week two

Optional reading

Overview of Normal Aging and Brain Changes

• Aging and Cognitive Decline: Normal aging leads to structural, biochemical, and molecular changes in the brain, contributing to cognitive decline.

• Importance of Understanding Aging: Understanding normal brain changes may guide further studies and interventions.

Key Changes in Normal Aging

Structural Changes

• Gross Changes:

  • Cerebral atrophy and volume loss (5% per decade after age 40).

  • Ventricular enlargement and sulci widening.

• Microscopic Changes:

  • Dendritic tree decreases, loss of synaptic density, neurodegeneration.

  • Lipofuscin accumulation and neurofibrillary tangles in gray matter (GM) and white matter (WM).

Biochemical and Metabolic Changes

• Neurotransmitter Systems:

  • Decline in acetylcholine receptors, monoamine levels (dopamine, serotonin) and disturbed signaling pathways.

  • Age-related changes in receptor binding and neurotransmitter availability affect cognitive function.

Cellular and Molecular Changes

• Mitochondrial Dysfunction:

  • Changes in mitochondrial DNA (mtDNA) and ATP production, promoting oxidative stress and apoptosis.

• Gene Expression Alterations:

  • Age-regulated changes in gene transcription, impacting neuronal health and cognitive processes.

  • Notably affects genes linked to synaptic function, stress response, and neurogenesis.

• Calcium Homeostasis Dysregulation:

  • Altered calcium influx through neuronal channels affecting synaptic plasticity and cognitive performance.

Specific Mechanisms of Decline

Electrophysiological Changes

• Action Potential Alterations:

  • Increased action potential threshold and decreased amplitude during aging, affecting neuronal excitability.

Inflammation and Oxidative Stress

• Role of ROS and Inflammatory Factors:

  • Microglial activation, chronic inflammation, and oxidative damage contribute to neuronal degeneration and cognitive decline.

Conclusion

• Normal aging entails complex structural and functional changes within the brain that can predispose individuals to neurodegenerative disorders. Monitoring these changes provides valuable insights for interventions aimed at

Lecture content

Ageing Population

• Current demographic in Australia: 16% are 65 years or older (approx. 3.9 million people)

  • Source: ABS 2019a

• Increased need for assistance among those aged 85 and over (28% need help vs. 7% for 65-84)

  • Source: AIHW 2015

Importance of Studying Psychology of Ageing

• Longevity necessitates understanding developmental changes across the lifespan

• Aim to enhance positive aging experiences

• Development of interventions based on findings

•  need to figurte out how to help so we can optimisde our own agaimng

What is Considered Old?

• Evolving perceptions of aging

• Distinction between 'young old' and 'old old' has changed over time

• Importance of examining various perspectives of aging beyond just chronological age

Stages of Adult Life

• Early Adulthood: 18-30s

• Middle Adulthood: 40s - mid 60s

• Older Adulthood: mid 60s onwards

  • Young Old: 65-74 years

  • Old Old: 75-84 years

  • Oldest Old: >85 years

Cultural Perspectives on Ageing

• Different cultural views on physical changes associated with aging

• Eastern cultures often hold older adults in higher esteem than Western cultures

  • Due to stronger collectivist traditions (Wilinska et al. 2018)

• Contradictory findings exist (North & Fiske, 2015)

• Call for more research in this area

Reflection Activity

• Pause and reflect on personal views about aging

• Consider differences in perspectives among friends

Neurobiological Changes Across Adult Lifespan

Brain Development in Early Adulthood

• Maturation of the prefrontal cortex is completed in early adulthood (Tierney & Nelson, 2009)

  • Increased myelination speeds neural impulses

  • Crucial for complex behavioral performance and executive functions

Ageing and Changes in the Brain

• Ageing increases risk for neurodegenerative diseases (Lee & Kim, 2022)

• Notable brain changes with age include

  • Cerebral atrophy: loss of neurons/connections

  • Decline in brain volume and weight by ~5% per decade after age 40

    • Significant acceleration after age 70 (Peters, 2006)

Regional Brain Volume Declines

• Shrinkage not uniform; frontal lobe and hippocampus exhibit more significant loss

