Bereitschaftspotential N egative cortical shift of the will

1. BereitschaftspotentialNegative cortical shift of the will Presentation by Daniel J. Furman 278303 - פוטנציאלים מעוררים והתנהגות – אביב 2013 פרופ' הלל פרת

2. Course Review: The main components we have studied thus far..

3. Course Review: Main Components Mismatch negativity (MMN) Adapted from Garrido et al., 2007

4. Course Review: Main Components MMN N1 Adapted from Hillyard et al., 1998

5. Course Review: Main Components MMN N1 N170 Adapted from Rossion et al., 2008

6. Course Review: Main Components MMN N1 N170 N2 Adapted from Hauk et al., 2008

7. Course Review: Main Components MMN N1 N170 N2 N400 Adapted from Kutas et al., 1998

8. Course Review: Main Components MMN N1 N170 N2 N400 P2 Adapted from Kotchoubey et al., 2002

9. Course Review: Main Components MMN N1 N170 N2 N400 P2 P3a P3b Adapted from Polich, 2007

10. Course Review: Main Components MMN N1 N170 N2 N400 P2 P3a P3b P600f Adapted from Eimer, 2000

11. Is there a single feature common to every component we have studied?

12. ?

13. Yes...

14. Yes... Every component occurs after an event

15. Bereitschaftspotential

16. Bereitschaftspotential Components occur beforeevents.

17. Discovery 'There is a delightful parallel between these impressively simple experiments and the experiments of Galileo Galilei who investigated the laws of motion of the universe with metal balls on an inclined plane' Sir John Eccles, 1980 Nobel Prize winning neurophysiologist As related in Deecke, Kornhuber (2003). The Bereitschaftspotential. p. 284

18. Discovery Beginning in 1964, LüderDeecke and Hans Kornhuber concurrently recorded EEG and EMG from subjects while they freely performed fast finger flexions. DeeckeKornhuber

19. Discovery Finger flexions were not cued by any type of stimuli. Rather, they were all self-paced, and thus, entirely volitional. Adapted from Quandtet al., 2012

20. Discovery Their analysis utilized a new technology - computerized averaging. Schematic of experimental setup: Adapted from Deecke & Kornhuber, 1976

21. Discovery Step 1: First action potential in EMG sent a trigger pulse to the recorder. This was the time-locking event. Adapted from Deecke & Kornhuber,1976

22. Discovery Step 2: Since the averaging computer was unable to reverse playback, the researchers manually turned over the tape. The computer then averaged signals occurring before the EMG-triggered event marker Researchers effectively analyzed signals in the pre-event time domain.

23. Discovery: Recap Step 1: “Impressively simple experiments”

24. Discovery: Recap Step 1: “Impressively simple experiments” Step 2: Ingenious reverse-playback analysis* From Deecke et al., 1976 *See slide notes for a trivial comment

25. Discovery: Recap Step 1: “Impressively simple experiments” Step 2: Ingenious reverse-playback analysis* Step 3: Conclusion From The Bereitschaftspotential. p. 2

26. Discovery: Recap Step 3: Conclusion The Bereitschaftspotential ( “readiness potential”) is a slow, two component, negative shift of the DC cortical potential that precedesself-paced voluntary movement eventsby 1500-1000ms. From The Bereitschaftspotential. p. 2

27. Discovery: Recap Step 3: Conclusion Note – We partially discussed this topic during week 5 From The Bereitschaftspotential. p. 2

28. Generators Above: Nissl-stained motor cortex. Left, drawing by Cajal illustrating a pyramidal neuron of the postcentralgyrus. Right, Photomicrograph from one of Cajal's Golgi preparations of a pyramidal neuron. (DeFelipe, 2002)

29. Generators Above: Nissl-stained motor cortex. Left, drawing by Cajal illustrating a pyramidal neuron of the postcentralgyrus. Right, Photomicrograph from one of Cajal's Golgi preparations of a pyramidal neuron. (DeFelipe, 2002)

30. Generators Fundamentally, the generators of motor-related potentials have been localized to cortical pyramidal cells that are aligned in parallel(Lopes da Silva et al., 1982) Historically difficult to tease apart the multiple contributors of BP when considering it a unitary phenomenon; since similar components precede willful movements of the wrist, arm, shoulder, hip, knee, foot, toes, speaking, writing and swallowing.(Schreiber et al., 1983, Pfurtscheller, G. et al., 2003) Lasting debate as to whether BP arises from parallel or sequential activity across regions. (Toma et al., 2001)

31. Generators However, there is a general consensus that the main generators of the BP are the bilateral primary sensorimotor (SM1) and medial frontocentral areas (MFC). • More precisely; the crown of the precentralgyrus (area 6) most active during early BP, anterior bank (area 4) of the central sulcus most active during late. (Toma & Hallet, 2003, in BP p127). Yousryet al., 1997 Central sulcus

32. Generators Yousry et al., 1997

33. Generators Different generators of the early BP and late BP, which is sometimes refered to as the NS’ (negative slope) Left: Fig. 8 in Toma et al., 2002. Schematic diagram of serial activation within the contralateral SM1. Summed vector of small black dipoles at each area presented as a large black dipole. For the BP, area 6 has been isolated as the most active contributor. From ~0.5 s preceding EMG onset, both area 6 and area 4 become active, likely generating the NS.

