabolism for individual subjects and assess the relationship between metabolic connectivity and cognitive function in ageing. The metabolic connectomes of 40 younger (mean 27.9 years; range 20-42) and 46 older (mean 75.8; 60-89) adults were characterised by high connectivity in the frontal, temporal, motor, parietal and medial cortices. Older age was associated with lower global integration of metabolic hub regions. In younger adults, a high proportion of glucose was used to support hubs in the frontal regions. Older adults used a higher proportion of a smaller energy budget to support mostly posterior hub regions. This metabolic network topology of older adults was associated with worse cognitive performance. We conclude that ageing is associated with a high glucose cost in hub regions and disrupted information transfer across the metabolic network. Our results highlight the fundamental role that metabolism plays in supporting information transfer in the brain and the unique insights that metabolic connectivity provides into the ageing brain.

Functional network disruption in cognitively unimpaired autosomal dominant Alzheimer’s disease: a magnetoencephalography study

Functional network disruption in cognitively unimpaired autosomal dominant Alzheimer’s disease: a magnetoencephalography study

α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor density underlies intraregional and interregional functional centrality.

Local and global functional connectivity densities (lFCD and gFCD, respectively), derived from functional magnetic resonance imaging (fMRI) data, represent the degree of functional centrality within local and global brain networks. While these methods are well-established for mapping brain connectivity, the molecular and synaptic foundations of these connectivity patterns remain unclear. Glutamate, the principal excitatory neurotransmitter in the brain, plays a key role in these processes. Among its receptors, the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is crucial for neurotransmission, particularly in cognitive functions such as learning and memory. This study aimed to examine the association of the AMPAR density and FCD metrics of intraregional and interregional functional centrality. Using [11C]K-2, a positron emission tomography (PET) tracer specific for AMPARs, we measured AMPAR density in the brains of 35 healthy participants. Our findings revealed a strong positive correlation between AMPAR density and both lFCD and gFCD-lFCD across the entire brain. This correlation was especially notable in key regions such as the anterior cingulate cortex, posterior cingulate cortex, pre-subgenual frontal cortex, Default Mode Network, and Visual Network. These results highlight that postsynaptic AMPARs significantly contribute to both local and global functional connectivity in the brain, particularly in network hub regions. This study provides valuable insights into the molecular and synaptic underpinnings of brain functional connectomes.

Deficient salience and default mode functional integration in high worry-proneness subject: a connectome-wide association study.

Worry has been conceptualized as a relatively uncontrollable chain of thought that increases the risk of mental problems, such as anxiety disorders. Here, we examined the link between individual variation in the functional connectome and worry proneness, which remains unclear. A total of 32 high worry-proneness (HWP) subjects and 25 low worry-proneness (LWP) subjects were recruited. We conducted multivariate distance-based matrix regression to identify phenotypic relationships in high-dimensional brain resting-state functional connectivity data from HWP subjects. Multiple hub regions, including key brain nodes of the salience network (SN) and default mode network (DMN), were identified in HWP subjects. Follow-up analyses revealed that a high worry-proneness score was dominated by functional connectivity between the SN and the DMN. Moreover, HWP subjects showed hypoconnectivity between the cerebellum and the SN and DMN compared with LWP subjects. This cross-sectional study could not fully measure the causal relationships between changes in functional networks and worry proneness in healthy subjects. Functional changes in the cerebellum-cortical region might affect the modulation of external stimuli processing. Together, our results provide new insight into the role of key networks, including the SN, DMN and cerebellum, in understanding the potential mechanism underlying the high worry dimension in healthy subjects.

Increasing hub disruption parallels dementia severity in autosomal dominant Alzheimer’s disease

Abstract Hub regions in the brain, recognized for their roles in ensuring efficient information transfer, are vulnerable to pathological alterations in neurodegenerative conditions, including Alzheimer’s disease (AD). Computational simulations and animal experiments have hinted at the theory of activity-dependent degeneration as the cause of this hub vulnerability. However, two critical issues remain unresolved. First, past research has not clearly distinguished between two scenarios: hub regions facing a higher risk of connectivity disruption (targeted attack) and all regions having an equal risk (random attack). Second, human studies offering support for activity-dependent explanations remain scarce. We refined the hub disruption index to demonstrate a hub disruption pattern in functional connectivity in autosomal dominant AD that aligned with targeted attacks. This hub disruption is detectable even in preclinical stages 12 years before the expected symptom onset and is amplified alongside symptomatic progression. Moreover, hub disruption was primarily tied to regional differences in global connectivity and sequentially followed changes observed in amyloid-beta positron emission tomography cortical markers, consistent with the activity-dependent degeneration explanation. Taken together, our findings deepened the understanding of brain network organization in neurodegenerative diseases and could be instrumental in refining diagnostic and targeted therapeutic strategies for AD in the future.

