Neuroimaging Studies Research Articles

Ventromedial frontoinsular connectivity is associated with long-term smoking behavior change in aging

Abstract A central question in the field of cognitive aging and behavioral neuroscience is what enables some individuals to successfully change their behavior more than others? Smoking is a significant risk factor for cognitive decline, particularly in vulnerable populations, including those who are at an elevated risk for Alzheimer’s disease (AD). Developing effective smoking reduction strategies is therefore a public health priority. The goal of the current study is to better understand the brain mechanisms underlying long-term smoking behavior change in cognitively normal, but at-risk, older adults. Neuroimaging and human lesion studies have implicated the insula and its functional network in subjective interoceptive awareness of cigarette craving and smoking-cue reactivity. We sought to characterize the extent to which anterior insular resting-state functional connectivity (RSFC) MRI predicted long-term smoking reduction (mean: 2.7 years, range 8 months–4 years) using a seed-to-voxel approach. Twenty-three (18 women; 26% APOE4 carriers; 61.5 years, SD = 3.7) cognitively unimpaired older individuals who smoked cigarettes at their baseline visit and have a first-degree family history of AD (at least one parent or multiple siblings affected) were included from a prospective longitudinal cohort, Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease (PREVENT-AD) in the current study. We found that reduced long-term smoking behavior was associated with enhanced antagonistic RSFC between bilateral anterior insula (aINS) and ventromedial prefrontal cortex (vmPFC). In a second pre-registered replication study within a larger, independent sample of 118 cognitively normal older adults who smoked cigarettes at baseline from the UK Biobank (73 women; 27.9% APOE4 carriers; 60.3 years, SD = 2.7), we found that baseline enhanced antagonistic RSFC between anterior insula and vmPFC predicted long-term smoking reduction (mean 5.2 years; ranging from 3 years to 7 years). To our knowledge, this is the largest study to examine the neural substrates of long-term smoking cessation in human aging. Our results suggest that antagonistic RSFC between aINS and vmPFC is a brain marker of future smoking reduction and disease prevention in older adults at risk for AD.

Structural Changes in Brain White Matter Tracts Associated with Overactive Bladder Revealed by Diffusion Tensor MRI: Findings from a LURN Cross-Sectional Case-Control Study.

To investigate structural changes in brain white matter tracts using diffusion tensor magnetic resonance imaging (DTI) in patients with overactive bladder (OAB). Treatment-seeking OAB patients and matched controls enrolled in the cross-sectional case-control Symptoms of Lower Urinary Tract Dysfunction Research Network Neuroimaging Study received a brain DTI scan. Microstructural integrity of brain white matter was assessed using fractional anisotropy (FA) and mean diffusivity (MD). OAB and urgency urinary incontinence (UUI) symptoms were assessed using the OAB Questionnaire Short-Form (OAB-q) and International Consultation on Incontinence Questionnaire-UI. The Lower Urinary Tract Symptoms (LUTS) Tool UUI questions and responses were correlated with FA values. Among 221 participants with evaluable DTI data, 146 had OAB (66 urinary urgency [UU]-only without UUI, 80 with UUI); 75 were controls. Compared with controls, participants with OAB showed decreased FA and increased MD, representing greater microstructural abnormalities of brain white matter tracts among OAB participants. These abnormalities occurred in the corpus callosum, bilateral anterior thalamic radiation and superior longitudinal fasciculus tracts, and bilateral insula and para-hippocampal region. Among participants with OAB, higher OAB-q scores were associated with decreased FA in the left inferior fronto-occipital fasciculus, P < .0001. DTI differences between OAB and controls were driven by the UU-only (OAB-dry) but not the UUI (OAB-wet) subgroup. Abnormalities in microstructural integrity in specific brain white matter tracts were more frequent in OAB patients. More severe OAB symptoms were correlated with greater degree of microstructural abnormalities in brain white matter tracts in patients with OAB.

Intergenerational transmission of brain structure and function in humans: a narrative review of designs, methods, and findings.

