**3. Heart rate variability (HRV) measurement for evaluation of autonomic activity**

HRV is a variation of inter-heartbeat intervals (**Figure 1**). The heart beats constantly but the rhythm is not regular. The heartbeat slows and accelerates, and the inter-heartbeat interval varies. It has been known that the heartbeat rhythm is composed of multiple components with different frequency ranges [7].

In HRV analysis, heartbeats or pulse beats are first identified conventionally by peak detection (**Figure 2**). The inter-beat interval trend made of the sequence of peak-to-peak intervals is processed by frequency analysis to yield the power spectrum of HRV. The power spectrum can reveal the presence of multiple heart rate rhythms with different frequencies ranges; high frequency (HF), low frequency (LF), very low frequency (VLF), and ultra-very low frequency (UVLF). HF and LF components are often used for the evaluation of autonomic activities in mental disorders, and

**Figure 1.** *Inter-heartbeat intervals increase and decrease presenting the heart rate variability (HRV).*

#### **Figure 2.**

*The methods for heart rate variability (HRV) measurement. RR intervals of electrocardiogram (ECG) are used for creating the RR interval trend graph, which contains both low and high-frequency components (LF and HF). The power spectrum of the trend graph is used to calculate LF and HF by integrating the power in the range designated for LF and HF (0.04–0.15 Hz, 0.15–0.4 Hz, respectively).*

their physiological bases have been clarified. The frequency ranges of HF and LF are usually set at 0.15–0.4 Hz and 0.04–0.15 Hz, respectively.

The rhythm of the HF component is related to breathing. Inspiration is accompanied by an increase in heart rate, and expiration by a decrease (**Figure 3**). This modulation is inhibited by the administration of anticholinergic agents such as atropine and is considered to be dependent on parasympathetic activity [8]. The physiological significance for the coupling of breathing rhythm and heart rhythm is not clarified but would be related to the maintenance of constant blood flow under the fluctuation of intrathoracic pressure during breathing activity.

LF component of HRV is generated under the control of baroreceptor [9], and is intimately related to blood pressure fluctuation. When the blood pressure is recorded continuously, the systolic peak fluctuates with an interval of about 10 to 20 seconds. This fluctuation is known as Mayer wave (**Figure 4**). Accompanying this blood pressure fluctuation, heartbeats also vary. When the systolic blood pressure is high, the inter-beat interval is long. When the blood pressure is low, the interval is short (**Figure 4**). It is a homeostatic control to stabilize the blood flow by adjusting the heart rate in response to the changes in blood pressure. Both sympathetic and parasympathetic systems are involved in generating the LF variation.

These observations indicate that HF variation controls the blood flow during various breathing rhythms. LF variation on the other hand stabilizes the blood flow during various activities that accompany changes in blood pressure. Both HF and LF variations serve as safety systems to avoid abrupt changes in blood flow in response to alterations of breathing and somatic condition, respectively. Blood pressure is adjusted automatically, but breathing is modified both unconsciously and consciously. Conscious control of breathing is observed not only during respiration

#### **Figure 3.**

*High frequency (HF) heart rate variability related to breathing. Inspiration (In) is accompanied by shortening of inter-beat interval measured with R-R interval of electrocardiogram (ECG). Expiration (Out) is accompanied by its elongation.*

#### **Figure 4.**

*Low frequency (LF) heart rate variability is dependent on blood pressure. Continuous measurement of blood pressure indicates systolic peaks fluctuate, generating Mayer wave. In response to Mayer wave, inter-heartbeat intervals vary. When the blood pressure is high, the inter-beat interval is long. When the blood pressure is low, it is short.*

but during various activities including speaking, singing, and shouting. In various conditions, the HF and LF safeties will be switched on or off to adjust the blood flow and to meet the physiological demand.

HRV is controlled by the autonomic nervous system; sympathetic and parasympathetic. HF variation is large when the parasympathetic system is activated. Interpretation of LF changes in terms of sympathetic or parasympathetic changes is complex because LF variation is controlled by both sympathetic and parasympathetic systems. LF/HF ratio is sometimes used as a parameter representing sympathetic activity, although it is not recommended in some studies [9]. LF/HF can be used to evaluate the balance between breathing-related autonomic activity and blood pressure-dependent autonomic activity.