  • Frontal lobe: ~12% volume loss

  • Temporal lobe: ~9% volume loss

  • Occipital and parietal lobes: no significant changes (Mori et al. 2020)

Neurotransmitter Changes

• Changes in synthesis with aging affect mood, sleep, and cognition

• Decreased acetylcholine linked to memory decline and dementia (Araujo et al., 2005)

  • Norepinephrine and dopamine: impact synaptic plasticity and neurogenesis

  • Reduced serotonin leads to mood changes

Effects of Oxidative Stress

• Reactive oxygen species damage mitochondria, prompting neurodegenerative diseases

• Changes in blood flow and neuronal structure contribute to cognitive decline

Physical Changes Across the Adult Lifespan

• Common changes include:

  • Decline in eyesight

  • Skin elasticity loss, increased wrinkles

  • Reduced bone mass, muscle mass decline, increased adipose tissue

  • Higher likelihood of infections and diseases

  • Decreased strength and mobility

Changes in Physical Activity Levels

• Decline in physical activity throughout adulthood

  • Related to fitness degradation and stereotypes

• Interventions like community walking programs seek to address this issue

Increased Incidence of Physical Illness

• Common illnesses: diabetes, cardiovascular disease, hypertension, arthritis, osteoporosis

• Psychological factors such as decline in confidence worsen physical activity levels and health outcomes

Risk of Falls with Age

• Falls: leading cause of injury, hospitalization, and death in older adults

• Cognitive impairment increases fall risk (Li & Harmer, 2022)

Ageing and the Healthcare System

• Implications of an aging population on health services

  • Increased demand and rising health costs (Source: AIWH)

Summary

• The significance of understanding age-related changes across the lifespan

• Importance of cultural consideration in aging perceptions

• Neurobiological and physical health declines with age

• Increased risk of falls contributes to healthcare challenges

4. Central Nervous System

As already mentioned, the nervous system is comprised of two major divisions - the peripheral nervous system and the central nervous system. Our attention will turn now to the central nervous system. 

The central nervous system (CNS) consists of the brain and the spinal cord. The brain and spinal cord perform vital functions; however, as structures they are quite vulnerable to damage. They are surrounded in fluid filled cavities and encased in many layers of protective covering (i.e. blood-brain barrier, meninges, bony encasing of skulls and vertebrae) that regulate the entry and exit of molecules into the CNS. This workbook will now briefly review the main functions of the brain and spinal cord.

Spinal Cord

The spinal cord is like a relay station in that all messages to and from the brain need to pass through the spinal cord. However, unlike a regular relay station, it not only routes messages to and from the brain, but also has its own system of automatic processes, called reflexes.

The spinal cord is functionally organized in 30 segments, corresponding with the spina; vertebrae. Each segment is connected to a specific part of the body through the peripheral nervous system. Nerves branch out from the spine at each vertebra. Sensory nerves bring messages in; motor nerves send messages out to the muscles and organs. Messages travel to and from the brain through every segment. The top of the spinal cord merges with the brain stem, where the basic processes of life (i.e. breathing and digestion) are controlled and base of the spinal cord ends just below the ribs (see image below).

Image: Anatomy Body System

As hinted above, some sensory messages are immediately acted on by the spinal cord, without any input from the brain. Withdrawal from heat and knee jerk are two examples. When a sensory message meets certain parameters (i.e. needing basic response for immediate action), the spinal cord initiates an automatic reflex. The signal passes from the sensory nerve to a simple processing center, which initiates a motor command within milliseconds.

Illustration of one type of spinal reflex - flexion withdrawal reflex 

Image: Human Physiology Academy

Although the spinal cord is protected by bony vertebrae and cushioned in cerebrospinal fluid, injuries can still occur. When the spinal cord is damaged in a particular segment, all lower segments are cut off from the brain, causing paralysis. Therefore, the lower on the spine damage is, the fewer functions an injured individual loses.

Brain

Our brain is a extraordinarily complex organ made up of billions of interconnected neurons and glia (introduced in the next section of this workbook). The human brain is a bilateral or two-sided structure that can be separated into distinct lobes. Each lobe is associated with certain set of functions, but, ultimately, all of the areas of the brain interact with one another to provide the foundation for our thoughts and behaviours.

