Network Changes in Insula and Amygdala Connectivity Accompany Implicit Suicidal Associations

Abstract

Limited knowledge exists regarding the neurobiology of suicidal thoughts, given that there are currently no direct probes of the suicidal state. This pilot study used magnetoencephalography (MEG) to evaluate correlates of the implicit association between the self and death compared to the self and life as objective markers of suicide risk. Healthy volunteers (HVs; n=21) completed a modified version of the Suicide Implicit Association Task (S-IAT) during MEG scanning. Gamma power-which is considered a proxy measure of excitation-inhibition balance-was directly compared in the self-death/self-life contrast. As a proof-of-concept, the ability of dynamic causal modeling to categorize HVs versus four individuals with recent suicide crisis (SC) was evaluated. In HVs, enhanced gamma power in both amygdala and anterior insula were found for the self-death compared with self-life contrast. In addition, connectivity estimates between early visual cortex, anterior insula, and amygdala correctly categorized SC participants with 77% to 82% sensitivity and 80% to 85% specificity. These findings, which implicate network-level changes in salience network and amygdala connectivity in mediating suicidal associations, require further replication in larger samples. Direct probing of suicidal thoughts with the S-IAT may provide foundational markers of neural circuits associated with suicide risk.

Implicit Cognition Tests for the Assessment of Suicide Risk: a Systematic Review

“…Imaging results detected an increased activation in the bilateral insula, medial prefrontal cortex, middle occipital cortex, and parahippocampal gyri during the self-death condition compared with the self-life condition in the test [58 •]. In another study, connectivity changes between the early visual cortex, amygdala, and anterior insula were observed during the S-IAT, and increased connectivity discriminated between participants with and without recent SAs [59].…”

The death-implicit association test and suicide attempts: a systematic review and meta-analysis of discriminative and prospective utility

“…This would inform the design of biological interventions that strengthen associations between the self and life and determine whether this is associated with lower rates of future suicidal behaviour. A limited number of studies have identified potential biomarkers of D-IAT scores (Ballard et al, 2019, 2020; Ho et al, 2018, 2021). For example, when completing the D-IAT during a functional MRI, healthy participants have higher blood-oxygen-dependent signal, during the death-me as compared to life-me blocks of the task (Ballard et al, 2019).…”

“…This difference is largest in the bilateral anterior insula and inferior frontal gyri. Similarly, magnetic encephalography has shown differences in functional connectivity between individuals in suicidal crisis and healthy controls when associating the self with life compared to death (Ballard, Gilbert, Fields, Nugent, & Zarate, 2020). Another pair of studies demonstrated that smaller striatal grey matter volume is both negatively associated with current D-IAT scores and predicts higher D-IAT scores 2-years later (Ho et al, 2018, 2021).…”

Suicidality Associated With Deep Brain Stimulation in Extrapyramidal Diseases: A Critical Review and Hypotheses on Neuroanatomical and Neuroimmune Mechanisms

“…Increased functional connectivity at this neuroanatomical region has been linked to increased SI and SA in patients with MDD (Kang et al, 2017;Alarcón et al, 2019). Association between the self and death in an exploratory study of the neurobiological origins of SI has also been attributed to amygdala activation (Wei et al, 2018;Ballard et al, 2020). Mechanistically, activation of the amygdala can exacerbate dopaminergic dysfunction (Lai and Chang, 2019) and consequently potentiating suicide risk as described above.…”