SAMENVATTING
NEUROSCIENTIFIC ASPECTS
Neural networks and reorganisation
Gitte Van Cleemput
, Gitte Van Cleemput
SAMENVATTING NEUROSCIENTIFIC ASPECTS
NEUROSCIENTIFIC METHODS
GOALS
- Deficits of neural recruitment underlying common neurological conditions;
- Insight into the compensatory neural networks in relation to acute and chronic disease evolution;
- Insight into the neural basis of motor learning, control and concepts of rehabilitation as applied to
hemiplegia and Parkinson’s disease
- Evidence on non-invasive neurostimulation as potential rehab tool
- Interpreting recent and relevant literature on neural networks
- Translate knowledge to the neurorehabilitation field;
- Critical and scientific attitude to concepts of neurorehabilitation.
INTRODUCTION
- Measuring ‘brain activity’ at the systems level (not single-cell)
- Non-invasive (not ‘inside’ the brain, but at the level of the scull)
- Fundamental research
o Motor control, motor learning
o Cognition
o Memory
o ...
- Clinical research
o Neural processes underlying ageing
o Neural basis of diseases (stroke, Parkinson, eplipsy, neurodevelopmental disorders..)
o Neural evaluation of disease progression
o Neural evaluation of interventions/ treatments
o …
OVERVIEW OF METHODS
- Magnetic Resonance Imaging (MRI)
- Diffusion Tensor Imaging (DTI)
- Functional Near-infrared Spectroscopy (FNIRS)
- Electro-EncephaloGraphy (EEG)
- Transcranial Magnetic Stimulation (TMS)
=> Equipment
=> Neurophysiological basis
=> Examples of Applications
2
, Gitte Van Cleemput
SAMENVATTING NEUROSCIENTIFIC ASPECTS
MAGNETIC RESONANCE IMAGING – MRI
WHAT ISN’T FMRI
fMRI is not bumpology
- Claims that bumps on the skull reflected exaggerated
functions/traits
- It lacked any mechanism underlying its claims.
- It used anecdotal, rather than scientific, evidence.
- Nevertheless, its central idea persisted:
o Localization of Function
fMRI is not mind-reading
fMRI is not invasive
- Positron Emission Tomography (PET)
- Intracranial Stimulation/Recording
- With fMRI nothing is injected!
WHAT IS (F)MRI
3 different modalities
- MRI = brain anatomy
- Functional MRI – fMRI = brain activity
- fc MRI = functional connectivity
3
, Gitte Van Cleemput
SAMENVATTING NEUROSCIENTIFIC ASPECTS
BIOLOGICAL BASIS OF MRI
- Measures brain anatomy
- Former name: (Nuclear) Magnetic Resonance Imaging
- Nothing to do with ‘radioactivity’, but with the magnetic properties of protons, in the nuclei of atoms
- Protons :
o have a mass
o are positive (+)
o have a spin (they turn around)
→ because they turn around, they have a small, but measurable magnetic field
- Protons are mostly found in water and fat tissue
- In a single molecule of water, H2O there are 10 protons (1 from each hydrogen and 8 from oxygen)
o E.g. a water cube of 2 x 2 x 5 mm contains
▪ 6 * 1015 protons
▪ 6.000.000.000.000.000
- In everyday life, the protons in our body are in balance, randomly oriented, but in balance
o Not one specific direction per proton
- Inside the MRI scanner, which is one giant magnet, the protons align to the magnetic field (B0). Either
in parallel (same direction) or anti-parallel (opposite direction)
o Some in parallel or anti-parallel
- The majority of atoms aligns in parallel, allowing to define the NET magnetisation of the protons in the
direction of B0
- Now, this is what happens if you are positioned in the scanner. And this magnetic field is ALWAYS on.
Proton is in ‘excitation state’
Emission of a radio frequency pulse by the head coil, induces a flip of the NET
magnetisation (instead of aligning to the Z-axis, the protons now align in the X-Y field)
4
, Gitte Van Cleemput
SAMENVATTING NEUROSCIENTIFIC ASPECTS
However, protons don’t like being in this ‘high-energy’ excitation
state’, and from the moment the radio frequency pulse is turned off,
it will ‘relax’ to its initial position (i.e., align back to the z-axis of the
B0 field).
During this ‘relaxation state’, the protons emit radio frequency
themselves, and this signal is measured.
