Understanding the brain: a work in progress

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

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High speed supercomputers IBM ASCI White TFLOPS DoE-Lawrence Livermore National Laboratory USAIBMASCI WhiteDoE-Lawrence Livermore National LaboratoryUSA 2002 NEC Earth Simulator TFLOPS Earth Simulator Center, JapanNECEarth SimulatorEarth Simulator CenterJapan 2004 IBM Blue Gene/L TFLOPS DoE/IBMIBMBlue Gene/LDoEIBM TFLOPS DoE/U.S. National Nuclear Security, Lawrence Livermore National Laboratory TFLOPSDoEU.S. National Nuclear SecurityLawrence Livermore National Laboratory 2007/ TFLOPS IBM Roadrunner PFLOPS DoE-Los Alamos National Laboratory PFLOPSIBMRoadrunner DoE-Los Alamos National Laboratory 2009 Cray Jaguar PFLOPS DoE-Oak Ridge National Laboratory, USACrayJaguarDoE-Oak Ridge National LaboratoryUSA

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

Neurons

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.

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!

Major subdivisions of the brain

Reticular activating system

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

Imitating the actions of others (mirror neurons) Control Autistic

How is information represented in the brain?

Advantages/disadvantages of spatial encoding

Correlation and pattern changes Advantages and disadvantages of temporal encoding

Inhale 5 sec 247ms

1234 Odor Concentration Number of elements in sequences Prestimulus During stimulus Number of elements in sequences Complexity of inhale-related sequences Prestimulus During stimulus Number of sequences detected Incidence of inhale-related sequences 1234 Odor Concentration Number of Sequences detected

1234 Odor Concentration Number of elements in sequences Prestimulus During stimulus Number of elements in sequences Complexity of inhale-related sequences Prestimulus During stimulus Number of sequences detected Incidence of inhale-related sequences 1234 Odor Concentration Number of Sequences detected

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

The Sensory Brain

Sensory maps - vision

Sensory maps - hearing

Somatosensory and motor maps

The somatosensory homunculus

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

The brain as an interpreter Illusions

Synaesthesia

We may all start off experiencing the world through synaesthesia

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

Face processing in the brain

Single cell vs population encoding

Quian-Quiroga et al (2005) Nature

Andrews et al J Neurosci (2010)

The brain as an interpreter

Encoding face identity and face emotion cues simultaneously

Operant discrimination between different faces Face discrimination learning

Brain rhythms and face recognition learning Hz 4-8Hz

Coupling between fast and slow oscillations (theta and gamma)

Phase locking between IT neuronal activity and theta

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

Correlations between discrimination performance and altered theta/gamma activity

Neural network models NL=0.002 L= NL= L= Theta ↑ Gamma ↓ Gamma ↑ Theta ↓

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

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

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

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

Decorrelation improves discriminability of patterns

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

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

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

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

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

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

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.

Establishing functional connections in the brain using Granger causality

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