Cognitive Neuroscience

Transcription

1 Cognitive Neuroscience Spring 2008: NS 244 Introduction to topics in cognitive neuroscience: perception, attention, executive control, memory, language, motor control, emotion, reward, development and aging.

2 Cognitive Neuroscience Lecture 1: Introduction Adam Gazzaley MD, PhD Course Overview What is Cognitive Neuroscience? What are the tools of Cognitive Neuroscience?

3 Course Overview Instructors: Adam Gazzaley - UCSF Neurology & Physiology Loren Frank - UCSF Physiology Flip Sabes - UCSF Physiology Ezequiel Morsella - SFSU Psychology Howard Rosen - UCSF Neurology Jennifer Mitchell - UCSF Gallo Center Silvia Bunge - UC Berkeley Psychology

4 Course Overview Time/Place: March 31 - June 9 (Mon & Wed) 5p - 7p Genentech Hall: Room S261 Format: Lecture followed by paper discussion. Website: s08.html Text book: Gazzaniga, Ivry, and Mangun Cognitive Neuroscience: The Biology of the Mind, 2nd Edition

5 Course Overview Expectations: Attend all lectures and discussions. Familiarize yourself with course material by reading textbook chapter prior to lectures. Read assigned paper(s) prior to attending the discussion and be prepared to participate. Students run the discussion and we will go around the room for presentations. Group presentations. Present either a short written or powerpoint/keynote critique of a cognitive neuroscience paper. Grading: Attendance and participation.

6 Date Lecturer Subject Monday, March 31 Adam Gazzaley Introduction Wednesday, April 2 Adam Gazzaley Lecture: Perception Monday, April 7 Adam Gazzaley Discussion: Perception Wednesday, April 9 Adam Gazzaley Lecture: Attention Monday, April 14 Adam Gazzaley Discussion: Attention Wednesday April 16 Adam Gazzaley Lecture: Executive Control Monday, April 21 Adam Gazzaley Discussion: Executive Control Wednesday, April 23 Loren Frank Lecture: Long-term Memory Monday, April 28 Loren Frank Discussion: Long-term Memory Wednesday, April 30 Ezequiel Morsella Lecture: Language Monday, May 5 Ezequiel Morsella Discussion: Language Wednesday, May 7 Howard Rosen/Jennifer Lecture: Emotion/Reward Monday, May 12 Howard Mitchell Rosen/Jennifer Discussion: Emotion/Reward Wednesday, May 14 Flip Mitchell Sabes Lecture: Motor Control Monday, May 19 Flip Sabes Discussion: Motor Control Wednesday, May 21 Silvia Bunge Lecture: Cognitive Development Tuesday, May 27 Silvia Bunge Discussion: Cognitive Development Wednesday, May 28 Adam Gazzaley Lecture: Cognitive Aging Monday, June 2 Adam Gazzaley Discussion: Cognitive Aging Wednesday, June 4 Adam Gazzaley Group Presentations Monday, June 9 Course Overview Course Evaluation

7 What is cognitive neuroscience?

8 Cognitive neuroscience The science of how the brain enables the mind The brain is the physical and biological matter contained within the skull, responsible for electrochemical neuronal processes. The mind consists of mental attributes, such as beliefs, desires, perceptions... Conciousness, thoughts, feelings, and all other manifestations of the mind are products of the activities of the brain.

9 Cognitive neuroscience A historical perspective: Where is the seat of the mind? Ancient Egyptians - Heart 1600s BC Plato - Brain BC Men ought to know that from nothing else but the brain come joys, delights, laughter and sports, and sorrow, griefs, despondency, and lamentations. And by this, in an especial manner, we acquire wisdom and knowledge, and we see and hear and know what are foul and what are fair. - Hippocrates Hippocrates - Brain BC Aristotle - Heart BC Galen - Brain BC

10 Cognitive neuroscience A historical perspective: Where is the seat of the mind? The brain as the seat of the mind was still questioned in the 17th Century. Galileo (1623)- Science should only be concerned with primary qualities, those of the external world that could be measured or weighed. So-called secondary qualities, such as love, beauty, meaning and value, lie outside the realm of science. Galileo Galilei ( ) Descartes (1662)- Dualism- The proposal of a mind- brain dichotomy.

