Sex Hormone-Specific Neuroanatomy of Takotsubo Syndrome: Is the Insular Cortex a Moderator?

Takotsubo syndrome (TTS), a transient form of dysfunction in the heart’s left ventricle, occurs predominantly in postmenopausal women who have emotional stress. Earlier studies support the concept that the human circulatory system is modulated by a cortical network (consisting of the anterior cingulate gyrus, amygdala, and insular cortex (Ic)) that plays a pivotal role in the central autonomic nervous system in relation to emotional stressors. The Ic plays a crucial role in the sympathovagal balance, and decreased levels of female sex hormones have been speculated to change functional cerebral asymmetry, with a possible link to autonomic instability. In this review, we focus on the Ic as an important moderator of the human brain–heart axis in association with sex hormones. We also summarize the current knowledge regarding the sex-specific neuroanatomy in TTS.

Distinct neural representations for prosocial and self-benefitting effort

Prosocial behaviours - actions that benefit others - are central to individual and societal well-being. Most prosocial acts are effortful. Yet, how the brain encodes effort costs when actions benefit others is unknown. Here, using a combination of multivariate representational similarity analysis and model-based univariate analysis during fMRI, we reveal how the costs of prosocial efforts are processed. Strikingly, we identified a unique neural signature of effort in the anterior cingulate gyrus for prosocial acts both when choosing to help others and when exerting force for their benefit. This pattern was absent for similar self-benefitting behaviour and correlated with individual levels of empathy. In contrast, the ventral tegmental area and the ventral insula signalled subjective value preferentially when choosing whether to exert effort to benefit oneself. These findings demonstrate partially distinct brain areas guide the evaluation and exertion of effort costs when acts are prosocial or self-benefitting.

Emotion Down- and Up-Regulation Act on Spatially Distinct Brain Areas: Interoceptive Regions to Calm Down and Other Affective Regions to Amp Up

Prior studies on emotion regulation identified a set of brain regions specialized for generating and controlling affect. Researchers generally agree that when up- and down-regulating emotion, control regions in the prefrontal cortex turn up or down activity in affect-generating areas. However, the assumption that turning up and down emotions produces opposite effects in the same affect-generating regions is untested. We call this assumption the ‘affective dial hypothesis.’ Our study tested this hypothesis by examining the overlap between the sets of regions activated during up-regulation and those deactivated during down-regulation in a large number of participants (N=105). We found that up- and down-regulation both recruit regulatory regions such as the inferior frontal gyrus and dorsal anterior cingulate gyrus but act on distinct affect-generating regions. While up-regulation increases BOLD signal in regions associated with emotion such as the amygdala, anterior insula, striatum and anterior cingulate gyrus as well as in regions associated with sympathetic vascular activity such as periventricular white matter, down-regulation decreases signal in regions receiving interoceptive input such as the posterior insula and postcentral gyrus. These findings indicate that up- and down-regulation do not generally exert opposing effects on the same affect-generating regions. Instead, they target different brain circuits.Significance StatementMany contexts require modulating one’s own emotions. Identifying the brain areas implementing these regulatory processes should advance understanding emotional disorders and designing potential interventions. The emotion regulation field has an implicit assumption we call the affective dial hypothesis: that both emotion up- and down-regulation modulate the same emotion-generating brain areas. Countering the hypothesis, our findings indicate that up- and down-modulating emotions target different brain areas. Thus, the mechanisms underlying emotion regulation differ more than previously appreciated for up- versus down-regulation. In addition to their theoretical importance, these findings are critical for researchers attempting to target activity in particular brain regions during an emotion regulation intervention.

Altered Functional Connectivity Patterns of Parietal Subregions Contribute to Cognitive Dysfunction in Patients with White Matter Hyperintensities

Background: The white matter hyperintensities (WMHs) are considered as one of the core neuroimaging findings of cerebral small vessel disease and independently associated with cognitive deficit. The parietal lobe is a heterogeneous area containing many subregions and play an important role in the processes of neurocognition. Objective: To explore the relationship between parietal subregions alterations and cognitive impairments in WHMs. Methods: Resting-state functional connectivity (rs-FC) analyses of parietal subregions were performed in 104 right-handed WMHs patients divided into mild (n = 39), moderate (n = 37), and severe WMHs (n = 28) groups according to the Fazekas scale and 36 healthy controls. Parietal subregions were defined using tractographic Human Brainnetome Atlas and included five subregions for superior parietal lobe, six subregions for inferior parietal lobe (IPL), and three subregions for precuneus. All participants underwent a neuropsychological test battery to evaluate emotional and general cognitive functions. Results: Differences existed between the rs-FC strength of IPL_R_6_2 with the left anterior cingulate gyrus, IPL_R_6_3 with the right dorsolateral superior frontal gyrus, and the IPL_R_6_5 with the left anterior cingulate gyrus. The connectivity strength between IPL_R_6_3 and the left anterior cingulate gyrus were correlated with AVLT-immediate and AVLT-recognition test in WMHs. Conclusion: We explored the roles of parietal subregions in WMHs using rs-FC. The functional connectivity of parietal subregions with the cortex regions showed significant differences between the patients with WMHs and healthy controls which may be associated with cognitive deficits in WMHs.

