Summary slides - Cognitive Neuropsychology:
Lecture 1: Introduction
Cognitive Neuropsychology – definition:
- The study of the relation between structure and function of the brain and specific cognitive functions
(e.g. language, memory, attention, …)
o by investigating these cognitive processes in normal healthy people
o by investigating the breakdown of these processes in brain-damaged individuals (as a result
of acquired brain damage or as a result of a developmental disorder)
Brain enthusiasm:
- Brain scans as evidence in court of law
- Brain scans might be overinterpreted by laypersons
- Good progress for several neurological syndromes, but less progress for psychiatric and mental
syndromes.
o Differences found for psychiatric and mental syndromes on a group level but difficult on an
induvial level.
Basis of neural signals:
- Neurons, with cell bodies in grey matter of cerebral
cortex and subcortical structures; white matter contains
axons.
- Without input (at rest), cell membrane of a neuron has
an electrical potential difference between in- and
outside of -70 mV
- Post-synaptic potential is determined by integrating
input of many synapses at the dendrites. It can hyper-
and depolarize.
- Neural communication:
o Input neurons (through neurotransmitters): action potentials over time
→ Membrane potential of post-synaptic neuron depolarizes or hyperpolarizes
o Over time, membrane potential of post-synaptic neuron changes in function of input it
receives = signal
Signal description:
- Simplest signal = sinusoidal oscillation
- Frequency: rate of change of signal, e.g. in the time dimension
o 1 Hz = completing a full cycle (going up & down) in one
second
o Biological signals never contain just one frequency
- Complex signals can be decomposed into frequency components
o Each has a particular frequency (e.g., 1 Hz, 2 Hz, 3 Hz, …)
o Amplitude: how much it goes up and down
o Phase: when it goes up and down
- Frequency spectrum: measured range of frequencies
o Highest frequency
▪ Limited by sampling frequency
▪ ½ * sampling frequency (Nyquist sampling theorem)
o Lowest frequency
1
, ▪ Limited by how long the signal is measured
▪ 1 / number of seconds measured
- Filtering: attenuating or excluding certain part of measured frequency spectrum (low-pass, high-pass
or band-pass)
- Spectrogram: strength of each signal component at each moment in time
Molecular and hemodynamic signals:
- Electrophysiological changes are connected to other kind of changes...
o At a smaller scale: movement of chemical substances and molecules
▪ E.g. depolarization: influx of Na+, repolarization: outward current of K+
▪ E.g. calcium concentration high in electrically active neurons → two-photon calcium
imaging
o At a larger scale: hemodynamics
▪ Blood supply is adjusted to current energy needs
- Energy consumption
o Electrophysiological events require energy
o Amplitude of potential changes not necessarily best predictor of energy consumption
▪ Action potential = passive chain of events that does not consume much energy
o Restoring resting potential requires energy → energy consumption of neuron could correlate
with number of action potentials
o Pre- and post-synaptic factors (e.g., neurotransmitter release) also require energy
o Exact energy distribution to different processes can vary (species, neuron type)
Maps in the brain:
- Clustering
o Noninvasive methods cannot achieve single neuron resolution
▪ Methods with highest spatial resolution still average signal from many neurons
- Neurons of similar functional properties are clustered together
o The more clustering, the more the averaged signal from many neurons corresponds to the
signal of the individual neurons → sensitivity of a noninvasive imaging technique depends
upon amount of clustering present
o Clustering on different spatial scales
▪ Topographic areas: for example the somatosensory homunculus but also for auditory
or occipital information
Overview of methods: three dimensions
- Temporal resolution: the smallest unit of time that can be differentiated by a method
- Spatial resolution: the smallest unit of space which can be resolved
2
, - Invasiveness: majority of methods are either fully invasive (skull needs to be penetrated) or not
invasive at all
o Invasive methods: used mostly in animal studies
o Non-invasive methods: also used for humans
Focus on less invasive techniques!
Measuring brain structure:
- Histology
o Cutting brain in pieces (e.g. slice of mouse brain)
o Process chemically for visualization of specific structure
▪ Makes us able to differentiate between the 6 brain layers, and between different
structures in the brain
- Structural magnetic resonance imaging (MRI)
o Investigation of anatomy in individuals
o Anatomical localization of functional findings
o Relate anatomical structure to differences between participants in e.g. behavior, disease
classification
Measuring hemodynamics:
- Changes in blood and tissue oxygenation, blood flow, and blood volume
- Temporal resolution of hemodynamic imaging is poorer compared to electrical imaging due to
slowness of hemodynamic events
o hemodynamic events take 16 sec to develop
- Spatial resolution varies strongly (but range smaller than for electrical signals):
o (invasive) optical imaging: columnar structure visible
o (non-invasive) fNIRS: several cm
Measuring electrophysiological activity:
- Spatial resolution, affected by
o Distance electrode and source of the signal
o Intermediate tissue (e.g. skull)
o Noninvasiveness: highest frequencies cannot be picked up
▪ Different frequency bands contain very different information!