Instability and Evolution of Shocked Clouds Formed by Orthogonal Collisions between Magnetized Filamentary Molecular Clouds

Filamentary molecular clouds are recognized as primary sites for the formation of stars. Specifically, regions characterized by the overlapping point of multiple filaments, known as hub regions, are often associated with active star formation. However, the formation mechanism of this hub structure is not well understood. Therefore, to understand the formation mechanism and star formation in hub structures, as a first step, we investigate the orthogonal collisions between two filaments using three-dimensional ideal magnetohydrodynamical simulations. As a model of initial filaments, we use an infinitely long filament in magnetohydrostatic equilibrium under a global magnetic field running perpendicular to the filament axis. Two identical equilibrium filaments, sharing the same magnetic flux, are arranged with their long axes perpendicular to each other and given an initial velocity perpendicular to their long axes to replicate an orthogonal collision. We find three types of evolution after the shocked cloud is formed: collapse, stable, and expansion modes. The energy balance just after the filaments completely collide explains the future evolution of the shocked cloud. If the magnitude of gravitational energy is larger than the sum of the kinetic, thermal, and magnetic energies, the shocked cloud evolves in collapse mode. If the magnitude of gravitational energy is less than the sum of these energies, the cloud evolves in stable mode when the kinetic energy is relatively small and in expansion mode when the kinetic energy is sufficiently large.

Mapping Lesion-Related Human Aggression to a Common Brain Network

BackgroundAggression exacts a significant toll on human societies and is highly prevalent among neuropsychiatric patients. The neural mechanisms of aggression are unclear and treatment options are limited. MethodsUsing a recently validated lesion network mapping technique, we derived an aggression-associated network by analyzing data from 182 patients who had experienced penetrating head injuries during their service in the Vietnam War. To test whether damage to this lesion-derived network would increase the risk of aggression-related neuropsychiatric symptoms, we used the Harvard Lesion Repository (N = 852). To explore potential therapeutic relevance of this network, we used an independent deep brain stimulation dataset of 25 patients with epilepsy, in which irritability and aggression are known potential side effects. ResultsWe found that lesions associated with aggression occurred in many different brain locations but were characterized by a specific brain network defined by functional connectivity to a hub region in the right prefrontal cortex. This network involves positive connectivity to the ventromedial prefrontal cortex, dorsolateral prefrontal cortex, frontal pole, posterior cingulate cortex, anterior cingulate cortex, temporal-parietal junction, and lateral temporal lobe and negative connectivity to the amygdala, hippocampus, insula, and visual cortex. Among all 24 neuropsychiatric symptoms included in the Harvard Lesion Repository, criminality demonstrated the most alignment with our aggression-associated network. Deep brain stimulation site connectivity to this same network was associated with increased irritability. ConclusionsWe conclude that brain lesions associated with aggression map to a specific human brain circuit, and the functionally connected regions in this circuit provide testable targets for therapeutic neuromodulation.

Aerodynamic optimization design and experimental verification of a high-load axial flow compressor

The performance and stable operating range of compressors are critical to the efficient operation of various turbomachinery systems. This paper proposes a multi-level optimization strategy combining the uni-uniform direct free deformation method, Linux partitioned CPU accelerated parallel computing technology, multi-objective particle swarm optimization algorithm and downhill simplex algorithm, which improves design efficiency. Numerical results show that after optimization design, the average value of peak efficiency and stall margin increases. The flow mechanism of compressor performance improvement after optimization lies in the reduction of a low-velocity separation zone in stator hub region. Moreover, the experiment study confirms the reliability and accuracy of the optimization design method and found that flow instability triggering mode, propagation characteristics of the stall cell, and surge frequency are changed after optimization design. Setting a probability distribution threshold for autocorrelation coefficient and cross-correlation coefficients can be used to predict the arrival of the surge condition.

