Neuroscience Lecture Notes
Lecture 1: Methods and Techniques
Cognitive Neuroscience
- Aim is to develop neuo-biologically grounded models of mental function and behavior
- Interested in human behavior in relation to the task environment and the neural
processes underlying mental processes
- Cognition: the set of mental functions that allow us to perceive external stimuli to extract
key information and hold it in memory and ultimately to generate thoughts and actions
that help to reach desired goals
Cognitive Science + Neuroscience
- Cognitive science: seeks to understand information processing associated with cognitive
functions like perception, memory and decision making
- Neuroscience: seeks to characterize the structure and function of the nervous system
(studies brain structures)
- Cognitive neuroscience: new discipline that applies research methods from
neuroscience to the functions and behaviors studied by cognitive science
- Cognitive neuroscientists use diverse research methods and experimental paradigms to
develop models of mental function and behavior
Neuroscience Techniques
- Spatial resolution + temporal resolution differs for the techniques
- All techniques have own strengths and weaknesses, some techniques are better suited
for certain research questions
- So far, no technique offers both high temporal and spatial resolution
,Combining Research Methods
- Convergence: combining results from multiple experimental paradigms to clarify a single
theoretical concept
→ Allows to explore topics in different ways, yields more convincing results
- Complementarity: different methods provide a different sort of information about brain
function
Meta-Analysis
- Improves the power and precision of experimental findings
- Quantitative meta-analysis: examine similarities in results of different studies
investigating the same cognitive function
- Quantitative meta-analysis: combine results from multiple studies into one single
statistical framework
- Semantic meta-analysis: combine studies based on similarity in underlying concepts
Research Methods
- Brain perturbation approach: starts with the brain; examine the effect of different
perturbations of the brain on cognitive performance (naturally occurring or experimentally
induced perturbations)
- Neuromonitoring approach: starts with cognitive functioning; cognitive process is
manipulated and brain activity is measured during task performance; examines effect of
cognitive function on brain activity
Naturally Occurring Perturbations
- Originally examined postmortem and associated with behavior observed during life
- Not (ethically) possible to induce lesions in living humans, but can be done in animals
- Brain damage: stroke, trauma, disease (e.g. alzheimer’s)
- Nun study: large number of catholic nuns were followed, very homogeneous group (no
history of drug use, no alcohol consumption, similar housing conditions); found that it is
not always possible to determine how damaged region is involved in cognitive
functioning
→ Sister Mary: very high mini-mental state exam score and high cognitive test
scores until she died at 101, after death severe signs of alzheimers were found
, → changes of the brain and changes in cognition do not always have a 1:1
relationship
Problems with Studying Naturally Occurring Perturbations
- Size and site of lesions are not under control of the experimenter
- Substantial inter-individual variation in lesions/damage and in brain activity supporting
functions
- Diaschisis: sudden change of function in a portion of the brain connected to a distant,
but damaged, brain area → Because brain areas don’t function in isolation
Dynamics of the Brain
- When people age the brain changes, but structural changes not necessarily
accompanied by changes in cognitive performance (brain can compensate, using
different strategies)
- Mental fatigue related to reversible changes in brain (can use strategies to compensate/
putting in more effort), age is related to irreversible changes
- Lateralized brain activation in younger people, similar pattern in low performing old
people; but bilateral brain activation in high performing old people (illustrates
compensating mechanism)
- Pundik et al. (2015): intensive treatment after stroke lead to bilateral brain activation
which was associated with recovery of proximal arm functioning
Experimentally Occurring Perturbations
- Pharmacological perturbations: e.g. examining effects of (long-term) drug use on
cognitive functioning; giving participants caffein
→ effects not very specific; e.g.caffeine affects multiple transmitters
- Intracranial brain stimulation: stimulating the brain by placing electrodes on or directly
into the brian
→ Invasive; use is limited in humans, most studies are done in animals
- Extracranial brain stimulation: non-invasive, side effects are rare, affects relatively large
area in superficial brain regions, can result in activation of nearby muscles
→ Transcranial magnetic stimulation (TMS): strong changing magnetic field is
created over a region of the brain which is eliciting an electrical field in underlying
brain tissue → affects neural processing in the stimulated area (tends to affect
relatively large area and can only be delivered to superficial brain regions)
- Optogenetics: ability to modulate activity in certain neurons by shining light on them, new
technique → use of light to control neurons that have been genetically modified to
express light-sensitive ion channels
→ High neuronal specificity and high temporal resolution
→ Can be used to restore and enhance functions (e.g. in Alzheimer’s)
→ Foreign agents will be attacked by immune system (this has to be solved first
before it can be used in humans)
→ Ethical issues (what are side effects of enhancing cognitive functioning?)
