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Childhood maladaptive aggression is associated with disrupted functional connectivity within amygdala-prefrontal circuitry. In this study, neural correlates of childhood aggression were probed using the intrinsic connectivity distribution, a voxel-wise metric of global resting-state brain connectivity. This sample included 38 children with aggressive behavior (26 boys, 12 girls) ages 8–16 years and 21 healthy controls (14 boys, 6 girls) matched for age and IQ. Functional MRI data were acquired during resting state, and differential patterns of intrinsic functional connectivity were tested in a priori regions of interest implicated in the pathophysiology of aggressive behavior. Next, correlational analyses tested for associations between functional connectivity and severity of aggression measured by the Reactive-Proactive Aggression Questionnaire in children with aggression. Children with aggressive behavior showed increased global connectivity in the bilateral amygdala relative to controls. Greater severity of aggressive behavior was associated with decreasing global connectivity in the dorsal anterior cingulate and ventromedial prefrontal cortex. Follow-up seed analysis revealed that aggression was also positively correlated with left amygdala connectivity with the dorsal anterior cingulate, ventromedial and dorsolateral prefrontal cortical regions. These results highlight the potential role of connectivity of the amygdala and medial prefrontal and anterior cingulate cortices in modulating the severity of aggressive behavior in treatment-seeking children.

We conducted meta-analysis in order to determine if there are significant differences in left and right amygdala volume in individuals with autism spectrum disorders (ASD) compared to a control group. Twenty-three studies fulfilled inclusion criteria for our study. Right amygdala volume was significantly larger in ASD patients compared to controls (Hedges’ g 0.44; 95% CI 0.04–0.83; Z = 2.26; p = 0.024), while there was no significant difference in left amygdala volume between ASD patients and controls (Hedges’ g 0.44; 95% CI − 0.10–0.98; Z = 1.67; p = 0.095). However, between-study heterogeneity was significant so there is an unequivocal need for new uniform magnetic resonance imaging (MRI) studies to get a more precise answer to the question of whether there is a difference in amygdala volume between ASD patients and controls.

It is of great clinical importance to explore more efficacious treatments for OCD. Recently, cognitive-coping therapy (CCT), mainly focusing on recognizing and coping with a fear of negative events, has been reported as an efficacious psychotherapy. However, the underlying neurophysiological mechanism remains unknown. This study of 79 OCD patients collected Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after four weeks of CCT, pharmacotherapy plus CCT (pCCT), or pharmacotherapy. Amygdala seed-based functional connectivity (FC) analysis was performed. Compared post- to pretreatment, pCCT-treated patients showed decreased left amygdala (LA) FC with the right anterior cingulate gyrus (cluster 1) and with the left paracentral lobule/the parietal lobe (cluster 2), while CCT-treated patients showed decreased LA-FC with the left middle occipital gyrus/the left superior parietal/left inferior parietal (cluster 3). The z-values of LA-FC with the three clusters were significantly lower after pCCT or CCT than pretreatment in comparisons of covert vs. overt and of non-remission vs. remission patients, except the z-value of cluster 2 in covert OCD. CCT and pCCT significantly reduced the Y-BOCS score. The reduction in the Y-BOCS score was positively correlated with the z-value of cluster 1. Our findings demonstrate that both pCCT and CCT with large effect sizes lowered LA-FC, indicating that FCs were involved in OCD. Additionally, decreased LA-FC with the anterior cingulate cortex (ACC) or paracentral/parietal cortex may be a marker for pCCT response or a marker for distinguishing OCD subtypes. Decreased LA-FC with the parietal region may be a common pathway of pCCT and CCT. Trial registration: ChiCTR-IPC-15005969.

Adolescents with conduct problems and low callous-unemotional traits are characterised by high levels of reactive aggression. Prior studies suggest that they can have exaggerated neural and behavioural responses to negative emotional stimuli, accompanied by compromised affect regulation and atypical engagement of prefrontal areas during cognitive control. This pattern may in part explain their symptoms. Clarifying how neurocognitive responses to negative emotional stimuli can be modulated in this group has potential translational relevance. We present fMRI data from a cognitive conflict task in which the requirement to visually scan emotional (vs. calm) faces was held constant across low and high levels of cognitive conflict. Participants were 17 adolescent males with conduct problems and low levels of callous-unemotional traits (CP/LCU); 17 adolescents with conduct problems and high levels of callous-unemotional traits (CP/HCU, who typically show blunted reactivity to fear), and 18 typically developing controls (age range 10–16). Control participants showed typical attenuation of amygdala response to fear relative to calm faces under high (relative to low) conflict, replicating previous findings in a healthy adult sample. In contrast, children with CP/LCU showed a reduced (left amygdala) or reversed (right amygdala) attenuation effect under high cognitive conflict conditions. Children with CP/HCU did not differ from controls. Findings suggest atypical modulation of amygdala response as a function of task demands, and raise the possibility that those with CP/LCU are unable to implement typical regulation of amygdala response when cognitive task demands are high. Supplementary Information The online version contains supplementary material available at 10.1007/s10802-021-00787-z.

Childhood maltreatment (CM) poses a serious risk to the physical, emotional and psychological well-being of children, and can advance the development of maladaptive behaviors, including conduct disorder (CD). CD involves repetitive, persistent violations of others' basic rights and societal norms. Little is known about whether and how CM influences the neural mechanisms underlying CD, and CD-characteristic neuroanatomical changes have not yet been defined in a structural magnetic resonance imaging (sMRI) study. Here, we used voxel-based morphometry (VBM) and surface-based morphometry (SBM) to investigate the influence of the CD diagnosis and CM on the brain in 96 boys diagnosed with CD (62 with CM) and 86 typically developing (TD) boys (46 with CM). The participants were 12-17 years of age. Compared to the CM- CD group, the CM+ CD group had structural gray matter (GM) alterations in the fronto-limbic regions, including the left amygdala, right posterior cingulate cortex (PCC), right putamen, right dorsolateral prefrontal cortex (dlPFC) and right anterior cingulate cortex (ACC). We also found boys with CD exhibited increased GM volume in bilateral dorsomedial prefrontal cortex (dmPFC), as well as decreased GM volume and decreased gyrification in the left superior temporal gyrus (STG) relative to TD boys. Regional GM volume correlated with aggression and conduct problem severity in the CD group, suggesting that the GM changes may contribute to increased aggression and conduct problems in boys with CD who have suffered CM. In conclusion, these results demonstrate previously unreported CM-associated distinct brain structural changes among CD-diagnosed boys.

Background There is evidence that the amygdala undergoes extensive development. The exact nature of this change remains less clear, with evidence suggesting linear, curvilinear, and null effects. The aim of this study was the identification of a normative reference of left and right amygdala development by parceling variance into separate effects of age and longitudinal growth. Methods Data came from the National Institutes of Health MRI Study of Normal Brain Development. Participants in this sample were 54% female and ranged in age from 5 to 18 years (mean = 11.37 years) at study entry. Results As predicted, the age at initial scan moderated the slope of both left and right amygdala volumes, demonstrating that the nature of longitudinal growth varies across age (i.e., steeper slopes observed among those first scanned at an early age). Follow-up analysis showed that the positive longitudinal growth slope becomes nonsignificant at 13.1 years of age for the left amygdala and at 14.5 years for the right amygdala, suggesting that growth of the left amygdala peaks earlier than growth of the right amygdala. Conclusions Findings suggest that rapid increases in volumes at early ages decline as youths enter adolescence and may turn to minor declines in volume during late adolescence or early adulthood.