11 Cognitive neuroscience A historical perspective: How does the brain enable the mind? Galen (177 AD)- the brain enables the mind by movement of fluids through the ventricles (CSF). - Animal spirits Galen BC Descartes (1649)- the mind enters the body through the pineal gland at the base of the skull. - gateway to the soul Rene Descartes ( )

12 Cognitive neuroscience A historical perspective: How does the brain enable the mind? Localization vs. Distribution The faculties and propensities of man have their seat in the brain. The faculties are not only distinct and independent of the propensities, but also the faculties among themselves, and the propensities among themselves, are essentially distinct and independent: they ought, consequently, to have their seat in parts of the brain distinct and independent of each other. - Letter from Franz Joesph Gall (1798) Localization Distribution

13 Cognitive neuroscience A historical perspective: How does the brain enable the mind? The Birth of Phrenology Localization Distribution

14 Cognitive neuroscience A historical perspective: How does the brain enable the mind? Behavioral experiments on cortical lesioned animals directly challenge phrenology All sensations, all perceptions, and all volitions occupy concurrently the same seat in these (cerebral) organs. -Flourens (1824) Florens work on distributed systems as observed through lesions in the cortex of animals suggested that the cortex cannot be divided into functional units! Pierre Flourens ( ) Localization Distribution

15 Cognitive neuroscience A historical perspective: How does the brain enable the mind? Neurological evaluation of brain-damaged patients swings the pendulum back to localization view... Epileptic patients moved in a progressive manner during seizure: topographic organization of body (motor cortex) Right versus left hemisphere seizures produced different deficits (visuospatial tasks) John Huglings Jackson ( ) Localization Distribution

16 Cognitive neuroscience A historical perspective: How does the brain enable the mind? Neurological evaluation of brain-damaged patients swings the pendulum back to localization... Described expressive aphasia in a patient with a lesion to the left frontal lobe. Paul Broca ( ) Localization Distribution

17 Cognitive neuroscience A historical perspective: How does the brain enable the mind? Neurological evaluation of brain-damaged patients swings the pendulum back to localization... Described a patient with the inverse language deficit- receptive aphasia. Lesion was left hemisphere, but posterior, near parietal/temporal boundary. Carl Wernicke ( ) Localization Distribution

18 Cognitive neuroscience A historical perspective: How does the brain enable the mind? Experimental animal evidence confirms functional localization... Fritsch & Hitzig (1870) identified motor cortex in the dog using electrical stimulation Stimulation here caused the dogs limbs to twitch on the opposite side of the body Eduard Hitzig ( ) Gustac Fritsch ( ) Localization Distribution

19 Cognitive neuroscience A historical perspective: How does the brain enable the mind? Experimental animal evidence confirms functional localization... Ferrier replicated F&H s experiments in the monkey and documented more detailed maps: different regions of motor cortex controlled different body parts Also, lesions to motor cortices produces weakness David Ferrier ( ) Localization Distribution

20 Cognitive neuroscience A historical perspective: How does the brain enable the mind? Further support of localization view at the cellular level... Categorized the brain into 52 distinct areas based on the cellular organization of the cortex in the respective regions, and therefore helped to support the localization view Korbinian Brodmann ( ) Localization Distribution

21 Cognitive neuroscience A historical perspective: How does the brain enable the mind? Controversy for localization vs. distribution on a cellular level... A big Mesh vs. discrete units? Santiago Ramon y Cajal ( ) Camillo Golgi ( ) Localization Distribution

22 Cognitive neuroscience A historical perspective: How does the brain enable the mind? The debate continues into the 20th century, with advocates on both sides: Distributed view Systematically lesioned different percentages of rats' brains and then tested them in mazes they had known well. This resulted in a gradual but consistent degradation in performance. Hence the engram is not a specific connection, but rather the sum of many connections. K.S. Lashley ( ) Localization Distribution

23 Cognitive neuroscience A historical perspective: How does the brain enable the mind? The debate continues into the 20th century, with advocates on both sides: Localization view One of the great neurosurgeons. While stimulating different areas of cortex of epileptic patients during neurosurgery found that activating multiple cells would produce specific results. Wilder Penfield ( ) Localization Distribution

24 Cognitive neuroscience A historical perspective: How does the brain enable the mind? The development of tracing methods in animals and humans emphasizes the extensive connectivity between brain regions. Diffusion Tensor Imaging in Humans Tract tracing in the Macaque Localization Distribution

25 Cognitive neuroscience What we believe now: How does the brain enable the mind? An integration of localization and distributed views represents a popular opinion- also known as connectionism. Cognitive information is represented in wide, overlapping, and interactive neuronal networks of the cerebral cortex. Such networks develop on a core of organized modules of elementary sensory and motor functions, to which they remain connected. Joaquín Fuster, Cortex & Mind (2003) Localization Distribution