- Quiroga et al. (2005): single unit recordings in epilepsy patients
o Theory that in every person there is only on neuron that responses to a picture of their
grandmother. For every different face a different neuron responds.
o Very exciting, but rare, ethical constraints, and difficult experimental control
→ less invasive techniques in humans
- Pitcher et al. (2011): EEG study
o Signal of EEG-electrodes on back of the head, averaged across many trials of viewing faces
(red) or chairs (blue)
3
, o Amplitude of N170 & P1 is stronger for faces versus chairs
o Due to low spatial resolution of EEG these components do not differentiate between
Aniston, Pitt, ..., and anatomical localization is poor
Peripheral measures:
- Always good to measure peripheral data, in addition to the variables you want to measure
- Skin conductance
o index of (sympathetic) arousal intensity in affective or cognitive processing
o highly variable, difference between subjects is huge
- Heart activity
o heart rate
o heart rate variability: measures influence of PNS on heart
o blood pressure: measure of stress
- Muscle activity
o Facial EMG (electromyography) as a tool for inferring affective states
- Eye measures
o Eye movements: good measure of visual attention
▪ Saccades (fast movements of the eyes): Very fast (20-40 ms), no new information is
acquired during saccades
▪ Fixations : Information acquisition occurs (mainly) during fixation
▪ Proudfoot et al. (2017) → Eye tracking in ALS patients
Trail making test A & B: connect the dots → 1-2--A-2-B-3-C etc.
o Pupil dilation
▪ indicative of intense emotional arousal toward both pleasant and unpleasant stimuli
and experiences
▪ Bradley et al. (2007): pupil dilation reflects SNS activity
Pupil diameter larger for pleasant & unpleasant conditions than for neutral
Lecture 2: EEG
Why use electroencephalogram (EEG)?
- Reaction time is the final outcome of sensory, decision and motor processes
- EEG can track the time course of these stages with millisecond precision
- EEG can inform us about cognitive processes when there is no behavioral response
Electrophysiological activity of the brain:
- Hans Berger reported the first non-invasive human EEG in 1929
What is measured by EEG?
- Post synaptic potentials at apical dendritic trees of pyramidal cells
o Action potentials can not be added up so not useful for EEG
o Post synaptic potentials can be added up so useful for
EEG.
- For brain electrical activity to be detectable through skull,
must be strong signal summed over many neurons
o All behaving similarly at same time
o All oriented in same way
▪ This way the potentials can be added up
without canceling each other out
4
Lecture 1: Introduction
Cognitive Neuropsychology – definition:
- The study of the relation between structure and function of the brain and specific cognitive functions
(e.g. language, memory, attention, …)
o by investigating these cognitive processes in normal healthy people
o by investigating the breakdown of these processes in brain-damaged individuals (as a result
of acquired brain damage or as a result of a developmental disorder)
Brain enthusiasm:
- Brain scans as evidence in court of law
- Brain scans might be overinterpreted by laypersons
- Good progress for several neurological syndromes, but less progress for psychiatric and mental
syndromes.
o Differences found for psychiatric and mental syndromes on a group level but difficult on an
induvial level.
Basis of neural signals:
- Neurons, with cell bodies in grey matter of cerebral
cortex and subcortical structures; white matter contains
axons.
- Without input (at rest), cell membrane of a neuron has
an electrical potential difference between in- and
outside of -70 mV
- Post-synaptic potential is determined by integrating
input of many synapses at the dendrites. It can hyper-
and depolarize.
- Neural communication:
o Input neurons (through neurotransmitters): action potentials over time
→ Membrane potential of post-synaptic neuron depolarizes or hyperpolarizes
o Over time, membrane potential of post-synaptic neuron changes in function of input it
receives = signal
Signal description:
- Simplest signal = sinusoidal oscillation
- Frequency: rate of change of signal, e.g. in the time dimension
o 1 Hz = completing a full cycle (going up & down) in one
second
o Biological signals never contain just one frequency
- Complex signals can be decomposed into frequency components
o Each has a particular frequency (e.g., 1 Hz, 2 Hz, 3 Hz, …)
o Amplitude: how much it goes up and down
o Phase: when it goes up and down
- Frequency spectrum: measured range of frequencies
o Highest frequency
▪ Limited by sampling frequency
▪ ½ * sampling frequency (Nyquist sampling theorem)
o Lowest frequency
1
, ▪ Limited by how long the signal is measured
▪ 1 / number of seconds measured
- Filtering: attenuating or excluding certain part of measured frequency spectrum (low-pass, high-pass
or band-pass)
- Spectrogram: strength of each signal component at each moment in time
Molecular and hemodynamic signals:
- Electrophysiological changes are connected to other kind of changes...
