Can the autonomic nervous system be controlled voluntarily?

Organization and General Functions of the Autonomic Nervous System

The two divisions of the autonomic nervous system are thesympathetic nervous system (SNS) and theparasympathetic nervous system (PNS). (The enteric nervous system of the gastrointestinal tract, which is discussed inChapter 22, is also sometimes considered to be part of the autonomic nervous system). In many cases, the SNS and PNS have opposing actions on various organs and processes, and regulation of bodily functions often involves reciprocal actions of the two divisions. For example, heart rate is elevated by SNS activity and decreased by PNS activity.

As a generalization, the SNS is said to mediatestress responses, such as the classicfight-or-flight response, and the PNS mediates “vegetative” responses, such as digestion. The fight-or-flight response is a generalized reaction to extreme fear, stress, or physical activity and results in a patterned response in many organ systems. The response includes elevated heart rate, cardiac output, and blood pressure, as well as bronchial dilation, mydriasis (dilation of pupils), and sweating. Although the sympathetic nervous system often responds in such patterned manners, the PNS may produce more selective effects—for example, during the sexual response.

The autonomic nervous system has as its central components the hypothalamus, brainstem, and spinal cord; peripherally, it consists of sympathetic and parasympathetic nerves. Areas within the hypothalamus and brainstem regulate and coordinate various processes through the autonomic nervous system, including temperature regulation, responses to thirst and hunger, micturition, respiration, and cardiovascular function. This regulation is in response to sensory input and occurs through the reciprocal regulation of the SNS and PNS.

 The fight-or-flight response was originally described in 1915 by Walter Canon, who also coined the term “homeostasis.” The fight-or-flight response can be characterized as the physiologic response to acute stress in which general­ized sympathetic activation occurs, resulting in effects such as tachycardia, bronchial dilation, mydriasis (dilation of the pupils), vasoconstriction in much of the body, piloerection, and inhibition of gastrointestinal motility. It has long been appreciated that the acute stress responses also involve activation of the hypothalamic-pituitary-adrenocortical endocrine axis (described in Section 7).

Peripherally, axons ofpreganglionic neurons of the SNS and the PNS emerge from the spinal cord and synapse withpostganglionic neurons at sympathetic and parasympathetic ganglia, respectively; in both cases,acetylcholine is the neurotransmitter, acting atnicotinic receptors on postganglionic neurons (Fig. 7.1). Postganglionic neurons then send motor axons to effector organs and tissues. The catecholaminenorepinephrine is released by postganglionic sympathetic axons and acts atadrenergic receptors of effector organs. One exception is the postganglionic axons that innervate sweat glands, which release acetylcholine. Furthermore, the adrenal medulla functions as part of the SNS. Preganglionic axons of the SNS extend to the adrenal gland, where they stimulate chromaffin cells of the adrenal medulla to releaseepinephrine (and to a lesser degree norepinephrine) into the bloodstream. Notably, in addition to releasing catecholamines (norepinephrine and epinephrine), some sympathetic postganglionic nerves release a number of adrenergiccotransmitters, includingneuropeptide Y, ATP, andsubstance P, among others. In the PNS, acetylcholine, acting atmuscarinic receptors, is the postganglionic neurotransmitter. These and other aspects of the two divisions of the autonomic nervous system are compared inTable 7.1 and illustrated inFigures 7.2 and7.3. Actions of the autonomic nervous system in various organ systems and tissues are listed inTable 7.2, along with the receptor types involved.

 Sweat gland secretion is stimulated by activation of the SNS. Most of the postganglionic sympathetic neurons innervating these glands are atypical, releasing the neurotransmitter acetylcholine instead of norepinephrine. Acetylcholine acts on muscarinic receptors, inducing sweat secretion. However, in some specific areas, such as the palms of the hands, adrenergic nerves stimulate sweat glands through the release of norepinephrine, which acts at α1 receptors to stimulate secretion.