Cerebral Hemispheres

The surface of the brain, known as the cerebral cortex is characterized by a distinctive pattern of folds or bumps, known as gyri, and grooves, known as sulci (singular sulcus). See illustration below. These gyri and sulci form important landmarks that allow us to separate the cerebral cortex into distinct functional centers. The most prominent sulcus, known as the longitudinal fissure, is the deep groove that separates the brain into two halves or hemispheres: the left hemisphere and the right hemisphere.

Illustration of sulci and gyri on the surface of the cerebral cortex. Note the longitudinal fissure that divides the cerebral hemispheres into bilateral regions. Image: Lumen Learning.

There is evidence specialization of function—referred to as lateralization—in each hemisphere. This lateralization is mainly regarding differences in language ability between cerebral hemispheres. Language comprehension and communication is localized in the left cerebral hemisphere regions for most of us. In terms of motor control, we know that left hemisphere controls the right half of the body, and the right hemisphere controls the left half of the body. The two hemispheres are connected by a thick band of neural fibres known as the corpus callosum, consisting of about 200 million axons. See illustration below. The corpus callosum allows the two hemispheres to communicate and exchange information.

Illustration of the corpus callosum that connects that cerebral hemispheres from the front (a) and side (b) view. The image on the right hand corner is a picture of a sheep brain with corpus callosum fibres exposed. Illustration and image: Lumen Learning.

In some cases of severe epilepsy, doctors elect to sever the corpus callosum as a means of controlling the spread of seizures. Depending on the extent of the corpus callosum fibers severed, some patients are left unable to integrate visual and verbal information. For instance, post-surgery patients maybe unable to name a picture that is shown in the patient’s left visual field because this information is only available in the largely nonverbal right hemisphere (see illustration below). 

Illustration of experiments performed with patients following split-brain procedures. Image: Nature

However, in some cases, despite extensive damage to the brain, some level of recovery is possible due to re-wiring of neural circuits such that undamaged parts of the brain take on new functions. The brain’s ability to change, adapt, and reorganize itself is known as neuroplasticity. Read the text-book chapters for a more detailed understanding of neuroplasticity and other insights gained through split-brain studies.

This workbook will now take a quick look at major lobes of the cerebral hemispheres.

Lobes of the Brain

The four lobes of the brain are the frontal, parietal, temporal, and occipital lobes.

Artist: Walter Crane

The frontal lobe is located in the forward part of the brain, extending back to a fissure known as the central sulcus. The frontal lobe is involved in reasoning, motor control, emotion, and language. It contains the areas such as: motor cortex which involved in planning and coordinating movement and the primary motor cortex, which commanding all voluntary movements. The frontal love also has a prefrontal cortex, which is responsible for higher-level cognitive functioning and a language center known as Broca’s area, which is essential for speech production.

The primary motor cortex has an additionally notable feature: it is highly specialized structure that localizes motor control for each body part. This is to say that each part of the body has a unique portion of the primary motor cortex devoted to it (motor homunculus – see figure below). As you can see by the illustration, the amount of space within the primary motor cortex is not dependent on the size of the structure, but rather the extent of motor movements that can be performed by that structure. Each individual finger has about as much dedicated brain space as your entire leg. Your lips and tongue, in turn, require about as much dedicated brain processing as all of your fingers and your hand combined. Functionally speaking, can you think of why this might be? 

Illustration of motor homunculus within the primary motor cortex (right hand side) and the sensory homunculus within the somatosensory cortex (left hand side). Image: Sharp Brains.

The brain’s parietal lobe is located immediately behind the frontal lobe, and is involved in processing information in relation to our sense of touch (tactile perception) and proprioception (understanding of the location of our body in relation to the world around us). It contains the somatosensory cortex, which is essential for processing sensory information from across the body, such as touch, temperature, and pain. Much alike the primary motor cortex, the somatosensory cortex is organized topographically, which means that spatial relationships that exist in the body are maintained on the surface of the somatosensory cortex (see illustration above). For example, the portion of the cortex that processes sensory information from the hand is adjacent to the portion that processes information from the wrist. 

The temporal lobe is located on the side of the head (temporal means “near the temples”), and is associated with hearing, memory, emotion, and some aspects of language. The auditory cortex, the main area responsible for processing information in relation to our sense of hearing, is located within the temporal lobe. Wernicke’s area, a region important for speech comprehension, is also located here. 

