Investigation Of The Feedforward And Feedback Pathways Of Painful And Tactile Processing In The Human Somatosensory System

Background and Objective:Painful and tactile information is processed in the somatosensory system of the human brain via reciprocal(i.e.,feedforward and feedback)projections between the thalamus and the primary and secondary somatosensory cortices(S1 & S2).Whether the hierarchical organization of information processing within this system differs between pain and touch remains unclear.In particular,two questions related to the ascending and descending pathways need to be addressed.For the ascending pathway(i.e.,'thalamus-S1' and 'thalamus-S2'),whether painful or tactile information is processed in parallel or in serial remains controversial.For the descending pathway,whether pain or touch processing involves corticothalamic feedback regulation also remains unclear.Here,we aimed to investigate the hierarchical organization for the processing of painful and tactile information in the 'thalamus-S1-S2' network using dynamic causal modelling(DCM)of high-temporal-resolution f MRI data.Materials and Methods:Sixty-two healthy volunteers participated in this study and informed consent was obtained from each participant.FMRI data were acquired from each subject during painful and tactile stimulation(TR=800ms)in two sessions and then preprocessed using the standard procedure(motion correction,spatial normalization and smoothing).The effective connectivity within the 'thalamus-S1-S2' network was examined using the following steps.First,individual-level and group-level pain and touch activation maps were obtained using first-level and second-level general linear model(GLM)analyses,respectively.Second,for each of the three regions(i.e.,thalamus,S1 and S2),we first identified the peak voxel from the group-level activation maps and then identified the nearest peak voxel from each individual's activation map.Third,regions of interest(ROIs)were created for each participant and each brain region as a sphere(5 mm radius)centered at the corresponding peak voxel of the individual activation map.Fourth,for each participant and ROI,the time series were extracted by calculating the first eigenvariate based on the time series of all voxels included in the given ROI.Fifth,a fully-connected DCM was specified and all connectivity parameters were estimated for each session of each subject.Sixth,an average DCM was created for each subject by averaging the two DCMs obtained from the two sessions using Bayesian averaging.Finally,Parametric Empirical Bayesian(PEB)and Bayesian Model Reduction(BMR)were used to estimate the group-level effects of each connectivity parameter.Results:We obtained three main findings:(1)regarding the ascending pathway,two feedforward connections(from the thalamus to S1 and from the thalamus to S2)were positively modulated by both painful and tactile inputs,indicating that both painful and tactile information was processed in parallel in S1 and S2;(2)regarding the descending pathway,the intrinsic connection from S1 to thalamus were significantly negative but was not modulated by painful and tactile inputs while the intrinsic connection from S2 to thalamus was not significant but was significantly and negatively modulated by both painful and tactile inputs,indicating that the feedback modulation on the thalamus activity exerted by S1 and by S2 were different;and(3)regarding the comparisons of DCM parameters between pain and touch,paired t tests based on the estimated individual DCMs further confirmed that there was no significant difference in the modulatory effects on any connection between nociceptive and tactile conditions(p>0.05,uncorrected),indicating that painful and tactile information processing adopted similar hierarchical organization in both ascending and descending pathways of this ?thalamus-S1-S2? network.Conclusion:Dynamic causal modelling of f MRI data with high temporal resolution revealed that nociceptive and tactile information processing have similar hierarchical organization within the ?thalamus-S1-S2‘ network in the human brain.For both nociceptive and tactile processing,a parallel hierarchy along the ascending thalamocortical pathways is adopted(i.e.,information is transmitted from the thalamus to both S1 and S2).The corticothalamic feedback regulations from the S1 and S2 to the thalamus are distinct – S1 generally exerts inhibitory corticothalamic feedback regulation independent of external stimulation whereas S2 provides additional inhibition to the thalamic activity during external stimulation,and these feedback regulations are also similar between nociceptive and tactile processing.These findings provide important insights on how nociceptive and tactile information is hierarchically processed within the somatosensory system in the human brain.