Intense Focused Ultrasound Preferentially Stimulates Transected Nerves Within Residual Limbs: Pilot Study.

Objective: Identifying pain generators in tissue deep in the skin can require uncomfortable, complicated, and invasive tests. We describe pilot studies testing the hypothesis that ultrasound image-guided, intense focused ultrasound (ig-iFU) can noninvasively and differentially stimulate the end of transected nerves in the residual limbs of amputee patients. Design: We applied iFU to the transected nerve ending as individual pulses with a length of 0.1 seconds using a carrier frequency of 2.0 MHz. After targeting, we gradually increased the iFU intensity to reach consistent patient-reported stimulation of the transected nerve ending. We also stimulated the proximal nerve, tissue near the nerve ending, and the intact contralateral nerve. We described the resulting sensations and correlated the results of the study participant's pre-iFU study responses to phantom and residual limb pain questionnaires. Results: iFU spatial and temporal average intensity values between 16 W/cm2 and 433 W/cm2 that were applied to the transected nerve ending and proximal nerve elicited sensations, including phantom limb sensations, while the same intensity applied to control tissue centimeters away from the nerve ending, or to the intact nerve on the contralateral limb, did not. Two out of 11 study participants reported only mild and transient pain created by iFU stimulation. Successful iFU intensity values correlated with neither phantom nor residual limb pain scores. Conclusions: Transected nerves had greater sensitivity to iFU stimulation than ipsilateral and contralateral control tissue, including intact nerve. These results support the view that ig-iFU may one day help physicians identify deep, tender tissue in patients who report experiencing pain.

Electric field distribution predicts efficacy of accelerated intermittent theta burst stimulation for late-life depression.

Introduction: Repetitive transcranial magnetic stimulation (rTMS) is a promising intervention for late-life depression (LLD) but may have lower rates of response and remission owing to age-related brain changes. In particular, rTMS induced electric field strength may be attenuated by cortical atrophy in the prefrontal cortex. To identify clinical characteristics and treatment parameters associated with response, we undertook a pilot study of accelerated fMRI-guided intermittent theta burst stimulation (iTBS) to the right dorsolateral prefrontal cortex in 25 adults aged 50 or greater diagnosed with LLD and qualifying to receive clinical rTMS. Methods: Participants underwent baseline behavioral assessment, cognitive testing, and structural and functional MRI to generate individualized targets and perform electric field modeling. Forty-five sessions of iTBS were delivered over 9 days (1800 pulses per session, 50-min inter-session interval). Assessments and testing were repeated after 15 sessions (Visit 2) and 45 sessions (Visit 3). Primary outcome measure was the change in depressive symptoms on the Inventory of Depressive Symptomatology-30-Clinician (IDS-C-30) from Visit 1 to Visit 3. Results: Overall there was a significant improvement in IDS score with the treatment (Visit 1: 38.6; Visit 2: 31.0; Visit 3: 21.3; mean improvement 45.5%) with 13/25 (52%) achieving response and 5/25 (20%) achieving remission (IDS-C-30 < 12). Electric field strength and antidepressant effect were positively correlated in a subregion of the ventrolateral prefrontal cortex (VLPFC) (Brodmann area 47) and negatively correlated in the posterior dorsolateral prefrontal cortex (DLPFC). Conclusion: Response and remission rates were lower than in recently published trials of accelerated fMRI-guided iTBS to the left DLPFC. These results suggest that sufficient electric field strength in VLPFC may be a contributor to effective rTMS, and that modeling to optimize electric field strength in this area may improve response and remission rates. Further studies are needed to clarify the relationship of induced electric field strength with antidepressant effects of rTMS for LLD.