Children often show cognitive and affective traits that are similar to their parents. Although this indicates a transmission of phenotypes from parents to children, little is known about the neural underpinnings of that transmission. Here, we provide a general overview of neuroimaging studies that explore the similarity between parents and children in terms of brain structure and function. We notably discuss the aims, designs, and methods of these so-called intergenerational neuroimaging studies, focusing on two main designs: the parent-child design and the multigenerational design. For each design, we also summarize the major findings, identify the sources of variability between studies, and highlight some limitations and future directions. We argue that the lack of consensus in defining the parent-child transmission of brain structure and function leads to measurement heterogeneity, which is a challenge for future studies. Additionally, multigenerational studies often use measures of family resemblance to estimate the proportion of variance attributed to genetic versus environmental factors, though this estimate is likely inflated given the frequent lack of control for shared environment. Nonetheless, intergenerational neuroimaging studies may still have both clinical and theoretical relevance, not because they currently inform about the etiology of neuromarkers, but rather because they may help identify neuromarkers and test hypotheses about neuromarkers coming from more standard neuroimaging designs.

Targeting thalamocortical circuits for closed-loop stimulation in Lennox-Gastaut syndrome

Abstract This paper outlines the therapeutic rationale and neurosurgical targeting technique for bilateral, closed-loop, thalamocortical stimulation in Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy. Thalamic stimulation can be an effective treatment for Lennox-Gastaut syndrome, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown. We aimed to identify a cortical target by synthesizing prior neuroimaging studies, and to use this knowledge to advance a dual thalamic (centromedian) and cortical (frontal) approach for closed-loop stimulation. Multi-modal brain network maps from 3 group-level studies of Lennox-Gastaut syndrome were averaged to define the area of peak overlap: simultaneous EEG-functional MRI of generalized paroxysmal fast activity, [18F]fluorodeoxyglucose PET of cortical hypometabolism, and diffusion MRI structural connectivity associated with clinical efficacy in a previous trial of thalamic deep brain stimulation. The resulting “hotspot” was used as a seed in a normative functional MRI connectivity analysis to identify connected networks. Intracranial electrophysiology was reviewed in the first two trial patients undergoing bilateral implantations guided by this hotspot. Simultaneous recordings from cortex and thalamus were analyzed for presence and synchrony of epileptiform activity. The peak overlap was in bilateral premotor cortex/caudal middle frontal gyrus. Functional connectivity of this hotspot revealed a distributed network of frontoparietal cortex resembling the diffuse abnormalities seen on EEG-functional MRI and PET. Intracranial electrophysiology showed characteristic epileptiform activity of Lennox-Gastaut syndrome in both the cortical hotspot and thalamus; most detected events occurred first in the cortex before appearing in the thalamus. Premotor frontal cortex shows peak involvement in Lennox-Gastaut syndrome and functional connectivity of this region resembles the wider epileptic brain network. Thus, it may be an optimal target for a range of neuromodulation therapies, including thalamocortical stimulation and emerging non-invasive treatments like focused ultrasound or transcranial magnetic stimulation. Compared to thalamus-only approaches, the addition of this cortical target may allow more rapid detections of seizures, more diverse stimulation paradigms, and broader modulation of the epileptic network. A prospective, multi-center trial of closed-loop thalamocortical stimulation for Lennox-Gastaut syndrome is currently underway.

Sex-Dependent Differences in the Neural Correlates of Cocaine and Emotional Cue-Reactivity in Regular Cocaine Users and Non-Drug-Using Controls: Understanding the Role of Duration and Severity of Use

Introduction: The development of cocaine use disorder in females is suggested to be more strongly related to neural mechanisms underlying stress-reactivity, whereas in males it is suggested to be more strongly related to neural mechanisms underlying drug cue-reactivity. Existing evidence, however, is based on neuroimaging studies that either lack a control group and/or have very small sample sizes that do not allow to investigate sex differences. Methods: The main objective of the current study was to investigate sex differences in the neural correlates of cocaine and negative emotional cue-reactivity within high-risk intranasal cocaine users (CUs: 31 males and 26 females) and non-cocaine-using controls (non-CUs: 28 males and 26 females). A region of interest (ROI) analysis was applied to test for the main and interaction effects of group, sex, and stimulus type (cocaine cues vs. neutral cocaine cues and negative emotional cues vs. neutral emotional cues) on activity in the dorsal striatum, ventral striatum (VS), amygdala, and dorsal anterior cingulate cortex (dACC). Results: There were no significant sex or group differences in cocaine cue-reactivity in any of the ROIs. Results did reveal significant emotional cue-reactivity in the amygdala and VS, but these effects were not moderated by group or sex. Exploratory analyses demonstrated that emotional cue-induced activation of the dACC and VS was negatively associated with years of regular cocaine use in female CUs, while this relationship was absent in male CUs. Conclusions: While speculative, the sex-specific associations between years of regular use and emotional cue-reactivity in the dACC and VS suggest that, with longer years of use, female CUs become less sensitive to aversive stimuli, including the negative consequences of cocaine use, which could account for the observed “telescoping effect” in female CUs.