The occipital lobe is located at the very rear of the brain, and contains the primary visual cortex, which is responsible for interpreting incoming visual information. The occipital cortex is organized retinotopically, which means there is a close relationship between the position of an object in a person’s visual field and the position of that object’s representation on the cortex. You will learn much more about how visual information is processed in the occipital lobe when you study sensation and perception.

For a interactive experience, go to the link below and explore the functional relationship between the 4 lobes of the brain, as well as the  brainstem and cerebellum.

Activity 7.2: Interactive Map of Human Brain

Thalamus and the Limbic System

Other areas of the forebrain (which includes the lobes that you learned about previously), are the parts located beneath the cerebral cortex, including the thalamus and the limbic system. The thalamus is a sensory relay for the brain. All of our senses, with the exception of smell, are routed through the thalamus before being directed to other areas of the brain for continued processing.

Illustration of some key structures - hypothalamus, amygdala and hippocampus- within the limbic system. Image: Lumen Learning.

The limbic system  is involved in processing both emotion and memory. Interestingly, the sense of smell projects directly to the limbic system; therefore, not surprisingly, smell can evoke emotional responses in ways that other sensory modalities cannot. The limbic system is made up of a number of different structures, but three of the most important are the hippocampus, the amygdala, and the hypothalamus (see illustration below). The hippocampus is an essential structure for learning and memory. The amygdala is involved in our experience of emotion and in binding emotional value to our memories. The hypothalamus regulates a number of homeostatic processes, including the regulation of body temperature, appetite, and blood pressure. The hypothalamus also serves as an interface between the nervous system and the endocrine system and in the regulation of sexual motivation and behavior.

While it is important to known that certain functions are localized to distinct regions of the brain, it is also important to understand how our brain integrates all incoming and outgoing information to produce the seamless perception of reality that most of us experience. In the below video Professor Julie Stout will explains some examples of integration of information within our nervous system.

From <https://learning.monash.edu/mod/book/view.php?id=3568719&chapterid=636252>

Neurons & The Action Potential

Our nervous system is made up of billions of individual cells. These cells act as the building blocks of our brain and can be broadly classified into two different groups: neurons and glia.

Neurons are highly specialised cells of the nervous systems that can transmit and receive electrical and chemical signals. At its core, the neurons ability to communicate with each other and other cell types drives all human behaviour. However, neurons cannot function in isolation.

Neurons are supported by glia, another group of specialised cells that provide essential nutrients and growth factors needed for neurogenesis, as well as neuronal repair and maintenance. They also play an information processing role that is largely complementary to neurons. This workbook will now review the structure and mechanisms of neurons and how neurons communicate within the nervous system.

Image: Fine Art America

Neurons

The human brain contains approximately 86 billion neurons. Most neurons share the same cellular components as other cells of the body, as well as some other unique characteristics. Like all cells, neurons have a cell body (known as the soma) which is surrounded by a permeable cell wall and a nucleus holding the hosts DNA. The neuron also contains organelles such as mitochondria, ribosomes, endoplasmic reticulum, Golgi apparatus that support the daily functioning of the cell. However, unlike many other cells of the body the neuron has a set of unique structures that enable it to send and receive electrical and chemical signals. These features are listed below and some of these features are shown in the diagram below:

Illustration of a neuron with typical cell feature (i.e. cell body) as well as unique distinguishing characteristics (i.e. dendrites, axon, synapse). Figure adapted from Concepts of Biology textbook by Charles Molnar and Jane Gair.

Type of Neurons

There are different types of neurons, and the functional role of a given neuron is very much dependent on its structure. There is an amazing diversity of neuron shapes and sizes found in different parts of the nervous system (see figure below).

There is great diversity in the size and shape of neurons throughout the nervous system. Examples include (a) a pyramidal cell from the cerebral cortex, (b) a Purkinje cell from the cerebellar cortex, and (c) olfactory cells from the olfactory epithelium and olfactory bulb. Figure adapted from Concepts of Biology textbook by Charles Molnar and Jane Gair.