Background Anxiety is frequent in Parkinson's disease (PD) and has a negative impact on disease symptoms and quality of life. The underlying mechanisms remain largely unknown. The aim of this study was to identify anatomical and functional changes associated to PD-related anxiety by comparing the volume, shape and texture of the amygdala, the cortical thickness as well as the functional connectivity (FC) of the fear circuit in patients with and without clinically relevant anxiety. Methods Non-demented PD patients were recruited, and anxiety was quantified using the Parkinson Anxiety Scale. Structural MRI was used to compare cortical thickness and amygdala structure and resting-state functional MRI to compare FC patterns of the amygdala and resting-state functional networks in both groups. Results We included 118 patients: 34 with (A+) and 84 without (A-) clinically relevant anxiety. Clusters of cortical thinning were identified in the bilateral fronto-cingulate and left parietal cortices of the A+ group. The texture and the shape of the left amygdala was different in the A+ group but the overall volume did not differ between groups. FC between the amygdala and the whole brain regions did not differ between groups. The internetwork resting-state FC was higher between the “fear circuit” and salience network in the A+ group. Conclusion Anxiety in PD induces structural modifications of the left amygdala, atrophy of the bilateral fronto-cingulate and the left parietal cortices, and a higher internetwork resting-state FC between the fear circuit and the salience network.

Objectives: To evaluate whether 3D amide proton transfer weighted (APTw) imaging based on magnetization transfer analysis can be used as a novel imaging marker to distinguish amnestic mild cognitive impairment (aMCI) patients from the normal elderly population by measuring changes in APTw signal intensity in the hippocampus and amygdala.Materials and Methods: Seventy patients with aMCI and 74 age- and sex-matched healthy volunteers were recruited for routine MRI and APT imaging examinations. Magnetic transfer ratio asymmetry (MTRasym) of the amide protons (at 3.5 ppm), or APTw values, were measured in the bilateral hippocampus and amygdala on three consecutive cross-sectional APT images and were compared between the aMCI and control groups. The independent sample t-test was used to evaluate the difference in APTw values of the bilateral hippocampus and amygdala between the aMCI and control groups. Receiver operator characteristic analysis was used to assess the diagnostic performance of the APTw. The paired t-test was used to assess the difference in APTw values between the left and right hippocampus and amygdala, in both the aMCI and control groups.Results: The APTw values of the bilateral hippocampus and amygdala in the aMCI group were significantly higher than those in the control group (left hippocampus 1.01 vs. 0.77% p < 0.001; right hippocampus 1.02 vs. 0.74%, p < 0.001; left amygdala 0.98 vs. 0.70% p < 0.001; right amygdala 0.94 vs. 0.71%, p < 0.001). The APTw values of the left amygdala had the largest AUC (0.875) at diagnosis of aMCI. There was no significant difference in APTw values between the left and right hippocampus and amygdala, in either group. (aMCI group left hippocampus 1.01 vs. right hippocampus 1.02%, p = 0.652; healthy control group left hippocampus 0.77 vs. right hippocampus 0.74%, p = 0.314; aMCI group left amygdala 0.98 vs. right amygdala 0.94%, p = 0.171; healthy control group left amygdala 0.70 vs. right amygdala 0.71%, p = 0.726).Conclusion: APTw can be used as a new imaging marker to distinguish aMCI patients from the normal elderly population by indirectly reflecting the changes in protein content in the hippocampus and amygdala.

Nonsuicidal self-injury (NSSI) is a common but poorly understood phenomenon in adolescents. This study examined the Sustained Threat domain in female adolescents with a continuum of NSSI severity (N = 142). Across NSSI lifetime frequency and NSSI severity groups (No + Mild NSSI, Moderate NSSI, Severe NSSI), we examined physiological, self-reported and observed stress during the Trier Social Stress Test; amygdala volume; amygdala responses to threat stimuli; and resting-state functional connectivity (RSFC) between amygdala and medial prefrontal cortex (mPFC). Severe NSSI showed a blunted pattern of cortisol response, despite elevated reported and observed stress during TSST. Severe NSSI showed lower amygdala–mPFC RSFC; follow-up analyses suggested that this was more pronounced in those with a history of suicide attempt for both moderate and severe NSSI. Moderate NSSI showed elevated right amygdala activation to threat; multiple regressions showed that, when considered together with low amygdala–mPFC RSFC, higher right but lower left amygdala activation predicted NSSI severity. Patterns of interrelationships among Sustained Threat measures varied substantially across NSSI severity groups, and further by suicide attempt history. Study limitations include the cross-sectional design, missing data, and sampling biases. Our findings highlight the value of multilevel approaches in understanding the complexity of neurobiological mechanisms in adolescent NSSI.

Young adults are at high risk for suicide, yet there is limited ability to predict suicidal thoughts and behaviors. Machine learning approaches are better able to examine a large number of variables simultaneously to identify combinations of factors associated with suicidal thoughts and behaviors. The current study used LASSO regression to investigate extent to which a number of demographic, psychiatric, behavioral, and functional neuroimaging variables are associated with suicidal thoughts and behaviors during young adulthood. 78 treatment seeking young adults (ages 18-25) completed demographic, psychiatric, behavioral, and suicidality measures. Participants also completed an implicit emotion regulation functional neuroimaging paradigm. Report of recent suicidal thoughts and behaviors served as the dependent variable. Five variables were identified by the LASSO regression: Two were demographic variables (age and level of education), two were psychiatric variables (depression and general psychiatric distress), and one was a neuroimaging variable (left amygdala activity during sad faces). Amygdala function was significantly associated with suicidal thoughts and behaviors above and beyond the other factors. Findings inform the study of suicidal thoughts and behaviors among treatment seeking young adults, and also highlight the importance of investigating neurobiological markers.