Multi-Graph Assessment of Temporal and Extratemporal Lobe Epilepsy in Resting-State fMRI

Epilepsy is a common neurological disorder that affects millions of people worldwide, disrupting brain networks and causing recurrent seizures. In this regard, investigating the distinctive characteristics of brain connectivity is crucial to understanding the underlying neural processes of epilepsy. However, the various graph-theory frameworks and different estimation measures may yield significant variability among the results of different studies. On this premise, this study investigates the brain network topological variations between patients with temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE) using both directed and undirected network connectivity methods as well as different graph-theory metrics. Our results reveal distinct topological differences in connectivity graphs between the two epilepsy groups, with TLE patients displaying more disassortative graphs at lower density levels compared to ETLE patients. Moreover, we highlight the variations in the hub regions across different network metrics, underscoring the importance of considering various centrality measures for a comprehensive understanding of brain network dynamics in epilepsy. Our findings suggest that the differences in brain network organization between TLE and ETLE patients could be attributed to the unique characteristics of each epilepsy type, offering insights into potential biomarkers for type-specific epilepsy diagnosis and treatment.

The Involvement of the Ventral Tegmental Area in the Electroacupuncture Alleviation of Anxiety-Like Behaviors Induced by Chronic Restraint Stress in Mice.

Emotional stress is a significant environmental risk factor for various mental health disabilities, such as anxiety. Electroacupuncture (EA) has been demonstrated to have pronounced anxiolytic effects. However, the neural mechanisms underlying these effects and their contribution to behavioral deficits remain poorly understood. Here, we addressed these issues using a classical mouse anxiety model induced by chronic restraint stress (CRS).Anxiety-like behaviors were evaluated with the open field test and elevated plus maze. Neuronal activation in various brain regions was marked using c-Fos, followed by calculations of interregional correlation to characterize a network that became functionally active following EA at the HT7 acupoint (EA-HT7). We selected the hub regions and further investigated their functions and connections in regulating anxiety-like behaviors by using a combination of chemogenetic manipulations and behavioral testing. CRS exposure induced anxiety-like behaviors. Interestingly, EA-HT7 mitigated these behavioral abnormalities. The c-Fos expression in 30 brain areas revealed a vital brain network for acupuncture responsiveness in naïve mice. Neural activity in the NAcSh (nucleus accumbens shell), BNST (bed nucleus of the stria terminalis), VMH (Ventromedial Hypothalamus), ARC (arcuate nucleus), dDG (dorsal dentate gyrus), and VTA (ventral tegmental area) was significantly altered following acupuncture. Notably, both c-Fos immunostaining and brain functional connectivity analysis revealed the significant activation of VTA following EA-HT7. Interestingly, blocking the VTA eliminated the anxiolytic effects of EA-HT7, whereas chemogenetic activation of the VTA replicated the therapeutic effects of EA-HT7. EA-HT7 has demonstrated benefits in treating anxiety and enhances brain functional connectivity. The VTA is functionally associated with the anxiolytic effects of EA-HT7.

More widespread functionality of posterior language area in patients with brain tumors.

Damage to the posterior language area (PLA), or Wernicke's area causes cortical reorganization in the corresponding regions of the contralateral hemisphere. However, the details of reorganization within the ipsilateral hemisphere are not fully understood. In this context, direct electrical stimulation during awake surgery can provide valuable opportunities to investigate neuromodulation of the human brain in vivo, which is difficult through the non-invasive approaches. Thus, in this study, we aimed to investigate the characteristics of the cortical reorganization of the PLA within the ipsilateral hemisphere. Sixty-two patients with left hemispheric gliomas were divided into groups depending on whether the lesion extended to the PLA. All patients underwent direct cortical stimulation with a picture-naming task. We further performed functional connectivity analyses using resting-state functional magnetic resonance imaging (MRI) in a subset of patients and calculated betweenness centrality, an index of the network importance of brain areas. During direct cortical stimulation, the regions showing positive (impaired) responses in the non-PLA group were localized mainly in the posterior superior temporal gyrus (pSTG), whereas those in the PLA group were widely distributed from the pSTG to the posterior supramarginal gyrus (pSMG). Notably, the percentage of positive responses in the pSMG was significantly higher in the PLA group (47%) than in the non-PLA group (8%). In network analyses of functional connectivity, the pSMG was identified as a hub region with high betweenness centrality in both the groups. These findings suggest that the language area can spread beyond the PLA to the pSMG, a hub region, in patients with lesion progression to the pSTG. The change in the pattern of the language area may be a compensatory mechanism to maintain efficient brain networks.

