Behavior Classification Using Multi-site LFP and ECoG Signals

Abstract-Deep Brain Stimulation (DBS) is an effective therapy that alleviates the motor signs of Parkinson’s disease (PD). Existing DBS is open loop, providing a time invariant stimulation pulse train that may generate cognitive, speech, and balance side effects. A closed-loop DBS system that utilizes appropriate physiological control variables may improve therapeutic results, reduce stimulation side effects, and extend battery life of pulse generators. Furthermore, by customizing DBS to a patient’s behavioral goal, side effects of stimulation may arise only when they are non-detrimental to the patient’s current goals. Therefore, classification of human behavior using physiological signals is an important step in the design of the next generation of closed-loop DBS systems. Ten subjects who were undergoing DBS implantation were recruited for the study. DBS leads were used to record bilateral STN-LFP activity and an electrocorticography (ECoG) strip was used to record field potentials over left prefrontal cortex. Subjects were cued to perform voluntary behaviors including left and right hand movement, left and right arm movement, mouth movement, and speech. Two types of algorithms were used to classify the subjects’ behavior, support vector machine (SVM) using linear, polynomial, and RBF kernels as well as lp-norm multiple kernel learning (MKL). Behavioral classification was performed using only LFP channels, only ECoG channels, and both LFP and ECoG channels. Features were extracted from the time-frequency representation of the signals. Phase locking values (PLV) between ECoG and LFP channels were calculated to determine connectivity between sites and aid in feature selection. Classification performance improved when multi-site signals were used with either SVM or MKL algorithms. Our experiments further show that the lp-norm MKL outperforms single kernel SVM-based classifiers in classifying behavioral tasks. References [1] H. M. Golshan, A. O. Hebb, S. J. Hanrahan, J. Nedrud, and M. H. Mahoor, “A multiple kernel learning approach for human behavioral task classification using STN-LFP signal,” EMBC, 38th IEEE International Conference on., pp.1030-1033, 2016. [2] H. M. Golshan, A. O. Hebb, S. J. Hanrahan, J. Nedrud, and M. H. Mahoor, “An FFT-based synchronization approach to recognize human behaviors using STN-LFP signal,” To appear in ICASSP, 42nd IEEE International Conference on., 2017

Human Behavior Recognition Ssing Brain LFP Signal in the Presence of the Stimulation Pulse

Design and Methodology This study concentrates on human behavior classification task using local field potential (LFP) signals recorded from three subjects with Parkinson’s disease (PD). Existing approaches mainly employ the LFP signals acquired under the stimulation/off condition. In practical situations, however, it is necessary to design a classification method capable of recognizing different human activities under the stimulation/on condition, where the classification task is more complicated due to the artifacts imposed by the high amplitude stimulation pulse (~1-3volts). We utilize the time-frequency representation of the acquired LFPs in the Beta frequency range (~10-30Hz) to develop a feature space based on which the classification is efficiently performed while the high frequency stimulation pulse (~130-180Hz) has no/limited impact on the classification performance. Original Data and Results All three participants had undergone DBS surgery with implanted DBS leads (Medtronic 3389, Minneapolis, MN, USA) in the subthalamic nucleus of the brain. The recording sessions required the participants to do several repetitions of designed “button press” and “reach” trials under the condition of stimulation on/off. On average, 60 recordings were performed for each trial. Our analysis on the power spectral density (PSD) of the data showed that the stimulation pulse mostly impacts the frequency components around the stimulation frequency (~140Hz). Using a linear-kernel SVM classifier for classifying the aforementioned trials based on the proposed feature space, we obtained a classification accuracy of ~88% and ~87% respectively for stimulation off and on cases. Conclusion PD incidence increases with advancing age and peaks among people in their 60s and 70s. The cost of PD in the United States is estimated to be $25 billion per year. Thus, advanced techniques to improve the performance of existing devices are highly demanded. Human behavior classification from brain signals is essential in developing the next generation of closed-loop deep brain stimulation (DBS) systems. A closed-loop DBS system that utilizes appropriate physiological control variables may improve therapeutic results, reduce stimulation side effects, and extend battery life of pulse generators

IL1B Induced Smad 7 Negatively Regulates Gastrin Expression

BACKGROUND: Helicobacter pylori elicited IL1B is one of the various modulators responsible for perturbation of acid secretion in gut. We have earlier reported that IL1B activated NFkB downregulates gastrin, a major modulator of acid secretion. However, we hypothesized that regulation of gastrin by IL1B would depend on the cell's ability to integrate inputs from multiple signaling pathways to generate appropriate biological response. PRINCIPAL FINDING: In this study, we report that IL1B induces Smad 7 expression by about 4.5 fold in gastric carcinoma cell line, AGS. Smad 7 resulted in transcriptional repression of gastrin promoter by about 6.5 fold when co-transfected with Smad 7 expression vector and gastrin-promoter luciferase in AGS cells. IL1B inhibited phosphorylation of Smad 3 and subsequently interfered with nuclear translocation of the positive Smad complex, thus occluding it off the gastrin promoter. IL1B promoter polymorphisms (-511T/-31C IL1B) are known to be associated with H. pylori associated gastro-duodenal ulcer. We observed that IL1B expressed from -31T promoter driven IL1B cDNA elicited 3.5 fold more Smad 7 than that expressed from the IL1B-31C variant in AGS cells. This differential activation of Smad 7 by IL1B promoter variants translated into differential downregulation of gastrin expression. We further analyzed Smad 7, NFkB, IL1B and gastrin expression in antral gut biopsy samples of patients with H. pylori associated duodenal ulcer and normal individuals. We observed that individuals with duodenal ulcer had significantly lower levels of IL1B, Smad 7, NFkB and corresponding higher level of gastrin expression. CONCLUSION: Pro-inflammatory cytokine IL1B repress gastrin expression by activating Smad 7 and subsequent inhibition of nuclear localization of Smad 3/4 complex. Polymorphic promoter variants of IL1B gene can modulate the IL1B expression which resulted in differential activation Smad 7 and consequent repression of gastrin expression, respectively. Analysis of H. pylori infected duodenal ulcer patient's gut biopsy samples also supported this observation

NF-kappaB Mediated Transcriptional Repression of Acid Modifying Hormone Gastrin

Helicobacter pylori is a major pathogen associated with the development of gastroduodenal diseases. It has been reported that H. pylori induced pro-inflammatory cytokine IL1B is one of the various modulators of acid secretion in the gut. Earlier we reported that IL1B-activated NFkB down-regulates gastrin, the major hormonal regulator of acid secretion. In this study, the probable pathway by which IL1B induces NFkB and affects gastrin expression has been elucidated. IL1B-treated AGS cells showed nine-fold activation of MyD88 followed by phosphorylation of TAK1 within 15 min of IL1B treatment. Furthermore, it was observed that activated TAK1 significantly up-regulates the NFkB subunits p50 and p65. Ectopic expression of NFkB p65 in AGS cells resulted in about nine-fold transcriptional repression of gastrin both in the presence and absence of IL1B. The S536A mutant of NFkB p65 is significantly less effective in repressing gastrin. These observations show that a functional NFkB p65 is important for IL1B-mediated repression of gastrin. ChIP assays revealed the presence of HDAC1 and NFkB p65 along with NCoR on the gastrin promoter. Thus, the study provides mechanistic insight into the IL1B-mediated gastrin repression via NFk