Abnormal Fractional Amplitude of Low-frequency Fluctuation Changes in Patients With Diabetic Optic Neuropathy: a Functional MRI Study

The present study was to assess the spontaneous changes in brain activity in patients with DON using functional magnetic resonance imaging (fMRI). 14 DON patients and 14 healthy controls (HCs) were enrolled. All participants underwent resting-state fMRI (rs-fMRI). The fractional amplitude of low-frequency fluctuation (fALFF) method was applied to evaluate neural activity changes. The Hospital Anxiety and Depression Scale (HADS) was used to assess the anxiety and depression status of participants. The independent sample t test and chi-squared test were applied to analyze demographics of DON patients and HCs. Receiver operating characteristic (ROC) curves were applied to analyze the variation in mean fALFF values between DON patients and HCs. The relationships between the fALFF values of brain regions and clinical behaviors in the DON group were analyzed using Pearson’s correlation analysis. In contrast to HCs, the fALFF value of DON patients was significantly higher in the right precentral gyrus (RPCG). However, the fALFF values in right anterior cingulate gyrus (RACG) and left middle cingulate gyrus (LMCG) were markedly decreased in DON patients. The area under the curve (AUC) of ROCs for each brain region showed high accuracy. Pearson's correlation analysis showed that fALFF values of the right anterior cingulate gyrus and left middle cingulate gyrus were negatively correlated with HADS scores, while fALFF values of the left middle cingulate gyrus were negatively correlated with DON disease duration. To sum up, we found abnormal spontaneous brain activities in regions related to cognitive and emotional dysfunction, eye movement disorder, and vision loss in patients with DON. These results may indicate the underlying neuropathological mechanisms of DON, and show that fALFF may be an effective method by which to distinguish patients with DON from healthy individuals.

Brain reactivity to humorous films is affected by insomnia

Study objectives Emotional reactivity to negative stimuli has been investigated in insomnia, but little is known about emotional reactivity to positive stimuli and its neural representation. Methods We used 3T fMRI to determine neural reactivity during the presentation of standardized short, 10-40-s, humorous films in insomnia patients (n=20, 18 females, aged 27.7 +/- 8.6 years) and age-matched individuals without insomnia (n=20, 19 females, aged 26.7 +/- 7.0 years), and assessed humour ratings through a visual analogue scale (VAS). Seed-based functional connectivity was analysed for left and right amygdala networks: group-level mixed-effects analysis (FLAME; FSL) was used to compare amygdala connectivity maps between groups. Results fMRI seed-based analysis of the amygdala revealed stronger neural reactivity in insomnia patients than in controls in several brain network clusters within the reward brain network, without humour rating differences between groups (p = 0.6). For left amygdala connectivity, cluster maxima were in the left caudate (Z=3.88), left putamen (Z=3.79) and left anterior cingulate gyrus (Z=4.11), while for right amygdala connectivity, cluster maxima were in the left caudate (Z=4.05), right insula (Z=3.83) and left anterior cingulate gyrus (Z=4.29). Cluster maxima of the right amygdala network were correlated with hyperarousal scores in insomnia patients only. Conclusions Presentation of humorous films leads to increased brain activity in the neural reward network for insomnia patients compared to controls, related to hyperarousal features in insomnia patients, in the absence of humor rating group differences. These novel findings may benefit insomnia treatment interventions.

Anterior cingulate gyrus acts as a moderator of the relationship between problematic mobile phone use and depressive symptoms in college students

This study aimed to investigate the brain grey matter volume (GMV) related to problematic mobile phone use (PMPU), and whether these regions of GMV play a potential moderating role in the relationship between PMPU and depressive symptoms. We recruited 266 students who underwent magnetic resonance imaging (MRI) scanning. PMPU and depressive symptoms were assessed by a self-rating questionnaire for adolescent PMPU and patient health questionnaire-9, respectively. A multiple regression model was performed to detect GMV and white matter (WM) integrity associated with PMPU by voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) methods, and the moderating analysis was conducted by PROCESS using SPSS software. VBM analysis found an inverse correlation between the GMV of the anterior cingulate gyrus (ACC) and right fusiform gyrus (FFG) with PMPU (PFDR < 0.05), and TBSS analysis revealed that fractional anisotropy (FA) in the body of the corpus callosum was negatively correlated with PMPU. The correlation between PMPU and depressive symptoms was moderated by the GMV of the ACC. These results suggest that the GMV of the ACC and right FFG, as well as FA in the body of the corpus callosum, was related to PMPU, and we further found that increased GMV of the ACC could reduce the relationship between PMPU and depressive symptoms in college students.

An Autopsy Case of Preclinical/Early Clinical Pick Disease

Here, we report a 74-year-old woman with a long history of schizophrenia but no clinical manifestation of dementia. Cause of death after autopsy was atherosclerotic heart disease. Although neuropathological investigation showed no significant brain atrophy, superficial microvacuolation with neuronal loss was restrictedly detected in the right anterior cingulate gyrus by microscopic examination. Pick bodies (PBs) positive for Bodian and Bielshowsky staining and 3-repeat-tau were detected in frontal and temporal lobes and limbic regions. Prevalence of PBs was most frequent in the right anterior cingulate gyrus and lateral base, followed by other neocortical regions of the frontal lobe, amygdala, and granular layer of the hippocampus. Although the number of glial inclusions was low, ramified astrocytes and various forms of astrocytes with AT8-positive inclusions were also found. Thus, the case may reflect preclinical or very early clinical Pick disease. Distribution of PBs does not necessarily have to be consistent with previously reported preclinical/early clinical Pick disease. These results show that tau pathology in the earlier stage of Pick disease may be heterogeneous, and the anterior cingulate gyrus may be initially affected in Pick disease. Neuropathological examination, including immunohistochemistry without case selection, is useful in identifying clinical and pathological manifestations of Pick disease.