Summary: The amygdala–pons connection within the pons-corticolimbic network is markedly stronger in people with major depressive disorder.
Source: University of Hong Kong
Major depressive disorder (MDD), commonly referred to as depression, is a serious psychiatric condition frequently linked to increased suicide risk and major functional impairment. Although an estimated 250 million people worldwide live with depression, the neural mechanisms that govern how sad information is processed—and how this processing differs between patients and healthy individuals—remain incompletely understood.
The pons, a compact structure situated near the base of the skull as part of the brainstem, has often been overlooked in human affective neuroscience. Emerging clinical and experimental evidence indicates that the pons contributes to emotional reactivity and the handling of affective information, suggesting it plays a role beyond basic autonomic and motor functions.
Most human research on emotional processing has focused on the cortico-limbic system—regions such as the amygdala and prefrontal cortex—while largely neglecting brainstem structures like the pons. This gap has limited a full understanding of the neural circuitry that sustains persistent sad mood in depression.
A team led by Professor Tatia Lee, Director of the State Key Laboratory of Brain and Cognitive Sciences at The University of Hong Kong, in collaboration with Professor Lin Chen of the Chinese Academy of Sciences, set out to clarify how the pons interacts with corticolimbic regions when processing sad information and how this interaction differs in clinical depression.
Their findings, published in Communications Biology, combine high-resolution task-based imaging with resting-state connectivity analyses. First, the researchers used 7 Tesla functional magnetic resonance imaging (7 T fMRI) in a sample of 41 healthy adults (ages 19–31) to map the neural regions selectively engaged when viewing sad stimuli. That task-based study confirmed involvement of the pons alongside the amygdala and other corticolimbic regions during sad-affect processing.
Building on those results, the team performed a second study using 3 Tesla fMRI to examine resting-state connectivity in a separate cohort composed of 49 individuals diagnosed with MDD and 39 matched healthy controls. The resting-state analysis was designed to reveal baseline functional connections between regions implicated in sad processing and to test whether those connections differ between people with and without depression.
A principal discovery was that amygdala–pons connectivity within the broader pons-corticolimbic network was significantly stronger in participants with major depressive disorder compared with healthy controls. Importantly, this increased connectivity correlated positively with the severity of depressive symptoms, indicating a link between the strength of amygdala–pons coupling and clinical presentation.
Professor Lee commented, “We speculate that the pons interacts with the amygdala to exchange signals following the reception of sad affective information. Hyperactive amygdala–pons connectivity may underpin common depressive symptoms such as loss of interest and motivation, low self-worth, and social withdrawal.”
The overlap observed between networks that process sad and fearful stimuli may further account for the frequent co-occurrence of depression and anxiety disorders. In other words, shared or adjacent circuits could make individuals susceptible to both conditions.
Because hyperactive amygdala–pons connectivity emerged as a robust indicator of depression and tracked symptom severity, the researchers suggest this connection could serve as a biomarker for identifying vulnerability to depression and monitoring clinical progression. The data also imply that visual exposure to sad information reinforces depressed mood by stimulating pons-related processing pathways, which in turn strengthens amygdala–pons coupling.
From a practical standpoint, these findings hint that interventions aimed at altering visual attention—reducing sustained focus on sad images or content—may aid mood regulation and improve overall mental health in people at risk for or living with depression. Such approaches could complement existing therapeutic strategies by targeting perceptual and attentional processes that feed into the identified circuitry.
About this major depressive disorder research news
Author: Press Office
Source: University of Hong Kong
Contact: Press Office – University of Hong Kong
Image: The image is in the public domain
Original Research: Open access.
“Amygdala–pons connectivity is hyperactive and associated with symptom severity in depression” by Jing Jun Wong et al., Communications Biology
Abstract
Amygdala–pons connectivity is hyperactive and associated with symptom severity in depression
Understanding how sad information is processed differently in people with depression could illuminate neural mechanisms that maintain persistent low mood. Using high-resolution 7 T fMRI, the researchers identified pons, amygdala, and corticolimbic regions specifically engaged when processing sad stimuli. A subsequent 3 T resting-state fMRI study compared functional connectivity in people with and without clinical depression. The results showed that only clinically depressed individuals demonstrated hyperactive amygdala–pons connectivity, and that the strength of this connectivity related to symptom severity. These findings suggest that visual sad information can reinforce depressed mood via pons activation and strengthened amygdala–pons coupling, and that guiding visual attention away from sad content may support mood regulation.