, Neuroimaging Approach
1. Intracranial electrophysiological recordings:
- Intracellular single-neuron recording (measuring action potentials, electrodes placed
within a cell): reflects output of one cell
→ Invasive so mostly used in animal
studies; animals are trained to
perform specific task (e.g. eye
movement) and during task
performance action potentials are
measured→ intensity of a stimulus is
encoded by the frequency of action
potentials
- Extracellular recordings (small group of
neurons): electrodes placed outside the
neuron and records activity from the neuron
and surrounding neurons
→ Measures action potentials and local
field potentials (LFP; synchronized
input from the neurons)
→ Can be performed in humans if electrodes are placed before surgery but mostly
in animals
Structure of Neurons
- Input into the cell delivered via dendrites
- Graded potential is elicited in dendrites and is delivered to cell body and axon hill
- When threshold is reached axon generates action potential
2. Electroencephalography (EEG): summed dendritic field
potentials of a large population of neurons; electrical brain activity is
measured at the scalp using surface electrodes
- Noninvasive
- Postsynaptic potentials of cortical pyramidal neurons produce
vertical dipoles perpendicular to the scalp which are the
predominate generators of EEG waves
- Electrodes are placed at predefined locations on the scalp
and named after underlying cortical regions (front to
back:F-C-P-O; side to side: T)
Lecture 1: Methods and Techniques
Cognitive Neuroscience
- Aim is to develop neuo-biologically grounded models of mental function and behavior
- Interested in human behavior in relation to the task environment and the neural
processes underlying mental processes
- Cognition: the set of mental functions that allow us to perceive external stimuli to extract
key information and hold it in memory and ultimately to generate thoughts and actions
that help to reach desired goals
Cognitive Science + Neuroscience
- Cognitive science: seeks to understand information processing associated with cognitive
functions like perception, memory and decision making
- Neuroscience: seeks to characterize the structure and function of the nervous system
(studies brain structures)
- Cognitive neuroscience: new discipline that applies research methods from
neuroscience to the functions and behaviors studied by cognitive science
- Cognitive neuroscientists use diverse research methods and experimental paradigms to
develop models of mental function and behavior
Neuroscience Techniques
- Spatial resolution + temporal resolution differs for the techniques
- All techniques have own strengths and weaknesses, some techniques are better suited
for certain research questions
- So far, no technique offers both high temporal and spatial resolution
,Combining Research Methods
- Convergence: combining results from multiple experimental paradigms to clarify a single
theoretical concept
→ Allows to explore topics in different ways, yields more convincing results
- Complementarity: different methods provide a different sort of information about brain
function
Meta-Analysis
- Improves the power and precision of experimental findings
- Quantitative meta-analysis: examine similarities in results of different studies
investigating the same cognitive function
- Quantitative meta-analysis: combine results from multiple studies into one single
statistical framework
- Semantic meta-analysis: combine studies based on similarity in underlying concepts
Research Methods
- Brain perturbation approach: starts with the brain; examine the effect of different
perturbations of the brain on cognitive performance (naturally occurring or experimentally
induced perturbations)
- Neuromonitoring approach: starts with cognitive functioning; cognitive process is
manipulated and brain activity is measured during task performance; examines effect of
cognitive function on brain activity
Naturally Occurring Perturbations
- Originally examined postmortem and associated with behavior observed during life
- Not (ethically) possible to induce lesions in living humans, but can be done in animals
- Brain damage: stroke, trauma, disease (e.g. alzheimer’s)
- Nun study: large number of catholic nuns were followed, very homogeneous group (no
history of drug use, no alcohol consumption, similar housing conditions); found that it is
