HESP602/422 Overview Structural brain imaging: Angiography Computerized Tomography (CT, also known as CAT) Structural Magnetic Resonance Imaging (MRI) Functional brain imaging: PET, fMRI Neuro-electrical recording/stimulation: Electrode recording/stimulation (single-, multiple-electrode) Electro-encephalography (EEG) Event-related brain potentials (ERP, form of EEG) Magnetic Encephalography (MEG) Transcranial magnetic stimulation (TMS) Cognitive testing Double dissociation method Psychological experiment Computer modeling/simulation Neural network modeling Why measure brain activation? Localization of brain function Critical and participating areas Determining timing of function controlled vs. automatic syntactic vs. semantic immediate processing vs short-term retention, normal vs. delayed activation / reduced amplitude) Determining spatial-temporal cooperation of regions in network Determining re-organization of function, after brain damage, spontaneous recovery, Tx Determining normal and delayed development of function Angiography Computerized Tomography (CT, CAT) Structural Magnetic Resonance Imaging (structural MRI) Transverse/Axial Coronal Sagital MRI SCANNER Nuclear Physics of structural MRI Hydrogen atoms in tissue have a random orientation become aligned in magnetic field emit energy when perturbed by a radio wave and wobbling back have a different density in gray versus white matter Functional neuroimaging Techniques PET, fMRI Measure increases/decreases in regional blood flow during information processing tasks and while at rest Active brain regions receive more blood, since blood caries oxygen & glucose used by neurons Overview PET image scanner measurement principles nuclear physics Positron Emission Tomography (PET) A PET SCANNER: injection of radioactive tracer into blood stream PET measurement principles Radio-active tracer O 15 Half life of about 2 minutes injected into blood flow greatest concentration in active brain areas consume oxygen and glucose in blood flow location and concentration measurable During decay positron emitted spontaneously collision with electron gamma ray released picked up by gamma ray detector Nuclear physics of PET scanning Radioactive tracer, e.g. H 2 O 15 Advantages & disadvantages PET Advantages Relatively good spatial resolution (5-10mm), better ERP/MEG, worse fMRI (1-3mm) Tracing of different biochemical processes Disadvantages Invasive (injection of radio-active tracer) Limited testing (due to decay of tracer 40 sec) Need to block stimuli by condition Poor temporal resolution Overview fMRI scanner same as scanner used for structural MRI measurement principles images description of brain activation Identification of participating voxels Correlation method Subtraction method Describing regions of interest (ROIs) Brodman areas Advantages versus disadvantages & limitations fMRI measurement principles Contrast agent hemoglobin (HB) naturally present in blood flow carried by oxygen paramagnetic in its deoxygenated state greatest concentration in active brain areas due to blood flow oxygenation response location and concentration measurable decrease in ratio of deoxygenated/oxygenated HB decrease in magnetic field signal of deoxygenated HB decrease in energy release of magnetically aligned and perturbed HB atoms. fMRI image superimposed on structural MRI image * | + The star is above the plus Description of brain activation Voxel Small brain area showing increased regional blood flow, in an experimental condition relative to a control condition (e.g., rest) Size depends on spatial resolution Precision of measurement in space E.g., 3mm x 3mm x 3mm Degree of brain activation Number of voxels Intensity of activation of a voxel Region of interest (ROI) Larger brain area observed in study (e.g., Wernickes area) Functional neuroimaging of adult males with dyslexia (Eden et al, 1996, Nature) Motion detection area Active in controls Inactive in dyslexics Identifying participating voxels I Identifying participating voxels II Subtraction method Brain activation Experimental condition Brain activation Control condition Brain activation Unique to Experimental Condition Example of the subtraction method Subtraction method Brain activation sentence verification Brain activation consonant strings Brain activation unique to sentence verification Another example of the subtraction method Subtraction method Brain activation moving dots Brain activation stationary dots Brain activation unique to moving dots 1) Molecular 2) External granular (A) 3) External pyramidal (A) 4) Internal granular (S) 5) Internal pyramidal (M) 6) Fusiform A = association S = sensory input M= motor output Layers of neo-cortex Regions of interest: Brodman areas Brodman areas (lateral view) Regions of interest: Brodman areas Advantages fMRI Non-invasive (versus PET) Best spatial resolution of non-invasive methods Electrode