Visual Perceptual Processing Abnormalities in Body Dysmorphic Disorder.

Phenomenological observations of individuals with body dysmorphic disorder (BDD), coupled with evidence from neuropsychological, psychophysical, and neuroimaging studies, support a model of aberrant visual perception characterized by deficient global/holistic, enhanced detail/local processing, and selective visual-attentional biases. These features may contribute to the core symptomatology of distorted perception of their appearance, in addition to misinterpretation of others' facial expressions and poor insight regarding their misperceived appearance defects. Insights from visual processing studies can contribute to the development of novel interventions, such as perceptual retraining and non-invasive neuromodulation. However, much remains to be understood about visual perception in BDD. Future research should leverage brain imaging modalities with high temporal resolutions and employ study designs that induce conflicts in multisensory integration, thereby advancing our mechanistic understanding of distorted visual perception observed in BDD.

SAN: Mitigating spatial covariance heterogeneity in cortical thickness data collected from multiple scanners or sites.

In neuroimaging studies, combining data collected from multiple study sites or scanners is becoming common to increase the reproducibility of scientific discoveries. At the same time, unwanted variations arise by using different scanners (inter-scanner biases), which need to be corrected before downstream analyses to facilitate replicable research and prevent spurious findings. While statistical harmonization methods such as ComBat have become popular in mitigating inter-scanner biases in neuroimaging, recent methodological advances have shown that harmonizing heterogeneous covariances results in higher data quality. In vertex-level cortical thickness data, heterogeneity in spatial autocorrelation is a critical factor that affects covariance heterogeneity. Our work proposes a new statistical harmonization method called spatial autocorrelation normalization (SAN) that preserves homogeneous covariance vertex-level cortical thickness data across different scanners. We use an explicit Gaussian process to characterize scanner-invariant and scanner-specific variations to reconstruct spatially homogeneous data across scanners. SAN is computationally feasible, and it easily allows the integration of existing harmonization methods. We demonstrate the utility of the proposed method using cortical thickness data from the Social Processes Initiative in the Neurobiology of the Schizophrenia(s) (SPINS) study. SAN is publicly available as an R package.

Lifestyle Modulators of Neuroplasticity in Parkinson's Disease: Evidence in Human Neuroimaging Studies.

Parkinson's disease (PD) is a neurodegenerative disease characterized by both motor and non-motor symptoms. A progressive neuronal loss and the consequent clinical impairment lead to deleterious effects on daily living and quality of life. Despite effective symptomatic therapeutic approaches, no disease-modifying therapies are currently available. Emerging evidence suggests that adopting a healthy lifestyle can improve the quality of life of PD patients. In addition, modulating lifestyle factors can positively affect the microstructural and macrostructural brain levels, corresponding to clinical improvement. Neuroimaging studies may help to identify the mechanisms through which physical exercise, dietary changes, cognitive enrichment, and exposure to substances modulate neuroprotection. All these factors have been associated with a modified risk of developing PD, with attenuation or exacerbation of motor and non-motor symptomatology, and possibly with structural and molecular changes. In the present work, we review the current knowledge on how lifestyle factors influence PD development and progression and the neuroimaging evidence for the brain structural, functional, and molecular changes induced by the adoption of positive or negative lifestyle behaviours.

52. Puberty, Sex and Fear Extinction: A Neuroimaging Study in Youth

52. Puberty, Sex and Fear Extinction: A Neuroimaging Study in Youth

Deconstructing pathological tau by biological process in early stages of Alzheimer disease: a method for quantifying tau spatial spread in neuroimaging