Posttraumatic stress disorder (PTSD) is associated with altered hypothalamic-pituitary-adrenal (HPA) axis function. Measurement of hair cortisol concentrations (HCC) allows retrospective assessment of HPA axis regulation over prolonged periods of time. Currently, research investigating HCC in PTSD remains sparse. Previous cross-sectional studies have included only civilian populations, although it is known that trauma type moderates associations between PTSD status and HPA axis function. We investigated differences in HCC between trauma-exposed female police officers with current PTSD (n = 13) and without current and lifetime PTSD (n = 15). To investigate whether HCC was associated with neural correlates of PTSD, we additionally performed exploratory correlational analyses between HCC and amygdala reactivity to negative affective stimuli. We observed significantly lower HCC in participants with PTSD than in participants without PTSD, d = 0.89. Additionally, within participants with PTSD, we observed positive correlations between HCC and right amygdala reactivity to negative affective (vs. happy/neutral) faces, r = .806 (n = 11) and left amygdala reactivity to negative affective (vs. neutral) pictures, r = .663 (n = 10). Additionally, left amygdala reactivity to negative faces was positively correlated with HCC in trauma-exposed controls, r = .582 (n = 13). This indicates that lower HCC is associated with diminished amygdala differentiation between negative affective and neutral stimuli. Thus, we observed lower HCC in trauma-exposed noncivilian women with PTSD compared to those without PTSD, which likely reflects prolonged HPA axis dysregulation. Additionally, HCC was associated with hallmark neurobiological correlates of PTSD, providing additional insights into pathophysiological processes in PTSD.Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Concentraciones de cortisol en cabello se asocian con la condición de TEPT y la reactividad de la amígdala a estímulos emocionales negativos en oficiales de policía mujeres BAJO NIVEL DE CORTISOL EN CABELLO EN PACIENTES MUJERES CON TEPT El trastorno de estrés postraumático (TEPT) está asociado con la función alterada del eje hipotálamo-hipófisis-adrenal (HPA). La medición de las concentraciones de cortisol en cabello (HCC por sus siglas en inglés) permite evaluar en forma retrospectiva la regulación del eje HPA en periodos prolongados. Actualmente las investigaciones de HCC en TEPT son escasas. Los estudios transversales previos solo han incluido población civil, aunque se sabe que el tipo de trauma modera las asociaciones entre la condición del TEPT y la función del eje HPA. Investigamos las diferencias en el HCC entre oficiales de policía de sexo femenino expuestos a trauma con TEPT actual (n = 13) y sin TEPT actual o a lo largo de su vida (n = 15). Para investigar si la HCC se asociaba con correlatos neurales del TEPT, adicionalmente realizamos un análisis exploratorio correlacional entre la HCC y reactividad de la amígdala a estímulos emocionales negativos. Observamos niveles significativamente más bajos de HCC en las participantes con TEPT que en las sin TEPT, d = 0.89. Adicionalmente, entre las participantes con TEPT, observamos correlaciones positivas entre HCC y la reactividad de la amígdala derecha a caras con emociones negativas (vs. felicidad/neutral), r = .806 (n = 11) y la reactividad de la amígdala izquierda a fotografías con emociones negativas (vs. Neutral) r = .663 (n = 10). Adicionalmente, la reactividad de la amígdala izquierda a caras con emociones negativas estuvo correlacionada positivamente con HCC en controles expuestos a trauma, r = .582 (n = 13). Esto indica que HCC más bajos se asocian con capacidad de diferenciación disminuida de la amígdala entre estímulos emocionales negativos y neutrales. Así, observamos niveles más bajos de HCC en mujeres no civiles expuestas a trauma con TEPT comparadas con aquellas sin TEPT, lo que probablemente refleja una prolongada desregulación del eje HPA. Adicionalmente, HCC se asoció con correlatos neurobiológicos distintivos del TEPT, proveyendo información adicional de los procesos patofisiológicos en el TEPT.Traditional and Simplified Chinese Abstracts by the Asian Society for Traumatic Stress Studies (AsianSTSS) 簡體及繁體中文撮要由亞洲創傷心理研究學會翻譯 Hair Cortisol Concentrations are associated with PTSD Status and Amygdala Reactivity to Negative Affective Stimuli in Female Police Officers Traditional Chinese 標題: 女警中, 毛髮中的皮質醇含量跟PTSD狀態和杏仁體對負面情感刺激的反應有關 撮要: 創傷後壓力症(PTSD)跟下丘腦-垂體-腎上腺軸(HPA)功能改變有關。在一段長時間裡, 測量毛髮中的皮質醇含量(HCC), 可對HPA軸的調節作回顧性評估。目前對於PTSD患者的HCC研究仍然很少。即使我們知道創傷類別對PTSD狀態和HPA軸的關連有調節作用, 過往的橫斷研究也只包含平民為樣本。本研究檢視有當前PTSD的受創女警(n = 13)和沒有當前和終生PTSD的女警(n = 15)之間HCC的差異。為探查HCC是否跟PTSD的神經關連因素相關, 我們額外對HCC以及杏仁體對負面情感刺激的反應進行探索性關連分析。相比無患PTSD的樣本, 患PTSD的樣本有顯著較低的HCC(d = 0.89)。此外, 患PTSD的樣本中, HCC跟右邊杏仁體對負面情感表情 (比對快樂/中性表情) 的反應有正向關連, r = .806 (n = 11), 亦跟左邊杏仁體對產生負面情感的圖片 (比對中性圖片) 的反應有正向關連, r = .663 (n = 10)。另外, 在受創的對照樣本中, 左邊杏仁體對負面表情的反應跟HCC有正向關連, r = .582 (n = 13)。結果反映, HCC較低跟杏仁體對負面情感和中性刺激的辨別能力減弱有關。因此, 相比無患PTSD的受創非平民女性, 患PTSD的有較低的HCC, 而那很可能反映有長期的HPA軸失調。HCC亦跟PTSD的神經生理關連因素特徵有關。研究結果加深了我們對PTSD的病理生理學過程的理解。 Simplified Chinese 标题: 女警中, 毛发中的皮质醇含量跟PTSD状态和杏仁体对负面情感刺激的反应有关 撮要: 创伤后压力症(PTSD)跟下丘脑-垂体-肾上腺轴(HPA)功能改变有关。在一段长时间里, 测量毛发中的皮质醇含量(HCC), 可对HPA轴的调节作回顾性评估。目前对于PTSD患者的HCC研究仍然很少。即使我们知道创伤类别对PTSD状态和HPA轴的关连有调节作用, 过往的横断研究也只包含平民为样本。本研究检视有当前PTSD的受创女警(n = 13)和没有当前和终生PTSD的女警(n = 15)之间HCC的差异。为探查HCC是否跟PTSD的神经关连因素相关, 我们额外对HCC以及杏仁体对负面情感刺激的反应进行探索性关连分析。相比无患PTSD的样本, 患PTSD的样本有显著较低的HCC(d = 0.89)。此外, 患PTSD的样本中, HCC跟右边杏仁体对负面情感表情 (比对快乐/中性表情) 的反应有正向关连, r = .806 (n = 11), 亦跟左边杏仁体对产生负面情感的图片 (比对中性图片) 的反应有正向关连, r = .663 (n = 10)。另外, 在受创的对照样本中, 左边杏仁体对负面表情的反应跟HCC有正向关连, r = .582 (n = 13)。结果反映, HCC较低跟杏仁体对负面情感和中性刺激的辨别能力减弱有关。因此, 相比无患PTSD的受创非平民女性, 患PTSD的有较低的HCC, 而那很可能反映有长期的HPA轴失调。HCC亦跟PTSD的神经生理关连因素特征有关。研究结果加深了我们对PTSD的病理生理学过程的理解。.

