Causal Methods Flashcards
Causal methods
Induce changes in brain activity
- directily, by influencing physical properties of neural tissue
- there are also indirect method such as mediaction etc.
–> even causal methods cannot infer causality with certainty!
Stimulation methods
= what is being applied at physical level
=/= effect on neural processing
Intracranial recordings and stimulation
- Invasive electrophysciology
Choice of electrode depends on clinical need and anatomical objective
- especially in epilepsy patients not responding to medical treatment
- mostly limbic and frontal regions
- electrodes removed prior to surgery
Electrocorticography ECoG
Use of electrodes placed directly on the exposed surface of the brain to record electrical activity from the cortex
Stereo-electroencephalography SEEG
Recording electroencephalographic signals via depth electrodes
- very similar to EEG, but with much much better signal to noise ratio and very hihg temporal and spatial resolution
- but depends on available subjects, limited time available, invasive and lack of control set
Microstimulation
Electrode inside neural tissue: only performed when electrodes are crucial for clinical purposes
–> mall electrical current:
- influences activity of neurons near the tip
- the larger the current, the wider the affected area
- too strong = damage (burn)
- strong = action potentials
- weak = membrane potential change
Deep brain stimulation DBS
Like microstimulation –> electrodes in deep structure of the brain
- parkinson’s disease
- severe depression and OCD
- neural pacemaker
- as a treatment through various mechanisms (enhancing, inhibiting or synchronizing activity)
Focused ultrasound stimulation FUS
Ultrasound
- focused volume of space in which waves propagate
- applied transcranially (bone reduced amplitude, but does not scatter the sound wave)
Ultrasound
Frequencies of a few hundred kHz (far beyond hearing range)
FUS stimulated region
Stimulated region looks like rugby ball
- loong axis: orthogonal to scalp surface, so can penetrate at least a cm
- spatial resolution = few mm
- higer than other non-invasive stimulation methodes in lateral directions
- typically guided by anatomical MRI
Can be used to lesion brain structures (high intensiy heats up and can burn)
Low-intensity FUS
Leads to neural stimulation
- non-thermal mechanical energy
- small displacements of cell
- hypothesized effects on properties of receptors
Transcranial magnetic stimulation TMS
Electromagnetic induction (Faraday’s principle; left hand rule magnet)
- electric current in coil
- generates transient magnetic field haaks op de coil
- induces second current in brain that flows parallel but in opposite direction
–> stimulates/depolarizes neurons
Shape of coil
Determines shape of magnetic field and induced current
- figure of 8 coil design
- more docused magnetic field
- more precise location of altered neural activity
Determinants properties and effect electrical current
- physical factors (distance to coil)
- biological factors
- physical parameters easier to characterize than biological parameters
- predicting effect on neural activity is difficult
Spatial resolution of TMS
- 1 cm
- TMS of occipital face area OFA only affects face processing
- TMS of extrastriate body area EBA only affects body processing
- these rgions are less than 2 cm apart
- but functional differentiation between adjacent subregions is not possible for all cortical areas
Temporal resolution in TMS
Very good temporal resolution
- if only a single or double pulse is applied
- limited by duration of puls (s) and number of time-points tested
Variants of TMS
Repetitive TMS
- multiple pulses (frequency; duration)
- influences temporal resolution
- stronger effect (also higher risks)
Single/double pulse TMS
Sometimes combined: rTMS first to establish causal link, fllowed by single/double pulse TMS for better temporal resolution
Control conditions TMS
Sham: turn coil by 90 degrees
- magnetic field does not influence neural activity
- difference easy to detect by participant
Stimulation of vertex = highest point of skull
- assumption: no/little effect on behavior
Where to stimulate with TMS
- international 10-20 EEG system: locates electrodes on scalp using standard cranial landmarks
- standardized function-guided procedure: rely upon functional criteria such as motor responses or phosphenes
- neuronavigation: using structural/anatomical MRI scan of participant
- fMRI-guided TMS: using an fMRI localiser task + neuronavigation
Potentials of TMS
- diagnostic value for testing connectivity between motor cortex and peripheral muscles (motor related disorders and adter a stroke)
- as part of clinical treatment
- major depression (alternative or electroconvulsive therapy)
- migraine (single pulse over visual cortex)
Transcranial current stimulation TCS
- principle similar to TMS but uses electrical stimualtion
- current flows from anode (depolarization of neuron, +, excitatory) to cathode (hyperpolarization of neuron, -, inhibitory
TCS
- typical current strength(effect size at neural level and sideeffects)
- control condition, often sham TCS
- poort spatial resolution: 5 cm (contact area 25 cm^2, uniform delivery of current)
- very poor temporal resolution (extended duration of stimulation and duration of effect)
Variants of TCS
- transcranial direct current stimulation tDCS
- transcranial alternating current stimulation tACS
- transcranial random noise stimulation tRNS
tDCS
Direct current in one direction; location of electrodes determines flow current
tACS
Alternating current at fixed frequency (test whether particular frequency ranges are involved)
tRNS
Alternating current based on random frequency spectrum
TMS vs tDCS
Slide 28
Potential of TCS
- small but robust effect on neural activity in particular circumstances
- can make subtreshold stimulus perceivable
- small effects accumulate over time
- larger sample sizes needed for accurate estimate of effect size
- but… TCS on human cadaver heads
Clinical groups
Patients with neurological conditions and disorders
- other methods are not possible or not ethical
Lesion studies
Rationale: if a brain region is damaged and a particular behavioral deficit occurs => brain region plays critical role in that particular behavior in normal healthy brain
- Assumption: modularity or localization -> discrete anatomical modules deal with different cognitive functions
- Assumption: universality -> brain regions subserve the same processes across individuals
Lesion symptom mpping
Inferring the function of a brain area by observing the behavioral consequences of damage to that area
- fMRI: does activity in brain area correlate with task?
- LSM: is brain area necessary for task?
Double Dissociation
Technique to determine whether 2 cognitive functions are independent = when lesions have converse effects on 2 distinct cognitive functions:
- brain lesion area A => disruption function but not B (same for lesion in B, but opposite)
–> Broca’s aphasia and Wernicke’s aphasia are good examples for this
Voxel based lesion symptom mapping VLSM
For every voxel you look at who have lesions in there and you look if the voxel is involved in the cognitive function. Compared with group without damage to that voxel
Advantages voxel based lesion symptom mapping
- directly comparable to fMRI and PET findings (common stereotactic space)
- behavioral data can be continuous (no biased patient groups)
- wide range of lesion size and location (no predefined regions of interest)
- nuisance variables as covariates
- observe lesion effects on multiple regions at once
Limitation VLSM
Damage may extend beyond the area of apparent injuty as seen on structual scans (white matter damage for example)
-> can use network-based lesion-symptm mapping
Network-based lesion-symptom mapping
Examines statistical relationship between network injury and behavioral performance
- can provide mre systematic assessment by evaluating brain damage as a comination of necrosis as well as disconnection
Limitations in lesion studies
- necessarily largely data-driven (depend on the patient)
- differential vulnerability (some areas are rarely damaged)
- damage often follows structural boundaries rather than funcitonal boundaries
On- vs off-medication conditions
- test de novo patients (never used medication) before and after their first medication (-> cean off-medication condition, problem with order effects)
- ask patients to do a day without their medicaiton (control order effects)
- mostly neurotransmitter medication
