The University of Tokyo;
Graduate School of Pharmaceutical Sciences;
Japan||Institute for Al and Beyond;
Tokyo 113-0033;
Tokyo 113-0032;
Japan;
Graduate School of Science;
Japan||Center for Information and Neural Networks;
National Institute of Information and Communications Technology;
Suita City;
Osaka 565-0871;
期刊名称：
Science
i s s n：
0036-8075
年卷期：
2024 年
384 卷
Jun.21 TN.6702 期
页 码：
1361-1368
页 码：
摘 要：
Physiological parameters such as heart rate (HR), blood pressure, and body temperature, which are predominantly controlled by the autonomic nervous system, can be intentionally modulated through specialized training that provides realtime feedback to the individual (1). Despite its potential for a wide range of clinical applications, the neural basis underlying brain-to-organ control during biofeedback remains poorly understood. Inspired by a previous investigation (2), we developed an experimental model of HR feedback using freely behaving rats to elucidate the neural mechanisms that govern HR feedback training and investigated the underlying neurophysiological activity. Our biofeedback training paradigm was designed to reduce HR in rats (Fig. 1A and movie S1). Electrocardiograms (ECGs) were monitored from the pectoralis major muscle (3) and the mean HR during a 1-s window was calculated every 100 ms from the RR intervals (the time between two consecutive R waves). The target HR to be achieved by the rats was set to be 15% lower than the mean baseline HR for 1 min before HR feedback training. Rats were informed every 2 s of the difference between the current HR and the target HR by the number of stimulation pulses delivered to the primary somatosensory (S1) cortex in the right or left hemisphere. Specifically, the higher the current HR was above the baseline HR, the more pulses were delivered to the right barrel cortex, whereas the lower the HR was below the baseline, the more pulses were delivered to the left barrel cortex (up to five pulses per stimulation). If rats reduced their HR below the target HR, the medial forebrain bundle (MFB) was stimulated as a neural reward (4). When rats received a total of 10 rewards, target HRs were updated to be 15% lower than the mean HR for the preceding 1 min so that rats continuously needed to reduce HR. This training was performed for 3 hours each day and was repeated for 5 consecutive days (Fig. 1B). The baseline HR before training on day 1 was 428 ± 21 beats per minute (bpm) (mean ± SD of 17 rats) and all rats tested were able to start lowering their HR within the first 30 min of training on day 1 (Fig. 1C). The HR dropped to 231 ± 14 bpm at the end of training on day 5, representing a 46.0 ± 4.8% decrease from the initial baseline on day 1 (Fig. 1D; note that detailed statistics are summarized in table S1). The MFB stimulation alone induced no apparent change in HR (fig. S1, A and B), and the barrel cortex stimulation did not alter whisker movement (fig. S1, C and D).
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