A medical device for coupling to a plurality of implantable electrodes, the medical device comprising: a therapy circuit configured to deliver electrical neurostimulation energy to the plurality of implantable electrodes; a biomarker sensing circuit configured to generate a sensed biomarker signal representative of a physiological biomarker of a subject including to sense a local field potential, LFP, signal; a signal processing circuit configured to determine phase amplitude coupling among electroencephalography, EEG, frequency bands in the sensed LFP signal; and a control circuit operatively coupled to the therapy circuit and biomarker sensing circuit, and configured to: initiate delivery of the electrical neurostimulation energy to the plurality of the implantable electrodes according to a first therapy regimen, wherein the first therapy regimen activates first neural elements; use the sensed biomarker signal to detect an efficacy reduction associated with the delivered electrical neurostimulation energy according to the first therapy regimen; and in response to detecting the efficacy reduction, change the delivery of the electrical neurostimulation from the first therapy regimen to a second therapy regimen when the phase amplitude coupling indicates that the efficacy of the electrical neurostimulation energy delivered during the first therapy regimen is reduced, wherein the second therapy regimen activates second neural elements different from the first neural elements. a therapy circuit configured to deliver electrical neurostimulation energy to the plurality of implantable electrodes; a biomarker sensing circuit configured to generate a sensed biomarker signal representative of a physiological biomarker of a subject including to sense a local field potential, LFP, signal; a signal processing circuit configured to determine phase amplitude coupling among electroencephalography, EEG, frequency bands in the sensed LFP signal; and a control circuit operatively coupled to the therapy circuit and biomarker sensing circuit, and configured to: initiate delivery of the electrical neurostimulation energy to the plurality of the implantable electrodes according to a first therapy regimen, wherein the first therapy regimen activates first neural elements; use the sensed biomarker signal to detect an efficacy reduction associated with the delivered electrical neurostimulation energy according to the first therapy regimen; and in response to detecting the efficacy reduction, change the delivery of the electrical neurostimulation from the first therapy regimen to a second therapy regimen when the phase amplitude coupling indicates that the efficacy of the electrical neurostimulation energy delivered during the first therapy regimen is reduced, wherein the second therapy regimen activates second neural elements different from the first neural elements. initiate delivery of the electrical neurostimulation energy to the plurality of the implantable electrodes according to a first therapy regimen, wherein the first therapy regimen activates first neural elements; use the sensed biomarker signal to detect an efficacy reduction associated with the delivered electrical neurostimulation energy according to the first therapy regimen; and in response to detecting the efficacy reduction, change the delivery of the electrical neurostimulation from the first therapy regimen to a second therapy regimen when the phase amplitude coupling indicates that the efficacy of the electrical neurostimulation energy delivered during the first therapy regimen is reduced, wherein the second therapy regimen activates second neural elements different from the first neural elements. <EOS>