Memory at your fingertips: how viscoelasticity affects tactile neuron signaling

Reviewer #1 (Public Review):

The authors investigate how the viscoelasticity of the fingertip skin can affect the firing of mechanoreceptive afferents and they find a clear effect of recent physical skin state (memory), which is different between afferents. The manuscript is extremely well-written and well-presented. It uses a large dataset of low threshold mechanoreceptive afferents in the fingertip, where it is particularly noteworthy that the SA-2s have been thoroughly analyzed and play an important role here. They point out in the introduction the importance of the non-linear dynamics of the event when an external stimulus contacts the skin, to the point at which this information is picked up by receptors. Although clearly correlated, these are different processes, and it has been very well-explained throughout. I have some comments and ideas that the authors could think about that could further improve their already very interesting paper. Overall, the authors have more than achieved their aims, where their results very much support the conclusions and provoke many further questions. This impact of the previous dynamics of the skin affecting the current state can be explored further in so many ways and may help us to better understand skin aging and the effects of anatomical changes of the skin.

At the beginning of the Results, it states that FA-2s were not considered as stimuli and did not contain mechanical events with frequency components high enough to reliably excite them. Was this really the case, did the authors test any of the FA-2s from the larger dataset? If FA-2s were not at all activated, this is also relevant information for the brain to signal that it is not a relevant Pacinian stimulus (as they respond to everything). Further, afferent receptive fields that were more distant to the stimulus were included, which likely fired very little, like the FA-2s, so why not consider them even if their contribution was low?

One question that I wondered throughout was whether you have looked at further past history in stimulation, i.e. not just the preceding stimulus, but 2 or 3 stimuli back? It would be interesting to know if there is any ongoing change that can be related back further. I do not think you would see anything as such here, but it would be interesting to test and/or explore in future work (e.g. especially with sticky, forceful, or sharp indentation touch). However, even here, it could be that certain directions gave more effects.

Did the authors analyze or take into account the difference between receptive field locations? For example, did afferents more on the sides have lower responses and a lesser effect of history?

Was there anything different in the firing patterns between the spontaneous and non-spontaneously active SA-2s? For example, did the non-spontaneous show more dynamic responses?

Were the spontaneously active SA-2 afferents firing all the time or did they have periods of rest - and did this relate to recent stimulation? Were the spontaneously active SA-2s located in a certain part of the finger (e.g. nail) or were they randomly spread throughout the fingertip? Any distribution differences could indicate a more complicated role in skin sensing.

Did the authors look to see if the spontaneous firing in SA-2s between trials could predict the extent to which the type 1 afferents encode the proceeding stimulus? Basically, does the SA-2 state relate to how the type 1 units fire?

In the discussion, it is stated that "the viscoelastic memory of the preceding loading would have modulated the pattern of strain changes in the fingertip differently depending on where their receptor organs are situated in the fingertip". Can the authors expand on this or make any predictions about the size of the memory effect and the distance from the point of stimulation?

In the discussion, it would be good if the authors could briefly comment more on the diversity of the mechanoreceptive afferent firing and why this may be useful to the system.

Also, the authors could briefly discuss why this memory (or recency) effect occurs - is it useful, does it serve a purpose, or it is just a by-product of our skin structure? There are examples of memory in the other senses where comparisons could be drawn. Is it like stimulus adaptation effects in the other senses (e.g. aftereffects of visual motion)?

One point that would be nice to add to the discussion is the implications of the work for skin sensing. What would you predict for the time constant of relaxation of fingertip skin, how long could these skin memory effects last? Two main points to address here may be how the hydration of the skin and anatomical skin changes related to aging affect the results. If the skin is less viscoelastic, what would be the implications for the firing of mechanoreceptors?

How long does it take for the effect to end? Again, this will likely depend on the skin's viscoelasticity. However, could the authors use it in a psychophysical paradigm to predict whether participants would be more or less sensitive to future stimuli? In this way, it would be possible to test whether the direction modifies touch perception.

Reviewer #2 (Public Review):

Summary:
The authors sought to identify the impact skin viscoelasticity has on neural signalling of contact forces that are representative of those experienced during normal tactile behaviour. The evidence presented in the analyses indicates there is a clear effect of viscoelasticity on the imposed skin movements from a force-controlled stimulus. Both skin mechanics and evoked afferent firing were affected based on prior stimulation, which has not previously been thoroughly explored. This study outlines that viscoelastic effects have an important impact on encoding in the tactile system, which should be considered in the design and interpretation of future studies. Viscoelasticity was shown to affect the mechanical skin deflections and stresses/strains imposed by previous and current interaction force, and also the resultant neuronal signalling. The result of this was an impaired coding of contact forces based on previous stimulation. The authors may be able to strengthen their findings, by using the existing data to further explore the link between skin mechanics and neural signalling, giving a clearer picture than demonstrating shared variability. This is not a critical addition, but I believe would strengthen the work and make it more generally applicable.

Strengths:
-Elegant design of the study. Direct measurements have been made from the tactile sensory neurons to give detailed information on touch encoding. Experiments have been well designed and the forces/displacements have been thoroughly controlled and measured to give accurate measurements of global skin mechanics during a set of controlled mechanical stimuli.
-Analytical techniques used. Analysis of fundamental information coding and information representation in the sensory afferents reveals dynamic coding properties to develop putative models of the neural representation of force. This advanced analysis method has been applied to a large dataset to study neural encoding of force, the temporal dynamics of this, and the variability in this.

Weaknesses:
-Lack of exploration of the variation in neural responses. Although there is a viscoelastic effect that produces variability in the stimulus effects based on prior stimulation, it is a shame that the variability in neural firing and force-induced skin displacements have been presented, and are similarly variable, but there has been no investigation of a link between the two. I believe with these data the authors can go beyond demonstrating shared variability. The force per se is clearly not faithfully represented in the neural signal, being masked by stimulation history, and it is of interest if the underlying resultant contact mechanics are.

Validity of conclusions:
The authors have succeeded in demonstrating skin viscoelasticity has an impact on skin contact mechanics with a given force and that this impacts the resultant neural coding of force. Their study has been well-designed and the results support their conclusions. The importance and scope of the work is adequately outlined for readers to interpret the results and significance.

Impact:
This study will have important implications for future studies performing tactile stimulation and evaluating tactile feedback during motor control tasks. In detailed studies of tactile function, it illustrates the necessity to measure skin contact dynamics to properly understand the effects of a force stimulus on the skin and mechanoreceptors.