Autonomic function during sleep-wake states

Changes in the autonomic nervous system function have been described during the sleep-wake cycle. During sleep, there is a reduction in hearth rate (HR) and blood pressure (BP). The lowest values of HR and BP are seen during NREM sleep, while during REM sleep, HR and BP levels increase up to the level of wakefulness (Schechtman et al., 1985; Rowe et al., 1999; Trinder et al., 2001). The heart rate variability (HRV) has been used to determine the influence of the sympathetic and parasympathetic tone in autonomic changes that occur during sleep. The HRV analysis is a noninvasive procedure based on the electrocardiogram that evaluates the balance between the sympathetic and parasympathetic tone (Deutschman et al., 1994; Sztajzel, 2004). It measures the variation between R-R intervals by quantifying its low frequency (LF) and HFOs. The LF (0.045–0.15 Hz) is modulated by the parasympathetic and sympathetic nervous system, with higher LF indicating greater sympathetic activity. The HF (0.15–0.4 Hz) is, on the other hand, mediated mainly by the parasympathetic system (Pichon et al., 2006; Mazzeo et al., 2011; Ernst, 2017). Conventionally, this analysis has been performed by means of a Fast Fourier Transformation to obtain the power spectral density of each frequency band (Sztajzel, 2004; Pichon et al., 2006). However, this approach has been challenged because it does not allow the investigator to determine the temporal localization of instantaneous changes in the R-R intervals. Therefore, the wavelet transform analysis has been proposed as a more precise analysis to assess the autonomic tone with time–frequency localization (Pichot et al., 1999; Lotric et al., 2000). By means of this analysis, it has been shown that during NREM sleep, there is an increase in the HF and a decrease in the LF component of the HRV, indicating an increase in parasympathetic tone during this sleep stage (Vaughn et al., 1995). Conversely, REM sleep is characterized by an augmented sympathetic tone, revealed by a higher LF component and a higher LF/HF ratio (Méndez et al., 2006; Cabiddu et al., 2012).

Functions of the autonomic nervous system

The ANS carries all motor outflow from the CNS to the major organs of the body, with the exception of the motor outflow to skeletal muscles. The parasympathetic and sympathetic systems are entirely linked to the CNS. Although part of the enteric nervous system receives autonomic input, most of the enteric system has local networks that are independent of the CNS. The ANS is not under voluntary control and regulates essential physiological processes such as:

Rate (chronotropic) and force (inotropic) of contraction of heart muscle (Ch. 11)

Secretions of exocrine glands: bronchial, salivary, sweat, etc.

Vascular smooth muscle and thus blood pressure

Smooth muscle contraction and relaxation: bronchial, enteric, eye, etc.

Energy metabolism, e.g. hepatic glycogenolysis, skeletal muscle glycogenolysis, fat cell lipolysis, pancreatic insulin secretion (seeCh. 3)

Some endocrine secretion (seeCh. 10).

The ANS is important pharmacologically because:

It controls the functions of almost all the major human organ systems.

The relative simplicity of the ANS in terms of receptor subtypes and the fact that there are only two main transmitters – ACh and norepinephrine – make study of the chemical transmission relatively easy.

The action of neurotransmitters can be mimicked and modified by drugs, which are synthetic analogues.

Diseases with ANS dysfunction are relatively common.

6.09.3.2.2 Biofeedback

Biofeedback is the regulation of autonomic nervous system functions, such as blood pressure, heart rate, and sweating, by the subject continually monitoring that function and being rewarded (usually simply by the knowledge of his or her success) for changing that activity in a desired direction. Feedback is usually conveyed either auditorily by the pitch of a continuous tone or by using a visual display.

