Changes in Phase Amplitude Coupling in Treatment-Resistant Depression (TRD) due to Deep

Brain Stimulation(DBS)

Presentation for IEEE EMBSRehman Ali

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

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.

General Algorithm for PAC Detection

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 neurologyBerman 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.

QUESTIONS ?

SUPPLEMENTARY INFORMATION

FOLLOWING SLIDES

Classification of Brain Oscillations

• Source: http://salvonostrato.com/wp/01-b-c-s-m-j-p-a

Basic Neuroanatomy for Parkinson’s Disease

• Source: http://en.wikipedia.org/wiki/Motor_cortex

• Source: http://editthis.info/psy3242/Basal_ganglia

Subcallosal Cingulate for DBS of TRD• Subcallosal Cingulate Gyrus• Subgenual Cingulate• Brodmann Area 25

Source: http://en.wikipedia.org/wiki/Cingulate_cortex