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Summary articles and learning goals Arousal and attention 2019
- Instelling
- Maastricht University (UM)
Summary articles and including learning goals of year
[Meer zien]Voorbeeld 4 van de 131 pagina's
Voorbeeld 4 van de 131 pagina's
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Arousal and attentionLearning goals Task 1: Arousal Theory and practice
1. What is stress? What is arousal?
2. What is the relationship between stress and arousal?
3. What are the models? What are the limitations and strong points?
4. What is the relationship between arousal/stress and cognitive performance?
5. How do we measure arousal/stress? (cortical, autonomic (physiological), endocrine)
6. What are the parts of the autonomous nervous system and how are they related to
arousal/stress?
7. What is the HPA-axis and how is it related to arousal and stress?
The Hypothalamic-Pituitary-Adrenal Axis: the actions of the central nervous system and potential
biomarkers (Olson, Marc, Grude, McManus, Kellermann)
Abstract
The adrenal glands are part of an adaptive system involved in the maintenance of a homeostatic
biological balance in response to stress.
- They release cortisol, epinephrine, and norepinephrine to preserve a healthy, but dynamic
equilibrium.
- Specific brain nuclei control adrenal gland function either through the actions of the HPA
axis, initiated by traditional HPA drivers like corticotrophin releasing factor (CRF) from the
hypothalamus, or through direct innervation by stimulated preganglionic sympathetic
nerves.
- The pathways can be activated by physical or emotional stressors as well as inflammatory
processes which can activate adrenal activity through the signalling of various cytokines.
- The continuum of hyperstimulation of the HPA axis from an acute insult to a chronic
saturation of the system is led by varying degrees of adrenal collapse eventually giving way
to adrenal fatigue.
- The functionality of the HPA axis can be evaluated with peripheral biomarkers such as
urinary epinephrine and norepinephrine and salivary cortisol. These HPA biomarkers help
practitioners identify contributing factors to various clinical conditions and provide insight
into potential intervention points.
By understanding the pathways that can lead to altered HPA axis activity and by using biomarkers to
assess HPA functionality, health care practitioners can make more informed clinical decisions to
enhance patient care.
Introduction
Excessive or constant stress leads to a biological system that begins to lose ground in its ability to
maintain chemical stability and instead allows pathological discord to rule.
- Stress = a state of threatened homeostasis and any alterations in the ability to respond to
stress may lead to disease.
- During stress changes in physiological functioning can occur, primarily led by the release of
glucocorticoids and the catecholamine neurotransmitters epinephrine and norepinephrine
from the adrenal glands.
1. Epinephrine and norepinephrine react on a variety of different tissues. Their function is
dependent on the type of adrenergic receptor that is expressed on the tissues they
are described as initiators of the fight or flight response, as they increase respiration and
heart rate, and trigger the release of glucose from energy stores.
2. The glucocorticoid cortisol contributes to carbohydrate, protein, and fat metabolism,
regulates blood glucose, and suppresses the immune system.
- Excess release of neurotransmitters and glucocorticoids from the adrenal glands, if left
unchecked, can advance the development of a number of pathological responses. The
control and release of these molecules from the adrenal glands is mediated through a
network of CNS neurons with resultant PNS effects, collectively known as the HPA axis.
,Arousal and attention
The CNS and PNS function together to coordinate actions of the endocrine and immune systems,
along with all other biological processes.
- Under healthy conditions, changes in internal and external milieu are received and
processed by the nervous system to elicit an appropriate action.
- When faced with excessive stress, whether physical or emotional, adaptive systems function
to maintain dynamic equilibrium.
- The ANS is part of the PNS and consists of sympathetic and parasympathetic division. The
HPA axis is an adaptive system in the sympathetic division that regulates the biological
response to stress through the release of glucocorticoids, epinephrine, and norepinephrine
in the periphery.
- These hormones and neurotransmitters can be measured as biomarkers to assess HPA
activity and the determinant central pathways.
The physiological consequences of stress and HPA activation appear as enhanced attention,
accelerated cardiac output and respiration, increased catabolism, and redirection of blood flow to
provide the highest perfusion to the brain, heart, and muscles. These physiological actions are
regulated by specific brain circuits.