Investigating the Star-forming Sites in the Outer Galactic Arm

We aim to investigate the global star formation scenario in star-forming sites AFGL 5157, [FSR2007] 0807 (hereafter FSR0807), [HKS2019] E70 (hereafter E70), [KPS2012] MWSC 0620 (hereafter KPS0620), and IRAS 05331+3115 in the outer Galactic arm. The distribution of young stellar objects in these sites coincides with a higher extinction and H2 column density, which agrees with the notion that star formation occurs inside the dense molecular cloud cores. We have found two molecular structures at different velocities in this direction; one contains AFGL 5157 and FSR0807, and the other contains E70, [KPS2012] MWSC 0620, and IRAS 05331+3115. All these clusters in our target region are in different evolutionary stages and might form stars through different mechanisms. The E70 cluster seems to be the oldest in our sample; AFGL 5157 and FSR0807 formed later, and KPS0620 and IRAS 05331+3115 are the youngest sites. AFGL 5157 and FSR0807 are physically connected and have cold filamentary structures and dense hub regions. Additionally, the near-infrared photometric analysis shows signatures of massive star formation in these sites. KPS0620 also seems to have cold filamentary structures with the central hub but lacks signatures of massive stars. Our analysis suggests molecular gas flow and the hub filamentary star formation scenario in these regions. IRAS 05331+3115 is a single clump of molecular gas favoring low-mass star formation. Our study suggests that the selected area is a menagerie of star-forming sites where the formation of the stars happens through different processes.

Impact of circumferential inlet distortion on different types of stall inceptions in a transonic compressor

The application of higher bypass ratios and lower pressure ratios significantly reduces specific fuel consumption with the development of turbofan engines. However, it also increases the risk of flow separation at the intake, leading to severe circumferential non-uniform inlet conditions. This study aimed to present an experimental investigation on instability evolutions of the compressor under circumferential non-uniform inlet conditions. Two stall inceptions regarding the different spatial scales and initial locations were selected to investigate this issue. The experiments were carried out on one tested rig, which the stall inceptions verified with the rotational speeds. At 65% design rotational speed (Ω), the stall inception was the spike, which was triggered by disturbances within serval pitches scale at the tip. Consequently, the spike-type stall inception was sensitive to circumferential distortion and led to a shrunk stall margin of the compressor. With the rotational speed increasing to 88%Ω, the stall inception switched to partial surge, which was induced by the flow blockage in the hub region around the full-annular. The results indicated that the partial surge was insusceptible to the circumferential distortion, which caused an extended stall margin with a lower stalled mass flow rate. In summary, the influence of distortion on the stability of the target compressor was found to be determined by the stall inception.

Beta activity in human anterior cingulate cortex mediates reward biases

The rewards that we get from our choices and actions can have a major influence on our future behavior. Understanding how reward biasing of behavior is implemented in the brain is important for many reasons, including the fact that diminution in reward biasing is a hallmark of clinical depression. We hypothesized that reward biasing is mediated by the anterior cingulate cortex (ACC), a cortical hub region associated with the integration of reward and executive control and with the etiology of depression. To test this hypothesis, we recorded neural activity during a biased judgment task in patients undergoing intracranial monitoring for either epilepsy or major depressive disorder. We found that beta (12–30 Hz) oscillations in the ACC predicted both associated reward and the size of the choice bias, and also tracked reward receipt, thereby predicting bias on future trials. We found reduced magnitude of bias in depressed patients, in whom the beta-specific effects were correspondingly reduced. Our findings suggest that ACC beta oscillations may orchestrate the learning of reward information to guide adaptive choice, and, more broadly, suggest a potential biomarker for anhedonia and point to future development of interventions to enhance reward impact for therapeutic benefit.

Altered morphometric similarity networks in insomnia disorder.

