Functional Neuroanatomy and Brain Organization

Functional neuroanatomy: study of brain structure and function

Involves understanding brain regions and their functions

Understanding communication between brain regions to help explain complex behaviours

Essential for

Understanding behaviour

Diagnosing and treating neurological disorders

Understanding functional neuroanatomy is crucial for advancing our understanding and treatments of neurological and neuropsychiatric disorders

Recall: cerebral cortex divided into lobes which each have their own regions and functions themselves

Frontal lobe, temporal lobe, occipital lobe, parietal lobe

Understanding functional neuroanatomy

Understanding functional neuroanatomy is crucial for advancing our understanding and treatment of neurological/psychiatric disorders for several reasons

Localization of brain function

Functional neuroanatomy provides insights into the localization of different brain functions

Understanding precise brain regions involved in different functions, we can better understand how these functions are disrupted in neurological/psychiatric disorders

E.g.. Amygdala is hyperactive in individuals with PTSD, leading to an exaggerated fear response even in non-threatening situations

Diagnosis of disorders

Knowledge of functional neuroanatomy can aid in the diagnosis of neurological/psychiatric disorders

Understanding the neuroanatomical basis of different disorders can aid in accurate diagnosis

E.g. we can look at brain region(s) known to be involved in a disease to see if those areas are affected in individual if we suspect they have the disease (e.g. Parkinson's disease; PD)

History of Functional Neuroanatomy

Functional neuroanatomy has a long and fascinating history, dating back to the early days of the 19th century (1808)

At the time, it was believed that all of our complex behavioural functions existed in the heart

There is no inclination that the brains were the real MVPs

Phrenology

But then came along phrenologists and the concept of phrenology (1808)

Phrenology was based on the idea that different parts of the brain are responsible for different personality traits

And differential personality traits could be measured through assessing the shape of a person's skull

Phrenologists used a phrenometer to measure bumps on the skull, believing that each bump corresponded to a trait or ability, with larger bumps indicating greater capacity for those traits or abilities

E.g. Phrenologists claimed that a person with a prominent bump in the "combativeness" region would have a strong tendency to pick fights

No scientific evidence to support this claim

Cellular Dissociation

Additionally, the shape of the skull doesn't necessarily correspond to the shape of the brain inside

Further behaviour is complex interplay between multiple regions

Despite its flaws, phrenology represents an early attempt to understand the relationship between the brain and behaviour

Despite its flaws, phrenology represents an early attempt to understand the relationship between the brain and behaviour

Feeling for bumps on the outside to predict personality obviously wasn't very accurate

The concept of phrenology paved the way for what we know today about modern neuroscience and the mapping of the brain

The hypothesis gave rise to another stepping stone in modern neuroscience, cellular dissociation

Cellular dissociation (1867) - the process of separating cells from a tissue or an organ for study or experimentation

Late 1800s/early 1900s

Phrenology indirectly led to the concept that the brain may have different structures that could be mapped.

Recall: at this time period (19th century) the understanding of the brain and its cellular composition was still limited

When cellular dissociation techniques came along this was huge for neuroscience

Enabled us to see that like other organs in the body, the brain had cells.

Allowed us to further explore these cells

In 19th century scientists didn't know brain was composed of neurons let alone other cells

Quick flashforward

Cellular dissociation techniques have led to cell culture where scientists can isolate and grow neurons in a dish

Has many applications in neuroscience

Effect of toxins on neurons

Study electrical properties

Screen potential drug candidates for neurological disorders

techniques have revolutionized the field and have led to many important discoveries about brain structure and function

Golgi staining

During this time (i.e. late 1800s - early 1900s), scientists also developed ways to stain cells and visualize them under a microscope

Not a form of cellular dissociation

It was staining that enabled neurons to be discovered

Discovery attributed to Santiago Ramon y Cajal and Camillo Golgi

Occurred via "Golgi Staining Method"

Form of staining brain tissue

"Golgi Staining Method" - developed by Camillo Golgi in the late 19th century (1873)

A silver chromate solution that selectively stains a small percentage of neurons

Provides a clear view of neuron cell bodies, dendrites, and axons with clarity

Enabled the first comprehensive visualization of neuronal architecture

Reticular vs. Neuron Doctrine

However at the time, Golgi thought that the nervous system (brain) was a continuous network of interconnected tissue (not neurons)

This is because less powerful microscopes likely made nerve cells look like a mesh of single thread

Didn't think that they were individual cells with distinct cellular boundaries

Golgi thought nervous system was a continuous reticular or net-like structure of tissue

known as the reticular theory

Flashforward a decade when the scientist Ramon y Cajal came onto the scene (1887)

"father of modern neuroscience"

Used Golgi staining to study brain and nervous system tissue in greater detail and focus