→ Proton emits radio frequency during ‘relaxation state’
(the head coil, both emits and measures radio frequencies)
T1-relaxation
The time it takes for a proton to relax to 63% of it’s initial state
(along the z-axis) is called T1
KEY PART: the velocity from the proton aligning back to its
initial position is different for different types of tissue
- Not all
tissues ‘relax’ the same way!
- Protons in fat (e.g. white matter), relax way faster,
than protons in liquid (e.g., cerebrospinal fluid)
- By measuring the relaxation in different tissues,
contrasts can be visualized!
- In so-called ‘T1-weighted’ images, liquid is dark (less energy emitted), and fat is
bright (more energy emitted)
Coronal slice Transverse slice Sagittal slice
MRI – EXAMPLE OF APPLICATION
Clinical: Localization of brain lesions
- Pre-surgical mapping (e.g. epilepsy)
- Prediction of disease progression
Long term motor function after neonatal stroke: Lesion localization above all
- Prediction of disease progression – example of CP
- Children tested at age 7
- Some developed CP others didn’t
- Lesions are more wide-spread in CP group, compared to group
without CP symptoms
With CP Without CP
5
, Gitte Van Cleemput
SAMENVATTING NEUROSCIENTIFIC ASPECTS
FUNCTIONAL MRI – FMRI
Functional Magnetic Resonance Imaging (fMRI): uses MRI to indirectly measure brain activity
- Based on the assumption that neuronal activity requires O2 which is carried by the blood;
- increased blood flow and resulting hemodynamics are foundation to fMRI
- The idea underpinning the technique – ‘localizing brain activity by measuring changes in blood flow’ -
is not new.
- The following description of an experiment performed by the Italian scientist Angelo Mosso can be
found in William James’ The Principles of Psychology, published in 1890:
o "The subject to be observed lay on a delicately balanced table which could tip downwards
either at the head or the foot if the weight of either end were increased. The moment
emotional or intellectual activity began in the subject, down went the balance at the head-
end, in consequence of the redistribution of blood in his system…"
- The reported success of this early experiment can only have been wishful thinking on the investigators
behalf. But the suggestion that blood flow is coupled to neural activity was insightful.
BIOLOGICAL BASIS FOR FMRI
- Same principle as MRI: contrasts in brain images based on measurement of magnetic relaxation
- Here however, it is not about protons, but about hemoglobin in the blood...
o Brain region active => increased O2 metabolism => increased blood flow
o fMRI measures the Blood Oxygen Level Dependent (BOLD) signal
BLOOD OXYGEN LEVEL DEPENDENT (BOLD) SIGNAL
- Oxyhemoglobin
o => diamagnetic (same as tissue)
- Deoxyhemoglobin
o => Paramagnetic (weak magneti)
o interacts with the magnetic signal of the MRI scanner
6
, Gitte Van Cleemput
SAMENVATTING NEUROSCIENTIFIC ASPECTS
1 voxel (“3D-pixel”) in visual cortex (size of up to 1x1x1mm =>
high spatial resolution!)
=> increase hemodynamic response
FMRI DESIGN
- fMRI always measures a change in BOLD response
o => you always need a baseline condition
- Most simple design: Block design
o Experimental condition: stimulus on
o Baseline condition: stimulus off
Conclusion: this region shows more brain activity during visual stimulation, than during baseline. … and that
makes sense because this is the visual cortex
- No results in the upper two parts (frontal cortex)
7
, Gitte Van Cleemput
SAMENVATTING NEUROSCIENTIFIC ASPECTS
FMRI EXAMPLE STUDY
Underconnectivity of the superior temporal sulcus predicts emotion recognition deficits in autism
BACKGROUND
Action perception network in the brain – Mirror System
- First discovered in Monkeys
- Parts of motor system activate during movement observation = “Mirror Neurons’
- Action perception
- Parts of motor system activate = MIRROR SYSTEM
Mirror System Functions
- Action recognition
- Action understanding
- Action imitation
- Empathy
- => link with Autism
o Difficulties with interpreting other’s behaviour/actions
o Difficulties with action imitation
RESEARCH QUESTION
Do people with autism activate regions of the mirror system to a lesser extent than control participants, when
they observe biological motions?