34. Generators Left: Figure 6 in Cui et al. 2000 Current source density maps of the BP. A) 3.42 sec before EMG onset B) 0.46 sec before EMG onset C) At EMG onset (0 sec) Over the full course of the BP, the generators are symmetrically distributed across the majority of the cortex. There is a substantial spike in activity of the frontal lobe in the 100ms before EMG onset.

35. Confirmation and Expansion • Since its discovery, the BP findings have been replicated across labs through several paradigms and different imaging techniques. • Research has expanded beyond simple movements, to studies of sequential, simultaneous, imagined, and movements of even greater complexity. (Benecke et al., 1985. Krancziochet al., 2010) • Research has also progressed to link the BP to disease states in pursuit of medical insights, and there has been steady interest in the BP as a prospective clinical tool.

36. BP as a tool Analysis of the BP, provides insight into preparatory cortical function. Therefore, the BP can be used as a tool to study a variety of phenomena related to cortical function and preparatory processes. This includes neurological and psychiatric pathologies.

37. Pathological manifestation Multiple distinct conditions to which changes in the amplitude, latency, and/or topographical distribution of BP have been consistently correlated • For some, the rationale behind the correlation is clear, for others, the link between BP and the pathology is obtuse

38. Pathological manifestationMain areas of research • Parkinson’s disease • Neurological disorder of motor functioning • Self-initiated movements are a challenge for patients • Pre-motor cortex implicated as a primary site of dysfunction BP correlation: Amplitude significantly reduced, several subsets of abnormalities have been linked with specific symptoms. (Dick et al, 1989. Jahanshahi et al. 1995)

39. Pathological manifestationMain areas of research • 2. Cerebellardisease • • Numerous causes of cerebellar disease •Cerebellum critical for fine motor skillsand balance. • • Execution of coordinated movements. BP correlation: Peakamplitudes reduced, mean amplitude before movement onset larger and earlier. (Wessel et al. 1994)

40. Pathological manifestationMain areas of research • 3. Schizophrenia •Disease of consciousness, volition • •Frontal lobe and SMA functional deficits •Motor abnormalities a co-morbidity. (King, 1965) • BP correlation: Amplitude magnitude inversely related to severity of negative symptoms, longer latencies. (Andreasen, 1982, 1984, Westphal, 2003, Singh et al. 1992)

41. Pathological manifestationMain areas of research • 4. Depression • •Disease of consciousness • • Frontal lobe deficits • •Psychomotor slowing a co-morbidity, including delayed reaction times • •Putatively caused, or severity impacted, by cerebellum damage (Konarski et al., 2005) • BP correlation: Lower amplitude, decreased onset latency, asymmetrical distribution to left hemisphere. (Khanna et al., 1989, Haag et al. 1994)

42. Pathological manifestationAdditional topics of BP intrigue 5. Focal lesions of the thalamus, basal ganglia, cerebellum, prefrontal, and/or parietal cortices (Jahandashi& Hallet, 2003) 6. Huntington’s disease (Johnson et al., 2001) 7. Dystonia(Deuschlet al., 1995)

43. Philosophical Implications • At the time of Deecke and Kornhuber's discovery, the traditions of behaviourism and Freudianism were still paramount. • By the 1960s, the words "will" and "volition" had been completely removed from the thesaurus of the American Psychological Association. • The Bereitschaftspotential was thus of immediate interest to psychologists and philosophers, who thought it to be proof of free will, since it revealed that brain activity preceded overt behavior. • Actions were understood to follow from conscious decision making, and similarly, inaction could follow from nearly identical activity increases: implying a "veto" power.

44. Philosophical Implications “In the brain there is causality from bottom up.. But also from top to bottom” (Deecke, 2012)

45. Philosophical Implications A tremendously interesting and active discussion on the topic continues in the literature even today, with LuderDeecke recently publishing article entitled: "There Are Conscious and Unconscious Agendas in the Brain and Both Are Important—Our Will Can Be Conscious as Well as Unconscious." For further reading on the topic, other eminent authors include: Benjamin Libet, Alfred Mele, Hans Helmut Kornhuber, and Daniel Dennett

46. “We have relative freedom, graded freedom, freedom in degrees, enabling us to make responsible decisions and be captains of our own destiny. We are not totally determined.” (Deecke, 2012)