Observed that the brain is composed of individual, discrete cells that transmit information through electrical and chemical signals

Lead to the Neuron Doctrine Theory

Neurons are the basic functional units of the nervous system that communicate through synapses, forming complex neural networks

Cytoarchitectonics

Both Golgi and Cajal paved ways for us to make significant discoveries about the structure and function of neurons

But what these two neuroscientists were also pioneers of was the field called cytoarchitectonics

Cytoarchitectonics is the study of the cellular organization/structure of the brain

Cytoarchitectonics allows examination of microscopic features of cells

Look at size, shape, arrangement, and distribution using staining techniques

In the brain we have come to realize that cells have different arrangements, shapes, and/or sizes in different areas (we now call structures)

Cells have different organizational patterns which make up structures

Structures correlate with function

Cytoarchitectonics has allowed us to discover that neurons and other types in different regions have different cellular structure and organization

Using staining techniques and examining the cytoarchitecture, we have come to realize that different brain regions exhibit distinct cytoarchitectonic patterns

Which we know now are often related to/have distinct functional properties

Has thus played a crucial role in brain mapping efforts

Brodmann

In the early 20th century (1905-1909), Brodmann meticulously mapped the human cortex using microscopic examinations of brain tissue

Stained the cerebral cortex and looked at the cellular structure (i.e. the cytoarchitecture)

Saw it was arranged differently (different areas had distinct cytoarchitectural patterns)

Labelled the structures

Led to identification of Brodmann areas (52 discrete areas; 44: human, 8: additional non-human)

In essence, Brodmann created a map of the brain, some of which is still used today

Further, for each of the areas Brodmann labelled he thought that each served a unique functional purpose

What we have learned is that different Brodmann areas are associated with various functions (functional localization), including sensory processing, motor control, language, memory, and emotion

Recall: Today the cerebral cortex is separated into different lobes

Each lobe of the brain has different structures responsible for different functions

Structures distinguished by cytoarchitecture (as determined by Brodmann)

Lobes contain different Brodmann area's and thus structures

Brodmann Areas and Function

Area 41/42 in the temporal lobe related to hearing/auditory perception

Areas 45 and 44 in the frontal lobe overlap with the Broca's area for language in humans

Situated in posterior superior temporal gyrus

Damage can result in difficulties with recognizing and discriminating between different sounds, including speech sounds

Damage results in Broca's aphasia - language disorder where people have difficulty producing words and forming grammatically correct sentences

Can still understand language (so area involved in speech production not comprehension)

Areas 17 and 18 in the occipital lobe related to vision

Primary visual area (known as primary visual cortex = area 17)

Damage can result in

Loss of vision despite no problems with eyes

Visual agnosia = condition in which an individual is unable to recognize familiar objects, faces, or places

Areas 1, 2 and 3 in the posterior gyrus of the parietal lobe = the somatosensory region

Process all bodily sensations, allows us to perceive temp, pain, touch, weight, etc.

Area 4 in the parietal gyrus of the frontal lobe = primary motor cortex.

Involved in controlling movement

Voluntary movement

E.g. pinching, grasping, etc.

Sends necessary motor commands to muscle to engage in action

Note area 6 - premotor cortex (planning and coordinating movement)

Let's say you are playing basketball

Brain needs to plan and coordinate and series of movements that involve your arms, hands, and legs

Brodmann area 6 (premotor cortex) responsible for organizing all these movements so they occur in the correct sequence and timing

The motor and sensory cortex

Mapped by Canadian Neurosurgeon Dr. Wilder Penfield (1950's)

Treated patients with severe epilepsy by destroying brain regions (nerve cells) where the seizures originated

Seizure often have a focal point of the brain (bursts of electrical activity)

Thus, wanted to destroy focal point

E.g. woman who smelled burnt toast (find area responsible = focal point --> get rid of it)

Penfield learned that if you stimulate the brain with electrical probes in conscious people you get different/particular responses depending on region you stimulate

What Penfield realized is when you stimulate different areas of the cortex you get different movements or sensations

For example if you take electrical probe and stimulate a brain area = might get someone smelling burnt toast

Different areas thus responsible for different movements/sensations

Eventually Penfield was able to stimulate enough people to map the areas of the cortex responsible for motor function and sensory perception of different body parts

He was able to map the motor and sensory cortex

Basically, he found that there is representation of the human body (homunculus-tiny person)

The "tiny human" refers to the concept of topographical organization in the motor and sensory cortex

Distorted

Topographical organization

neural spatial representation of the body in the motor or sensory cortex that correspond to different body parts

The motor cortex has a topographical map of the body

Different regions of the motor cortex control different body parts

Larger areas of the cortex are devoted to controlling body parts that require more precise movements