The idea that a person, with training, can selectively influence the activity of a particular autonomic function, notably in the direction of diminished arousal, has been in existence for a long time and is traditionally associated with Eastern practices such as meditation and yoga. It has been claimed that practitioners of these forms of meditation have the ability to attenuate their vital functions (e.g. heart rate) to an extraordinary degree. In contrast, Western scientific interest in autonomic control has been a recent development and was stimulated by the work of Miller and his colleagues on the operant conditioning of autonomic responses in animals, particularly the curarized rat. This research was significant from a theoretical standpoint because the findings suggested that autonomic and visceral responses, hitherto held only to be amenable to alteration by classical conditioning, could be modified by positive reinforcement within an instrumental or operant-conditioning paradigm. Around that time also, interest had been shown (Kamiya, 1969) in the operant conditioning of the alpha EEG rhythm (as a means of achieving altered states of consciousness) and of changes in skin conductance (Shapiro, Crider, & Tursky, 1964) and heart rate (Engel & Hansen, 1966). However, these studies on humans were criticized by Katkin and Murray (1968) for their lack of controls for mediating responses such as breathing.

Despite the many problems encountered in replicating some of the above animal laboratory work, it proved very influential and a wide range of clinical applications have been investigated since then and have focused mainly on two types of problem. First, anxiety and stress disorders, where the aim of biofeedback is to reduce general arousal levels; and, second, disorders presenting as somatic problems (e.g., pain, tension headaches, and irritable bowel syndrome), which may be triggered or exacerbated by overarousal and where again the biofeedback is either aimed at general relaxation or is targeted more specifically to the affected organ or function in order to achieve self-regulation.

Biofeedback techniques associated with generalized arousal reduction have included from the outset alpha rhythm EEG feedback (Budzynski & Stoyva, 1973) and other methods such as electrodermal (skin conductance) feedback (usually from the hand) and surface EMG feedback, for example, from the frontalis muscle, or in combination. The latter techniques are now more commonly used and may also be employed to augment systematic in vitro or in vivo desensitization by enabling closer monitoring of the return-to-relaxation phase, and thereby assisting patients to achieve this (Stoyva & Budzynski, 1993).

Procedurally, treatment by biofeedback begins with an assessment of the patient's presenting problem and an explanation of the rationale of biofeedback. Initial training sessions with the therapist enable the patient to become more attuned to cognitions and bodily events that are associated with increase in arousal. This training has been reported to be productive in establishing anxiety-evoking cognitions in the case of generalized anxiety (Budzynski & Stoyva, 1973). This stage is followed by daily practice at home (multiple short sessions) until mastery of the target response has been achieved and the patient can be weaned off the biofeedback device. Again, it should be noted that biofeedback is often combined in treatment with other self-relaxation methods, such as autogenic training or progressive relaxation (Lehrer et al., 1993).

Autonomic Nervous System

The age-related changes in autonomic nervous system (ANS) function are very diverse, and are likely to be associated with many of the age-related changes observed in drug response and toxicity across many therapeutic classes of drugs. Cardiovagal function is diminished, as indicated by age-related decreases in resting heart rate and beat-to-beat heart rate variability. Older individuals have lower vagal tone, as indicated by less increase in heart rate with atropine administration. Other findings consistent with this conclusion are that older individuals have decreased heart rate variation with deep breathing and reduced increases in heart rate in response to standing. Baroreflex function is also impaired in the healthy elderly, and this is accentuated in the presence of illness common in older patients, such as hypertension and diabetes mellitus [56]. Cardiac sympathetic function is also altered, as demonstrated by decreased tachycardic response to isoproterenol and increased circulating plasma norepinephrine concentrations [57, 58]. An integrated response that reflects many of these age-related changes is that of orthostatic hypotension, which is substantially increased in older individuals [59]. The degree of orthostatic decrease in blood pressure in older patients may be particularly evident in the postprandial state, and may be exacerbated when older patients are treated with diuretics [60, 61]. Thermoregulatory homeostasis is also impaired in the elderly, who have a higher thermoreceptor threshold and decreased sweating when perspiration is initiated [56].

