Week 6: Neuroscience research methods- strengths and limitations

What are the aims of research methods in behavioural neuroscience?

• To understand how the brain produces behaviour

• Identify the functions that are required for performing a behaviour and determine what circuits of neurons are responsible for each of these functions

Name some methods and uses of neuroscience research methods

What does spatial resolution in imaging techniques refer to?

The ability to locate structures/activity in the brain ('where something happens').

What does temporal resolution in imaging techniques refer to?

The ability to detect changes in brain activity over a given time period ('when something happens').

What significant event happened to Phineas Gage? (1848)

An iron rod was driven through his head, destroying much of his left frontal lobe.

• Despite the traumatic brain injury, it didn't affect his cognitive functioning - yet he experienced a personality change

Outline the case of 'Tan' (1861)

• Louis Victor Leborgne could understand language but only utter the syllable 'tan'

• French surgeon Paul Broca connected the clinical symptoms (loss of speech) to specific anatomical damage (left frontal lobe) → Broca’s area

What has been suggested about the behavioural effects of brain damage?

If removing structure X changes behaviour Y, then structure X contributes to behaviour X

What do lesion studies tend to involve?

• Naturally occurring lesions (human research participants e.g. Phineas Cage)or induced lesions (animal studies)

• Experimental ablation: The oldest method used in neuroscience, still in common use in animal studies.

• Brain tissue is deliberately destroyed, removed or inactivated and alterations in behaviour observed.

What is experimental ablation?

A method in neuroscience where brain tissue is deliberately destroyed or removed to observe changes in behavior.

Which 4 ways are lesions created?

1. Surgical lesions

2. Radiofrequency (RF) lesions

3. Excitotoxic lesions

4. Temporary inactivation

What are radiofrequency (RF) lesions?

Lesions created by passing electrical current through tissue to destroy it.

→ can damage both neurons and passing axons

What are excitotoxic lesions?

More precise lesions compared to RF lesions

What is temporary inactivation?

GABA receptors

Reversible effects

What are 2 historical methods to visualise lesions?

1. Histological staining

2. Immunocytochemical methods

What is histology?

The study of cells and tissues at the microscopic level.

What is histological staining?

Interactions between charged dyes and cells to visualise cell and tissue structure - not specific proteins/molecules

What is the purpose of immunocytochemical methods?

To visualise specific molecules, neurotransmitters, or receptors in the brain.

What is meant by tracing neural connections?

Injecting tracers into specific brain regions

What is the difference between anterograde and retrograde labelling within tracing neural connections?

Anterograde labeling traces efferent neurons from cell body to axon terminals, while retrograde labeling traces afferent neurons from axon terminals to cell body.

How does tract tracing work?

• Use a stereotaxic apparatus to target a specific brain region

• They would be injected into a living brain, transported along the axons,

• Animal is euthanised

• Tissue is sectioned & histological staining reveals the labelled pathways.

What is Diffusion Tensor Imaging (DTI)?

A non-invasive imaging method used to visualize brain structure and connectivity.

Name some strengths and limitations of lesion studies

STRENGTHS

• moderate to high spatial resolution

CONS

• other structures might be damaged

• poor temporal resolution

• does not account for compensation

Name some strengths and limitations of tract tracing

STRENGTHS

• high/very high spatial resolution

CONS

• poor temporal resolution

• invasive, not used in humans

Name some strengths and limitations of Diffusion Tensor Imaging (DTI)

STRENGTHS

• non-invasive, can be used in humans

CONS

• moderate resolution

• cannot show individual axons/connections

What are neuroimaging studies?

The use of methods to visualise the structure and function of the brain

What do structural brain scans tell us?

They tell us what the brain looks like and allows locating an area that has been affected by a condition like a stroke or a lesion

What do functional brain scans tell us?

They tell us which part of the brain is actively doing something (i.e. which area of the brain activates under particular conditions).

What does a Computerised Tomography (CT) scan do?

Uses X-ray measurements to generate horizontal images of the brain, revealing structural abnormalities.

• contrast dye helps differentiate between normal and abnormal structures

What are the pros and cons of CT scans?

PROS

• good spatial resolution

• widely available, fast

• cheap

CONS

• radiation exposure

• poor temporal resolution; cannot track brain activity in real time

What is the function of Magnetic Resonance Imaging (MRI) and what does it measure?

• To create detailed images of the brain using strong magnetic fields.

• Changes in brain activity by detecting blood flow variations.

How do MRI’s work?

What are the pros and cons of MRIs?

PROS

• good spatial resolution

• relatively accessible

• non-invasive

CONS

• poor temporal resolution

• expensive

• noisy

• participant lies perfectly still

• cannot be used with metal implants

What did the Maguire et al (2000) study show?