See the video of Professor Julie Stout below as she provides and explanation of the inexorable link between structure and function at the level of individual neurons. Professor Julie also introduces the action potential and the process of signal transduction explained in the next section of the workbook below.

 Video 3: Structure Function Relationship of Neurons

Neural Networks & Process of Signal Transduction

Neurons typically function within a group of other neurons, known as neural networks. Communication between neurons underpins co-ordination and synchronization within neural networks required for all human behaviour, from simple actions such as a motor reflex to more advanced functions like making a memory or a decision. Neurons are able to carry electrical impulses due to their polarised cell membranes. Neuronal cell membranes are impermeable to charged particles or ions and in order to enter or exit the cell these ions need to pass through protein channels that span the lipid membrane. Ion channels that change their structure in response to voltage changes are called voltage-gated ion channels. Voltage-gated ion channels regulate the relative concentrations of different ions inside and outside the cell.

A neuron at rest is negatively charged: the inside of a cell is approximately 70 millivolts more negative than the outside (−70 mV, note that this number varies by neuron type and by species). This voltage is called the resting membrane potential.

The Action Potential

Normally the voltage gated channels along the axon are closed, but changes in the environment (i.e. neurotransmitter signal from pre-synaptic neuron) can trigger sections of the cell membrane to depolarise by causing the gates to swing open and allowing an influx of positively charged ions. When this happens, it causes a depolarization in the adjoining section of the membrane by allowing the neighbouring channels to open. In this way as the sequence continues, it creates a wave of changes in electrochemical potential that spreads down the axon. This wave of electrochemical potential is called an action potential (see figure below).

The action potential is conducted down the axon as the axon membrane depolarizes, then repolarizes. Figure adapted from Concepts of Biology Textbook by Charles Molnar and Jane Gair. 

Once the sodium channels open, the neuron completely depolarizes to a membrane potential of about +40 mV. Action potentials are considered an “all-or nothing” event, in that, once the threshold potential is reached, the neuron always completely depolarizes. Once depolarization is complete, the cell must now “reset” its membrane voltage back to the resting potential. To accomplish this, the Na+ channels close and cannot be opened. This begins the neuron’s refractory period, in which it cannot produce another action potential because its sodium channels will not open (see the diagram below)

6. Chemical Synapse: Neurotransmitters & Hormones

Neuronal communication is referred to as an electrochemical event. The movement of the action potential down the length of the axon represents the first part of this communication – the electrical event. However, in order for the adjoining neuron to receive the incoming message, there also needs to be a movement of the neurotransmitter across the synaptic space. This represents the chemical portion of the process.

The synapse or “gap” is the place where information is transmitted from one neuron to another. Synapses usually form between axon terminals and dendritic spines, but this is not universally true. There are also axon-to-axon, dendrite-to-dendrite, and axon-to-cell body synapses. The neuron transmitting the signal is called the presynaptic neuron, and the neuron receiving the signal is called the postsynaptic neuron. Note that these designations are relative to a particular synapse—most neurons are both presynaptic and postsynaptic.

Illustration of a pre-synaptic neuron signalling to a post-synaptic neuron. Image: Cognitive Sciences Stack Exchange

Chemical Communication via Neurotransmitters

Neurotransmitters are the chemicals stored within a neuron’s axon terminal in little parcels (vesicles). If an action potential is fired, these vesicles open up and the neurotransmitter is released into the synaptic cleft. Each type of neuron typically has a particular type of neurotransmitter it releases and neurons that operate within a particular neurotransmitter systems are linked to specific cognitive and behavioural functions (see diagram below). 

Illustration of the chemical structure of common neurotransmitters and the functions associated with each neurotransmitter system. Image: Compound Interest Chemistry.

From its point of release in the pre-synaptic neuron, neurotransmitters reach the adjoining post-synaptic neuron and ‘bind to’ receptors. Neurotransmitters only bind to their own specific receptors in a lock-and-key type of fit. Each neurotransmitter can bind to several different receptor types and can have different effects depending on the type of receptor to which it binds. When a receiving or postsynaptic cell is reached by a neurotransmitter, a change called a postsynaptic potential makes the cell either more or less likely to fire again. A depolarised membrane will cause an excitatory postsynaptic potential (EPSP) and the neuron will be likely to fire an action potential. A hyperpolarised membrane will cause an inhibitory postsynaptic potential (IPSP) and the neuron will be less likely to fire. Postsynaptic potentials alone fade as they spread across the postsynaptic neuron. It is the combined impact of the many EPSPs and IPSPs at the junction of the axon and cell body that determines whether or not an action potential will occur.