We aimed to determine the alterations in the subcortical structures of patients with idiopathic generalized epilepsy with tonic–clonic seizures (IGE-GTCS) via MRI volumetry and vertex-based shape analysis and to evaluate the relationships between MRI measures and drug responses. In a follow-up sample of 48 patients with IGE-GTCS and 48 matched normal controls (NCs), high-resolution 3D T1WI was performed at baseline. After 1 year of follow-up, 31 patients were classified as seizure free (SF) and 17 as drug resistant (DR). The volumes of subcortical structures were extracted, and vertex-based shape analysis was performed using FSL-Integrated Registration and Segmentation Toolbox (FSL-FIRST). Comparisons among groups were calculated adjusting for covariates [age, sex, and intracranial volume (ICV)]. Analysis of the relationships among imaging biomarkers along with frequency and duration was assessed using partial correlations. The differential imaging indicators were used as features in a linear support vector machine (LSVM). The DR group displayed significant regional atrophy in the volume of the left amygdala compared with NCs (p = 0.004, false discovery rate corrected) and SF patients (p = 0.029, uncorrected). Meanwhile, vertex-based shape analysis showed focal inward deformation in the basolateral subregion of the left amygdala in DR compared with the results for SF and NC (p < 0.05, FWE corrected). There were significant correlations between the volume changes and seizure frequency (r = −0.324, p = 0.030) and between shape (r = −0.438, p = 0.003) changes and seizure frequency. Moreover, the volume of the left thalamus in the DR group was significantly correlated with seizure frequency (r = −0.689, p = 0.006). The SVM results revealed areas under the receiver operating characteristic curve of 0.82, 0.68, and 0.88 for the classification between SF and DR, between SF and NC, and between DR and NC, respectively. This study indicates the presence of focal atrophy in the basolateral region of the left amygdala in patients with IGE drug resistance; this finding may help predict drug responses and suggests a potential therapeutic target.

Many influential authors maintain that, even if emotions are conscious experiences, the processing of information that produces emotions is usually unconscious. This chapter discusses the nonconscious aspects of emotional processing and the critical role played in them by the right hemisphere. This chapter first reviews the studies that have demonstrated the existence of unconscious or subconscious forms of emotional processing and then discusses the data supporting the hypothesis that the right hemisphere is dominant for the processing of emotions. After these topics are reviewed, the chapter will discuss investigations that have shown that the right and left amygdala have different roles in the processing of emotional stimuli, the former being involved in nonconscious and the latter in conscious forms of emotional learning. This chapter will also address the distinction proposed by Freud between "removed" and "nonremoved" forms of unconscious processing and will consider whether "nonremoved preverbal implicit memories" have a preferential link with the right hemisphere. The possibility that the right hemisphere may play a critical role not only in the formation of nonremoved subconscious memories but also in the development of denial phenomena, resulting from dynamic processes of unconscious repression, will also be discussed.

Children differ in their response to environmental exposures, with some being more sensitive to contextual factors than others. According to theory, such variability is the result of individual differences in neurobiological sensitivity to environmental features, with some individuals generally more affected by both negative and/or positive experiences. In this exploratory study we tested whether left and right amygdala and hippocampus volumes (corrected for total brain size) account for individual differences in response to environmental influences in a sample of 62 boys. Cumulative general environmental quality, ranging from low to high, was measured across the first 9 years and child behavior was reported by teachers when boys were 12–13 years old. According to analyses, only the left amygdala volume – not any of the other brain volumes – emerged as an important brain region for sensitivity to positive environmental aspects. Boys with a larger left amygdala benefited significantly more from higher environmental quality than boys with a smaller left amygdala whilst not being more vulnerable to lower quality. Besides providing preliminary evidence for differences in environmental sensitivity due to brain structure, the results also point to the left amygdala as having a specific role regarding the response to environmental influences.

Although the diagnoses based on phenomenology have many practical advantages, accumulating evidence shows that schizophrenia and autism spectrum disorder (ASD) share some overlap in genetics and clinical presentation. It remains largely unknown how ASD-associated polygenetic risk contributes to the pathogenesis of schizophrenia. In the present study, we calculated high-resolution ASD polygenic risk scores (ASD PRSs) and selected optimal ten ASD PRS with minimal P values in the association analysis of PRSs, with schizophrenia to assess the effect of ASD PRS on brain neural activity in schizophrenia cases and controls. We found that amplitude of low-frequency fluctuation in left amygdala was positively associated with ASD PRSs in our cohort. Correlation analysis of ASD PRSs with facial emotion recognition test identified the negative correlation of ASD PRSs with negative emotions in schizophrenia cases and controls. Finally, functional enrichment analysis of PRS genes revealed that neural system function and development, as well as signal transduction, were mainly enriched in PRS genes. Our results provide empirical evidence that polygenic risk for ASD contributes to schizophrenia by the intermediate phenotypes of left amygdala function and emotion recognition. It provides a promising strategy to understand the relationship between phenotypes and genotypes shared in mental disorders.

Social attachment systems are disrupted for refugees through trauma and forced displacement. This study tested how the attachment system mitigates neural responses to threat in refugees with posttraumatic stress disorder (PTSD). Refugees with PTSD (N = 28) and refugee trauma-exposed controls (N = 22) viewed threat-related stimuli primed by attachment cues during a functional magnetic resonance imaging scan. Group differences and the moderating effects of avoidant or anxious attachment style and grief related to separation from family on brain activity and connectivity patterns were examined. Separation grief was associated with increased amygdala but decreased ventromedial prefrontal cortical (VMPFC) activity to the attachment prime and decreased VMPFC and hippocampal activity to attachment primed threat in the PTSD (vs trauma-exposed control) group. Avoidant attachment style was connected with increased dorsal frontoparietal attention regional activity to attachment prime cues in the PTSD group. Anxious attachment style was associated with reduced left amygdala connectivity with left medial prefrontal regions to attachment primed threat in the PTSD group. Separation grief appears to reduce attachment buffering of threat reactivity in refugees with PTSD, while avoidant and anxious attachment style modulated attentional and prefrontal regulatory mechanisms in PTSD, respectively. Considering social attachments in refugees could be important to post-trauma recovery, based within changes in key emotion regulation brain systems.

Background To quantitatively evaluate the brain MRI morphological abnormalities in patients with cyclin-dependent kinase-like 5 deficiency disorder (CDD) on a group level and longitudinally. Methods We performed surface-based MRI analysis on high-resolution T1-weighted images on three CDD patients scanned at age of three years, and compared with 12 age- and gender-matched healthy controls. We further examined the longitudinal morphological changes in one patient with a follow-up of 5 years. Results CDD patients presented significant reductions in total intracranial volume, total gray matter (GM) volume and subcortical GM volume compared to controls. For subcortical regions, significant GM volume reductions were seen in the brain stem, bilateral thalamus, bilateral hippocampus, bilateral cerebellum and left amygdala. Although GM volume of cortical mantle did not show statistical differences overall, significant reduction was detected in bilateral parietal, left occipital and right temporal lobes. Cortical thickness exhibited significant decreases in bilateral occipital, parietal and temporal lobes, while surface area did not show any significant differences. Longitudinal follow-up in one patient revealed a monotonic downward trend of relative volume in the majority of brain regions. The relative surface area appeared to gain age-related growth, whereas the relative cortical thickness exhibited a striking progressive decline over time. Conclusions Quantitative morphology analysis in children with CDD showed global volume loss in the cortex and more notably in the subcortical gray matter, with a progressive trend along with the disease course. Cortical thickness is a more sensitive measure to disclose cortical atrophy and disease progression than surface area.

