Measuring brain activity - week 6

MBB1

Background to brain “imaging”

• Brain imaging assess brain structure and function “non-invasively” without dissection or damage to the brain.

• Neuropsychological methods link function to brain damage but with no control of lesion size or location in the brain. So it is difficult to identify similar patients and replicate findings – “experiments of nature”

Electroencephalography (EEG)

• EEG refers to both electroencephalography (the equipment/ method) and electroencephalogram (the data output – “writings of electricity from the head”)

• 1924 - first human EEG

  • Hans Berger

• 1934 - first demonstration of epileptiform spikes with EEG

  • Fisher & Lowenback

• Now one of the main diagnostic tests for epilepsy

EEG - Strengths

• good temporal resolution (can discriminate very brief events in time).

• Relatively cheap ($10,000-$100,000 per system). Many psychology departments owning multiple EEG systems

• Portable and possible to record EEG while people are moving around (important in the detection of epileptic seizures that can require people to wear an EEG cap for many days).

• Safe and well tolerated by participants - no real risks associated with placing recording electrodes on a person, beyond mild discomfort.

EEG - Limitations

• Poor spatial resolution. With more electrodes the spatial resolution can be improved, but it still difficult to determine precisely from which area of the underlying brain the signal has come.

• Typically only detects activity on the surface of the cortex. It is very hard to detect activity from more central regions within the brain, as the electrodes are attached to the outside of the scull

Electrophysiology – Single Neurons

• Hodgkin & Huxley recorded action potentials (electrical signals) in the giant axon of Atlantic squid in 1952 (won Nobel prize in 1963)

• A subsequent explosion of research in the following decades was based on technical advancements

  • Development of microelectrodes

  • “multi-unit” recording electrodes

• Much of the sensory and motor cortex was mapped using these methods in animal studies

• Hubel & Wiesel mapped the development and functional organisation of the visual system (won Nobel prize in 1981)

Electrophysiology – Single Neurons - Strengths

• Records directly from individual neurons so is the best method to use if you want to know what the neurons are doing

Electrophysiology – Single Neurons - Limitations

• High risks of infection as this technique is “invasive” penetrating the brain.

• It is only possible to record from a few (up to ~ 100 neurons at a time with multielectrode arrays), so can only record individual neurons or small network activity.

Magnetic Resonance Imaging (MRI)

• MRI exploits the magnetic properties of brain tissue.

• MRI coil generates a VERY strong magnetic field (The earth’s magnetic field is about 1/1000 tesla, whereas the field created by an MRI scanner is between 1.5 and 7 tesla)

MRI- Structural Imaging

• Magnetic field passes through the person’s head causing hydrogen atoms to align with the magnetic field.

• Radio frequency waves temporarily disrupt this alignment causing a signal that can be detected by this machine.

• Because different areas of brain tissue contain different amounts of water (H2O), they emit different signals.

• Analysis software converts detected signals into very detailed images of different structures in the brain

• Diffusion Tensor Imaging (DTI) – uses the same MRI equipment to detect the large axon tracts (“white matter”) that flow through the brain and connect different regions of cortex.

fMRI- Functional Imaging

• Cognitive processes use energy

  • The production of energy uses oxygen from hemoglobin (blood)

• Oxygenated blood

  • Doesn’t distort surrounding magnetic field

• Deoxygenated blood

  • Distorts surrounding magnetic field

  • = blood vessels became more visible as blood oxygen decreased

• Blood-oxygen-level-dependent (BOLD) signal tracks the ratio of oxygenated vs deoxygenated blood

• BOLD dominates fMRI studies that map human brain function

• As the brain region uses energy there is an increase in blood flow to the region.

• Because fMRI images reflect the change in oxygen levels in the blood (not the neurons directly) there is a delay of a few seconds between time of neural activity and change in blood oxygen levels.

MRI - Strengths

• Very high spatial resolution, identifying exactly where in the brain different structures are or different function is occurring.

• MRI is also a very valuable tool because it can identify specific anatomical/Structural and functional properties of different brain regions.

MRI - Limitations

• MRI machines are very expensive and can cost ~$1million for the latest equipment.

• The equipment is also very large equipment and requires a specialist facility with multiple rooms to enable staff to work and the machine to be kept within a magnetically shielded room.

• Some safety risks associated with the large magnet, so it is important to ensure that no metal enters the MRI room.

• Requires specialist staff with radiography training (due to the cost and safety concerns).

Positron Emissions Tomography (PET)

• Uses radioactive substances knowns as tracers to visualise glucose metabolism or the neurotransmitter/ receptor function

• Can also use radioactive tracers to bind selectively to proteins of interest.