- Neuronal impairment of the brain circuits prevents adrenal neurotransmitters and hormones
from performing their required biological functions, consequently leading t a state of
imbalance and various pathological conditions.
- Measuring of biomarkers has thus become an important tool to predict the CNS circuitry
that underlies the discordance in HPA axis function.
The hypothalamic-pituitary-adrenal axis
The neurocircuitry of the HPA axis = the HPA axis is organized into three distinct regions:
- The hypothalamus, specifically the paraventricular nucleus (PVN) is the hypothalamic
reguion that uses corticotrophin-releasing hormone (CRH) to stimulate the pituitary.
- The pituitary gland releases andrenocorticotrophin hormone (ACTH) when stimulated,
which is transported in general circulation to the adrenal
cortex of the adrenal glands.
- The adrenal glands rapidly synthesize and release cortisol into
the blood where it participates in the response to stress and
maintenance of homeostasis throughout the body. The
adrenal gland is the effector organ of the HPA axis and its
actions are essential to maintaining homeostasis. Also neural
projections from the CNS affect adrenal activity by acting at
different levels of the HPA axis.
Sympathetic innervation of adrenal gland = one pathway that
regulates adrenal function involves sympathetic preganglionic fibers
that project to the adrenal medulla to elicit the release of epinephrine and norepinephrine as
hormones into circulation. Stress can initiate the pathway through the
activation of the lateral hypothalamus (LH) and rostral ventrolateral
medulla (RVLM).
(figure 1)
Neural input to hypothalamic paraventricular nucleus = stimulation
of the adrenal glands via the classical hypothalamic-pituitary pathway
is also under stringent control by the CNS. The amygdala and
hippocampus, which are important for emotion, behaviour and
memory are included. Strong emotions or emotional memories can
trigger the amygdala and hippocampus to stimulate the PVN.
,Arousal and attention
Increased PVN activity causes enhanced cortisol release leading to a rise in vigilance to deal with the
stressor.
(figure 2)
Cytokines from an inflammatory response can also contribute to PVN activation. Upon insult or
injury, cytokines released by immune cells can alter brain chemistry in two ways:
- Humoral pathway, whereby cytokines are released into systemic circulation and can act on
circumventricular organs such as the area postrema (AP). The circumventricular organs are
areas of the brain that have incomplete blood-brain barriers and can therefore detect and
relay chemical signals to the brain. The cytokines thus directly alter CNS function without the
use of transport systems.
- Neural pathway, whereby cytokines released by immune cells in lymphoid tissue activate the
vagus nerve to signal to the brain that an inflammatory process is occurring. The vagus nerve
projects to the NTS, causing stimulation of the PVN, which again leads to enhanced adrenal
activity and cortisol release.
Specialized stress pathways = different types of stress (physiological and emotional) activate the HPA
axis through separate, but convergent, pathways. Although different types of stress are involved in
different circuits, the end result culminates in HPA activation and glucocorticoid release.
- Physiological or ‘real’ stress is detected by somatic, visceral, or circumventricular pathways.
True physical changes in the body, including respiratory and cardiovascular changes, pain,
and elevated levels of circulating inflammatory mediators, represent a current, tangible
threat to homeostasis. This sensory information is communicated through ascending vagus
nerves and circumventricular organs that converge on the NTS, which integrates the sensory
input and passes it along to the PVN.
- Emotional or anticipated stress response can happen without a primary sensory stimulus.
Emotional stress elicits HPA activation in anticipation of a potential homeostatic disruption.
Limbic brain regions such as the amygdala and hippocampus are heavily involved in
emotional processing, behaviour, and memory, and will stimulate the PVN when activated.