Block design
- Baseline: Black screen, with white cross
- Experimental condition: Biological Motion
8
NEUROSCIENTIFIC ASPECTS
Neural networks and reorganisation
Gitte Van Cleemput
, Gitte Van Cleemput
SAMENVATTING NEUROSCIENTIFIC ASPECTS
NEUROSCIENTIFIC METHODS
GOALS
- Deficits of neural recruitment underlying common neurological conditions;
- Insight into the compensatory neural networks in relation to acute and chronic disease evolution;
- Insight into the neural basis of motor learning, control and concepts of rehabilitation as applied to
hemiplegia and Parkinson’s disease
- Evidence on non-invasive neurostimulation as potential rehab tool
- Interpreting recent and relevant literature on neural networks
- Translate knowledge to the neurorehabilitation field;
- Critical and scientific attitude to concepts of neurorehabilitation.
INTRODUCTION
- Measuring ‘brain activity’ at the systems level (not single-cell)
- Non-invasive (not ‘inside’ the brain, but at the level of the scull)
- Fundamental research
o Motor control, motor learning
o Cognition
o Memory
o ...
- Clinical research
o Neural processes underlying ageing
o Neural basis of diseases (stroke, Parkinson, eplipsy, neurodevelopmental disorders..)
o Neural evaluation of disease progression
o Neural evaluation of interventions/ treatments
o …
OVERVIEW OF METHODS
- Magnetic Resonance Imaging (MRI)
- Diffusion Tensor Imaging (DTI)
- Functional Near-infrared Spectroscopy (FNIRS)
- Electro-EncephaloGraphy (EEG)
- Transcranial Magnetic Stimulation (TMS)
=> Equipment
=> Neurophysiological basis
=> Examples of Applications
2
, Gitte Van Cleemput
SAMENVATTING NEUROSCIENTIFIC ASPECTS
MAGNETIC RESONANCE IMAGING – MRI
WHAT ISN’T FMRI
fMRI is not bumpology
- Claims that bumps on the skull reflected exaggerated
functions/traits
- It lacked any mechanism underlying its claims.
- It used anecdotal, rather than scientific, evidence.
- Nevertheless, its central idea persisted:
o Localization of Function
fMRI is not mind-reading
fMRI is not invasive
- Positron Emission Tomography (PET)
- Intracranial Stimulation/Recording
- With fMRI nothing is injected!
WHAT IS (F)MRI
3 different modalities
- MRI = brain anatomy
- Functional MRI – fMRI = brain activity
- fc MRI = functional connectivity
3
, Gitte Van Cleemput
SAMENVATTING NEUROSCIENTIFIC ASPECTS
BIOLOGICAL BASIS OF MRI
- Measures brain anatomy
- Former name: (Nuclear) Magnetic Resonance Imaging
- Nothing to do with ‘radioactivity’, but with the magnetic properties of protons, in the nuclei of atoms
- Protons :
o have a mass
o are positive (+)
o have a spin (they turn around)
→ because they turn around, they have a small, but measurable magnetic field
- Protons are mostly found in water and fat tissue
- In a single molecule of water, H2O there are 10 protons (1 from each hydrogen and 8 from oxygen)
o E.g. a water cube of 2 x 2 x 5 mm contains
▪ 6 * 1015 protons
▪ 6.000.000.000.000.000
- In everyday life, the protons in our body are in balance, randomly oriented, but in balance
o Not one specific direction per proton
- Inside the MRI scanner, which is one giant magnet, the protons align to the magnetic field (B0). Either
in parallel (same direction) or anti-parallel (opposite direction)
o Some in parallel or anti-parallel
- The majority of atoms aligns in parallel, allowing to define the NET magnetisation of the protons in the
direction of B0
- Now, this is what happens if you are positioned in the scanner. And this magnetic field is ALWAYS on.
Proton is in ‘excitation state’
Emission of a radio frequency pulse by the head coil, induces a flip of the NET
magnetisation (instead of aligning to the Z-axis, the protons now align in the X-Y field)
4
, Gitte Van Cleemput
SAMENVATTING NEUROSCIENTIFIC ASPECTS
However, protons don’t like being in this ‘high-energy’ excitation
state’, and from the moment the radio frequency pulse is turned off,
it will ‘relax’ to its initial position (i.e., align back to the z-axis of the
B0 field).
During this ‘relaxation state’, the protons emit radio frequency
themselves, and this signal is measured.