o At a smaller scale: movement of chemical substances and molecules
▪ E.g. depolarization: influx of Na+, repolarization: outward current of K+
▪ E.g. calcium concentration high in electrically active neurons → two-photon calcium
imaging
o At a larger scale: hemodynamics
▪ Blood supply is adjusted to current energy needs
- Energy consumption
o Electrophysiological events require energy
o Amplitude of potential changes not necessarily best predictor of energy consumption
▪ Action potential = passive chain of events that does not consume much energy
o Restoring resting potential requires energy → energy consumption of neuron could correlate
with number of action potentials
o Pre- and post-synaptic factors (e.g., neurotransmitter release) also require energy
o Exact energy distribution to different processes can vary (species, neuron type)
Maps in the brain:
- Clustering
o Noninvasive methods cannot achieve single neuron resolution
▪ Methods with highest spatial resolution still average signal from many neurons
- Neurons of similar functional properties are clustered together
o The more clustering, the more the averaged signal from many neurons corresponds to the
signal of the individual neurons → sensitivity of a noninvasive imaging technique depends
upon amount of clustering present
o Clustering on different spatial scales
▪ Topographic areas: for example the somatosensory homunculus but also for auditory
or occipital information
Overview of methods: three dimensions
- Temporal resolution: the smallest unit of time that can be differentiated by a method
- Spatial resolution: the smallest unit of space which can be resolved
2
, - Invasiveness: majority of methods are either fully invasive (skull needs to be penetrated) or not
invasive at all
o Invasive methods: used mostly in animal studies
o Non-invasive methods: also used for humans
Focus on less invasive techniques!
Measuring brain structure:
- Histology
o Cutting brain in pieces (e.g. slice of mouse brain)
o Process chemically for visualization of specific structure
▪ Makes us able to differentiate between the 6 brain layers, and between different
structures in the brain
- Structural magnetic resonance imaging (MRI)
o Investigation of anatomy in individuals
o Anatomical localization of functional findings
o Relate anatomical structure to differences between participants in e.g. behavior, disease
classification
Measuring hemodynamics:
- Changes in blood and tissue oxygenation, blood flow, and blood volume
- Temporal resolution of hemodynamic imaging is poorer compared to electrical imaging due to
slowness of hemodynamic events
o hemodynamic events take 16 sec to develop
- Spatial resolution varies strongly (but range smaller than for electrical signals):
o (invasive) optical imaging: columnar structure visible
o (non-invasive) fNIRS: several cm
Measuring electrophysiological activity:
- Spatial resolution, affected by
o Distance electrode and source of the signal
o Intermediate tissue (e.g. skull)
o Noninvasiveness: highest frequencies cannot be picked up
▪ Different frequency bands contain very different information!
- Quiroga et al. (2005): single unit recordings in epilepsy patients
o Theory that in every person there is only on neuron that responses to a picture of their
grandmother. For every different face a different neuron responds.
o Very exciting, but rare, ethical constraints, and difficult experimental control
→ less invasive techniques in humans
- Pitcher et al. (2011): EEG study
o Signal of EEG-electrodes on back of the head, averaged across many trials of viewing faces
(red) or chairs (blue)
3
, o Amplitude of N170 & P1 is stronger for faces versus chairs
o Due to low spatial resolution of EEG these components do not differentiate between
Aniston, Pitt, ..., and anatomical localization is poor
Peripheral measures:
- Always good to measure peripheral data, in addition to the variables you want to measure
- Skin conductance
o index of (sympathetic) arousal intensity in affective or cognitive processing
o highly variable, difference between subjects is huge
- Heart activity
o heart rate
o heart rate variability: measures influence of PNS on heart
o blood pressure: measure of stress
- Muscle activity
o Facial EMG (electromyography) as a tool for inferring affective states
- Eye measures
o Eye movements: good measure of visual attention
▪ Saccades (fast movements of the eyes): Very fast (20-40 ms), no new information is
acquired during saccades
▪ Fixations : Information acquisition occurs (mainly) during fixation
▪ Proudfoot et al. (2017) → Eye tracking in ALS patients
Trail making test A & B: connect the dots → 1-2--A-2-B-3-C etc.
o Pupil dilation
▪ indicative of intense emotional arousal toward both pleasant and unpleasant stimuli
and experiences
▪ Bradley et al. (2007): pupil dilation reflects SNS activity
Pupil diameter larger for pleasant & unpleasant conditions than for neutral
Lecture 2: EEG
Why use electroencephalogram (EEG)?
- Reaction time is the final outcome of sensory, decision and motor processes
- EEG can track the time course of these stages with millisecond precision
- EEG can inform us about cognitive processes when there is no behavioral response
Electrophysiological activity of the brain:
- Hans Berger reported the first non-invasive human EEG in 1929
What is measured by EEG?
- Post synaptic potentials at apical dendritic trees of pyramidal cells
o Action potentials can not be added up so not useful for EEG
o Post synaptic potentials can be added up so useful for
EEG.
- For brain electrical activity to be detectable through skull,
must be strong signal summed over many neurons
o All behaving similarly at same time
o All oriented in same way
▪ This way the potentials can be added up
without canceling each other out
4