Chronic stress effects = the HPA axis is an innate system that is meant to respond to an acute
stressor and then terminate that response via negative feedback mechanisms. This is crucial to the
survival of an organism. However, chronic HPA stimulation due to ongoing physical or emotional
stress can lead to unresponsiveness of hypothalamic nuclei. Additionally, if the adrenals maintain a
high level of activity to mobilize cortisol, epinephrine, and norepinephrine, the stores of these
hormones may become depleted. Thus, these events lead to adrenal insufficiency, which reduces
the gland’s ability to maintain homeostasis. An insufficient adrenal response to stress or an immune
challenge prevents the body from being able to deal with the stress or fight off infection.
overall, the HPA axis receives input from a variety of central and peripheral sources, and it is the
integration of these signals that allows this system to produce the appropriate homeostatic
response. However, excessive stimulation of the HPA axis by one or more of these inputs can disrupt
its ability to maintain homeostasis, which could lead to a disease state.
Biomarkers of HPA activity = Neurotransmitter and hormone measurements can be used as
indicators of biological imbalances and may help improve our understanding of complex disease
states. In many areas of medicine, biomarkers aid in diagnosis, prognosis, and predicting treatment
efficacy. In psychiatry, diagnostic and treatment decisions are made by evaluating subjective
measures such as clinical signs and symptoms. Biomarkers are needed to monitor responses to
treatment and to predict clinical outcome.
In the past, biomarker assessments have been viewed as irrelevant to symptomatology because
measures had included peripheral biological fluids, such as blood, urine, and saliva, but not CNS
, Arousal and attention
markers, such as CSF and brain tissue. The CNS and PNS must not be viewed as separate entities. The
pathways described above demonstrate that the CNS and PNS communicate via direct neuronal
projections. Therefore, it is possible to obtain inferences on central profiles through the
measurement of peripheral biomarkers such as urinary neurotransmitters and salivary hormones.
Using HPA biomarkers to assess clinical symptoms = Altered HPA axis activity has widespread effects
throughout the body, and can contribute to changes in energy, sleep, mood, cognition, weight and
the cardiovascular system, among others. HPA axis hypoactivity has been associated with chronic
fatigue syndrome (CFS), possible due to blunted ACTH and CRH responses.
- Studies found that:
1. there is an association between the development of obesity and adrenal activity,
2. In older patients, higher salivary cortisol levels are correlated with impaired declarative
memory.
3. Altered HPA axis activity has effects on mood and behaviour (characteristic of a variety
of psychiatric disorders)
These studies support the use of HPA biomarker measurements to
understand the biochemical contributors to various clinical conditions.
Assessment of epinephrine, norepinephrine, and cortisol, given their
neurochemical involvement in HPA axis activity and their association with
psychiatric disorders, could provide the necessary biochemical targets to
determine underlying cause and predict treatment outcome.
It is hypothesized that the body increases adrenal activity to mobilize resources when necessary to
efficiently evade a stressor. Because the HPA axis plays an integral role in responding to different
types of stressors and incorporating signals from the CNS and PNS, it serves as a biochemical
“middleman” that utilizes specific neurotransmitters and hormones as chemical signals. By
understanding of how stress mediated by CNS pathways can provoke alterations in urinary
neurotransmitter and salivary cortisol measurements.
Using HPA biomarkers to assess treatment = Data suggests that urinary neurotransmitters and
salivary hormones can predict treatment outcome and monitor treatment efficacy. HPA biomarkers
can also be used to monitor non-pharmacological treatment. The fact that there is a direct
involvement of the CNS in the release of neurotransmitters in the periphery explains why the CNS
and PNS must be viewed as parts of a single integrated system. Although there are clear anatomical
separations between the CNS and PNS, their functional roles cannot be viewed separately. By
understanding the neurocircuitry that enables centrally acting compounds to manipulate peripheral
markers and the correlative parallels between the neurotransmitters in the CNS and the periphery,
predictions on treatment choice as well as outcome can be made via the measurement of peripheral
biochemistry.
Concluding remarks
Stress is typically associated with emotional and social demands. Whether stress occurs due to a
traumatic event, divorce, or a severe burn, brain pathways are initiated to activated the HPA axis.
This leads to release of cortisol, epinephrine, and norepinephrine into the periphery. The production
of these hormones from the adrenal gland is essential to overall health and wellbeing. However,
continuation of stressors can leave an individual at risk for developing mood disorders or infections
caused by pathophysiological functioning of the adrenal gland.
The urinary epinephrine and norepinephrine and salivary cortisol testing have an important role in
clinical practice as representative biomarkers of HPA axis activity.
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