The mechanisms linking maternal stress in pregnancy with infant neurodevelopment in a sexually dimorphic manner are poorly understood. We tested the hypothesis that maternal hypothalamic-pituitary-adrenal axis activity, measured by hair cortisol concentration (HCC), is associated with microstructure, structural connectivity, and volume of the infant amygdala. In 78 mother-infant dyads, maternal hair was sampled postnatally, and infants underwent magnetic resonance imaging at term-equivalent age. We found a relationship between maternal HCC and amygdala development that differed according to infant sex. Higher HCC was associated with higher left amygdala fractional anisotropy (β = 0.677, p=0.010), lower left amygdala orientation dispersion index (β = −0.597, p=0.034), and higher fractional anisotropy in connections between the right amygdala and putamen (β = 0.475, p=0.007) in girls compared to boys. Furthermore, altered amygdala microstructure was only observed in boys, with connectivity changes restricted to girls. Maternal cortisol during pregnancy is related to newborn amygdala architecture and connectivity in a sexually dimorphic manner. Given the fundamental role of the amygdala in the emergence of emotion regulation, these findings offer new insights into mechanisms linking maternal health with neuropsychiatric outcomes of children., eLife digest Stress during pregnancy, for example because of mental or physical disorders, can have long-term effects on child development. Epidemiological studies have shown that individuals exposed to stress in the womb are at higher risk of developmental and mood conditions, such as ADHD and depression. This effect is different between the sexes, and the biological mechanisms that underpin these observations are poorly understood. One possibility is that a baby’s developing amygdala, the part of the brain that processes emotions, is affected by a signal known as cortisol. This hormone is best known for its role in coordinating the stress response, but it also directs the growth of a fetus. Tracking fetal amygdala changes as well as cortisol levels in the pregnant individual could explain how stress during pregnancy affects development. To investigate, Stoye et al. recruited nearly 80 volunteers and their newborn children. MRI scans were used to examine the structure of the amygdala, and how it is connected to other parts of the brain. In parallel, the amount of cortisol was measured in hair samples collected from the volunteers around the time of birth, which reflects stress levels during the final three months of pregnancy. Linking the brain imaging results to the volunteers’ cortisol levels showed that being exposed to higher cortisol levels in the womb affected babies in different ways based on their sex: boys showed alterations in the fine structure of their amygdala, while girls displayed changes in the way that brain region connected to other neural networks. The work by Stoye et al. potentially reveals a biological mechanism by which early exposure to stress could affect brain development differently between the sexes, potentially informing real-world interventions.

Perceived social support enhances well-being and prevents stress-related ill-being. A recent structural neuroimaging study reported that the amygdala volume is positively associated with perceived social support. However, it remains unknown how neural activity in this region and functional connectivity (FC) between this and other regions are related to perceived social support. To investigate these issues, resting-state functional magnetic resonance imaging was performed to analyze the fractional amplitude of low-frequency fluctuation (fALFF). Perceived social support was evaluated using the Multidimensional Scale of Perceived Social Support (MSPSS). Lower fALFF values in the bilateral amygdalae were associated with higher MSPSS scores. Additionally, stronger FC between the left amygdala and right orbitofrontal cortex and between the left amygdala and bilateral precuneus were associated with higher MSPSS scores. The present findings suggest that reduced amygdala activity and heightened connectivity between the amygdala and other regions underlie perceived social support and its positive functions.

Subthreshold depression (StD) affects people who experience clinically relevant depressive symptoms, which does not meet the diagnostic criteria for major depressive disorder (MDD). StD represents an ideal model for understanding the pathophysiological mechanisms of depression. Impaired emotion processing is a core feature of depression; careful investigation is required to better understand the neural correlates of emotion processing in depressed populations. In the current study, we explored whether the resting-state functional connectivity of the amygdala, a hub that taps a wide range of brain areas involved in emotion processing, is altered in individuals with StD when compared with healthy controls. Resting-state imaging data was collected from 59 individuals with StD and 59 age- and gender-matched controls. We found that the resting-state functional connectivity of the left amygdala with the cognitive control network and the left insula was significantly lower in people with StD than that in healthy controls. Such association was not observed in the right amygdala. Furthermore, functional connectivity strength between the left amygdala and the left precuneus was positively associated with depressive symptoms in individuals with StD. Our findings are in line with those reported in subjects with MDD, which may assist in further elucidating the pathophysiological mechanisms of depression, and contribute to the development of tailored treatments for individuals with StD who are at high risk of developing MDD.

Objective To identify amygdalar volumetric differences associated with posttraumatic stress disorder (PTSD) in individuals with comorbid mild traumatic brain injury (mTBI) compared with those with mTBI-only and to examine the effects of intracranial volume (ICV) on amygdala volumetric measures. Setting Marine Corps Base and VA Healthcare System. Participants A cohort of veterans and active-duty military personnel with combat-related mTBI (N = 89). Design Twenty-nine participants were identified with comorbid PTSD and mTBI. The remaining 60 formed the mTBI-only control group. Structural images of brains were obtained with a 1.5-T MRI scanner using a T1-weighted 3D-IR-FSPGR pulse sequence. Automatic segmentation was performed in Freesurfer. Main measures Amygdala volumes with/without normalizations to ICV. Results The comorbid mTBI/PTSD group had significantly larger amygdala volumes, when normalized to ICV, compared with the mTBI-only group. The right and left amygdala volumes after normalization to ICV were 0.122% ± 0.012% and 0.118% ± 0.011%, respectively, in the comorbid group compared with 0.115% ± 0.012% and 0.112% ± 0.009%, respectively, in the mTBI-only group (corrected P Conclusions The ICV normalization analysis performed here may resolve previous literature discrepancies. This is an intriguing structural finding, given the role of the amygdala in the challenging neuroemotive symptoms witnessed in casualties of combat-related mTBI and PTSD.

Finding neural features of suicide attempts (SA) in major depressive disorder (MDD) may be helpful in preventing suicidal behavior. The ventral and medial prefrontal cortex (PFC), as well as the amygdala form a circuit implicated in emotion regulation and the pathogenesis of MDD. The aim of this study was to identify whether patients with MDD who had a history of SA show structural and functional connectivity abnormalities in the amygdala and PFC relative to MDD patients without a history of SA. We measured gray matter volume in the amygdala and PFC and amygdala-PFC functional connectivity using structural and functional magnetic resonance imaging (MRI) in 158 participants [38 MDD patients with a history of SA, 60 MDD patients without a history of SA, and 60 healthy control (HC)]. MDD patients with a history of SA had decreased gray matter volume in the right and left amygdala (F = 30.270, P = 0.000), ventral/medial/dorsal PFC (F = 15.349, P = 0.000), and diminished functional connectivity between the bilateral amygdala and ventral and medial PFC regions (F = 22.467, P = 0.000), compared with individuals who had MDD without a history of SA, and the HC group. These findings provide evidence that the amygdala and PFC may be closely related to the pathogenesis of suicidal behavior in MDD and implicate the amygdala-ventral/medial PFC circuit as a potential target for suicide intervention.

BACKGROUND In experimental placebo and nocebo studies, neutral control treatments are often administered for comparison with active treatments, but are of little interest, as, on average, they result in little change. Yet, when considered at an individual level, they fluctuate between baseline and subsequent measurements and may reveal important information about participants' placebo/nocebo responding tendencies. METHODS In a paradigm involving application of creams paired with positive, negative and neutral expectations, some subjects rated identical stimuli in the neutral condition as more painful while others as less painful after treatment with inert cream. We divided subjects into two groups based on the median split in these pre-post responses in the neutral control condition, and investigated (a) fMRI signal differences (post minus pre) between the two groups in neutral condition, and (b) seed-based resting state connectivity of the bilateral amygdala, known to be involved in emotional self-regulation, as well as ambiguous stimulus processing and aversive learning. RESULTS The results suggested that subjects who rated the same pain stimuli after treatment with explicitly neutral cream as more painful showed stronger fMRI activation of the amygdala during the experiment and had higher connectivity between the left amygdala and the striatum at rest. Neutral pre-post changes predicted behavioural placebo/nocebo response in this and two independent datasets. CONCLUSION These findings suggest that measuring pre-post change in the neutral control condition might provide important information about subjects' individual differences in placebo/nocebo response. SIGNIFICANCE Pre-post changes in pain ratings in neutral conditions are modulated by amygdala activity and connectivity and can be used to predict placebo/nocebo responses.

