He found that in order to produce response, the weaker the stimuli the longer must be the intervals between them. It follows from this, that after a discharge the irritability in response to strong stimuli reappears more rapidly than for weak, i.e., that they only _gradually_ regain their maximum. The exact periods of time for the course of the return of irritability for the heart have unfortunately not been so far ascertained. On the other hand, the investigations of _Ishikawa_[134] furnish the material for the construction of the restitution curve for the centers of the spinal cord of the frog. _Ishikawa_ did not employ the threshold of stimulation as an indicator for the course of restitution, but used instead the duration of the reflex time following on a stimulus of a certain strength. The reflex time is greatly prolonged after an excitation of extended duration and only regains its normal value in the same degree as restitution takes place. By a great number of painstaking experiments _Ishikawa_ ascertained the duration of the reflex time at intervals of thirty seconds to one minute, and obtained figures which show that restitution does actually take place, at first rapidly and then with constantly decreasing speed. The detailed study of the course of self-regulation of the individual forms of living substance will doubtless be more exactly determined in the near future. But even at the present we are fully justified in describing the form of restitution curve as a _logarithmic_ in type. Therefore, a relative refractory period must be present in every metabolic self-regulation after an excitation, during which stronger stimuli produce response, while weaker are still without result. This is a fact which, as we shall see later, is of fundamental importance for the comprehension of the various kinds of interference responses to stimuli. [133] _Bowditch_, 1. c. [134] _Hidetsurumaru Ishikawa_: “Ueber die scheinbare Bahnung.” Zeitschrift f. allgem. Physiologie Bd. XI, 1910.