Neuroimaging studies often quantify tau burden in standardized brain regions to assess Alzheimer disease (AD) progression. However, this method ignores another key biological process in which tau spreads to additional brain regions. We have developed a metric for calculating the extent tau pathology has spread throughout the brain and evaluate the relationship between this metric and tau burden across early stages of AD. 445 cross-sectional participants (aged≥50) who had MRI, amyloid PET, tau PET, and clinical testing were separated into disease-stage groups based on amyloid positivity and cognitive status (older cognitively normal control, preclinical AD, and symptomatic AD). Tau burden and tau spatial spread were calculated for all participants. We found both tau metrics significantly elevated across increasing disease stages (p<0.0001) and as a function of increasing amyloid burden for participants with preclinical (p<0.0001, p=0.0056) and symptomatic (p=0.010, p=0.0021) AD. An interaction was found between tau burden and tau spatial spread when predicting amyloid burden (p=0.00013). Analyses of slope between tau metrics demonstrated more spread than burden in preclinical AD (β=0.59), but then tau burden elevated relative to spread (β=0.42) once participants had symptomatic AD, when the tau metrics became highly correlated (R=0.83). Tau burden and tau spatial spread are both strong biomarkers for early AD but provide unique information, particularly at the preclinical stage. Tau spatial spread may demonstrate earlier changes than tau burden which could have broad impact in clinical trial design. This research was supported by the Knight Alzheimer Disease Research Center (Knight ADRC, NIH grants P30AG066444, P01AG026276, P01AG003991), Dominantly Inherited Alzheimer Network (DIAN, NIH grants U01AG042791, U19AG03243808, R01AG052550-01A1, R01AG05255003), and the Barnes-Jewish Hospital Foundation Willman Scholar Fund.

A cautionary tale on the effects of different covariance structures in linear mixed effects modeling of fMRI data.

With the steadily increasing abundance of longitudinal neuroimaging studies with large sample sizes and multiple repeated measures, questions arise regarding the appropriate modeling of variance and covariance. The current study examined the influence of standard classes of variance-covariance structures in linear mixed effects (LME) modeling of fMRI data from patients with pediatric mild traumatic brain injury (pmTBI; N = 181) and healthy controls (N = 162). During two visits, participants performed a cognitive control fMRI paradigm that compared congruent and incongruent stimuli. The hemodynamic response function was parsed into peak and late peak phases. Data were analyzed with a 4-way (GROUP×VISIT×CONGRUENCY×PHASE) LME using AFNI's 3dLME and compound symmetry (CS), autoregressive process of order 1 (AR1), and unstructured (UN) variance-covariance matrices. Voxel-wise results dramatically varied both within the cognitive control network (UN>CS for CONGRUENCY effect) and broader brain regions (CS>UN for GROUP:VISIT) depending on the variance-covariance matrix that was selected. Additional testing indicated that both model fit and estimated standard error were superior for the UN matrix, likely as a result of the modeling of individual terms. In summary, current findings suggest that the interpretation of results from complex designs is highly dependent on the selection of the variance-covariance structure using LME modeling.

All Three Supersystems-Nervous, Vascular, and Immune-Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage.

The recently published DISCHARGE-1 trial supports the observations of earlier autopsy and neuroimaging studies that almost 70% of all focal brain damage after aneurysmal subarachnoid hemorrhage are anemic infarcts of the cortex, often also affecting the white matter immediately below. The infarcts are not limited by the usual vascular territories. About two-fifths of the ischemic damage occurs within ~ 48h; the remaining three-fifths are delayed (within ~ 3weeks). Using neuromonitoring technology in combination with longitudinal neuroimaging, the entire sequence of both early and delayed cortical infarct development after subarachnoid hemorrhage has recently been recorded in patients. Characteristically, cortical infarcts are caused by acute severe vasospastic events, so-called spreading ischemia, triggered by spontaneously occurring spreading depolarization. In locations where a spreading depolarization passes through, cerebral blood flow can drastically drop within a few seconds and remain suppressed for minutes or even hours, often followed by high-amplitude, sustained hyperemia. In spreading depolarization, neurons lead the event, and the other cells of the neurovascular unit (endothelium, vascular smooth muscle, pericytes, astrocytes, microglia, oligodendrocytes) follow. However, dysregulation in cells of all three supersystems-nervous, vascular, and immune-is very likely involved in the dysfunction of the neurovascular unit underlying spreading ischemia. It is assumed that subarachnoid blood, which lies directly on the cortex and enters the parenchyma via glymphatic channels, triggers these dysregulations. This review discusses the neuroglial, neurovascular, and neuroimmunological dysregulations in the context of spreading depolarization and spreading ischemia as critical elements in the pathogenesis of cortical infarcts after subarachnoid hemorrhage.

Bipolar disorders and schizophrenia: discrete disorders?