The sensory cortex also has a topographical map of the body

It enables us to "feel different sensations"

E.g. stimulate different intensities (hot, cold, pain)

Different regions of the sensory cortex process information from different body parts

Larger of the cortex are devoted to processing sensory information from body parts that are more sensitive or have more sensory receptors

P. Gage

So far we know that the 1800s and 1900s brought about some pretty huge stepping stones in functional neuroanatomy

E.g. phrenology --> cellular dissociation --> cytoarchitecture --> brain mapping by Brodmann (1900s) --> motor and sensory cortex (1950s)

But there was another major case study that allowed us to realize different parts of the brain do different things

On September 13th 1848, Gage was working as a railway construction foreman when an iron rod penetrated his left cheekbone and exited through the top of his head, damaging his frontal lobes

Specifically the prefrontal cortex

Despite the severity of the injury, Gage survived and was able to walk and talk soon after the accident

But Gage was a changed man

Before the accident, Gage was described as responsible and hardworking, but after the injury, his personality changed dramatically

He became impulsive, aggressive, and socially inappropriate, making difficult for him to keep a job and maintain relationships

Gage's case demonstrated that the frontal lobes (or front part of the brain as it was known at the time) plays a crucial role in regulating personality and behaviour

In addition to personality changes, Gage also experienced deficits in working memory, which is crucial for decision making and planning

Gage was unable to complete tasks that required planning and organization, suggesting that his working memory was impaired

Gage's case provided insight into the role of the frontal lobes in working memory and decision making

PFC and Working memory

Working memory is a type of short-term memory that helps us keep information in mind for a short period of time so we can use it for a task at time

Helps us to make decisions based on information presented

Analogy = reading menu at a restaurant

As you read the menu you hold previous options to compare and ultimately make a decision

Damage to working memory --> unable to hold multiple options leading to indecision and confusion

Experiments have shown that the PFC (particularly the dorsolateral PFC) is active during a time working memory is active

E.g. hungry monkey's shown food and then remembering where it was placed for small period = dorsolateral PFC active

Phineas Gage's case remains one of the most influential in neuroscience history, paving the way for future research on the role of the frontal lobes in behaviour and cognition

Subcortical structures and memory

Beneath the cortex lies subcortical structures

Involved in more basic functions such as movement, sensation, and emotion

Also involved in more complex behaviours as well

Similar to fascinating history of understanding the cortex, the study of subcortical regions also has come interesting history

One of the most important/famous cases that allowed us to understand a subcortical region in the brain is the case of Henry Gustav Molaison (1926-2008)

The case of H.M pivotal in understanding the role of the hippocampus in memory

Demonstrated the critical role of the hippocampus in the formation of new memories

Removal resulted in anterograde amnesia - inability to form new long term memories

Showed that memory is not a unitary system but rather is divided into different types (e.g. episodic vs. procedural memory)

Episodic memory

A conscious memory of a personal experience

E.g. remembering your first day of school or what you ate for dinner yesterday

Hippocampus initially encodes before sending to other areas, also retrieves from these areas.

Procedural memory

Memory for skills and habits

Involves unconscious retrieval and execution of learned behaviours (not consciously relieved)

E.g. riding a bike or typing on a keyboard

Cerebellum, motor cortex, basal ganglia

Mirror Drawing task

In this task, H.M. and control participants were asked to trace the outline of a star while looking at it in a mirror, which causes the hand movements to be reversed.

Over several trials H.M. and the control participants improved their performance and were able to accurately trace the star outline.

However, when H.M. was asked if he had ever done the task before, he did not remember doing it even though he showed improvement in performance.

This suggests that H.M.'s procedural memory was intact, as he was able to learn and improve on a task without consciously remembering doing it before

Recap: Hippocampus is a brain structure located in the medial temporal lobe that plays a critical role in episodic memory and long term memory storage

Spatial navigation is the ability to orient oneself and navigate through the environment

Also plays a role in spatial navigation

One of the most fascinating discoveries related to the hippocampus and spatial navigation is the existence of place cells

Place cells = neurons found in the hippocampus that fire selectively in specific locations in the environment

E.g. become active when an animal is in a specific location in its environment

Discovered in the 1970s by John O'Keefe and colleagues... but how?

Recorded electrical activity of neurons in hippocampus of rats as they moved around in an enclosed space

When recording electrical activity - found that certain neurons only fired when rat was in a particular location in the space

Place cells are now thought to be critical for spatial navigation and memory

They allow animals (and humans) to create a mental map of their environment and navigate through it

O'Keefe's work has greatly advanced our understanding of how the brain processes spatial information

Discovery was a pivotal moment in history of neuroscience

Greatly advanced our understanding of how the brain processes spatial information and has opened up new avenues for research and treatment of neurological disorders