• PET is currently used as a diagnostic tool for Alzheimer’s Disease (detecting buildup of Amaloid protein)

Positron Emissions Tomography (PET) - strengths

• Can detect different chemicals in the brain associated with either the metabolism (energy consumption), or specific neurotransmitter levels or receptors.

Positron Emissions Tomography (PET) - Limitations

• Expensive and requires specialist facilities and staff

• Relatively low spatial resolution compared to MRI

• The signal requires radioactive tracers to be injected into a participant’s blood (it is considered very safe, but it is important that the risks are managed with the appropriate safety precautions).

Brain Modification - Introduction

• Using different methods brain regions can be permanently removed/destroyed or the brain activity can be temporarily decreased.

• Brain areas can also be stimulated to enhance or increase brain activity in that region.

Brain Modification - Introduction - Medical Treatment

• Many psychiatric and neurological conditions are associated with abnormal brain functions. Treatment of these disorders will often target the abnormal brain processes involved.

• In some cases, such as epilepsy or brain tumour, treatment might involve removal of sections of abnormal brain tissue.

• Drugs can also be used to selectively target abnormal function of specific neurotransmitter systems

Brain Modification - Introduction - Enhancement

• Refers to the improvement of healthy function to above or better than normal. In contrast to medical use, which aims to improve impairments to achieve healthy function.

• There is increasing claims around the use of both brain stimulation and drugs to improve brain function beyond typical normal levels.

• This is an area that has attracted a lot of attention from neuroethicists.

Brain Modification - Introduction - Scientific Research

• Brain modulation techniques offer powerful tools for research.

• Unlike brain imaging techniques like fMRI which provide correlational information, brain modulation provides information about causation and whether a given brain region is necessary for a particular task.

• In the past, naturally occurring brain damage has provided information about the role of different brain areas (i.e. Broca’s area in language production). New techniques to modify specific brain regions or process in living people, make it possible to test hypotheses and directly examine the links to behaviour.

Ablation Studies

• The term ablation = “to carry away”

• Deliberate lesions allow a relatively high degree of precision

• e.g the limbic system contains a number of small structures including the hippocampus and amygdala

  • Ablations in monkeys show only that the hippocampus plays a role in learning and memory

• For research purposes this was limited to animal studies. Human ablation was used for medical treatment.

Surgical ablation

• Portugese physician Egas Moniz introduced the prefrontal leucotomy for the relief of psychiatric disorders

• This worked linked personality to the frontal lobes

• Based on reports that removing the frontal lobes of a chimpanzee made it calmer and more cooperative

• While results for patients were not always positive, clinician’s at the time considered the procedure successful

• Moniz awarded Nobel Prize for this discovery

Frontal Leucotomy

• Clinically two methods for frontal Leucotomy (note these are disturbing and no longer performed!)

• A leucotome was inserted into one of several holes drilled in the skull. The wire was then extruded from the tip and the leucotome rotated to remove a core of tissue.

• Alternatively, a cutting implement was inserted above the eyelid, pushed through the base of the skull (which is very thin and brittle just above the eyes), and rocked from side to side to slice through the frontal lobes, thus separating them from the rest of the brain.

• Initial impression of improvements

  • Led to its widespread use

  • Subsequently shown to be ineffective

• Profound personality consequences

  • Apathy

  • Emotional unresponsiveness

  • Disinhibition

  • Inability to plan

• Popularised by Walter Freeman in the 40’s and 50’s

  • 40,000 operations in the USA

Electrical brain stimulation

• Electrical stimulation has also been used to reveal precise localisation of cortical function

• In 1870, Fritsch & Hitzig (Germany) electrically stimulated part of the frontal cortex in dogs; induced contractions of specific muscles on the opposite side of the body

Non-invasive electrical brain stimulation - ECT

• Electroconvulsive Therapy (ECT) invented in Italy in the 1930s

• It was already known that seizures reduced psychiatric symptoms

• As early as the 1500s, seizure inducing agents were used to treat psychiatric conditions

• ECT originally used to treat a range of mental illnesses

  • Now used to treat severe depression

• Mechanism of action is unknown

  • electrical stimulation of the frontal lobes needs to be strong enough to cause a seizure

Non-invasive electrical brain stimulation - tDCS

• A range of non-invasive methods for electrical brain stimulation now exist, however the efficacy and safety remains debated.

• The most common method is transcranial direct current stimulation (tDCS)

Non-invasive magnetic brain stimulation - TMS

• In Transcranial Magnetic stimulation (TMS), a coil carrying an electrical current generates a brief, focal magnetic pulse which activates a small region of cortex (approximately 10 – 15 mm) underlying the coil.

• The activation acts like a ‘virtual lesion’, temporarily disrupting the tissue for a few hundred milliseconds. The technique is painless (unless it triggers muscle contraction)

Pharmacology / Drugs

• Drugs can impact every stage of neurotransmitter function from synthesis to release to receptor binding