Timing a conditioned stimulus to an individually optimized cardiorespiratory state enhanced early sensory responses (N1-P2) but did not improve trace eyeblink conditioning learning outcomes compared to a standard diastole-during-expiration control condition.
Key Findings
Results
The cardiorespiratory state associated with the largest N1-P2 auditory sensory response varied across participants and did not differ between age groups.
41 young adults and 19 older adults completed a passive auditory task with simultaneous electrocardiogram, respiration, and electroencephalogram recording.
An individually optimized bodily state (combination of cardiac and respiratory phase) was identified for each participant based on their largest N1-P2 response.
Optimal states were idiosyncratic and not uniform across the sample.
No significant difference in the distribution of optimal states was found between young and older adult groups.
Results
Presenting the conditioned stimulus at the individually optimized cardiorespiratory state evoked a larger N1-P2 auditory response than presenting it at diastole during expiration.
Participants were randomized to a Personalized group (CS timed to individually optimized state) or a Control group (CS timed to diastole during expiration).
The Personalized group showed a significantly larger N1-P2 response to the conditioned stimulus than the Control group.
This confirmed that individual optimization of stimulus timing successfully enhanced early sensory cortical processing of the CS.
The N1-P2 response magnitude was used as a proxy for attention and stimulus salience.
Results
Enhanced early sensory processing of the conditioned stimulus did not improve trace eyeblink conditioning (TEBC) outcomes.
Conditioned responding, peak performance, learning rate, and the proportion of good learners did not differ between the Personalized and Control groups.
This was contrary to the authors' hypothesis that a more salient CS would facilitate associative learning.
The authors note that 'the low reliability of the individually determined optimal state limits this conclusion.'
TEBC involved pairing a tone CS with an airpuff unconditioned stimulus directed toward the eye, with a trace interval separating them.
Results
Older adults showed inferior trace eyeblink conditioning performance compared to young adults across multiple measures.
Older adults learned more slowly than young adults.
Older adults made fewer conditioned responses than young adults.
Older adults were less aware of the tone-airpuff association than young adults.
The sample included 41 young adults and 19 older adults.
Age group differences in TEBC were observed regardless of whether CS timing was personalized or standardized.
Background
The study examined whether individual variation in the body-brain relationship could be leveraged to enhance both sensory processing and associative learning.
Previous studies suggested that presenting a CS at diastole during expiration enhances both sensory responses and TEBC, but not all participants learn.
The authors hypothesized that individual optimization of CS timing would improve upon the standard diastole-during-expiration approach.
The study design used a between-subjects comparison of a Personalized group versus a Control group undergoing TEBC.
Individual variation in optimal cardiorespiratory states had been 'overlooked' in prior research according to the authors.
Discussion
The low reliability of the individually determined optimal cardiorespiratory state was identified as a key limitation of the study's conclusions.
The authors explicitly state that 'the low reliability of the individually determined optimal state limits this conclusion' regarding the null effect on TEBC.
Future studies were recommended to examine whether timing external stimuli to specific bodily states effectively influences behaviour in tasks relying on rapid sensory processing.
The optimal state identification was based on a passive auditory task conducted prior to the conditioning phase.
What This Means
This research suggests that the timing of sounds relative to a person's heartbeat and breathing cycle affects how strongly the brain processes those sounds. The researchers found that by identifying each person's unique optimal combination of heart and breathing phase — the moment when their brain shows the strongest response to a tone — they could reliably produce a bigger brainwave response (called N1-P2) compared to using a one-size-fits-all timing approach based on diastole during expiration. This finding confirms that individual differences in the body-brain relationship are real and measurable.
However, despite successfully enhancing this early sensory brain response, the personalized timing approach did not help people learn a simple associative task called trace eyeblink conditioning, where participants were trained to blink in anticipation of an air puff after hearing a tone. Learning rates, the number of learned responses, and the proportion of people who successfully learned the task were all similar between those who received personalized stimulus timing and those who received the standard timing. This suggests that making a stimulus more salient to the brain's early sensory systems does not automatically translate into better associative learning.
The study also found that older adults performed worse on the eyeblink conditioning task than younger adults — they learned more slowly, produced fewer conditioned responses, and were less consciously aware of the tone-airpuff relationship. The authors caution that their conclusions about the lack of learning benefit are tentative, partly because the individually determined optimal body state was not highly reliable from the identification session to the learning session. This research opens questions about when and how bodily states influence cognition, and highlights the importance of considering individual differences when studying how the body and brain interact.
Santhana Gopalan P, Nokia M. (2026). Optimized Cardiorespiratory State at Tone Onset Enhances Sensory Responses but Not Associative Learning in Healthy Adults.. The European journal of neuroscience. https://doi.org/10.1111/ejn.70722