Previous studies on structural covariance network (SCN) suggested that patients with insomnia disorder (ID) show abnormal structural connectivity, primarily affecting the somatomotor network (SMN) and default mode network (DMN). However, evaluating a single structural index in SCN can only reveal direct covariance relationship between two brain regions, failing to uncover synergistic changes in multiple structural features. To cover this research gap, the present study utilized novel morphometric similarity networks (MSN) to examine the morphometric similarity between cortical areas in terms of multiple sMRI parameters measured at each area. With seven T1-weighted imaging morphometric features from the Desikan-Killiany atlas, individual MSN was constructed for patients with ID (N = 87) and healthy control groups (HCs, N = 84). Two-sample t-test revealed differences in MSN between patients with ID and HCs. Correlation analyses examined associations between MSNs and sleep quality, insomnia symptom severity, and depressive symptoms severity in patients with ID. The right paracentral lobule (PCL) exhibited decreased morphometric similarity in patients with ID compared to HCs, mainly manifested by its de-differentiation (meaning loss of distinctiveness) with the SMN, DMN, and ventral attention network (VAN), as well as its decoupling with the visual network (VN). Greater PCL-based de-differentiation correlated with less severe insomnia and fewer depressive symptoms in the patients group. Additionally, patients with less depressive symptoms showed greater PCL de-differentiation from the SMN. As an important pilot step in revealing the underlying morphometric similarity alterations in insomnia disorder, the present study identified the right PCL as a hub region that is de-differentiated with other high-order networks. Our study also revealed that MSN has an important potential to capture clinical significance related to insomnia disorder.

Patterns of neuronal activation following ethanol-induced social facilitation and social inhibition in adolescent cFos-LacZ male and female rats

Alcohol-associated social facilitation together with attenuated sensitivity to adverse alcohol effects play a substantial role in adolescent alcohol use and misuse, with adolescent females being more susceptible to adverse consequences of binge drinking than adolescent males. Adolescent rodents also demonstrate individual and sex differences in sensitivity to ethanol-induced social facilitation and social inhibition, therefore the current study was designed to identify neuronal activation patterns associated with ethanol-induced social facilitation and ethanol-induced social inhibition in male and female adolescent cFos-LacZ rats. Experimental subjects were given social interaction tests on postnatal day (P) 34, 36, and 38 after an acute challenge with 0, 0.5 and 0.75 g/kg ethanol, respectively, and β-galactosidase (β-gal) expression was assessed in brain tissue of subjects socially facilitated and socially inhibited by 0.75 g/kg ethanol. In females, positive correlations were evident between overall social activity and neuronal activation of seven out of 13 ROIs, including the prefrontal cortex and nucleus accumbens, with negative correlations evident in males. Assessments of neuronal activation patterns revealed drastic sex differences between ethanol responding phenotypes. In socially inhibited males, strong correlations were evident among almost all ROIs (90 %), with markedly fewer correlations among ROIs (38 %) seen in socially facilitated males. In contrast, interconnectivity in females inhibited by ethanol was only 10 % compared to nearly 60 % in facilitated subjects. However, hub analyses revealed convergence of brain regions in males and females, with the nucleus accumbens being a hub region in socially inhibited subjects. Taken together, these findings demonstrate individual and sex-related differences in responsiveness to acute ethanol in adolescent rats, with sex differences more evident in socially inhibited by ethanol adolescents than their socially facilitated counterparts.

Socially activated neurons in the anterior cingulate cortex are essential for social behavior in mice

Social behavior, defined as any mode of communication between conspecifics is regulated by a widespread network comprising multiple brain structures. The anterior cingulate cortex (ACC) serves as a hub region interconnected with several brain regions involved in social behavior. Because the ACC coordinates various behaviors, it is important to focus on a subpopulation of neurons that are potentially involved in social behavior to clarify the precise role of the ACC in social behavior. In this study, we aimed to analyze the roles of a social stimulus-responsive subpopulation of neurons in the ACC in social behavior in mice. We demonstrated that a subpopulation of neurons in the ACC was activated by social stimuli and that silencing the social stimulus-responsive subpopulation of neurons in the ACC significantly impaired social interaction without affecting locomotor activity or anxiety-like behavior. Our current findings highlight the importance of the social stimulus-responsive subpopulation of neurons in the ACC for social behavior and the association between ACC dysfunction and impaired social behavior, which sheds light on therapeutic interventions for psychiatric conditions.

Disrupted cerebellar structural connectome in spinocerebellar ataxia type 3 and its association with transcriptional profiles

Abstract Spinocerebellar ataxia type 3 (SCA3) is primarily characterized by progressive cerebellar degeneration, including gray matter atrophy and disrupted anatomical and functional connectivity. The alterations of cerebellar white matter structural network in SCA3 and the underlying neurobiological mechanism remain unknown. Using a cohort of 20 patients with SCA3 and 20 healthy controls, we constructed cerebellar structural networks from diffusion MRI and investigated alterations of topological organization. Then, we mapped the alterations with transcriptome data from the Allen Human Brain Atlas to identify possible biological mechanisms for regional selective vulnerability to white matter damage. Compared with healthy controls, SCA3 patients exhibited reduced global and nodal efficiency, along with a widespread decrease in edge strength, particularly affecting edges connected to hub regions. The strength of inter-module connections was lower in SCA3 group and negatively correlated with the Scale for the Assessment and Rating of Ataxia score, International Cooperative Ataxia Rating Scale score, and cytosine–adenine–guanine repeat number. Moreover, the transcriptome–connectome association study identified the expression of genes involved in synapse-related and metabolic biological processes. These findings suggest a mechanism of white matter vulnerability and a potential image biomarker for the disease severity, providing insights into neurodegeneration and pathogenesis in this disease.

