Transcranial focused ultrasound modulates the emergence of learned helplessness via midline theta modification
André Forster, Johannes Rodrigues, Philipp Ziebell, Joseph L. Sanguinetti, John J.B. Allen, Johannes Hewig
Journal of Affective Disorders 2023, 329, 273-284 · 10.1016/j.jad.2023.02.032
Abstract
Background Helplessness and hopelessness are states closely related to depressive disorders. They ensue following the anticipated absence of valid behavioral options to alleviate an aversive state. One neural structure involved in the detection of such options, is the cingulate cortex (CC), which conveys the evaluation of behavior against the value of its outcome. Accordingly, CC-related EEG measures are thought to correlate to feedback evaluation but also to anxious and conflict-related states, signaling the need for further adaptation to current requirements. Against this background, this study investigated the role of CC functioning in the emergence and prevention of helpless/hopeless states by applying low-intensity transcranial focused ultrasound (litFUS) neuromodulation prior to a learned helplessness task. Method In a randomized controlled double blind experimental setup with 55 participants, litFUS was used to inhibit the right lateral prefrontal cortex (lPFC), a region closely connected to CC modulation. Participants were instructed to play 8 games of chess against a computer that was unbeatable to them, while an EEG was recorded. Theta oscillation in midline electrodes, playing performance and self-rate measures on cognitive, affective and physiological parameters were assessed. Results The results show a considerable influence of litFUS neuromodulation of the lPFC on midline theta activity (Fz and Pz electrode position) which in turn correlated to several psychological variables including self-report data on emotion, cognition, and arousal as well as behavioral measures (playing performance). Limitations Due to the small sample size and sample characteristics, results cannot be generalized to the field of clinical application. A replication of results in larger samples and in context of other sonication parameters is needed to increase the robustness of results and to maximize the efficacy of litFUS application. Conclusions We conclude that the development of learned helplessness/hopelessness could be positively influenced in its course by litFUS neuromodulation of the right lPFC. In line with previous results, especially the posterior midline electrode Pz seems to be an interesting target for further research in this field as theta activity at this electrode is correlated to control perception and motivated behavior. To our knowledge, this is the first study to use neuromodulation to monitor and manipulate the development of helplessness in the laboratory.
Abstract via europepmc.
Exposures
Exposure 1: litFUS to right lateral prefrontal cortex (lPFC) prior to a learned-helplessness chess task
Target: dorsolateral prefrontal cortex — “right lateral prefrontal cortex (lPFC), F8 electrode position”
Device: other named manufacturer · Thync (Los Gatos, USA) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | not reported | ⚑ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | 0.5 | ✓✓✓ |
| Sonication duration (s) | 120 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
A single 2-minute application of litFUS (duty cycle 0.5%, i.e. active modulation time of only 0.6 s) was delivered to the F8 electrode position (right lPFC) via a gel pad, using a device manufactured by Thync, before participants played 8 games of chess against an unbeatable computer opponent. EEG, ECG and electrodermal measures were prepared afterward, so theta power was recorded approximately 30-90 minutes after litFUS administration (offline effects). Sham stimulation used the same transducer aimed away from the head so that a comparable audible sound was produced without therapeutic ultrasound delivery.
Flags from extraction
n_subjects— Only participants in the litFUS group (n=14) received real ultrasound; the Sham group (n=13) had the transducer aimed away from the head, and the Control/Experimental groups (n=15 each) had no contact with the ultrasound device at all.exposures[0].fundamental_frequency_khz— Sonication parameters (frequency, pressure, intensity, PRF, pulse duration) are only shown in Fig. 2 ('The modulation itself is described by the parameters provided in Fig. 2'), which could not be read from the extracted text; recorded as not_reported rather than read off a figure.exposures[0].timing.waveform— Waveform coded as 'pulsed' based on the stated duty cycle of 0.5% (i.e., not continuous); PRF and individual pulse duration are not stated in the text.n_sessions_per_subject— The procedure describes a single lab visit with one litFUS administration before the chess task, but no sentence explicitly states the number of sessions per participant.