I. INTRODUCTION
Characteristic patterns of biorhythms represent a defining feature of complex system in body. Intact regulation of its complexity from intrinsic dynamic, interdependent and nonlinear relationships exhibits systemic stability which indeed, plays a vital role in homeostasis. Changes of homeostatic level indicate the physiological response to stimulus as a feedback loop control. Loss of control leads to any disturbance and eventually, disease. Modulation of autonomic control is a key determinant for brain-heart axis interaction which it represents the whole system complexity. It is well known that cardiac autonomic function through sympathetic and parasympathetic out flows reflects in heart rate variation [1]. Several studies of heart rate variability (HRV) have been proposed by time domain, frequency domain and nonlinear analysis and it is a dynamic study tool for reliable quantitative approach to physiological complex as well as disease orientation [2]. Recently, nonlinear fashion of HRV which reflects closed-loop version of the dynamics is widely proposed for HRV quantification. Cerebrovascular Reactivity (CVR) represents the capacity of distal cerebral arteries to a vasoactive stimulus and is proposed as a dynamic cerebral autoregulation. It has been reported that mean flow velocity (Vmean) of the large basal cerebral arteries reflects cerebral perfusion with respect to regional flow distribution, autoregulatory response, and CO2-reactivity in normal [3]. Cerebral autoregulation refers to myogenic properties of cerebral arteries maintaining cerebral perfusion despite changes in mean arterial blood pressure (mABP) within a range of 50–150 mmHg. Furthermore, it is defined as a dynamic and a static response for maintaining cerebral blood flow (CBF) in normal range, 30–50 m11/100g/min. The dynamic term describes the response of cerebral arteries to vasodilation in order to keep blood volume in normal. is a primary determinant that regulates cerebral autoregulation. Intact cerebral autoregulation reflects normal cerebral reserve function of brain. Poor CVR result has been shown in lacunar infarction of stroke [4]. In 2001, CupiniLM.etal, reported a strong linkage between impaired CVR by breath holding-induced hypercapnia and subcortical infarction [5]. Therefore, we hypothesized that increasing CO2 in blood (hypercapnia during breath holding induced CVR triggers vasodilatation through parasympathetic drive assessed by nonlinear HRV. In this study, we aimed to investigate the complexity of neuromodulation by heart rate variability (HRV) to cerebral reserve function during cerebrovascular reactivity by breath holding induced hypercapnia and subsequently, cerebral vasodilatation. We assessed cerebral reserve function by CVR test associated with brain-heart axis control by frequency domain and nonlinear HRV analysis. All results and these developing protocol and technique will be applied and studied in small artery and lacunar infarction stroke.