One way to design a metric of CNS function is to start with observations of cerebral cortical activity that are unique to the CNS but do not occur in the periphery. For example, from in vivo animal studies, we know that delivery of two different frequencies of sinusoidal stimulation at D2 and D3 (see below) will result in peripheral responses that reflect the frequency of stimulation at each site. However, activity at the cortical representations of D2 and D3 will each reflect a composite frequency of the two. In other words, those adjacent cortical ensembles will interact, and if the stimulus is long enough (roughly 200msec), the ensembles will become synchronized.
One interesting finding is that delivering synchronized stimuli to the two digit tips will make the two digits “functionally” linked in the cortex. That is, if a robust stimulus (the synchronizing stimuli can be very weak) is delivered to one digit tip, then there will be cortical activation at the cortical sites that correspond to both digit tips. Thus, synchronizing the cortical ensembles associated with the two digit tips results in a stimulus to one digit evoking a response at both cortical loci. This suggests that delivering a synchronizing stimulus to two adjacent digit tips would make it more difficult for a person to localize the stimulus.
Design of perceptual task: One perceptual task that tests a subject’s ability to localize a stimulus is called Temporal Order Judgment (TOJ). Two stimuli (usually 1500 micron taps) are delivered to two different digit tips, and the subject is queried as to which came first.
Using a modified von Bekesy tracking method, the minimum interval between the two stimuli that a subject can still assess temporal order is determined. This value, for healthy controls, is typically around 30msec. If two conditioning/synchronizing stimuli are applied to the two digit tips (50 microns in amplitude), this TOJ value will typically increase 3-4 fold, due to the functional linkage that was generated by the synchronization. In populations in which functional connectivity is significantly altered, this value does not increase. For example, in the graph at the left, the TOJ values for individuals with autism is demonstrated to NOT increase with the 25Hz synchronizing stimulus. Thus, altered connectivity in this population group results in better performance than controls on this particular task.
Validation studies in non-human primate: In the figure at left, extracellular recordings from SI cortex show prominent activity that is evoked by stimulation on a digit tip (“on-RF”). The recording associated with the cortical activity evoked by stimulating the adjacent digit tip (“off-RF”) does not demonstrate a pronounced increase in activity with stimulation to the first receptive field. However, weak or sub-threshold vibration prior to the stimulus (note the absence of activity prior to the 0 ms time on the graphs in the lower half of the figure) results in cortical activity being evoked at both the on-RF and off-RF sites. Thus, synchronizing the cortical ensembles associated with the two digit tips results in a stimulus to one digit evoking a response at both cortical loci. This suggests that delivering a synchronizing stimulus to two adjacent digit tips would make it more difficult for a person to localize the stimulus, which is the case in healthy controls (see above).

