The majority of people in the U.S. report at least one major adverse childhood experience (ACE; 62%), and 25% report 3+ ACEs (Merrick et al., 2018). Even a single ACE doubles the risk for multiple psychiatric disorders by adolescence, while 4+ ACEs leads to a 4–10x increase in risk for psychiatric disorders (e.g., depression odds ratio: 10; ADHD odds ratio: 4) (Bomysoad and Francis, 2020). While there are now multiple evidence-based treatments for psychological stress and trauma, even the most efficacious interventions still do not improve symptoms in 30–50% of trauma patients (Murray et al., 2013; Watkins et al., 2018). This heterogeneity in treatment response may be due to the fact that available interventions do not directly target and/or modulate stress-related neurobiological mechanisms that underlie psychiatric symptoms (Etkin, 2020).

Cognitive control or “executive function” refers to self-regulatory control processes used when automatic or proponent behaviors are insufficient to meet environmental demands (e.g., actively inhibiting an action impulse) (Diamond, 2013; Miyake et al., 2000). Cognitive control deficits emerge after childhood maltreatment and these deficits are associated with a more severe psychiatric presentation (Johnson et al., 2021). Cognitive control deficits are a core transdiagnostic feature across the spectrum of psychiatric disorders (Masand and Pae, 2015; Millan et al., 2012; Etkin et al., 2013; Snyder et al., 2015) that correlate with concurrent psychiatric symptoms and also predict the later emergence of psychiatric symptoms (Huang-Pollock et al., 2017; Han et al., 2016; Vuontela et al., 2013; Wante et al., 2017; Hatoum et al., 2017; Rinsky and Hinshaw, 2011; Banaschewski et al., 2012; Gardiner and Iarocci, 2018; Khurana et al., 2015, 2017). However, behavioral measures of cognitive control do not integrate modern technology and do not provide a direct measure of brain activity (Bilder, 2011; Bilder and Reise, 2019). Electroencephalography (EEG) is an electrophysiological technique that measures brain electrical activity via scalp electrodes (Jasper and Carmichael, 1935). Neural oscillations are rhythmic patterns or waves that are measured via EEG and reflect the culmination of neuronal activity occurring during cognitive demands or at rest (Mathalon and Sohal, 2015). These oscillatory dynamics across the brain are a core foundation of neuronal communication and brain rhythm organization (Buzsaki GW, 2012). Different oscillatory frequencies process or encode different aspects of cognition, particularly as it relates to cognitive control processes (Mathalon and Sohal, 2015; Kavanaugh et al., 2019; Widge and Miller, 2019).

Activity within the theta band (4–8 Hz) over the midline/midfrontal cortex (i.e., midline theta power [MTP]), measured via EEG is a well-established oscillatory biomarker of cognitive control, and increased MTP in response to cognitive control task demands is associated with successful behavioral control (Cavanagh and Frank, 2014). Despite the established utility of MTP, only a small number of prior human and rodent studies have examined MTP within the context of early life stress/trauma. The Bucharest Early Intervention Project (BEIP) showed that foster care placement was associated with relatively increased frontal theta power (during resting state) in early childhood and decreased mediofrontal theta power in adolescence; these theta power metrics were associated with clinical symptoms in childhood and adolescence (e.g. (Buzzell et al., 2020; McLaughlin et al., 2010),). Reduced frontal theta power during cognitive control demands (i.e., no-go demands) prospectively predicted internalizing and substance use symptoms in adolescents who had experienced childhood sexual trauma (Meyers et al., 2019). In a mouse model, early life stress was associated (during resting state, after acute lab-based stress exposure) with increased theta power and theta-gamma coupling in the ventral hippocampus and with anxiety-like behaviors. Reduced theta power in multiple cortical regions was found when stress-susceptible rats were exposed to an experimental stress condition (Theriault et al., 2021). While some literature suggests reduced theta activity is associated with stress and adversity, some mixed findings suggest a role for potentially moderating variables.

Human and animal models have shown differential effects of childhood stress on males and females, but the degree of consistency and replication across findings remains limited (White and Kaffman, 2019). A recent review revealed that findings in males related to decreased limbic system gray matter and increased salience network connectivity, and findings in females were related to an overactive amygdala and decreased salience network connectivity (Helpman et al., 2017). Regarding findings specific to theta, in the stress exposure experiment referenced above (Theriault et al., 2021), reduced theta power in stress-exposed rats was restricted to the cingulate cortex and hippocampus in males, while it was found in global cortical regions in females (Theriault et al., 2021). Findings suggest stress exposure may have some sex-specific patterns to the implicated neural functions.

Early childhood stress/adversity is known to increase vulnerability to later stressors (i.e., stress sensitization). Despite clear symptom-level findings, neuroimaging findings have been less consistent. Seo and colleagues found that those adults with a low level of cumulative lifetime adversity showed an expected stress-induced activation in orbitofrontal and hippocampal regions, while decreased stress-induced activation was found in adults with high cumulative lifetime adversity (Seo et al., 2014). Further, increased reward-related functional connectivity between striatum and prefrontal cortex was found in young adults with both greater levels of childhood maltreatment and recent life stress, compared to those with lower levels of either exposure (Hanson et al., 2018). Taken together, these findings suggest that early life and recent stress exposures may interact to influence neural mechanisms in a manner that is more complex than simple cumulative effects, supporting the notion that stress during early development may alter (e.g., potentially either via blunting or sensitizing) acute responses to new stressors in adulthood.

In sum, there is an established link of childhood adversity and stress with neural and symptom-level sequalae, and that biological sex and early versus recent stress may have important effects. The objective of this study was to examine the relationship between childhood stress exposure and midline theta power, and the moderating role of gender and preschool adversity. To examine this objective, this study collected EEG recording during a child-themed go/no-go task and report of recent stressful events and symptoms in school-aged children (n = 53) as part of a longitudinal sample of preschool adversity.