1. Changes in Phase Amplitude Coupling in Treatment- Resistant Depression (TRD) due to Deep Brain Stimulation(DBS) Presentation for IEEE EMBS Rehman Ali

2. What is Phase Amplitude Coupling (PAC)? Type of Cross-Frequency Coupling (CFC) Between a low frequency and a high frequency oscillation Analyzed between the phase of the low frequency oscillation and the amplitude envelope of the high frequency oscillation Theorized to play a functional role in neural oscillations: Low frequency oscillations over a large region modulating high frequency oscillations over a smaller population of neurons High-frequency power may be activated along a low-frequency phase

3. Why PAC? To explore palliative effects of DBS Shown to play an important role in DBS of Parkinson’s disease: PAC between Beta phase and Gamma amplitude at Subthalamic Nucleus and Motor Cortex decreases with DBS. Aberrant PAC demonstrates possible mechanism by which DBS alleviates Parkinson’s disease We want to do the same with TRD Subcallosal Cingulate is site of DBS Heterogenous Patient Population: Only criteria for TRD is failure of four other therapeutic approaches de Hemptinne C, Ryapolova-Webb ES, Air EL, Garcia PA, Miller KJ, Ojemann JG, Ostrem JL, Galifianakis NB, Starr PA (2013) Exaggerated phase-amplitude coupling in the primary motor cortex in Parkinson disease. Proc Natl Acad Sci U S A 110:4780-4785.

4. General Algorithm for PAC Detection

5. Electrical Engineering Challenges Band-Pass Filters Design Bandwidth of the band-pass filter Shape of band-pass filter Correlational Metrics PAC All are imperfect/incomplete Best to use every kind possible Transient vs. Stationary Coupling Comparative investigation ongoing: Validation: Need Synthetic Signals How to generate Synthetic Signals? How to compare? Future: real-time comodulograms Hardware optimized to algorithms and vice-versa for real-time computing on GPUs Convenient for clinical neurology Berman JI, McDaniel J, Liu S, Cornew L, Gaetz W, Roberts TP, Edgar JC (2012) Variable bandwidth filtering for improved sensitivity of cross-frequency coupling metrics. Brain connectivity 2:155-163.

6. QUESTIONS ?

7. SUPPLEMENTARY INFORMATION FOLLOWING SLIDES

8. Classification of Brain Oscillations Source: http://salvonostrato.com/wp/01-b-c-s-m-j-p-ahttp://salvonostrato.com/wp/01-b-c-s-m-j-p-a

9. Basic Neuroanatomy for Parkinson’s Disease Source: http://en.wikipedia.org/wiki/Motor_cortex Source: http://editthis.info/psy3242/Basal_ganglia

10. Subcallosal Cingulate for DBS of TRD Subcallosal Cingulate Gyrus Subgenual Cingulate Brodmann Area 25 Source: http://en.wikipedia.org/wiki/Cingulate_cortex