47. References The Bereitschaftspotential. (2003). Edited by MarjanJahanshahi and Mark Hallet. Kluwer Academic/Plenum Publishers, New York, USA Andreasen, N. (1982). "Negative symptoms in schizophrenia. Definition and reliability" Arch Gen Psychiatry. Andreasen, N. (1984). "Scale for assessment of negative symptoms (SANS)" Iowa City. University of Iowa Benecke, R., Dick, J., Rothwell, J., Day, B., Marsden, C. (1985). "Increase of the Bereitschaftspotential in simultaneous and sequential movements." NeurosciLett. Cui, R., Huter, D., Egkher, A., Lang, W., Lindinger, G., Deecke, L. (2000) "High resolution DC EEG mapping of the Bereitschaftspotential preceding simple or complex bimanual sequential finger movement." Exp Brain Res Deecke, L., Grozinger, B., Kornhuber, H. (1976)."Voluntary Finger Movement in Man: Cerebral Potentials and Theory." Biol. Cybernetics Deecke, L., Lang, W., Beisteiner, R., Lindinger, G., Cui, R. (1997)." Movement-Related Potentials and Magnetic Fields: New Evidence for SMA Activation Leading MI Activation Prior to Voluntary Movement."  To appear in  Proceddings of the 14th International Congress of EEG and Clinical Neurophysiology, Florence, Italy. Deecke, L., Lang, W., Beisteiner, R., Uhl, F., Lindinger, G., Cui, R. (1998).  "Experiments in Movement Using DC-EEG, MEG, SPECT and FMRI.  Current Progress in Functional Brain Mapping - Science and Applications." London.  Smith-Gordon & Co Ltd. Deecke, L. (2012) "There Are Conscious and Unconscious Agendas in the Brain and Both Are Important—Our Will Can Be Conscious as Well as Unconscious." Brain Sci. DeFelipe, J. (2002). “Sesquicentenary of the birthday of Santiago Ramón y Cajal, the father of modern neuroscience.” Trends Neurosci. Deuschl, G., Toro, C., Matsumoto, J., Hallett, M. (1995). "Movement-related cortical potentials in writer's cramp." Ann Neurol.

48. References Dick, J., Rothwell, J., Day, B., Cantello, R., Buruma, O., Gioux, M., Benecke, R., Berardelli, A., Thompson, P., Marsden, C.(1989). "The Bereitschaftspotential is abnormal in Parkinson's disease." Brain Eimer, M. (2000). "Event-related brain potentials distinguish processing stages involved in face perception and recognition." Clinical Neurophysiology Folstein, J., Von Petten, C. (2008). "Influence of cognitive control and mismatch on the N2 component of the ERP: A review." Psychophysiology Garrido, M., Kilner, J., Kiebel, S., Stephan, K., Friston, K. (2007). "Dynamic causal modelling of evoked potentials: a reproducibility study." NeuroImage Haag, C., Kathmann, N., Hock, C., Günther, W., Voderholzer, U., Laakmann, G. (1994) "Lateralization of the Bereitschaftspotential to the left hemisphere in patients with major depression." Biol Psychiatry Hauk, O., Shtyrov, Y., Pulvermuller, F. (2008). "The time course of action and action-word comprehension in the human brain as revealed by neurophysiology." Journal of Physiology, Paris. Hillyard, S., Anllo-Vento, L. (1998). "Event-related brain potentials in the study of visual selective attention." Proc. Natl. Acad. Sci. USA. Jahanshahi, M., Jenkins, H., Brown, R., Marsden, C., Passingham, R., Brooks, C. (1995). "Self-initiated versus externally-triggered movements: I. An investigation using regional cerebral blood flow and movement-related potentials in normals and in patients with Parkinson's disease." Brain Johnson, K., Cunnington, R., Iansek, R., Bradshaw, J., Georgiou, N., Chiu, E. (2001). "Movement-related potentials in Huntington's disease: movement preparation and execution." Exp Brain Res. Khanna, S., Mukundan, C., Channabasavanna, S. (1989). "Bereitschaftspotential in melancholic depression." Biol Psychiatry.

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50. References Mele, A. (2005). "Decisions, Intentions, Urges, and Free Will: Why Libet Has Not Shown What He Says He Has." In Explanation and Causation: Topics in Contemporary Philosophy; Campbell, J. O’Rourke, M., Shier, D., Eds.; MIT Press: Boston, MA, USA. Pfurtscheller, G., Neuper, C. (2003). "Movement and ERD/ERS." The Bereitschaftspotential. p191-206 Quandt, F., Reichert, C., Hinrichs,H., Heinze, H., Knight, R., Rieger, J. (2012) "Single trial discrimination of individual finger movements on one hand: a combined MEG and EEG study." Neuroimage. Rossion, B., Jacques, C. (2008). "Does physical interstimulus variance account for early electrophysiological face sensitive responses in the human brain? Ten lessons on the N170." NeuroImage. Schreiber, H., Lang, M., Lang, W., Kornhuber, A., Heise, B., Keidel, M., Deecke, L., Kornhuber, H. (1983). "Frontal hemispheric differences in the Bereitschaftspotential associated with writing and drawing." Hum Neurobiol. Singh, J., Knight, R., Rosenlicht, N., Kotun, J., Beckley, D., Woods, D. (1992). "Abnormal premovement brain potentials in schizophrenia." Schizophr Res. Tarkka, I. (1994). "Electrical source localization of human movement-related cortical potentials." International Journal of Psychophysiology The Beatles: Anthology. (2000). San Francisco: Chronicle Books. ISBN 0-8118-2684-8.