Data that conclusively establish that altered drug effects result from impaired ANS function are sparse, perhaps due to the difficulty in ascribing a particular drug effect to a particular ANS function. However, increased orthostatic hypotension seen at baseline, in addition to drugs that cause sympathetic blockade, such as typical neuroleptics and tricyclic antidepressants, is likely to be a contributing factor to the increased incidence of hip fracture noted in patients receiving these drugs [62]. Similarly, the anticholinergic effects of many drugs, including antihistamines and neuroleptics, may not only accentuate orthostatic blood pressure changes but also be associated with greater cognitive impairment in older individuals. Impaired thermoregulation under baseline conditions may also be accentuated by administration of these drugs because they have potent anticholinergic effects that further disable thermoregulatory responses. It is unclear at this time how age-related ANS changes may relate to the cardiac proarrhythmic effects of drugs that prolong the electrocardiographic QT interval. However, there is a clear association of increasing age with the proarrhythmic effects of neuroleptic drugs [63]. It is clear that these ANS changes markedly alter systemic cardiovascular responses to a drug such as the α- and β–adrenergic blocking drug labetalol, which, as shown in Figure 26.6, lowers blood pressure to a greater extent in older than in younger hypertensive patients while decreasing heart rate to a much lesser extent [64].

Body–mind interaction during meditation

A series of studies have indicated that meditation regulates ANS function and induces physiological changes such as oxygen consumption, HR, respiratory amplitude and rate, SCR, HRV, and other indexes. These findings suggest the dominance of parasympathetic activity following meditation practice. Moreover, the awareness of bodily sensations and the practice of meditation techniques focusing on full awareness and presence of the body (bodifulness) also facilitate the mindfulness aspect of meditation practices. This notion is in line with the embodiment literature that body posture and state change mental processes such as emotional processing, the retrieval of autobiographical memories, and cortisol concentrations (Dijkstra, Kaschak, & Zwaan, 2007; Hennig et al., 2000; Huang, Galinsky, Gruenfeld, & Guillory, 2011; Niedenthal, 2007; Tang et al., 2019). In other words, our body postures change our chemistry, our bodies change our minds, and our minds change our behavior (Tang, 2017; Tang et al., 2015).

Does meditation change neurophysiology? A systematic review of EEG studies of mindfulness meditation examined EEG power outcomes in each bandwidth, in particular the power differences between meditation state and control state. It also examined outcomes relating to hemispheric asymmetry and event-related potentials (ERP). The results suggested that the meditation state was most commonly related to enhanced alpha and theta power when compared to an eyes-closed resting state. However, there were no consistent patterns observed in beta, delta, and gamma bandwidths. This copresence of elevated alpha and theta power may signify a state of relaxed alertness and calmness which together leads to health and well-being (Lomas, Ivtzan, & Fu, 2015).

To further study the mechanisms of body–mind interaction, we applied brain imaging and physiology measures after five sessions of IBMT (mindfulness meditation) and relaxation training in two randomized studies. We first found stronger subgenual/ventral ACC activity in the IBMT group (Tang et al., 2010). Given that this brain area has also been linked to ANS activity (Bush, Luu, & Posner, 2000; Critchley, 2004; Posner, Sheese, Rothbart, & Tang, 2007), we then measured the HRV and SCR, two indexes of sympathetic and parasympathetic activities. During and after training the IBMT group showed significantly better physiological reactions in HR and respiratory amplitude and rate compared to the relaxation control. We also found that compared to relaxation training, IBMT significantly improved HF HRV and reduced SCR, suggesting better parasympathetic regulation (see Fig. 5.1A and B), while EEG power showed greater ACC theta brain activity. Frontal midline ACC theta power correlated with HF HRV, suggesting control by the ACC over parasympathetic activity. These results indicate that after five sessions of training, the meditation group showed better regulation of the ANS through a ventral midline brain system than the relaxation group. This changed brain state and activity probably reflect training in the coordination of body and mind through meditation, as these changes were not observed in the control group. Therefore ACC and ANS may serve as mediating brain mechanisms underlying meditation-related improvements in attention control and emotion regulation as well as other behavior (Tang, 2017; Tang et al., 2009).

From a practice perspective, meditation relying solely on mind control (without body engagement) often leads to a “dry” practice experience, that is, practitioners put lots of effort into control and usually find it difficult to achieve meditative states. As a result, this process is usually associated with mental fatigue, negative emotion, and difficulty in learning to meditate. This is consistent with previous findings that brain and mind work together to support meditation states (Kerr, Sacchet, Lazar, Moore, & Jones, 2013; Tang et al., 2007, 2015, 2019).