26 Cognitive neuroscience Integration of multiple disciplines Cognitive psychology: How the mind processes information Neurology: Function and pathology of the nervous system Neuroscience: Mechanisms of the nervous system neuroanatomy neurophysiology neurochemistry Computer science/artificial intelligence: How can computers perform tasks? Can we simulate cognition with neural-like models

27 Cognitive neuroscience What is thought and how does thinking occur? Representations Cognitive Psychology The content of thought How information is internalized Processes The manipulation of representations How information is transformed Capabilities (e.g., why we don t forget faces) Limitations (e.g., why we can t remember names) Accomplished via detailed task-based approaches (paradigms) coupled with sensitive behavioral performance recordings (e.g., chronometics & psychophysics)

28 Cognitive neuroscience Behavioral Neurology Emphasis on linking structure with function to understand brain pathology. e.g., How is a particular cognitive disability generated by a specific brain lesion? left frontal hemisphere strokes lead to expressive aphasia degeneration of neurons in the substantia nigra lead to Parkinson s disease. Important for clinical evaluation and treatment. Predicting recovery from language problems after a stroke Prescribing appropriate treatment for an older person with new onset of coordination problems. Accomplished via task-based approach to characterize precise nature of deficits, and diagnostic tests (e.g., imaging, EEG)

29 Cognitive neuroscience Neuroscience Study the structure and function of the nervous system. Includes investigations at many levels: cellular (neurons, glial cells...) molecular (neurotransmitters, genes, hormones...) systems (vision, motor...) Each of these can be studied in terms of: anatomy physiology chemistry

30 Cognitive neuroscience Computer science/ AI / neural networks Computers and modeling to investigate how computations are carried out in the brain. Artificial lesions can be used to test the validity of a neural network models. Integration of neural and computer systems- Brain Computer Interface (BCI) Signal Processing Methodology

31 Cognitive neuroscience Birth of a new field Coined in late 1970 s- Michael Gazzaniga and George Miller

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33 What are the tools of cognitive neuroscience

34 Cognitive Psychology Behavioral paradigms Behavioral measures: RT, accuracy, signal detection Computer Science Computer modeling Signal processing Neurology/Neuropsychology Lesions (naturally occurring- strokes, tumor...) Structural neuroimaging: MRI (volumetric, DTI...) Electrical recording: EEG Neuroscience (anatomy/physiolgy/chemistry) Single-unit physiology Lesions (induced- cooling, electrolytic, genetic, chemical...) Emerged with new field Metabolic neuroimaging: fmri, PET Electromagnetic neuroimaging: ieeg, ecog MEG Transcranial magnetic stimulation

35 Cognitive Psychology Methods: Task-based paradigms are designed to test hypotheses and behavioral responses on recorded as the dependent measures. Examples: representations: How do we represent letters? processes: How do we search our memory, parallel of serial?

36 Cognitive Psychology: Representations Posner s Categorization Task (1986) Task: Both vowels or both consonants= same One vowel and one consonant = different Increase in RT for different conditions reveals that the brain derives multiple representations for the same stimulus (even simple ones): physical aspects, letter identity and category.

37 Cognitive Psychology: Processes Posner s Categorization Task (1986) As the interval of time is lengthened between stimuli, the difference in RT between physically identity and phonetic identity decreases. Suggests that the internal representation of the first letter is transformed during the interval into a more abstract representation of the letter s phonetic identity.

38 Cognitive Psychology: Processes Sternberg s Memory Retrieval Task (1975) Remember: A K L M

39 Cognitive Psychology: Processes Sternberg s Memory Retrieval Task (1975) Target: L

40 Cognitive Psychology: Processes Sternberg s Memory Retrieval Task (1975) Remember: B S D P F T

41 Cognitive Psychology: Processes Sternberg s Memory Retrieval Task (1975) Target: S

42 Cognitive Psychology: Processes Sternberg s Memory Retrieval Task (1975) Reaction time (msec) Number of items in memory set Increase in RT reflects time required to sequentially scan memory, that is, it is not processed in parallel.

43 Cognitive Psychology: Constraints on processing Stroop Task (1935) Task: Name the color of each stimulus as fast as possible RED GREEN RED BLUE BLUE GREEN BLUE RED RED GREEN RED BLUE BLUE GREEN BLUE RED Increase in RT for different conditions reveals that there are multiple representations of the same stimuli. Processing is constrained by interference.

44 Strengths: Measuring response time and signal detection methodology permits detailed analyses of representations and cognitive processes. Behavioral paradigms and measures can be used in physiological experiments to related brain to mind. Weaknesses: Cognitive Psychology Cognitive psychology models can be proposed and tested without considering biological issues. For some processes there are no direct behavioral measures (e.g., ignoring) or the output is the product of multiple processes.