A single neuron can receive both excitatory and inhibitory inputs from multiple neurons, resulting in local membrane depolarization (EPSP input) and hyperpolarization (IPSP input). All these inputs are added together at the axon hillock. If the EPSPs are strong enough to overcome the IPSPs and reach the threshold of excitation, the neuron will fire. Figure adapted from Concepts of Biology Textbook by Charles Molnar and Jane Gair. 

Neuromuscular Junction

Unlike neurons within the central nervous system, neurons in the peripheral nervous system can synapse onto muscles or organs to trigger a direct action. When a neuron synapses onto a muscle, a neurotransmitter (typically acetylcholine) is released and binds onto corresponding receptors in the muscle tissue. The synapse between the neuron and muscle cell where the neurotransmitter is released is known as the neuromuscular junction.The binding of acetylcholine to the receptor can depolarize the muscle fiber, causing a cascade that eventually results in muscle contraction (see video below). The most rapid acting neurotoxins such as nerve gas and venoms in poisonous snakes can act by inhibiting the functioning of the acetylcholine at the neuromuscular junction. This can result in paralysis and respiratory arrest. 

 Video 4: The Neuromuscular Junction

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Much like neurotransmitters, hormones are chemical messengers that bind to a receptor in order to send their signal. However, unlike neurotransmitters, which are released in close proximity to cells with their receptors, hormones are secreted into the bloodstream and travel throughout the body, affecting any cells that contain receptors for them. Thus, whereas neurotransmitters’ effects are localized, the effects of hormones are widespread. Also, hormones are slower to take effect, and tend to be longer lasting.

Chemical Communication via Hormones (Endocrine System)

The endocrine system consists of a series of glands that produce chemical substances known as hormones. Hormones regulate behaviours such as aggression, mating, and parenting. The relationship between hormones and behaviour is bi-directional as behaviour can also influence hormone concentration. For example, breastfeeding stimulates the release of oxytocin, ‘the feel good’ hormone which fosters love, nurturing, and an emotional bonding between mother and child. Hormones are involved in regulating bodily functions and are ultimately controlled through interactions between the hypothalamus (in the central nervous system) and the pituitary gland (in the endocrine system). The brain exercises control over bodily functions through the hypothalamus. Take for instance the butterflies in your stomach that appear when you are around someone you like.  The brain is also the major target of hormonal secretions and thus the communication between the body and the brain is best described as bidirectional in nature.

The next section of the workbook briefly introduces you to the major endocrine glands and the role of the hormones secreted by these glands.

Major Endocrine Glands

The pituitary gland descends from the hypothalamus, which is located at the base of the brain (see image below). The pituitary is referred to as the “master gland” because its messenger hormones control all the other glands in the endocrine system. One of main roles of the pituitary gland is to carry out instructions from the hypothalamus. In addition to messenger hormones, the pituitary also secretes growth hormone, endorphins for pain relief, and a number of key hormones that regulate fluid levels in the body.

Illustration of the major endocrine glands in the body (Image: Lumen Learning)

Located in the neck, the thyroid gland releases hormones that regulate growth, metabolism, and appetite.

The adrenal glands sit atop our kidneys and secrete hormones involved in the stress response, such as epinephrine (adrenaline) and norepinephrine (noradrenaline).

The pancreas is an internal organ that secretes hormones that regulate blood sugar levels: insulin and glucagon. These pancreatic hormones are essential for maintaining stable levels of blood sugar throughout the day by lowering blood glucose levels (insulin) or raising them (glucagon).

The gonads secrete sexual hormones, which are important in reproduction, and mediate both sexual motivation and behavior. The female gonads (ovaries) secrete estrogens and progesterone, and the male gonads (testes) secrete androgens, such as testosterone.

Disorders of the Nervous System

As a way to summarise the multiple communication pathways within the nervous system, in the video below Professor Julie Stout will discuss some of the common disorders that arise due to disease affecting one or more of the processes involved in neural communication.