An Improved Human Anxiety-Specific Biomarker: Frequency Band, Modality Specificity, Personality, Pharmacology, and Source Characterisation
|Institution:||University of Otago|
|Keywords:||Anxiety; Biomarker; EEG; Anxiolytic Drugs; SST|
|Full text PDF:||http://hdl.handle.net/10523/5585|
Anxiety disorders are among the most common mental illness in the western world with a major impact on disability. But their diagnosis has lacked objective biomarkers. McNaughton and colleagues previously developed a human EEG anxiety biomarker, goal-conflict-specific-rhythmicity (GCSR) in the stop signal task (SST). However, their version of the SST had some statistical limitations and was not suitable for clinical translation because of the narrow band GCSR and frequency shifts between experiments. Our aim was to modify the SST in a way that would overcome all the statistical limitations and produce larger amplitude GCSR. Go-stop (approach-avoidance) conflict in the SST generates rhythmic activity in the right frontal area as a result of activation of the behavioural inhibition system. We developed an SST in which short and long stop signal delays (SSDs) were controlled by average Go reaction time, while intermediate SSDs tracked 50% correct stopping to maximise goal conflict. This new procedure provides balanced numbers of trials across delay groups and prevents overlap in their values. Right frontal (F8) GCSR was extracted as the difference in EEG Fourier power between matching stop and go trials of a quadratic contrast of the three delay values (subtraction of average EEG power of short and long SSDs from the EEG power of intermediate SSD). Separate experiments assessed frequency spectrum (with both visual and auditory stop stimuli), personality relations, drug sensitivity (both auditory and visual stop stimuli) and source localisation. GCSR had a frequency range (4-12Hz) similar to that of rodent hippocampal rhythmical slow activity (RSA); correlated significantly with trait anxiety scores in initial and later blocks; and was reduced by three chemically distinct anxiolytic drugs in the auditory SST (administered double-blind): buspirone (10mg), triazolam (0.25mg), and pregabalin (75mg) and two chemically distinct anxiolytics; buspirone (10mg) and triazolam (0.25mg) in the visual SST. This anxiolytic drug sensitivity was similar to that of the rodent RSA assay from which GCSR was derived. GCSR was located in the medial frontal gyri, right inferior frontal gyri and superior frontal gyri, known to control SST stopping. GCSR, measured in our new form of the SST should be suitable as a biomarker for one specific type of anxiety disorder in testing of groups of anxiety disorder patients and in the development of measures suitable for individual diagnosis.