BackgroundWith similarities in heritability, neurobiology and symptomatology, the question has been raised whether schizophrenia and bipolar disorder are truly distinctive disorders or belong to a continuum. This narrative review summarizes common and distinctive findings from genetics, neuroimaging, cognition and clinical course that may help to solve this ethiopathogenetic puzzle.MethodsThe authors conducted a literature search for papers listed in PubMed and Google Scholar, using the search terms “schizophrenia” and “bipolar disorder” combined with different terms such as “genes”, “neuroimaging studies”, “phenomenology differences”, “cognition”, “epidemiology”. Articles were considered for inclusion if they were written in English or Spanish, published as full articles, if they compared subjects with schizophrenia and bipolar disorder, or subjects with either disorder with healthy controls, addressing differences between groups.ResultsSeveral findings support the hypothesis that schizophrenia and bipolar disorder are discrete disorders, yet some overlapping of findings exists. The evidence for heritability of both SZ and BD is obvious, as well as the environmental impact on individual manifestations of both disorders. Neuroimaging studies support subtle differences between disorders, it appears to be rather a pattern of irregularities than an unequivocally unique finding distinguishing schizophrenia from bipolar disorder. The cognitive profile displays differences between disorders in certain domains, such as premorbid intellectual functioning and executive functions. Finally, the timing and trajectory of cognitive impairment in both disorders also differs.ConclusionThe question whether SZ and BD belong to a continuum or are separate disorders remains a challenge for further research. Currently, our research tools may be not precise enough to carve out distinctive, unique and undisputable differences between SZ and BD, but current evidence favors separate disorders. Given that differences are subtle, a way to overcome diagnostic uncertainties in the future could be the application of artificial intelligence based on BigData.LimitationsDespite the detailed search, this article is not a full and complete review of all available studies on the topic. The search and selection of papers was also limited to articles in English and Spanish. Selection of papers and conclusions may be biased by the personal view and clinical experience of the authors.

The emergence of AI in mental health: A transformative journey

This paper traces the evolution of Artificial Intelligence (AI) in psychiatry, from early attempts like the ELIZA program to the integration of neuroimaging studies and the emergence of digital interventions. Utilizing deep learning models, AI now demonstrates high accuracy in classifying psychiatric disorders, such as schizophrenia based on functional connectivity patterns. The rise of AI chat/therapy bots, exemplified by Woebot and Tess, addresses mental health challenges, providing accessible and effective cognitive behavioral therapy tools. Innovative interventions like avatar therapy and intelligent animal-like robots contribute to broadening therapeutic perspectives. While AI-based interventions offer advantages in reducing stigma and increasing accessibility, challenges including diagnostic accuracy, legal responsibilities, and privacy concerns must be carefully considered. Despite challenges, the significant potential of AI in psychiatry calls for large, controlled trials, national standards, and responsible integration into clinical practice. The convergence of AI and psychiatry represents a technological revolution poised to transform mental health care delivery globally.

Differences in the neural correlates of schizophrenia with positive and negative formal thought disorder in patients with schizophrenia in the ENIGMA dataset.

Formal thought disorder (FTD) is a clinical key factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, the relationship between FTD symptom dimensions and patterns of regional brain volume loss in schizophrenia remains to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles by enrolling a large multi-site cohort acquired by the ENIGMA Schizophrenia Working Group (752 schizophrenia patients and 1256 controls), to unravel the neuroanatomy of FTD in schizophrenia and using virtual histology tools on implicated brain regions to investigate the cellular basis. Based on the findings of previous clinical and neuroimaging studies, we decided to separately explore positive, negative and total formal thought disorder. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but positive and negative FTD demonstrated a dissociation: negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD also showed associations with microglial cell types. These results provide an important step towards linking FTD to brain structural changes and their cellular underpinnings, providing an avenue for a better mechanistic understanding of this syndrome.

Altered Functional Connectivity during Mild Transient Respiratory Impairment Induced by a Resistive Load.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without altering transcutaneous oxygen saturation. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptual area (postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores. These findings may provide new insights into the visual networks that contribute to mild respiratory impairments.

Atypical procedural learning in children with developmental coordination disorder: A combined behavioral and neuroimaging study

While procedural learning (PL) has been implicated in delayed motor skill observed in developmental coordination disorder (DCD), few studies have considered the impact of co-occurring attentional problems. Furthermore, the neurostructural basis of PL in children remains unclear. We investigated PL in children with DCD while controlling for inattention symptoms, and examined the role of fronto-basal ganglia-cerebellar morphology in PL. Fifty-nine children (6–14 years; nDCD = 19, ncontrol = 40) completed the serial reaction time (SRT) task to measure PL. The Attention-Deficit Hyperactivity Disorder Rating Scale-IV was administered to measure inattention symptoms. Structural T1 images were acquired for a subset of participants (nDCD = 10, ncontrol = 28), and processed using FreeSurfer. Volume was extracted for the cerebellum, basal ganglia, and frontal regions. After controlling for inattention symptoms, the reaction time profile of controls was consistent with learning on the SRT task. This was not the case for those with DCD. SRT task performance was positively correlated with cerebellar cortical volume, and children with DCD trended towards lower cerebellar volume compared to controls. Children with DCD may not engage in PL during the SRT task in the same manner as controls, with this differential performance being associated with atypical cerebellar morphology.

