Background: Although transcranial magnetic stimulation (TMS) has shown promising therapeutic effects in various disorders, treatment responses still vary considerably. This could be due to the use of suboptimal target definition like the various gold-standard approaches including 5cm, EEG-F3 and neuronavigation methods based on structural landmarks. Objective/Hypothesis: Functional MRI localisers using emotion-processing paradigms could be advantageous as they reveal dorsolateral prefrontal cortex (DLPFC) activation clusters recruited in an individual. In this thesis, we compared conventional targeting approaches with regard to the spatial distance to the individual activation peaks obtained in fMRI.
Methods: Fifteen healthy volunteers (7f/8m, mean age: 25.33 ± 2.9 years) participated in the study and performed facial emotion discrimination tasks (EDT). Euclidean distances to seven commonly-used DLPFC targets were calculated for each subject‘s EDT activation peak within the group-level DLPFC activation cluster. In addition, twenty-eight patients diagnosed with acute MDD (16f/12m, mean age: 28.7 ± 7.1) were examined for reproducibility of EDT paradigm and compared versus thirty-three healthy volunteers (15f/18m, mean age: 27.5 ± 6.8 years). The three most prominent targeting approaches were examined using concurrent TMS/fMRI setup on three healthy volunteers (2f/1m, mean age: 25.7 ± 0.3).
Results: In line with previous findings, EDT processing caused statistically significant activation of bilateral DLPFC. Group-averaged distances of the different target definition approaches to the EDT maxima ranged from 16 to 40.59 mm. Targeting approaches that are generally considered less effective (such as the 5cm method and EEG-F3 targeting) showed the highest spatial distances to individual functional activation peaks. While functional localiser maxima varied considerably across the group, individual maxima showed high spatial reproducibility with 3.4mm and 5.4mm mean intra-session and inter-session distance, respectively. Comparable variability was found in the clinical sample. In addition, we show herein successful TMS stimulation using concurrent TMS/fMRI in three subjects. Decreased activity of anterior cingulate cortex (ACC), an important region in major depressive disorder, was found only with the functional localiser targeting approach.
Conclusion(s): We conclude that EDT may be used for obtaining single-subject activation clusters in DLPFC. Based on this, individually localised DLPFC with fMRI show considerable inter-subject variability and therefore using the same target for all subjects is suboptimal. We showed high reliability in patients and controls. Due to the functional specificity of EDT, we expect higher treatment response in comparison to previously used localisers and therefore suggest future usage of functional localisers for determining stimulation targets.
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