Brain and Cognition Cognitive Neuroscience If the brain were simple enough to understand, we would be too stupid to understand it 1
The Chemical Synapse 2
Chemical Neurotransmission At rest, the synapse (presynaptic side) contains numerous synaptic vesicles filled with neurotransmitter, intracellular calcium levels are very low (1). Arrival of an action potential: voltage-gated calcium channels open, calcium enters the synapse (2). Calcium triggers exocytosis and release of neurotransmitter (3). Vesicle is recycled by endocytosis (4). 3
Chemical Neurotransmission Once released, the neurotransmitter molecules diffuse across the synaptic cleft (about 20-50 nm wide). When they arrive at the postsynaptic membrane, they bind to neurotransmitter receptors ( lock-and-key mechanism). Two main classes of receptors: Transmitter-gated ion channels G-protein-coupled receptors Transmitter-gated ion channels: transmitter molecules bind on the outside, cause the channel to open and become permeable to either Na + (depolarizing, excitatory effect) or Cl (hyperpolarizing, inhibitory effect). G-protein-coupled receptors have slower, longer-lasting and diverse postsynaptic effects. They can have effects that change an entire cell s metabolism. 4
Excitatory Effects of Neurotransmitters EPSP = Excitatory Post- Synaptic Potential 5
Inhibitory Effects of Neurotransmitters IPSP = Inhibitory Post- Synaptic Potential 6
Integration of Synaptic Inputs In the CNS, many EPSP s are needed to generate an AP in a single neuron. A single EPSP has, in general, very little effect on the state of a neuron (this makes computational sense). On average, the dendrite of a cortical pyramidal cell receives ~10000 synaptic contacts, of which several hundred to a thousand are active at any given time. The adding together of many EPSP s in both space and time is called synaptic integration. 7
Synaptic Integration (a)single input single EPSP. (b)three APs arriving simultaneously at different parts of the dendrite add together to produce a larger response (spatial summation). (c)three APs arriving in quick succession in the same fiber can also result in a larger response (temporal summation). 8
Integration of Synaptic Inputs Distal and proximal synaptic inputs: 9
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Anatomy-Exterior View 11
Anatomy-Major Structures 12
Anatomy-Interior View 13
Anatomy-Four Lobes 14
Anatomy-Major Areas Four Lobes: Frontal Lobe Parietal Lobe Temporal Lobe Occipital Lobe Thalamus Cerebellum 15
Anatomy-Association Corti 16
Major Areas- Speech Pathways 17
gyrus sulcus Cortical Anatomy Motor Cortex Broca s Area Auditory Cortex Representation of Imaging Data Sets: - 3-D based - Surface based Visual Cortex 18
Cortical Anatomy The macaque monkey cortex - unfolded. Felleman and Van Essen, 1991. 19
Cortical Anatomy 20
Methods of Cognitive Neuroscience Neurobiology: Neuroanatomy Neurophysiology Neuroimaging Techniques PET MRI/fMRI EEG MEG Evidence from Dysfunction Lesions Diseases of the CNS Cognitive Psychology Computational Approaches 21
Methods of Cognitive Neuroscience 22
Neurobiology Neuroanatomy and neurophysiology are often conducted in animal systems (monkey, cat, etc.). Neuroanatomy: - Large-scale anatomy of the brain - Subdivisions of the cortex - Neuronal subtypes, layers - Morphology of single neurons 23
Neurobiology Neurophysiology: - Recording of neural activity, often in the context of a stimulus or task (single-cell recording, local field potential recording, multi-electrode recording). - Electrical stimulation of neurons to study their role in perception or movement (micro-stimulation, surface stimulation) 24
Methods Comparison Method Space Time Neural Correlate ------------------------------------------------------------- PET coarse coarse brain activation, metabolic (5 mm) (sec.) rate of tissue, incorporation of glucose, oxygen utiliz., receptor distribution, 2D-3D capable. fmri coarse coarse blood oxygenation state, (2 mm) (1 sec.) regional blood flow, oxygenated/deoxygenated hemoglobin, 2D-3D, in register with struct. Scan. EEG coarse fine electrical (field) potentials, (?) (msec) surface electrodes arranged on skull, limited depth, inverse problem, unknown source locations, allows correlation measures. MEG coarse fine magnetic (field) potentials, (?) (msec) SQUIDs arranged around head, sensitive to noise, similar advantages and drawbacks as EEG. 25
EEG The electroencephalogram (EEG) measures the activity of large numbers (populations) of neurons. First recorded by Hans Berger in 1929. EEG recordings are noninvasive, painless, do not interfere much with a human subject s ability to move or perceive stimuli, are relatively low-cost. Electrodes measure voltage-differences at the scalp in the microvolt (μv) range. Voltage-traces are recorded with millisecond resolution great advantage over brain imaging (fmri or PET). 26
EEG Standard placements of electrodes on the human scalp: A, auricle; C, central; F, frontal; Fp, frontal pole; O, occipital; P, parietal; T, temporal. 27
EEG 28
EEG 29
