Human Hippocampus Arbitrates Approach-Avoidance Conflict

Abstract

SummaryAnimal models of human anxiety often invoke a conflict between approach and avoidance [1, 2]. In these, a key behavioral assay comprises passive avoidance of potential threat and inhibition, both thought to be controlled by ventral hippocampus [2–6]. Efforts to translate these approaches to clinical contexts [7, 8] are hampered by the fact that it is not known whether humans manifest analogous approach-avoidance dispositions and, if so, whether they share a homologous neurobiological substrate [9]. Here, we developed a paradigm to investigate the role of human hippocampus in arbitrating an approach-avoidance conflict under varying levels of potential threat. Across four experiments, subjects showed analogous behavior by adapting both passive avoidance behavior and behavioral inhibition to threat level. Using functional magnetic resonance imaging (fMRI), we observe that threat level engages the anterior hippocampus, the human homolog of rodent ventral hippocampus [10]. Testing patients with selective hippocampal lesions, we demonstrate a causal role for the hippocampus with patients showing reduced passive avoidance behavior and inhibition across all threat levels. Our data provide the first human assay for approach-avoidance conflict akin to that of animal anxiety models. The findings bridge rodent and human research on passive avoidance and behavioral inhibition and furnish a framework for addressing the neuronal underpinnings of human anxiety disorders, where our data indicate a major role for the hippocampus.

Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes

“…Lesion and optogenetics studies have demonstrated an essential role for the ventral HPC in anxiety and fear (Kjelstrup et al, 2002; Kheirbek et al, 2013). Further, a series of well designed studies in humans demonstrated the importance of the ventral HPC in anxiety-related behaviors associated with approach–avoidance conflicts similar to the ones tested in this study (Bach et al, 2014). Although there remains a debate as to whether smaller hippocampal volume represents a premorbid or an acquired trait in PTSD, our results suggests that a structurally reduced hippocampus may predispose rats to exhibit aberrant post-traumatic stress responses.…”

Animal to human translational paradigms relevant for approach avoidance conflict decision making

“…Both of these studies implicated the anterior hippocampus (in addition to PFC and amygdala). Bach and colleagues (2014) additionally offered evidence that the anterior hippocampus particularly tracked level of threat and that individuals with hippocampal sclerosis are less impacted by threat (consistent with animal work described above).…”

“…It has been confirmed that the hippocampus plays a role in processing exploratory conflict, and may be involved in biasing behavior away from rewarding outcomes (Bach et al, 2014; O'Neil et al, 2015; Schumacher et al, 2016). Human behavioral research with both approach-avoidance conflict and open field paradigms has supported the impact of anxiety and gender on avoidance behavior and/or thigmotaxis (Aupperle et al, 2011; Kallai et al, 2007; Walz et al, 2016), thus partially validating the use of such paradigms as preclinical animal paradigms.…”

“…O'Neil et al (2015) and Bach et al (2014) aimed to identify the potential role of the hippocampus in approach-avoidance conflict, given its putative role in animal models. The former involved a task in which face and scene images were associated with either gain or loss of points.…”

The cognitive architecture of anxiety-like behavioral inhibition.

“…Unsurprisingly, the study of such approach/avoidance conflict has a long history in experimental psychology (Miller, 1944). Across species boundaries and specific task designs, approach/avoidance conflict elicits particular behaviors (Aupperle, Sullivan, Melrose, Paulus, & Stein, 2011; Bach et al, 2014; Calhoon & Tye, 2015; Gray, 1982; Gray & McNaughton, 2000; Rodgers, Cao, Dalvi, & Holmes, 1997). This includes passive avoidance of the situation, behavioral inhibition (BI)—interruption of ongoing actions and suppression of overt approach or avoidance—and exploratory actions for risk assessment.…”