recording (< 1mm) > fMRI (1-3mm) > PET (5-10mm) > MEG > ERP Shows all participating areas, not just critical ones Single-subject studies are possible Disadvantages & limitations fMRI Poor temporal resolution Precision of measurement in real time Electrode recording > ERP/MEG > fMRI/PET No differentiation between neuro-electrical excitation and inhibition Difficult to use with subjects and to obtain good measurements Sensitivity to head motion Contra indicators Pregnancy, Obesity, Metal parts (pacemakers, shrapnel, glasses) Relatively weak signal increases (1-3%) Very expensive to acquire, use & maintain fMRI/PET > MEG > ERP Personnel intensive: Neuro-radiologist, Nurse, Physicist, Statistician, Computer Scientist, Cognitive Psychologists, Research SLP Overview single/multiple electrode recording / stimulation Single electrode recording Encoding of information through firing rate Binding of information through synchronization Mapping of somato-sensory & primary motor cortex Multiple electrode recording in epilepsy patients Advantages vs. disadvantages & limitations Single-electrode recording in monkeys Encoding of information thru neural firing rate For example, detection orientation visual bar Encoding of information thru neural firing rate. For example, detection of movement direction Encoding of information thru synchronous firing For example, visual binding Electrical stimulation Multi-electrode recording & stimulation in epilepsy patients Example of single electrode recording: a neuron in the hippocampus responds selectively to sad faces Fried, I., MacDonald, K.A., Wilson, C.L. (1997). Single neuron activity in human hippocampus and amygdala during recognition of faces and objects. Neuron, 18, 753-65 Advantages versus disadvantages of single / multiple electrode recording / stimulation Disadvantages Invasive Only in patients who have to undergo surgery and give their informed consent for additional research Not necessarily typical of normal brain Possible danger of damaging artery/vein & causing hemorrhaging Advantages Best possible spatial & temporal resolution Differentiation between excitation & inhibition Study of activation dynamics of neural network Overview: Electro-encephalography (EEG) Scalp-attached electrodes Positioning of electrodes What aspect of brain activity does EEG measure? Need for signal amplification and averaging EEG frequency bands & states of consciousness Event-related brain potentials (ERPs) Measures EEG time-locked to presentation of a stimulus event Example of peripheral ERP component (auditory evoked potential) Example of central ERP component (N400 to semantic violations) Inverse problem (explaining in part poor spatial resolution) Advantages versus disadvantages & limitations Scalp-attached electrodes Checking impedances of scalp electrodes International 10-20 system: ensures electrodes are placed over specific cerebral locations C=central, O=occipital, F= frontal, P= parietal, T=Temporal Subscript: odd (1,3,5,7) left, even (2,4,6,8) right hemisphere, z=midline Nasion=point between forehead and nose, Inion=bump at back of skull EEG and brain activity EEG & Brain activity EEG measures post-synaptic currents (PSPs) in large numbers of neurons, especially on apical dendrites of pyramidal cells (70% of cells in neocortex) Necessary conditions for measuring this signal Aligned orientation of dendrites (not random, but e.g. parallel) Synchronous activation of few hundred thousand neurons Signal amplification & averaging EEG Frequency bands DELTA: <4 hz (deep sleep, coma) THETA: 4-8 hz (hippocampal and limbic activity: memory, emotion) ALPHA: 8-12 hz (alert, but not actively processing information, most prominent over occipital and frontal lobe, e.g., when eyes closed) BETA: 13-30hz (alert and actively processing information) GAMMA: >30-35 hz (Related to stream of consciousness? Binding of information from different brain modulates into coherent percept, sustained by re-entrant, positive feedback loops of neuronal cell- assemblies onto themselves). Note. Hz = number oscillations per second (e.g., 3 Hz below) 0ms 1000ms (1sec) EEG profiles & consciousness The auditory evoked potential: example of an event related potential Example of a central ERP component: N400 to semantic violations (Kutas & Hilyard, 1980) Changes in EEG coherence during cognitive tasks (Haarmann, Cameron, & Ruchkin, submitted) Inverse problem in EEG/MEG how many sources? location of sources? Source localization ERP & eye movement artifacts Eye movements & blinks produce fluctuating electrical fields in same frequency range as neurons Eyeball generates dipole field with positive and negative charge between which current flows Propagated back across scalp (brain acts as volume conductor) Eye movements & blinks therefore contaminate ERP recording Solutions 1) instruction to subject: fixate & do not move eyes 2) after experiment