45 Computer Science Methods: Computer modeling/simulations Braitenberg Simulation (1984) Behavioral differences arise from a slight variation in how sensory information is mapped onto motor processes.

46 Strengths: Computer simulations provide a useful way to develop theory and guide experimental design and interpretation. Signal processing advances have aided in interpreting multidimensional data from cognitive experiments. BCI has numerous practical applications and teaches us how neural systems operate. Weaknesses: Computer Science Computer simulations usually use radical simplifications in modeling the nervous system and usually model simple behaviors.

47 Cognitive Neurology Methods: Task-based studies of patients with naturally occurring brain lesions (e.g., strokes, tumor...) Diagnostic tests to better understand pathology: Electrical recording: EEG Structural neuroimaging: CT, MRI (volumetric, DTI...) Metabolic neuroimaging: PET

48 Cognitive Neurology Neuropyschology Comparisons between two groups of patients (or patient and control) across two tasks can lead to powerful conclusions based on single and double dissociations. No Distractor Distractor WM accuracy 90% 75% LTM accuracy 75% 90%

49 Cognitive Neurology Neuropyschology Multiple cases can be combined to find area of overlap. Naturally occurring lesions

50 Cognitive Neurology Electroencephalography (EEG) (1912) Electrical signals associated with neural activity can be detected at the scalp.

51 Cognitive Neurology Electroencephalography (EEG) (1912) Mostly used clinically to assess seizures and sleep states.

52 Cognitive Neurology Structural Imaging: Computed Axial Tomography (CAT scan) (1972)

53 Cognitive Neurology Structural Imaging: Magnetic Resonance Imaging (MRI) (1980)

54 Cognitive Neurology Metabolic Imaging: Positron Emission Tomography (PET) (1976) Two γ-rays are emitted along the line passing through the site of positron-electron interaction. A fast timing circuit detects a temporal coincidence of the two γ-rays reaching a pair of radiation detectors. An array of radiation detectors provides tomographic measurements of the tissue concentration of positron-labelled compounds in 2D space.

55 Strengths: Cognitive Neurology Remains the gold standard for evaluating which brain regions are critical for a given function. Offers guidance into what questions may have the most impact on the human condition. Tools have been directly adapted to cognitive neuroscience. Weaknesses: Task-based analysis on patients is limited for explaining normal mental activity. Lesion size and location is variable.

56 Neuroscience Methods: Physiology Microelectrode recordings Anatomy Lesions induced - cooling, electrolytic Chemistry Manipulations genetic, pharmacological.

57 Neuroscience: Physiology Electrode recordings

58 Neuroscience: Physiology Retinotopic maps Tonotopic maps

59 Neuroscience: Physiology Strengths: Very high spatial and temporal resolution. Weaknesses: Only sample a small number of neurons. Aggregate behavior of neurons might be more than the sum of its parts. Lead to development of multi-electrode technology. Electrode recording is a correlational technique. Difficult to establish causality and necessity. Practical limitations in applying it to humans.

60 Neuroscience: Anatomy/Chemistry Lesions/Manipulations By altering a system, the role of structure, chemical or a gene on a behavior can be assessed. Non-reversible lesions: electrolytic, aspirations, knife cut, genetic knockouts Reversible lesions: Cooling, pharmacologically Rampon et al. (2000)

61 Adapted and new methods for cognitive neuroscience. Electromagnetic neuroimaging: qeeg, ecog, MEG Metabolic neuroimaging: fmri, PET Study of naturally-occurring lesions Transcranial magnetic stimulation (TMS)

62 Electromagnetic Neuroimaging: EEG High Density recordings Event-related Potentials (ERPs) Spectral Analysis

63 Electromagnetic Neuroimaging: EEG Strengths: High temporal resolution (milliseconds). Direct electrical correlate of neural activity (LFP) Inexpensive (relative to PET and MRI). Less restrictive environment (relative to MRI) Weaknesses: Poor spatial resolution (~cerebral lobe). Electrical signals are distorted as they pass through brain, skull and scalp Inverse problem

64 Electromagnetic Neuroimaging: MEG Small magnetic fields generated by active neurons are detected with multiple SQUIDS. Superconducting Quantum Interference Devices

65 Electromagnetic Neuroimaging: MEG Strengths relative to EEG: Higher spatial resolution. Signal is not distorted by passage through the brain, skull and scalp. Weaknesses relative to EEG: MEG selectively measures the activity in the sulci, whereas EEG measures activity both in the sulci and at the top of the cortical gyri. Expensive.