EEG Many neurons need to sum their activity in order to be detected by EEG electrodes. The timing of their activity is crucial. Synchronized neural activity produces larger signals. 30
The Electroencephalogram A simple circuit to generate rhythmic activity 31
The Electroencephalogram Two ways of generating synchronicity: a) pacemaker; b) mutual coordination 1600 oscillators (excitatory cells) un-coordinated coordinated 32
EEG EEG potentials are good indicators of global brain state. They often display rhythmic patterns at characteristic frequencies 33
EEG EEG suffers from poor current source localization and the inverse problem 34
EEG EEG rhythms correlate with patterns of behavior (level of attentiveness, sleeping, waking, seizures, coma). Rhythms occur in distinct frequency ranges: Gamma: Beta: Alpha: Theta: Delta: 20-60 Hz ( cognitive frequency band) 14-20 Hz (activated cortex) 8-13 Hz (quiet waking) 4-7 Hz (sleep stages) less than 4 Hz (sleep stages, especially deep sleep ) Higher frequencies: active processing, relatively de-synchronized activity (alert wakefulness, dream sleep). Lower frequencies: strongly synchronized activity (nondreaming sleep, coma). 35
EEG Power spectrum: 36
EEG - ERP ERP s are obtained after averaging EEG signals obtained over multiple trials (trials are aligned by stimulus onset). 37
Sensing Techniques-Cat Scans 38
Sensing Techniques-Cat Scans 39
Sensing Techniques-Cat Scans Cat Scans use x-rays to show structures Really precise maps Hard to determine functions 40
PET Positron Emission Tomography Requires the injection of a positron-emitting radioactive isotope (tracer) Examples: C-11 Glucose analogs (metabolism) O-15 water (blood flow or volume) C-11 or O-15 carbon monoxide PET tracers must have short half-life, e.g. C-11 (20 min.), O-15 (2 min.). Cyclotron! Positron + electron 2 gamma ray beams. Gamma radiation is detected by ring of detectors, source is plotted in 2-D producing an image slice. 41
Sensing Techniques-PET Radioactive element decays, gives off positron Positron moves a short distance and gives off two gamma rays in opposite directions 42
Sensing Techniques-PET 43
PET Scans Eyes Closed White Light Complex Scene 44
PET Scans Episodic Task Semantic Task Difference 45
PET Scans 46
PET - Examples In cognitive studies, a subtraction paradigm is often used. 47
PET - Examples Another example of control and task states, and of averaging over subjects: Marc Raichle 48
PET - Examples (a) Passive viewing of nouns; (b) Hearing of nouns; (c ) Spoken nouns minus viewed or heard nouns; (d) Generating verbs. M. Raichle 49
PET - Examples M. Raichle 50
PET - Examples PET images taken at different times, e.g. during learning, can be compared. M. Raichle 51
PET - Examples PET images are pretty to look at... and can be combined with other imaging modalities, here MRI. 52
MRI - fmri The Physics (sort of)... Subjects are placed in a strong external magnetic field. Spin axes of nuclei orient within the field. External RF pulse is applied. Spin axes reorient, then relax. During relaxation time, nuclei send out pulses, which differ depending on the microenvironment (e.g. water/fat ratio). fmri functional MRI Allows fast acquisition of a complete image slice in as little as 20 ms. Several slices are acquired in rapid succession and the data is examined for statistical differences. Hemoglobin is brighter than deoxyhemoglobin. Oxygenated blood is brighter - active areas are brighter. BOLD-fMRI 53
PET - MRI in Comparison 54
Sensing Techniques-fMRI Functional Magnetic Nuclear Resonance Imaging Similar to Pet, uses radio frequency information given off by water Gives better time (6 seconds) and spatial (2 mm) resolution than Pet or Cat scans Technology still under revision Slight danger to subjects Expensive ($300 an hour) 55
MRI Scans 56
fmri - Examples 57
fmri High-Resolution Mapping Kim et al., 2000 58
PET and fmri - Similarities and Differences - Different biological signal. Yet, both pick up a signal related to bulk metabolism (not electricity). - fmri has better temporal (<100 ms) and spatial resolution (1 mm and less) - fmri does not involve radioactive tracers and subjects can be measured repeatedly, over many trials. - PET images generally represent idealized averages. fmri images are often registered with structural scans to show individual anatomy. - For both, images can be aligned for multiple subjects. - fmri is widely available, PET is not. - fmri does not allow localization of neurotransmitters or receptors etc. - For both, it can be tricky to get stimuli to the subject. 59
Data Analysis Issues Neuroimaging (PET/fMRI): Activation values, spatial resolution, averaging, image alignment and registration. EEG/MEG: Current source localization (inverse problem), time domain data sets, frequency power spectrum, correlation and coherency. 60
Summary Appropriate technology depends on question ERP has good temporal resolution CAT, Pet, MRI have good to fair spatial resolution, only PET has any functional capture fmri has reasonably good spatial, reasonably good temporal, but is expensive 61