Suicide is among the most important global health concerns; accordingly, an increasing number of studies have shown the risks for suicide attempt(s) in terms of brain morphometric features and their clinical correlates. However, brain studies addressing suicidal vulnerability have been more focused on demonstrating impairments in cortical structures than in the subcortical structures. Using local shape volumes (LSV) analysis, we investigated subcortical structures with their clinical correlates in depressed patients who attempted suicide. Then we compared them with depressed patients without a suicidal history and age‐ and sex‐matched healthy controls (HCs; i.e., 47 suicide attempters with depression, 47 non‐suicide attempters with depression, and 109 HCs). Significant volumetric differences were found between suicidal and nonsuicidal depressed patients in several vertices: 16 in the left amygdala; 201 in the left hippocampus; 1,057 in the left putamen; and 140 in the left pallidum; 1 in the right pallidum; and 6 in the bilateral thalamus. These findings indicated subcortical alterations in LSV in components of the limbic–cortical–striatal–pallidal–thalamic circuits. Moreover, our results demonstrated that the basal ganglia was correlated with perceived stress levels, and the thalamus was correlated with suicidal ideation. We suggest that suicidality in major depressive disorder may involve subcortical volume alterations., Using local shape volumes (LSV) analysis, significant volumetric differences were found between suicidal and nonsuicidal depressed patients in the left amygdala, left hippocampus, left putamen, bilateral pallidum, and thalamus. These findings propose that suicidality in major depressive disorder may involve subcortical volumetric alterations.

Patients with major depressive disorder (MDD) exhibit gray matter volume (GMV) reductions in limbic regions. Clinical variables-such as the number of depressive episodes-seem to affect volume alterations. It is unclear whether the observed cross-sectional GMV abnormalities in MDD change over time, and whether there is a longitudinal relationship between GMV changes and the course of disorder. We investigated T1 structural MRI images of 54 healthy control (HC) and 37 MDD patients in a 3-Tesla-MRI with a follow-up interval of 3 years. The Cat12 toolbox was used to analyze longitudinal data (p 0.05, FWE-corrected, whole-brain analysis; flexible factorial design). Interaction effects indicated increasing GMV in MDD in the bilateral amygdala, and decreasing GMV in the right thalamus between T1 and T2. Further analyses comparing patients with a mild course of disorder (MCD; 0-1 depressive episode during the follow-up) to patients with a severe course of disorder (SCD; 1 depressive episode during the follow-up) revealed increasing amygdalar volume in MCD. Our study confirms structural alterations in limbic regions in MDD patients and an association between these impairments and the course of disorder. Thus, we assume that the reported volumetric alterations in the left amygdala (i.e. volumetric normalization) are reversible and apparently driven by the clinical phenotype. Hence, these results support the assumption that the severity and progression of disease influences amygdalar GMV changes in MDD or vice versa.

Gambling disorder (GD) is characterized by continual gambling despite negative consequences. Risky decision-making is a hallmark of the disorder. We applied a tool from behavioral economics for assessing probability cognition in both gain and loss domains to GD. We aimed to examine the alteration of probability cognition and its relationship with brain structure in GD. Forty-six GD patients and 52 age-matched healthy controls (HCs) conducted a risky choice task in which subjects should choose between a sure and a risky option in both loss and gain domains. The distortion and elevation parameters of the probability weighting function were estimated. We compared the parameters between GD and HC and examined their relationships with the striatum and amygdala volumes in GD. GD showed greater elevation parameter in the gain domain and smaller regional gray matter volume in the left amygdala than HC. The elevation parameter in the gain domain showed a negative correlation with the left amygdala volume in GD. Altered probability cognition in the gain domain but not in the loss domain might be more relevant to risky decision-making in GD. Our findings indicate that alteration in the amygdala might play a significant role in risky decision-making of GD. Longitudinal studies are recommended to examine the causal relationship between brain abnormalities and risky decision-making in GD.

Dai Han,1–3 Mei Li,4 Minjun Mei,4 Xiaofei Sun4 1Institutes of Psychological Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China; 2Children and Adolescents Mental Health Joint Clinic, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China; 3Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou, Zhejiang, China; 4Mental Health Education and Counseling Center, Hangzhou Normal University, Hangzhou, Zhejiang, China Background: Alexithymia is a multifaceted personality trait characterized by emotional dysfunction.Methods: In this study, the functional and structural features of the emotion network in alexithymia were investigated using resting-state functional MRI (rsfMRI), voxel-based morphometry (VBM), functional connectivity (FC) analysis, and diffusion tensor imaging (DTI). Alexithymic and non-alexithymic students were recruited from the local university. The intrinsic neural activity and gray matter density of the brain regions in the emotion network were measured using rsfMRI and VBM; the FC and structural connectivity of the brain regions in the emotion network were measured using FC analysis and DTI.Results: The altered intrinsic neural activity in V1, rostral dorsal anterior cingulate cortex, and left amygdala, and the weak FC between V1 and left superior temporal gyrus and V1 and left paracentral lobule in alexithymia subjects were identified. However, no alteration of the structure and structural connectivity of the emotion network was identified.Conclusion: The results indicated that the development of alexithymia might have been caused only by slight alteration of the neural activity. Furthermore, the results suggest that noninvasive treatment technologies for improving the brain activity are suitable for alexithymic individuals. Keywords: emotion network, rsfMRI, VBM, functional connectivity, structural connectivity

To examine the amygdala volume in 2–5-year-old preschool children with autism and explore the relationship between amygdala volumes based on MRI findings and clinical features. A total of 39 cases with clinically diagnosed autism were collected. The oblique coronal T1 weighted image (T1WI) sequence was used to measure the volume of amygdala and the MRI signals were measured and analyzed. The data were compared to that of 24 age-matched healthy children and correlated to the clinical manifestations. The autism and the control groups were subject to brain scanning in 1 week after Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) review. The 39 cases, diagnosed with autism, were associated with social and behavioral deficits through clinical observation, physical and neurological examination, and assessments according to DSM IV, and the range of ABC scores in the autism group was 47–124, with an average score of 84.7 ± 24.1. Abnormal MRI signals were found in 19/78 (24.4%) amygdala in the autism group, the amygdala lesions showed punctuate or flaky low signal, slightly low signal, low to iso-signal, slightly high signal, or iso to high-signal intensity on T1 weighted three-dimendional fast low angle shot(T1FL3D) images. The right amygdala volume average was 1.088 ± 0.38 cm3, while that of the left amygdala was 1.04 ± 0.41 cm3, without any statistically significant difference (t = 0.533, p = 0.596) in the autism group. Among the 24 cases in the control group, the right amygdala volume average was 0.754 ± 0.194 cm3, while that of the left amygdala was 0.666 ± 0.252 cm3; the autism group had a significantly larger right and left amygdala volumes as compared to the age-matched typically developing group with a significant positive correlation between age and right amygdala volume (r = 0.406, p = 0.01). The preschool children with autism had significantly larger bilateral amygdala volumes as compared to age-matched typically developing children, the amygdala lesions may show abnormal signal. A relationship between age and right amygdala volume in the preschool children with autism was established.