66 Cognitive Neuroscience Toolbox Electromagnetic Neuroimaging: ECoG (electrocorticography) Electrode recordings directly on the exposed surface of the brain.

67 Metabolic Neuroimaging The first cognitive neuroimaging technique... E = mc 2??? Angelo Mosso Italian physiologist ( ) The subject to be observed lay on a delicately balanced table which could tip downward either at the head or at the foot if the weight of either end were increased. The moment emotional or intellectual activity began in the subject, down went the balance at the head-end, in consequence of the redistribution of blood in his system. -- William James, Principles of Psychology (1890)

68 Task A involves a cognitive process of interest Task B is as similar as possible except that it does not involve the cognitive process of interest Identify regions that are more active during Task A than B Metabolic Neuroimaging: PET Cognitive Subtraction

69 Metabolic Neuroimaging: PET Posner, M.I. & M.E. Raichle, Images of Mind, 1994

70 Strengths: Measures glucose metabolism in addition to blood flow. Other molecules can be tagged (e.g., dopamine receptors, amyloid) Weaknesses: Metabolic Neuroimaging: PET Not a direct measure of neural activity Fair spatial resolution (~1 cm) Poor temporal resolution (~1 min at best). Involves the injection of a radioactive isotope, so number of exposures are limited in a given individual. Requires proximity to a cyclotron.

71 Blood Oxygen Level Dependent (BOLD) Signal Identified in early 1990s Metabolic Neuroimaging: fmri An indirect measure of neural activity Based on oxygenated and deoxygenated blood having different magnetic properties Increased neural activity Increased blood flow Surplus of freshly oxygenated blood Increase in oxy/ deoxy-hemoglobin ratio Increased BOLD signal

72 Metabolic Neuroimaging: fmri Presentation: Visual and Auditory, Somatosensory Recording: Motor response, eye-movements, respiratory rate, galvanic skin response, pulse, EEG

73 Metabolic Neuroimaging: fmri

74 Metabolic Neuroimaging: fmri Activation Statistics Functional images ~2s fmri Signal (% change) ROI Time Course Time Condition Condition 1 Statistical Map superimposed on anatomical MRI image Time Condition 2... ~ 5 min

75 Metabolic Neuroimaging: fmri Block Design Experimental Designs Event-related Design Wagner et al, 1998

76 Metabolic Neuroimaging: fmri Physiological Interpretation The BOLD signal correlates more with local field potentials (LFPs) more than action potentials. Measure of neural activity driven by postsynaptic potentials on synchronously active large populations of neurons. Primarily reflects neuronal input and local processing, rather than output signals (spikes). Logothetis et al, 2001

77 Metabolic Neuroimaging: fmri Strengths: Good spatial resolution (~1 mm). Can be easily coupled with structural analysis (volumes, DTI) No radioactivity. Weaknesses: Fair temporal resolution (~1 sec) Expensive. Indirect correlate of neural activity. Correlational technique.

78 Naturally occurring lesions Voxel-based lesion symptom mapping (VLSM) Patients with lesions in a given voxel were compared to those without lesions in that voxel on different behavioral measures. fluency auditory comprehension Bates et al, 2003

79 Transcranial Magnetic Stimulation (TMS) -1980s Method for non-invasive stimulation of cerebral cortex Trigger current flow through coil. Generate magnetic field over cortex. Cause massive firing of neurons in underlying cortex. Depending on pulse parameters can have an excitatory or inhibitory influence. (rtms= repetitive TMS, sptms= single pulse TMS) Minimal side effects: Not painful or harmful to tissue (external or internal). Occasional headaches (1-2%) (electrical current) Spatial resolution of ~ 1 cm.

80 Transcranial Magnetic Stimulation (TMS) TMS pulse can be directed to a cortical structure or functionally identified brain area via stereotaxic localization.

81 Transcranial Magnetic Stimulation (TMS) Behavioral responses and/or physiological responses (e.g. EEG) can be recorded after repetitive pulses (rtms) or single pulses (sptms) at different times relative to stimulus presentation.

82 Transcranial Magnetic Stimulation (TMS) Strengths: Can assess necessity of a brain region for a function and causality in its influence on another region (vs. fmri/eeg/pet). Is temporary, so limited plasticity (vs. natural lesions) Reasonably high spatial resolution (1 cm) (vs. natural lesions) Weaknesses: Lack of comfort for subject. Limited to accessible cortical areas. Still uncertain as to its exact physiological effects.

83 Resolution in Space and Time

84 Next class on Wednesday Perception