The research team\u00a0led by Miriam Klein-Fl\u00fcgge, PhD, associate professor of psychiatry and experimental psychology at the University of Oxford, has been investigating the potential use of transcranial ultrasound stimulation (TUS) for the treatment of depression and other psychiatric disorders.\u00a0TUS uses\u00a0low intensity\u00a0focused ultrasound for neuromodulation purposes.\u00a0The group recently conducted a mechanistic study to confirm whether the basolateral amygdala (BLA) of the brain\u00a0was responsible for\u00a0resolving emotional ambiguity, a state in which a person cannot\u00a0identify\u00a0emotions that are subtle and uncertain.\u00a0<\/p>\n
In phase one, the researchers created and\u00a0validated\u00a0a computer-based emotional ambiguity learning task.\u00a0In\u00a0the task,\u00a0healthy\u00a0participants\u00a0(n=29) were shown\u00a0happy, angry,\u00a0or neutral\u00a0faces and asked\u00a0to\u00a0decide whether to\u00a0approach\u00a0(push left button)\u00a0or\u00a0avoid\u00a0(push right button)\u00a0each\u00a0face.\u00a0If the participant chose approach, the face would\u00a0grow\u00a0larger; if avoid was chosen, the face would\u00a0shrink\u00a0smaller. The participant was then given\u00a0feedback on whether their response was\u00a0accurate\u00a0(with a goal of learning from that feedback).\u00a0After collecting data over multiple sessions,\u00a0the\u00a0team\u00a0validated\u00a0the task as a\u00a0measure\u00a0of emotional biases and\u00a0feedback\u00a0learning.\u00a0Baseline MRIs were also performed on each participant during phase one.\u00a0<\/p>\n
The next step was to apply TUS to\u00a0determine\u00a0whether it would\u00a0affect\u00a0the\u00a0emotional ambiguity\u00a0processes.\u00a0Correct transducer placement was registered to\u00a0the previously\u00a0acquired\u00a0MRI. Participants\u00a0were\u00a0tested\u00a0at\u00a0three\u00a0separate visits with one of the following noninvasive interventions:\u00a0TUS\u00a0to the amygdala, TUS to the mid-insula as control region,\u00a0or\u00a0a\u00a0sham\u00a0procedure. After each TUS session, the\u00a0participant\u00a0underwent further MRI scanning, with each full session\u00a0lasting\u00a01.5 to 2 hours.\u00a0<\/p>\n
Investigators applied the TUS\u00a0bilaterally\u00a0to\u00a0each brain region\u00a0with the Brainbox\u00a0NeuroFUS\u00a0Pro system\u00a0using\u00a0a 212 kHz Sonic Concepts\u00a0NeuroFUS\u00a0Pro transducer. The treatment\u00a0was continuously tracked by the\u00a0Brainsight\u00a0neuronavigation\u00a0system.\u00a0The TUS\u00a0was sequentially delivered for a duration of 80 seconds to each hemisphere at a 5-Hz pulse repetition frequency, 20-ms pulse width, 200-ms pulse repetition interval, and 10% duty cycle.\u00a0After undergoing TUS, participants were moved into a\u00a07T MRI scanner\u00a0for the collection of\u00a0task\u00a0fMRI, resting-state fMRI, and magnetic resonance spectroscopy data.\u00a0<\/p>\n
The study revealed that applying\u00a0bilateral\u00a0TUS\u00a0to the BLA:\u00a0<\/p>\n
Was a safe, precise, and efficient way to perturb neural activityAffected various measures of neural activity, including decreasing resting-state connectivity between the BLA and its mono-\/di-synaptically connected regionsChanged metabolites with a decreased excitation\/inhibition balance in the glutamate\/gamma-aminobutyric acid ratio (no change in glutamate\/increase in gamma-aminobutyric acid)Altered participant responses to emotionally ambiguous stimuli (increased tendency to approach neutral faces)Changed participant response speed to emotionally ambiguous stimuli (increased reaction time to happy and neutral faces)<\/p>\n
\u201cThis study revealed that the BLA plays a role in detecting and resolving emotional ambiguity,\u201d said Dr. Klein-Fl\u00fcgge. \u201cGiven the amygdala is a key brain region with abnormal metabolism in mood disorders, the ability to modulate its activity noninvasively and see effects on emotional processing is an exciting step for us and the field. Future investigations on mood disorder patients are likely to be informed by these results.\u201d<\/p>\n
The authors also noted that the\u00a0bilaterality of the stimulation protocol\u00a0was\u00a0likely significant\u00a0to the\u00a0emotional processing and behavior\u00a0findings.\u00a0<\/p>\n
This\u00a0project\u00a0was funded by the\u00a0Wellcome\u00a0Trust\u00a0with\u00a0investigators also acknowledging\u00a0various individual funding sources.\u00a0<\/p>\n