relay limbic and visceral information (62). The medial dorsal nucleus (commonly called the paraventricular thalamic nucleus) relays signals from the amygdala and other subcortical regions to the anterior cingulate, orbitofrontal, and prefrontal cortices (62). Preclinical models have shown that the paraventricular nucleus determines reactions to threats (63) and controls fear circuits in the amygdala (64). Furthermore, the paraventricular nucleus has been consistently shown to be responsive to both acute and chronic stressors because it is densely innervated by neurotransmitters involved in the stress-response system (65,66). This nucleus also plays a role in habituation to chronic stress and may use a cholecystokinin-mediated pathway to alter hypothalamic-pituitary-adrenal axis function in chronically stressed individuals, as evidenced by studies in rodent models (67,68). Although the development of the paraventricular nucleus and its prenatal function (69) is not well studied, it is possible that the thalamus is responding to chronic maternal stress signals arising from living in a high-crime area, which may in turn affect later regulation of threat and the hypothalamic-pituitary-adrenal axis. Neonatal alterations in thalamic connectivity may also be important for behavior because alterations in the paraventricular nucleus, among other portions of the thalamus, have been associated with a variety of poor psychiatric outcomes (65,70). Table 1. Violent Crime and Neonatal Frontolimbic Connectivity Variable Amygdala-Hippocampus Amygdala-aDMN Thalamus-aDMN Thalamus-aFPN b Observations 319 R2 /R2 Adjusted 0.11/0.10 Model p Value ,.001a q Values corrected for multiple comparisons using a false discovery rate procedure. aDMN, anterior default mode network; GA, gestational age; PMA, postmenstrual age. a Statistically significant at a = 0.05. Prenatal Crime Exposure and Neonatal Brain Function 6 Biological Psychiatry - -, 2022; -:-–- www.sobp.org/journal Biological Psychiatry Type of Crime Exposure While living in a neighborhood with either high violent or high property crime was related to decreases in thalamus-aDMN connectivity, violent crime exposure was related to amygdala-hippocampus connectivity whereas property crime was not. However, these standardized beta weights were not significantly different from one another using the Z test described in Paternoster et al. (71) (see the Supplement). Furthermore, different areas had high property crime levels as opposed to high violent crime levels, so different mothers in our sample may have been affected by different types of crime (Figure 1). Future studies would be needed to further investigate whether the type of crime exposure, including specific crimes within these categories (e.g., murder), have differential effects on brain function. Psychosocial and Biological Stress The results indicate that self-reported maternal psychosocial stress partially mediated the relationship between prenatal crime exposure and neonatal thalamus-DMN connectivity, but not the other associations investigated. One potential explanation for this is that psychosocial and biological stress levels are not always correlated, especially in chronically stressed individuals (72,73). Although acute laboratory-based stressors have been shown to induce biological stress reactivity [e.g., as indexed by cortisol and cytokines], these biological responses are not always strongly related to individuals’ self-reported stress experiences (74,75). In addition, it is possible that perceived psychosocial stress measures more closely index some mechanisms of stress (e.g., cortisol, cytokines, tryptophan, catecholamines) than others (76). As such, biological stress pathways that are not well indexed by psychosocial stress may be mediating crime-brain relationships and not accounted for in our models. It is also possible that multiple biological stress mechanisms may respond to neighborhood crime and, in turn, affect different functional connections in the brain. Finally, mothers may be underreporting their psychosocial symptoms because these were assessed in a survey rather than a clinical interview. Future studies will need to examine which mechanisms of biological stress, if any, mediate the relationships between living in a high-crime area and functional connectivity. Limitations While there are several strengths of using objective crime metrics as opposed to survey measures of violence exposure, we were unable to control for direct exposure to crime that occurred during pregnancy because these measures were not included in the study. The crime/legal and physical danger domains of the Stress and Adversity Inventory were examined in supplementary analyses, but these measures represent lifetime stressor exposure that included, but was not limited to, pregnancy. Future work will be necessary to distinguish between the effects of living in a high-crime area and being either a victim or witness of criminal behavior. In addition, this study was not able to assess how long each mother lived in a highcrime neighborhood. It may be the case that chronic exposure to dangerous neighborhoods (or even exposure during a particular period, such as early childhood) shapes mothers’ stress responsivity to crime. Future Directions This study demonstrates neonatal alterations in frontolimbic resting-state functional connectivity that are