Non-invasive ultrasound study reveals causal role of the amygdala in interpreting uncertain emotions.
Scientists at the University of Oxford have demonstrated, for the first time, that a key emotional centre deep in the human brain directly influences how we interpret ambiguous social cues.
In a new study, published in Neuron , researchers used low-intensity focused ultrasound to temporarily and non-invasively alter activity in the amygdala - a region known to be involved in emotion and affected in depression. They found that this changed how people responded to facial expressions, particularly when those expressions were emotionally unclear.
The findings provide rare causal evidence in humans about how the brain processes uncertainty in emotional situations, with potential implications for understanding mental health conditions.
Miriam Klein-Flügge , Associate Professor and Wellcome Henry Dale and ERC-UKRI Fellow at the Oxford Centre for Integrative Neuroimaging (OxCIN) , said: 'It has not been previously possible to change activity in deep areas of the human brain without requiring surgery. Oxford has been a key player in establishing a new, non-invasive neurostimulation technique called transcranial ultrasound stimulation (TUS), over many years, and this is the first study that applies this stimulation to the human amygdala - one of the key centres for emotion processing - while also measuring very precise neuroimaging signals to assess how we have changed the brain.'
What the study found
When the amygdala was temporarily modulated, participants became more likely to approach neutral (emotionally ambiguous) faces, suggesting they interpreted them more positively.
Participants also took longer to respond to neutral and happy faces, indicating increased difficulty distinguishing between similar emotional signals.
Brain imaging showed that stimulation reduced communication between the amygdala and other brain regions and altered its internal chemical balance.
Importantly, the effects were specific: learning from feedback was unchanged, and stimulating a different brain region produced different behavioural effects.
How the research was done
The team used a cutting-edge technique called transcranial focused ultrasound stimulation (TUS) , which allows scientists to safely and precisely influence activity in deep brain regions without surgery.
Healthy volunteers received brief ultrasound stimulation targeting the amygdala before completing a behavioural task involving emotional facial expressions and decision-making. High-resolution brain scans were used to confirm that the stimulation had the intended biological effects.
The researchers measured these changes in multiple ways: they showed changes in important brain metabolites (GABA), and in the region's functional connectivity, which indicates how it speaks to other parts of the brain. But they also showed changes in how people perceive ambiguous emotional expressions in faces.
Professor Klein-Flügge added: 'This is a paper that we believe will shift and propel the field - the amygdala is a core region changed in mood disorders, including depression and anxiety, and while we applied ultrasound in healthy participants in this first study, an obvious next step is to see if abnormal amygdala metabolism can be restored in patients. There are still very few places worldwide that can do this type of research.
'By showing that we can safely and precisely influence deep brain regions, this opens up exciting possibilities for future research and, potentially, new treatments. The next step is to see how these mechanisms operate in people with mood disorders.'
The researchers hope to apply this approach in clinical populations to better understand and potentially treat conditions such as depression, where emotional interpretation is often altered.
The paper, ' Low-intensity focused ultrasound to human amygdala reveals a causal role in ambiguous emotion processing and alters local and network activity ', is published in Neuron .