Purpose The purpose of this study was to examine cortical thickness and subcortical volumes in professional rugby players with an extensive history of concussions compared to control subjects. Method Participants included 24 active and former professional rugby league players [Age M(SD) = 33.3(6.3); Range = 21–44] with an extensive history of concussion and 18 age- and education-matched controls with no history of neurotrauma or participation in contact sports. Participants underwent T1-weighted imaging and completed a neuropsychological battery, including two tests of memory. Whole brain cortical thickness analysis and structural volume analysis was performed using FreeSurfer version 6.0. Results Professional rugby league players reported greater alcohol consumption (p, Highlights • No differences in cortical thickness were observed in rugby players compared to controls. • Smaller hippocampal and amygdala volumes were observed in rugby players. • Greater alcohol use was associated with smaller bilateral hippocampi and left amygdala volumes in rugby players.

Background The possibility of using biological measures to predict the trajectory of symptoms among adolescent psychiatric inpatients has important implications. This study aimed to examine emotion regulation ability (measured via self-report) and a hypothesized proxy in resting-state functional connectivity [RSFC] between the amygdala and frontal brain regions as baseline predictors of internalizing symptom recovery during inpatient care. Methods 196 adolescents (61% female; M age = 15.20; SD = 1.48) completed the Achenbach Brief Problem Monitor (BPM) each week during their inpatient care. RSFC ( n = 45) and self-report data of emotion regulation ( n = 196) were collected at baseline. Results The average internalizing symptom score at admission was high ( α 0 = 66.52), exceeding the BPM's clinical cut off score of 65. On average, internalizing symptom scores declined significantly, by 0.40 points per week ( p = 0.004). While self-reported emotion regulation was associated with admission levels of internalizing problems, it did not predict change in symptoms. RSFC between left amygdala and left superior frontal gyrus was significantly associated with the intercept—higher connectivity was associated with higher internalizing at admission—and the slope— higher connectivity was associated with a more positive slope (i.e., less decline in symptoms). RSFC between the right amygdala and the left superior frontal gyrus was significantly, positively correlated with the slope parameter. Conclusions Results indicate the potential of biologically-based measures that can be developed further for personalized care in adolescent psychiatry.

Tobacco use disorder is frequently comorbid with emotional disorders, each exerting reciprocal influence on the other. As an important hub for emotional processing, amygdala may also play a critical role in tobacco addiction. Therefore, we aimed to investigate the volume and spontaneous activity of the amygdala in nicotine-dependent individuals and their relationships with cigarette use. A total of 84 smokers (aged 22-54 years) and 41 nonsmokers (aged 26-56 years) were enrolled in the present study. 3D-T1 weighted images and resting-state fMRI images were acquired from all participants. We used ROI-wise volume, fractional amplitude of low frequency fluctuation (fALFF) and resting-state functional connectivity (FC) to assess structural and functional changes of the amygdala in the smokers. There was no significant difference between smokers and nonsmokers on amygdala volume (p > 0.05). When compared to nonsmokers, increased fALFF in the right amygdala was observed in smokers (p = 0.024). In addition, increased FC between the left amygdala and the right precuneus and decreased FC between the right amygdala and the right orbitofrontal cortex (OFC) was found in smokers. In smokers, these amygdala measures did not correlate with any measures of cigarette use. The results revealed that the amygdala function but not volume was affected in nicotine addiction. When considering the fALFF and FC results, we propose that the OFC top-down control may regulate the amygdala activity in nicotine addicts. The pattern of amygdala-based FC in smokers revealed in our study may provide new information about the brain circuitry of tobacco dependence.

The amygdala plays an important role in the computation of internal reward signals. In animals it has been shown to enable a stimulus to indicate the current value of a reinforcer. However, the exact nature of the current value representations in humans remains unknown. Specifically, do neurons of the human amygdala represent current value signals only in tasks requiring valuation? We recorded from 406 neurons in the amygdala, orbitofrontal cortex, parahippocampal cortex, entorhinal cortex, and hippocampus of 6 neurosurgical patients while subjects repeatedly viewed 40 different pictures of sweet or salty “junk food” items in 2 different tasks. Neural activity during stimulus inspection in a valuation task reflected food preferences in the amygdala, orbitofrontal cortex, hippocampus, and entorhinal cortex. Notably, only left amygdala activity represented these food preferences even in a sweet–salty classification task. Valuation signals of the left amygdala thus appear to be stimulus-, not-task driven.

This study evaluated the susceptibility effects using quantitative susceptibility mapping (QSM) as a marker for regional brain iron alternations in diabetic rat brains. Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 7) and age-matched lean Long-Evans Tokushima Otsuka (LETO) control rats (n = 8) were scanned using a three-dimensional gradient-echo sequence in a 3 Tesla MRI to map QSM. The correlation analysis was performed to evaluate the relationship between the QSM value and the body weight and the fasting blood glucose value of the rats. QSM values in the OLETF group were significantly increased in hippocampi and thalami, as compared with those of the LETO group. The QSM values of the OLETF rats were negatively correlated with the body weight in putamen and were significantly correlated with the fasting blood glucose level in the left amygdala and right thalamus. With higher QSM values in diabetic rats than in control rats, QSM values in the diabetic group were significantly correlated with the body weight and the fasting blood glucose level, indicating that the QSM technique should be helpful to noninvasively investigate iron overload in the diabetic brain.

The human amygdala is sensitive to stimulus characteristics, and growing evidence suggests that it is also responsive to cognitive framing in the form of evaluative goals. To examine whether different evaluations of stimulus characteristics shape amygdala activation, we conducted a preregistered replication of Cunningham, Van Bavel, and Johnsen’s (2008) study demonstrating flexible mapping of amygdala activation to stimulus characteristics, depending on evaluative goals. Participants underwent functional MRI scanning while viewing famous names under three conditions: They were asked to report their overall attitude toward each name, their positive associations only, or their negative associations only. We observed an interaction between condition and rating type, identified as the effect of interest in Cunningham et al. (2008). Specifically, postscan positivity, but not negativity, ratings predicted left amygdala activation when participants were asked to evaluate positive, but not negative, associations with the names. These results provide convergent evidence that cognitive framing, in the form of evaluative goals, can significantly alter whether amygdala activation indexes positivity or negativity.