not always possible to determine how damaged region is involved in cognitive
functioning
→ Sister Mary: very high mini-mental state exam score and high cognitive test
scores until she died at 101, after death severe signs of alzheimers were found
, → changes of the brain and changes in cognition do not always have a 1:1
relationship
Problems with Studying Naturally Occurring Perturbations
- Size and site of lesions are not under control of the experimenter
- Substantial inter-individual variation in lesions/damage and in brain activity supporting
functions
- Diaschisis: sudden change of function in a portion of the brain connected to a distant,
but damaged, brain area → Because brain areas don’t function in isolation
Dynamics of the Brain
- When people age the brain changes, but structural changes not necessarily
accompanied by changes in cognitive performance (brain can compensate, using
different strategies)
- Mental fatigue related to reversible changes in brain (can use strategies to compensate/
putting in more effort), age is related to irreversible changes
- Lateralized brain activation in younger people, similar pattern in low performing old
people; but bilateral brain activation in high performing old people (illustrates
compensating mechanism)
- Pundik et al. (2015): intensive treatment after stroke lead to bilateral brain activation
which was associated with recovery of proximal arm functioning
Experimentally Occurring Perturbations
- Pharmacological perturbations: e.g. examining effects of (long-term) drug use on
cognitive functioning; giving participants caffein
→ effects not very specific; e.g.caffeine affects multiple transmitters
- Intracranial brain stimulation: stimulating the brain by placing electrodes on or directly
into the brian
→ Invasive; use is limited in humans, most studies are done in animals
- Extracranial brain stimulation: non-invasive, side effects are rare, affects relatively large
area in superficial brain regions, can result in activation of nearby muscles
→ Transcranial magnetic stimulation (TMS): strong changing magnetic field is
created over a region of the brain which is eliciting an electrical field in underlying
brain tissue → affects neural processing in the stimulated area (tends to affect
relatively large area and can only be delivered to superficial brain regions)
- Optogenetics: ability to modulate activity in certain neurons by shining light on them, new
technique → use of light to control neurons that have been genetically modified to
express light-sensitive ion channels
→ High neuronal specificity and high temporal resolution
→ Can be used to restore and enhance functions (e.g. in Alzheimer’s)
→ Foreign agents will be attacked by immune system (this has to be solved first
before it can be used in humans)
→ Ethical issues (what are side effects of enhancing cognitive functioning?)
, Neuroimaging Approach
1. Intracranial electrophysiological recordings:
- Intracellular single-neuron recording (measuring action potentials, electrodes placed
within a cell): reflects output of one cell
→ Invasive so mostly used in animal
studies; animals are trained to
perform specific task (e.g. eye
movement) and during task
performance action potentials are
measured→ intensity of a stimulus is
encoded by the frequency of action
potentials
- Extracellular recordings (small group of
neurons): electrodes placed outside the
neuron and records activity from the neuron
and surrounding neurons
→ Measures action potentials and local
field potentials (LFP; synchronized
input from the neurons)
→ Can be performed in humans if electrodes are placed before surgery but mostly
in animals
Structure of Neurons
- Input into the cell delivered via dendrites
- Graded potential is elicited in dendrites and is delivered to cell body and axon hill
- When threshold is reached axon generates action potential
2. Electroencephalography (EEG): summed dendritic field
potentials of a large population of neurons; electrical brain activity is
measured at the scalp using surface electrodes
- Noninvasive
- Postsynaptic potentials of cortical pyramidal neurons produce
vertical dipoles perpendicular to the scalp which are the
predominate generators of EEG waves
- Electrodes are placed at predefined locations on the scalp
and named after underlying cortical regions (front to
back:F-C-P-O; side to side: T)