→ Proton emits radio frequency during ‘relaxation state’
(the head coil, both emits and measures radio frequencies)
T1-relaxation
The time it takes for a proton to relax to 63% of it’s initial state
(along the z-axis) is called T1
KEY PART: the velocity from the proton aligning back to its
initial position is different for different types of tissue
- Not all
tissues ‘relax’ the same way!
- Protons in fat (e.g. white matter), relax way faster,
than protons in liquid (e.g., cerebrospinal fluid)
- By measuring the relaxation in different tissues,
contrasts can be visualized!
- In so-called ‘T1-weighted’ images, liquid is dark (less energy emitted), and fat is
bright (more energy emitted)
Coronal slice Transverse slice Sagittal slice
MRI – EXAMPLE OF APPLICATION
Clinical: Localization of brain lesions
- Pre-surgical mapping (e.g. epilepsy)
- Prediction of disease progression
Long term motor function after neonatal stroke: Lesion localization above all
- Prediction of disease progression – example of CP
- Children tested at age 7
- Some developed CP others didn’t
- Lesions are more wide-spread in CP group, compared to group
without CP symptoms
With CP Without CP
5
, Gitte Van Cleemput
SAMENVATTING NEUROSCIENTIFIC ASPECTS
FUNCTIONAL MRI – FMRI
Functional Magnetic Resonance Imaging (fMRI): uses MRI to indirectly measure brain activity
- Based on the assumption that neuronal activity requires O2 which is carried by the blood;
- increased blood flow and resulting hemodynamics are foundation to fMRI
- The idea underpinning the technique – ‘localizing brain activity by measuring changes in blood flow’ -
is not new.
- The following description of an experiment performed by the Italian scientist Angelo Mosso can be
found in William James’ The Principles of Psychology, published in 1890:
o "The subject to be observed lay on a delicately balanced table which could tip downwards
either at the head or the foot if the weight of either end were increased. The moment
emotional or intellectual activity began in the subject, down went the balance at the head-
end, in consequence of the redistribution of blood in his system…"
- The reported success of this early experiment can only have been wishful thinking on the investigators
behalf. But the suggestion that blood flow is coupled to neural activity was insightful.
BIOLOGICAL BASIS FOR FMRI
- Same principle as MRI: contrasts in brain images based on measurement of magnetic relaxation
- Here however, it is not about protons, but about hemoglobin in the blood...
o Brain region active => increased O2 metabolism => increased blood flow
o fMRI measures the Blood Oxygen Level Dependent (BOLD) signal
BLOOD OXYGEN LEVEL DEPENDENT (BOLD) SIGNAL
- Oxyhemoglobin
o => diamagnetic (same as tissue)
- Deoxyhemoglobin
o => Paramagnetic (weak magneti)
o interacts with the magnetic signal of the MRI scanner
6
, Gitte Van Cleemput
SAMENVATTING NEUROSCIENTIFIC ASPECTS
1 voxel (“3D-pixel”) in visual cortex (size of up to 1x1x1mm =>
high spatial resolution!)
=> increase hemodynamic response
FMRI DESIGN
- fMRI always measures a change in BOLD response
o => you always need a baseline condition
- Most simple design: Block design
o Experimental condition: stimulus on
o Baseline condition: stimulus off
Conclusion: this region shows more brain activity during visual stimulation, than during baseline. … and that
makes sense because this is the visual cortex
- No results in the upper two parts (frontal cortex)
7
, Gitte Van Cleemput
SAMENVATTING NEUROSCIENTIFIC ASPECTS
FMRI EXAMPLE STUDY
Underconnectivity of the superior temporal sulcus predicts emotion recognition deficits in autism
BACKGROUND
Action perception network in the brain – Mirror System
- First discovered in Monkeys
- Parts of motor system activate during movement observation = “Mirror Neurons’
- Action perception
- Parts of motor system activate = MIRROR SYSTEM
Mirror System Functions
- Action recognition
- Action understanding
- Action imitation
- Empathy
- => link with Autism
o Difficulties with interpreting other’s behaviour/actions
o Difficulties with action imitation
RESEARCH QUESTION
Do people with autism activate regions of the mirror system to a lesser extent than control participants, when
they observe biological motions?
Block design
- Baseline: Black screen, with white cross
- Experimental condition: Biological Motion
8