The amygdala plays a key role in many affective behaviors and psychiatric disorders that differ between men and women. To test whether human amygdala volume (AV) differs reliably between the sexes, we performed a systematic review and meta-analysis of AVs reported in MRI studies of age-matched healthy male and female groups. Using four search strategies, we identified 46 total studies (58 matched samples) from which we extracted effect sizes for the sex difference in AV. All data were converted to Hedges g values and pooled effect sizes were calculated using a random-effects model. Each dataset was further meta-regressed against study year and average participant age. We found that uncorrected amygdala volume is about 10% larger in males, with pooled sex difference effect sizes of g=0.581 for right amygdala (κ=28, n=2022), 0.666 for left amygdala (κ=28, n=2006), and 0.876 for bilateral amygdala (κ=16, n=1585) volumes (all p values0.001). However, this difference is comparable to the sex differences in intracranial volume (ICV; g=1.186, p.001, 11.9% larger in males, κ=11) and total brain volume (TBV; g=1.278, p0.001, 11.5% larger in males, κ=15) reported in subsets of the same studies, suggesting the sex difference in AV is a product of larger brain size in males. Among studies reporting AVs normalized for ICV or TBV, sex difference effect sizes were small and not statistically significant: g=0.171 for the right amygdala (p=0.206, κ=13, n=1560); 0.233 for the left amygdala (p=0.092, κ=12, n=1512); and 0.257 for bilateral volume (p=0.131, κ=5, n=1629). These values correspond to less than 0.1% larger corrected right AV and 2.5% larger corrected left AV in males compared to females. In summary, AV is not selectively enhanced in human males, as often claimed. Although we cannot rule out subtle male-female group differences, it is not accurate to refer to the human amygdala as "sexually dimorphic."

Borderline Personality Disorder (BPD) is characterized by affective instability, but self-injurious behavior appears to have an emotion-regulating effect. We investigated whether pain-mediated affect regulation can be altered at the neural level by residential Dialectical Behavior Therapy (DBT), providing adaptive emotion regulation techniques. Likewise, we investigated whether pain thresholds or the appraisal of pain change after psychotherapy. We investigated 28 patients with BPD undergoing DBT (self-referral), 15 patients with treatment as usual and 23 healthy control subjects at two time points 12 weeks apart. We conducted an fMRI experiment eliciting negative emotions with picture stimuli and induced heat pain to investigate the role of pain in emotion regulation. Additionally, we assessed heat and cold pain thresholds. At first measurement, patients with BPD showed amygdala deactivation in response to painful stimulation, as well as altered connectivity between left amygdala and dorsal anterior cingulate cortex. These effects were reduced after DBT, as compared with patients with treatment as usual. Pain thresholds did not differ between the patient groups. We replicated the role of pain as a means of affect regulation in BPD, indicated by increased amygdala coupling. For the first time, we could demonstrate that pain-mediated affect regulation can be changed by DBT.

Background Schizophrenia is associated with core emotional dysfunctions. At the neural level, functional neuro-imaging studies have highlighted fronto-limbic alterations during emotion processing in schizophrenia, as well as impaired connectivity between the amygdala and the prefrontal cortex. However, the direction of the impaired fronto-limbic connections remains largely unknown. To clarify this issue, we performed an effective connectivity study on emotion processing in schizophrenia. Methods Forty-one healthy individuals and 39 schizophrenia patients (DSM-IV criteria) viewed negative, positive and neutral images during an fMRI session. Effective connectivity between significantly activated regions was examined using Granger causality and psychophysical interaction analyses. Results Subjective ratings of emotionally neutral images were higher in schizophrenia patients than in controls. Across groups, significant activations were observed in the dorso-medial prefrontal cortex (dmPFC) and the bilateral amygdala. The Granger connectivity from the right amygdala to the dmPFC was significantly reduced in schizophrenia patients, relative to controls, during the negative and neutral conditions. The Granger connectivity from the left amygdala to the dmPFC was significantly reduced in schizophrenia patients, relative to controls, during the positive condition. Discussion The finding of a reduced lagged connectivity from the bilateral amygdala to the dmPFC in schizophrenia suggests that the bottom-up mechanisms involved in the processing of highly arousing emotional stimuli are impaired in this disorder. The finding of an impaired lagged connectivity from the right amygdala to the dmPFC during the processing of emotionally neutral stimuli in schizophrenia is novel and may explain why these patients tend to confer emotional significance to irrelevant stimuli.

Previous findings indicate age-related differences in frontal-amygdala connectivity during emotional processing. However, direct evidence for age differences in brain functional activation and connectivity during emotional processing and concomitant behavioral implications is lacking. In the present study, we examined the impact of aging on the neural signature of selective attention to emotional information during working memory (WM) encoding. Participants completed an emotional WM task in which they were asked to attend to emotional targets and ignore irrelevant distractors. Despite an overall reduction in accuracy for older relative to younger adults, no behavioral age effect was observed as a function of emotional valence. The functional connectivity patterns of left ventrolateral prefrontal cortex showed that younger adults recruited one network for encoding of both positive and negative emotional targets and this network contributed to higher memory accuracy in this cohort. Older adults, on the other hand, engaged two distinct networks for encoding of positive and negative targets. The functional connectivity analysis using left amygdala further demonstrated that older adults recruited one single network during encoding of positive as well as negative targets whereas younger adults recruited this network only for encoding of negative items. The engagement of amygdala functional network also contributed to higher memory performance and faster response times in older adults. Our findings provide novel insights into the differential roles of functional brain networks connected to the medial PFC and amygdala during encoding of emotionally-valenced items with advancing age.

Emotion words constitute a special class of verbal stimuli which can quickly activate the limbic system outside the left-hemisphere language network. Such fast response to emotion words may arise independently of the left occipitotemporal area involved in visual word-form analysis and rely on a distinct amygdala-dependent emotion circuit involved in fearful face processing. Using a hemifield priming paradigm with fMRI, we explored how the left and right amygdala systems interact with the reading network during emotion word processing. On each trial, participants viewed a centrally presented target which was preceded by a masked prime flashed either to the left or right visual field. Primes and targets, each denoting negative or positive nouns, could be either affectively congruent or incongruent with each other. We observed that affective congruency produced parallel changes in neural priming between the left frontal and parietotemporal regions and the bilateral amygdala. However, we also found that the left, but not right, amygdala exhibited significant change in functional connectivity with the neural components of reading as a function of affective congruency. Collectively, these results suggest that emotion words activate the bilateral amygdala during early stages of emotion word processing, whereas only the left amygdala exerts a long-distance regulatory influence over the reading network via its strong within-hemisphere connectivity.

In the present paper, we aimed to investigate hippocampus and amygdala volumes in a group of patients with antisocial personality disorder and hypothesized that hippocampus and amygdala volume alterations would be observed. It was measured hippocampus and amygdala volumes of twenty patients with antisocial personality disorder and those of healthy control subjects. We found that both sides of hippocampus and amygdala volumes of patients with antisocial personality disorder were statistically significantly reduced compared to those healthy control subjects, and observed statistically important correlations between the left and right and left hippocampus and left amygdala volumes, and age, some results on scale scores. Consequently, the present study suggest that hippocampus and amygdala volumes of patients with antisocial personality disorder had abnormally smaller than those of healthy control subjects, considering that these abnormalities might be associated with at least some clinical features of antisocial personality disorder. However, longitudinal studies are needed to assess causality of this relationship.

The current study examined the link between temperamental reactivity in infancy and amygdala development in middle childhood. A sample (n = 291) of four-month-old infants was assessed for infant temperament, and two groups were identified: those exhibiting negative reactivity (n = 116) and those exhibiting positive reactivity (n = 106). At 10 and 12 years of age structural imaging was completed on a subset of these participants (n = 75). Results indicate that, between 10 and 12 years of age, left amygdala volume increased more slowly in those with negative compared to positive reactive temperament. These results provide novel evidence linking early temperament to distinct patterns of brain development over middle childhood.