A Unifying Model for Discordant and Concordant Results in Human Neuroimaging Studies of Facial Viewpoint Selectivity.

Recognizing faces regardless of their viewpoint is critical for social interactions. Traditional theories hold that view-selective early visual representations gradually become tolerant to viewpoint changes along the ventral visual hierarchy. Newer theories, based on single-neuron monkey electrophysiological recordings, suggest a three-stage architecture including an intermediate face-selective patch abruptly achieving invariance to mirror-symmetric face views. Human studies combining neuroimaging and multivariate pattern analysis (MVPA) have provided convergent evidence of view selectivity in early visual areas. However, contradictory conclusions have been reached concerning the existence in humans of a mirror-symmetric representation like that observed in macaques. We believe these contradictions arise from low-level stimulus confounds and data analysis choices. To probe for low-level confounds, we analyzed images from two face databases. Analyses of image luminance and contrast revealed biases across face views described by even polynomials-i.e., mirror-symmetric. To explain major trends across neuroimaging studies, we constructed a network model incorporating three constraints: cortical magnification, convergent feedforward projections, and interhemispheric connections. Given the identified low-level biases, we show that a gradual increase of interhemispheric connections across network-layers is sufficient to replicate view-tuning in early processing stages and mirror-symmetry in later stages. Data analysis decisions-pattern dissimilarity measure and data recentering-accounted for the inconsistent observation of mirror-symmetry across prior studies. Pattern analyses of human fMRI data (of either sex) revealed biases compatible with our model. The model provides a unifying explanation of MVPA studies of viewpoint selectivity and suggests observations of mirror-symmetry originate from ineffectively normalized signal imbalances across different face views.

How does the macroenvironment influence brain and behaviour-a review of current status and future perspectives.

The environment influences brain and mental health, both detrimentally and beneficially. Existing research has emphasised the individual psychosocial 'microenvironment'. Less attention has been paid to 'macroenvironmental' challenges, including climate change, pollution, urbanicity, and socioeconomic disparity. Notably, the implications of climate and pollution on brain and mental health have only recently gained prominence. With the advent of large-scale big-data cohorts and an increasingly dense mapping of macroenvironmental parameters, we are now in a position to characterise the relation between macroenvironment, brain, and behaviour across different geographic and cultural locations globally. This review synthesises findings from recent epidemiological and neuroimaging studies, aiming to provide a comprehensive overview of the existing evidence between the macroenvironment and the structure and functions of the brain, with a particular emphasis on its implications for mental illness. We discuss putative underlying mechanisms and address the most common exposures of the macroenvironment. Finally, we identify critical areas for future research to enhance our understanding of the aetiology of mental illness and to inform effective interventions for healthier environments and mental health promotion.

Re-examining the Mysterious Role of the Cerebellum in Pain.

Pain is considered a multidimensional experience that embodies not merely sensation, but also emotion and perception. As is appropriate for this complexity, pain is represented and processed by an extensive matrix of cortical and subcortical structures. Of these structures, the cerebellum is gaining increasing attention. Although association between the cerebellum and both acute and chronic pain have been extensively detailed in electrophysiological and neuroimaging studies, a deep understanding of what functions are mediated by these associations is lacking. Nevertheless, the available evidence implies that lobules IV-VI and Crus I are especially pertinent to pain processing, and anatomical studies reveal that these regions connect with higher-order structures of sensorimotor, emotional, and cognitive function. Therefore, we speculate that the cerebellum exerts a modulatory role in pain via its communication with sites of sensorimotor, executive, reward, and limbic function. On this basis, in this review, we propose numerous ways in which the cerebellum might contribute to both acute and chronic pain, drawing particular attention to emotional and cognitive elements of pain. In addition, we emphasise the importance of advancing our knowledge about the relationship between the cerebellum and pain by discussing novel therapeutic opportunities that capitalize on this association.