Found that London taxi drivers had more grey matter in the hippocampus compared to non-taxi drivers

How do functional magnetic resonance (fMRI) work? What do they show?

Works: When neurons are active, they use oxygen, blood flow increases fMRI measures changes in blood flow

Shows: visualisation of brain activity associated with performing a cognitive task and/or behaviour

What are the pros and cons of fMRIs?

PROS

• good spatial resolution

• non-invasive

• relatively accessible

CONS

• poor to moderate temporal resolution (seconds)

• loud environment

How do Electroencephalograms (EEGs) work?

• When many neurons fire together they produce tiny electrical fields; EEG records this electrical activity.

• During an EEG procedure, small disc-type electrodes are placed on the scalp surface.

• Electrodes pick up brain’s electrical signals and send them to electroencephalogram.

• EEG records neuronal impulses as wavy lines (brain waves) onto a computer screen.

Outline the differences in EEG rhythms

• Frequency band - how fast the waves are

• Morphology - shape

• Topography - where on scalp

• Amplitude - how tall the waves are

• Reactivity - response to simulation

• Symmetry

What are some applications of EEGs?

• Used in clinical settings to diagnose conditions such as epilepsy or sleeping disorders

• EEG-based research on functional networks in cognitive and effective processing

What are some pros and cons of EEGs?

PROS

• excellent temporal resolution (milliseconds)

• tolerant of subject movement

• non-invasive/salient

CONS

• low spatial resolution compared to fMRI

• analysis of acquired data can be very complex

• poorly measures neural activity that occurs below the upper layers of the brain (cortex)

What is Transcranial Magnetic Stimulation (TMS)? Outline the steps involved

A method that uses magnetic pulses to influence neuronal activity in the brain.

• A TMS machine sends a strong electric current to a coil.

• This gives rise to a fluctuating magnetic pulse which goes through the skull into the brain.

• The pulses trigger electrical charges changing the activity of nearby neurons.

How is TMS used to treat aphasia? (Fernandez-Romero, 2025) - excitatory TMS

-TMS over left dorsolateral cortex in people with progressive aphasia

-TMS Vs controls

-Slower decline in brain metabolism and improvements in language with active TMS

Reconnect trial

How is TMS used for motor perception? (Walsh and Cowey, 2000) - inhibitory

-TMS over MT/V5 area in visual cortex

- “If MT/V5 is active and necessary for motion perception then disrupting it with TMS during motion viewing should impair motion perception”

-Hypothesis confirmed- Region functionally necessary

What are the pros and cons of TMS?

PROS

• good temporal resolution (milliseconds)

• can be combined with other methods to record response to simulation

• non-invasive

CONS

• stimulates superficial cortical areas - cannot reach deep structures

• moderation spatial resolution - compared to fMRI

• interindividual variability due to anatomy/neurotransmitter levels

How does Positron Emission Tomography (PET) work?

• Radiotracer is injected into blood stream

• Crosses blood brain barriers

• Binds to specific receptors

• PET scanner detects positron emissions

• Signal reflects binding potential (BP)

What do PET scans show?

Metabolic and neurotransmitter activity

What are the pros and cons of PET scans?

PROS

• can measure specific molecules or neurotransmitter systems, e.g. dopamine uptake

• silent

• great diagnostic value

CONS

• comparatively poor spatial and temporal resolution (minutes) compared t0fMRI

• invasive - required use of radioactive tracers

Name 3 future directions in neuroimaging

1. Use of AI

2. Human Connectome Project

3. UK Biobank Imaging Study

How can AI be used as a future direction of neuroimaging?

• AI allows to:

enhance image resolution;

reconstruct 3D brain images from MRI, CT or PET scans,

identify and labels brain structures

predict disease progression

What is the Human Connectome Project?

Aims to connect brain structure, function, and behaviour, providing open-access data to study brain connectivity.

What is the UK Biobank Imaging Study?

A study using MRI/fMRI/DTI to understand risk factors for conditions like dementia and depression.

What is the significance of the Reconnect trial in TMS research?

It showed that TMS over the left dorsolateral cortex can slow decline in brain metabolism and improve language in people with progressive aphasia.

What does the term 'resolution' refer to in neuroimaging?

The clarity and detail of the images produced by imaging techniques.

What is the role of contrast dye in CT scans?

To help differentiate between normal and abnormal brain structures.

What are the applications of EEG in clinical settings?

To diagnose conditions such as epilepsy or sleep disorders.

What is the significance of the frequency band in EEG?

It indicates how fast the brain waves are oscillating.

What does the term 'morphology' refer to in EEG analysis?

The shape of the brain waves recorded.