discard trials on which eye blink occurs 3) estimate & remove part of signal due to eye movement & blinks (e.g., Haarmann, Cameron, Ruchkin, Cognitive Brain Research, in press) Advantages & Disadvantages of EEG/ERP Advantages Excellent temporal resolution Multi-modal measure amplitude, polarity, continuous in time, frequency-specific, coherence Relatively low cost: ERP < MEG < fMRI, PET Many peripheral and central ERP components are known Disadvantages Poor spatial resolution (inverse problem) Many trials needed for averaging Sensitive to eye movement artifacts (but can be filtered out) Time consuming attachment of electrodes Overview MEG MEG scanner Squid technology Examples of MEG measurements Advantages/disadvantages MEG scanner MEG scanner consists of SQUIDs Superconducting Quantum Interference Device Detects magnetic flux Between 100-300 squids in whole-head MEG system connected to sensor coils that lie in a configuration that roughly follows the curvature of the head Placed in magnetically shielded room 1000 fold attenuation of environmental magnetic noise Traffic, elevators, jumping on floor, turning of chair Cooled by liquid helium Subject is shielded from cold temperature Examples of MEG measurements Scalp plot Topographic map MEG trace Anatomical overlay of MEG data Advantages MEG Fully non-invasive no need for injection of radioactive tracer, ionizing radiation such as X-rays, exposure to magnetic field, or attachment electrodes Excellent temporal resolution (same as ERP) Multi-modal measure (same as ERP) amplitude, continuous in time, frequency-specific, coherence Medium cost: ERP < MEG < fMRI, PET Disadvantages MEG Poor spatial resolution (due to inverse problem), but better than ERP In-homogeneities at scalp/skull affect conduction of electrical but not magnetic field Sensitive to tangential but not radial component of brain activity Tangential = perpendicular to banks of sulci Radial = perpendicular to crowns of gyri (& scalp) Many trials needed for averaging (same as ERP) Sensitive to eye movement artifacts (same as ERP), but can be filtered out Overview of Transcranial Magnetic Stimulation (TMS) Stimulating coil inducing TMS Operating principles of TMS Effects of TMS Uses of TMS Advantages & disadvantages of TMS TMS stimulating coil TMS stimulating coil TMS operation principles Stimulating coil Coil has round shape or figure 8 shape Produces clicking sound Brief current pulses of several kiloamperes Causes time-varying magnetic field, about 2 Tesla strong, perpendicular to direction of current (right hand rule), 100-200 microseconds Induces current flow in opposition direction in neural tissue without known damage FDA approved pulse sequences at thumb-twitch intensity Electrode-less electrical stimulation of brain Effects of TMS Sensation of scalp being drawn up Muscle twitches Interference with sensation e.g., flashes & blind spots in vision No reports of evoked memories or smells Short-lasting effects Single-burst stimulation Long-lasting effects Repeated stimulation Effects can last Up to few minutes to hours Low-frequency stimulation (<1Hz) causes depression of activity e.g., when over auditory cortex of Schizophrenics, reduced auditory hallucinations High-frequency stimulation (>1Hz) causes enhanced activity (possibly mediated by raising of baseline activity of neurons) Faster picture naming with temporal lobe stimulation Faster problem solving with PFC stimulation (Grafman, Neurology) Uses of TMS Mapping of brain regions Motor mapping TMS causes muscle twitching, especially, as coil is over the cortical area that controls a particular muscle Electrodes attached to muscle measure its response Visual suppression mapping TMS causes transient blind spot (e.g., subject cannot report a letters identity) What does visual cortex of congenitally blind person do? Possible Treatment of neuropsychiatric / neuropsychological impairments, such as Depression & Parkinsons 20-30min/day, 2-4 weeks, over left PFC TMS used in motor mapping (Leventon, MIT) Index finger Forearm Biceps Jaw TMS used to suppress vision in left (red) and right (blue) visual field (Leventon, MIT) Advantages/disadvantages of TMS Advantages Fairly non-invasive stimulation of brain No intra-cranial electrode implantation More focal than electrode stimulation (as in ECT), since skull does not interfere with magnetic field No anesthesia or analgesics are required Artificial lesions What areas are critical for a function (versus fMRI what areas are participating in function) No need for patients to study brain operation Treatment effects, not merely passive measurement Disadvantages occasional mild headache Depth of stimulation limited to 2cm below surface of skull Due to attenuation of magnetic field with log of distance Double dissociation method Neural Network Neural network model (Haarmann & Usher, 2001; see also Haarmann, Just, & Carpenter, 1997)