The neural and genetic underpinnings of different developmental trajectories of Attention-Deficit/Hyperactivity Symptoms in children and adolescents

BackgroundThe trajectory of attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents, encompassing descending, stable, and ascending patterns, delineates their ADHD status as remission, persistence or late onset. However, the neural and genetic underpinnings governing the trajectory of ADHD remain inadequately elucidated.MethodsIn this study, we employed neuroimaging techniques, behavioral assessments, and genetic analyses on a cohort of 487 children aged 6–15 from the Children School Functions and Brain Development project at baseline and two follow-up tests for 1 year each (interval 1: 1.14 ± 0.32 years; interval 2: 1.14 ± 0.30 years). We applied a Latent class mixed model (LCMM) to identify the developmental trajectory of ADHD symptoms in children and adolescents, while investigating the neural correlates through gray matter volume (GMV) analysis and exploring the genetic underpinnings using polygenic risk scores (PRS).ResultsThis study identified three distinct trajectories (ascending-high, stable-low, and descending-medium) of ADHD symptoms from childhood through adolescence. Utilizing the linear mixed-effects (LME) model, we discovered that attention hub regions served as the neural basis for these three developmental trajectories. These regions encompassed the left anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), responsible for inhibitory control; the right inferior parietal lobule (IPL), which facilitated conscious focus on exogenous stimuli; and the bilateral middle frontal gyrus/precentral gyrus (MFG/PCG), accountable for regulating both dorsal and ventral attention networks while playing a crucial role in flexible modulation of endogenous and extrinsic attention. Furthermore, our findings revealed that individuals in the ascending-high group exhibited the highest PRS for ADHD, followed by those in the descending-medium group, with individuals in the stable-low group displaying the lowest PRS. Notably, both ascending-high and descending-medium groups had significantly higher PRS compared to the stable-low group.ConclusionsThe developmental trajectory of ADHD symptoms in the general population throughout childhood and adolescence can be reliably classified into ascending-high, stable-low, and descending-medium groups. The bilateral MFG/PCG, left ACC/mPFC, and right IPL may serve as crucial brain regions involved in attention processing, potentially determining these trajectories. Furthermore, the ascending-high pattern of ADHD symptoms exhibited the highest PRS for ADHD.

Mendelian randomization analyses support causal relationships between tinnitus of different stages and severity and structural characteristics of specific brain regions

This study aims to delineate the causal relationships between idiopathic tinnitus in different stages and severity and the morphological properties in specific brain regions. We utilized a two-sample bidirectional Mendelian randomization (MR) analysis to ascertain the causal effects of brain structural attributes on varying severities and stages of tinnitus. Our approach involved harnessing genetic variables derived from extensive genome-wide association studies as instrumental variables, centered mainly on pertinent single-nucleotide polymorphisms associated with tinnitus. Subsequently, we integrated this data with brain structural imaging inputs to facilitate the MR analysis. We also applied reverse MR analysis to pinpoint the critical brain regions implicated in the onset of tinnitus. Our analysis revealed a demonstrable causal relationship between tinnitus and brain structural alterations, including changes primarily within the auditory cortex and hub regions of the limbic system, as well as portions of the frontal-temporal-occipital circuit. We found that individuals exhibiting cortical thickness alterations in the bilateral peri-calcarine and right superior occipital gyrus might have previously experienced tinnitus. Changes in the cortical areas of the right rectus, left inferior frontal gyrus, and right pars-orbitalis appeared unrelated to tinnitus. Furthermore, moderate tinnitus patients showed more pronounced structural alterations. This study substantiates that tinnitus could instigate substantial structural alterations mainly within the auditory-limbic-frontal-visual system, while the reciprocal causality was not supported. Moreover, the data underscores that moderate, rather than severe, tinnitus precipitates the most significant structural changes. Morphological alterations in several specific brain areas either indicate a history of tinnitus or bear no relation to it.