1. Understanding the brain: a work in progress

2. The brain performs an incredible range of functions Controls body functions and motivates us to obtain appropriate resources to maintain life Movement Detect and interpret sensory information and social cues Attend to specific things rather than others Learn and remember information and integrate it with past knowledge Guide behaviour through emotional responses Generate conscious awareness of the external environment, self and others

6. 0.5 5

7. High speed supercomputers 2000-2010 2000 IBM ASCI White 7.226 TFLOPS DoE-Lawrence Livermore National Laboratory USAIBMASCI WhiteDoE-Lawrence Livermore National LaboratoryUSA 2002 NEC Earth Simulator 35.86 TFLOPS Earth Simulator Center, JapanNECEarth SimulatorEarth Simulator CenterJapan 2004 IBM Blue Gene/L 70.72 TFLOPS DoE/IBMIBMBlue Gene/LDoEIBM 2005 136.8 TFLOPS DoE/U.S. National Nuclear Security, Lawrence Livermore National Laboratory 280.6 TFLOPSDoEU.S. National Nuclear SecurityLawrence Livermore National Laboratory 2007/8 478.2 TFLOPS IBM Roadrunner 1.026 PFLOPS DoE-Los Alamos National Laboratory 1.105 PFLOPSIBMRoadrunner DoE-Los Alamos National Laboratory 2009 Cray Jaguar 1.759 PFLOPS DoE-Oak Ridge National Laboratory, USACrayJaguarDoE-Oak Ridge National LaboratoryUSA

8. IBM Sequoia Supercomputer 20 PFLOPS speed 1.6 PFLOPS memory 318m2 96 racks 7megawatts

9. Neurons

11. Neuroglial cells Astrocytes - anchor neurons to blood vessels and transport of nutrients/ waste. Have receptors, produce growth factors and modulate synaptic transmission. Signal to one another via gap junctions using calcium. Microglia - defence against pathogens and monitor the condition of neurons. Ependymal cells - line the fluid-filled cavities in brain and spinal cord. Produce, transport, and circulate the cerebrospinal fluid. Oligodendrocytes - produce the myelin sheath in the CNS which insulates and protects axons.

12. P P PP P Glu PresynapticTermi nal Glu Ca ++ GLUR (Group- I ) iGLUR GLUR (Group- II,III ) GPCR ATP cAMP CamK- II CamK- IV CamK- II Calm PKC DAG IP3RIP3R PKC c-Raf MEKs Akt ERK1/2 p90RSK S133 CBP p300 Co-factor RNA Pol- II Gene Expression Gene Expression PKA GsGs GG GG GG GG GG GG GG GG GG Growth Factors Growth Factors Growth Factor Receptor Growth Factor Receptor TF II B CREB Pathway Neuron PLC TATA CRE SRE P Elk1 CREBCREB CREBCREB TBP Hormones/ Neurotransmitters IP3 PI3K GRB2 SOS Ac PI CaCn Ras 2009 ProteinLounge.com 2009 ProteinLounge.com C The molecular brain!

13. Major subdivisions of the brain

14. Reticular activating system

15. Neural plasticity Learning – turning the gain up and the noise down

16. Imitating the actions of others (mirror neurons) Control Autistic

17. How is information represented in the brain?

18. Advantages/disadvantages of spatial encoding

19. Correlation and pattern changes Advantages and disadvantages of temporal encoding

20. Inhale 5 sec 247ms

21. 1234 Odor Concentration 10 11 12 1314 Number of elements in sequences Prestimulus During stimulus 0 2 4 6 8 10 12 14 16 Number of elements in sequences Complexity of inhale-related sequences Prestimulus During stimulus 0 100 200 300 400 Number of sequences detected Incidence of inhale-related sequences 1234 Odor Concentration Number of Sequences detected 0 100 200 300 400

22. 1234 Odor Concentration 10 11 12 1314 Number of elements in sequences Prestimulus During stimulus 0 2 4 6 8 10 12 14 16 Number of elements in sequences Complexity of inhale-related sequences Prestimulus During stimulus 0 100 200 300 400 Number of sequences detected Incidence of inhale-related sequences 1234 Odor Concentration Number of Sequences detected 0 100 200 300 400

23. Combined spatial and temporal encoding Most robust solution, allowing brains to be a reasonable size Makes it easier to both separate, integrate and decode information

24. The Sensory Brain

25. Sensory maps - vision

26. Sensory maps - hearing

27. Somatosensory and motor maps

28. The somatosensory homunculus

29. Integration of sensory information Multisensory brain areas One sense can influence interpretation of another one (see a mouth shape the word “bait” and hear the word “gate”, you think you hear “date”) – McGurk Illusion Facial expressions, even if not consciously perceived, modify the perception of emotion in the voice of the speaker

30. The brain as an interpreter Illusions

31. Synaesthesia

34. We may all start off experiencing the world through synaesthesia

36. Neural encoding of faces "Who are you?", "how do you feel?" "do i like you"?” Answers in <300 milliseconds!

37. Face processing in the brain

39. Single cell vs population encoding

40. Quian-Quiroga et al (2005) Nature

41. Andrews et al J Neurosci (2010)

42. The brain as an interpreter

43. Encoding face identity and face emotion cues simultaneously

44. Operant discrimination between different faces Face discrimination learning

47. Brain rhythms and face recognition learning 30-120Hz 4-8Hz

48. Coupling between fast and slow oscillations (theta and gamma)

49. Phase locking between IT neuronal activity and theta

50. >75% of IT electrodes show coupling between theta phase and gamma amplitude I 5µV

51. Correlations between discrimination performance and altered theta/gamma activity

52. Neural network models NL=0.002 L= 0.0035 NL=0.0001 L= 0.00055 Theta ↑ Gamma ↓ Gamma ↑ Theta ↓

53. Decreased synchronization as theta/gamma ratio increases Downstream neuron Model IT

54. Excitatory neurons Synch (1) De-synch (2) Downstream neuron Output (1)(2) How desynchronization alone can produce potentiation

55. Excitatory neurons Synch (1) De-synch (2) Downstream neuron Output (1)(2) How desynchronization alone can produce potentiation

57. Excitatory neurons Synch (1) De-synch (2) Downstream neuron Output (1)(2) How desynchronization alone can produce potentiation Decorrelation reduces noise

58. Decorrelation improves discriminability of patterns

60. The problems of consciousness There is no single seat of consciousness in the brain Many things are processed without conscious awareness Often similar patterns of brain activation are seen when information is processed with or without conscious awareness There are different levels of consciousness Individuals may be aware even when they show no obvious signs of consciousness

61. Spatial imageryMotor imagery Assessing conscious awareness in “vegetative state” brain damaged patients

62. Study found 10% of vegetative state patients could perform motor/spatial imagery tasks Monti et al (2010) New Eng J Med

63. Using brain imaging to enable vegetative state patients to communicate Monti et al (2010) New Eng J Med

64. PP

65. Alkire et al (2008) Science Effects of anaesthesia and sleep on cortical integration

66. Reduced unidirectional information flow and long distance connections, and increased short-loop feedback Effects of deep anaesthesia on cortical processing

67. How does consciousness emerge? Perhaps widespread and integrated flow of activity in the neocortex generates a metarepresentation. When information is processed unconsciously a metarepresentation does not form due to lack of integrated flow between cortical processing nodes.

68. Establishing functional connections in the brain using Granger causality

69. Future progress Stronger links between mathematicians, computer scientists and neuroscientists A greater emphasis on revealing key functional connectivity changes in the brain Provide a better understanding of temporal/patterning aspects of neural encoding Further advances in technologies for measuring the activity of the working brain