Body–mind interaction (or body–brain interaction) occurs following other meditation methods given that the parasympathetic system (e.g., breathing amplitude and rate, SCR, HRV) also engages the brain during meditation. A study explored the brain–heart interactions in a group of monks with many years of experience in traditional Tibetan Buddhist meditation using EEG and ECG (electrocardiogram, a recording of the electrical activity of the heart). The hypothesis was that meditation should reflect changes in the neural representations of visceral activity, such as cardiac behavior, and that meditation should also induce the integration of neural and visceral systems and change the spontaneous whole-brain spatiotemporal dynamics. Compared to the control group, the monk group showed different transient modulations of the neural response to heartbeats in the default mode network (DMN), along with large-scale network reconfigurations in the theta and gamma bands of EEG activity following meditation. The temporal-frontal network connectivity in the EEG theta band was negatively correlated with the duration of meditation experience, and gamma oscillations accompanied theta oscillations during meditation. Overall, these data support the hypothesis. However, one puzzle in the study is the gamma–theta relationship during meditation, since the gamma band was very fast whereas the theta band was slow. It remains unclear how these two bands work together to induce brain and heart changes (Jiang et al., 2019). The DMN has been consistently associated with self-related processing and also with autonomic regulation such as HR and HRV. Some prominent works have demonstrated that these two functions are coupled in the DMN since selfhood is grounded in the neural monitoring of internal organs (Babo-Rebelo, Richter, & Tallon-Baudry, 2016). Another study examined the interaction between state (compassion vs neutral) and group (novice vs expert meditator) and their effect on the relation between HR and brain activity during the presentation of emotional sounds in each state. Results showed stronger positive coupling in the dorsal ACC between HR and brain activity during compassion meditation states compared to the neutral state (Lutz et al., 2009). Similarly, our study revealed a positive correlation between frontal midline theta ACC activity and HF HRV after five sessions of IBMT (Tang et al., 2010). Therefore the ACC appears to play a key role in the brain–heart interactions and network dynamics and seems to be critical for meditation practice and meditative states (Tang et al., 2015).

Investigations

Investigations can be considered to detect or confirm polyneuropathy, to test ANS function, and to test the function and nerve supply of the bladder and EUS.

Peripheral nerve conduction studies, often supplemented by needle EMG examination of distal limb muscles, supports a diagnosis of polyneuropathy and distinguishes the demyelinating from the axonal type. The involvement of somatic nerve fibers in the lower sacral segments can be demonstrated by needle EMG of the EAS muscle (and other striated muscles of the perineum and pelvic floor) and by testing of sacral reflex responses. However, even in patients with proven polyneuropathy and LUTD, the electrophysiologic abnormalities in lower-limb nerves are more pronounced (easier to demonstrate) than the abnormalities of the pudendal nerve function. All mentioned studies evaluate only the large-diameter nerve fibers that are less relevant in LUTD. There is no routine electrophysiologic test for bladder smooth muscle and its innervation. Thermal thresholds assess the function of small-diameter nerve fibers.

Autonomic tests may be performed to demonstrate involvement of the ANS. If abnormalities are found, it is inferred that the bladder may be similarly affected. The potential pitfalls are evident, as bladder autonomic innervation itself is not tested. Tests include the thermoregulatory sweat test, quantitative sudomotor axon reflex test, sympathetic skin response test, and quantitative sensory testing Santiago et al., 2000; Low et al., 2003). A skin biopsy with a quantification of pilomotor nerves may also be performed to evaluate involvement of thin autonomic nerve fibers.

Assessment of LUT should include history and determination of residual urine as a minimum.

Urodynamic tests will reveal bladder sensory and motor function. Pressure–flow cystometry directly reveals the function of bladder afferents, but any lesion of autonomic (motor) fibers can only be inferred.

Is the autonomic nervous system voluntary or involuntary?

Which nervous system we can voluntarily control?