Premises to open discussion. The Neuroscience of Types of Learning

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1 Brains are creative and figure things out, particularly when appropriately motivated The Neuroscience of Types of Learning American Dental Education Association San Antonio, TX March 16, 2014 Presented by: Michael J. Friedlander, Ph.D. Executive Director, Virginia Tech Carilion Research Institute, Roanoke, VA Associate Provost for Health Sciences, Virginia Tech Professor, Biological Sciences and Biomedical Engineering, Virginia Tech Senior Dean for Research, Virginia Tech Carilion School of Medicine Professor, Psychiatry and Behavioral Medicine, Virginia Tech Carilion School of Medicine I RECEIVE NO COMMERICAL SUPPORT AND HAVE NO CONFLICTS Weir et al., Science, 297: 981, 2002; Posted on YouTube, 2007 Premises to open discussion Learning and memory are ubiquitous processes in the animal kingdom essential for survival; snails do it, flies do it, fish do it, birds do it (and yes, bees do it), mice do it, humans do it; Humans are biological and social creatures that have evolved and created institutions and organizational structures that integrate our capacity to learn. The debate is over brain makes minds Brains/minds function (and can be studied) at multiple levels

2 Information is learned and stored over multiple time domains, engaging multiple neural pathways A goal for Sunday morning before St. Patrick s day: Become conscious and appreciate, understand and apply current knowledge of how learning and memory work in order to guide teachers and learners to optimize the assimilation, comprehension and retention of the foundations, principles, reasoning skills and necessary facts in order that they may access and apply this knowledge effectively Learning: The acquisition of an altered behavioral response due to an environmental stimulus Memory: The processes through which learned information is stored Consolidation: The process by which memories are rendered stable and lasting Changes in behavior are ultimately subserved by alterations in the nature, strength or number synaptic contacts between neurons Greenough et al., PNAS, 1985

3 Maybe not the best comprehensive model for a dental learner E Kandel, Principles of Neuroscience Maybe not the best comprehensive model for a dental learner but a starting point! Lets start with the P word

4 Mr. McGuire: I just want to say one word to you - just one word. Ben: Yes sir. Mr. McGuire: Are you listening? Ben: Yes I am. Mr. McGuire: 'Plastics.' Ben: Exactly how do you mean? Mr. McGuire: There's a great future in plastics. Think about it. Will you think about it? Ben: Yes I will. Mr. McGuire:! Enough said. That's a deal. Mr. McGuire: I just want to say one word to you - just one word. Ben: Yes sir. Mr. McGuire: Are you listening? Ben: Yes I am. Mr. McGuire: 'Plastics.' Ben: Exactly how do you mean? Mr. McGuire: There's a great future in plastics. Think about it. Will you think about it? Ben: Yes I will. Mr. McGuire: Enough said. That's a deal. Mr. McGuire: I just want to say one word to you - just one word. Ben: Yes sir. Mr. McGuire: Are you listening? Ben: Yes I am. Mr. McGuire: 'Plastics.' Ben: Exactly how do you mean? Mr. McGuire: There's a great future in plastics. Think about it. Will you think about it? Ben: Yes I will. Mr. McGuire: Enough said. That's a deal. Mr. McGuire: I just want to say one word to you - just one word. Ben: Yes sir. Mr. McGuire: Are you listening? Ben: Yes I am. Mr. McGuire: 'Plastics.' Ben: Exactly how do you mean? Mr. McGuire: There's a great future in plastics. Think about it. Will you think about it? Ben: Yes I will. Mr. McGuire: Enough said. That's a deal.

5 The mature brain is functionally reorganizing all the time on the fly What are synapses? whole human brain individual neuron axon dendrite individual synapse Tops down functional reorganization of the brain changing what we perceive based on expectations What are synapses? whole human brain individual neuron Berns et al, Biological Psychiatry, 58: 2005 Communication sites between neurons or between neurons and other target tissues (muscle, glands, etc) axon dendrite individual synapse

6 Synaptic transmission responses at the neuromuscular junction has high fidelity and shows little/no plasticity Adult human brain billion neurons, 100 trillion synapses; (lots but no, not more stars than in the universe!) Boyd & Martin, mm Fregnac and Friedlander Synaptic transmission responses at the neuromuscular Junction has high fidelity and shows little/no plasticity Adult human brain billion neurons, 100 trillion synapses; (lots but no, not more stars than in the universe!) and they are fickle, variable and subject to change in response to experience and that is a really good thing! Boyd & Martin, mm Fregnac and Friedlander

7 The hippocampus structure key to learning Hippocampal long term potentiation (LTP) and long term depression (LTD) functional changes in synaptic strength: proposed biological substrates for learning, memory and forgetting LTP LTD Sayer, Friedlander and Redman Coincidence detection NMDA receptors Learning also triggers long lasting structural changes in synapses Francis Crick was right (again) our brains are twitching Sayer, Friedlander and Redman 1990 Bhatt et al, Ann Rev Physiol., 2009 F-actin in dendritic spines

8 After initial triggering, memories form and exist not as isolated molecular changes within individual neurons alone but across large scale interactive neuronal networks (cognits) Fuster, J. Cog Neurosci, 2009 EPSP Amplitude (mv) mv 100 ms LTP Normalized EPSP Amplitude n=48 EPSP Amplitude (mv) EPSP Amplitude (mv) 10 mv ms mv No Effect LTD ms 10 Normalized EPSP Amplitude Normalized EPSP Amplitude n= n= Time (min) Time (min) The history of the neurons and the synaptic circuits in which they are functionally embedded matters (Ismailov and Friedlander, J. Neuroscience, 2005) EPSP Amplitude (mv) mv 100 ms LTP Normalized EPSP Amplitude n=48 EPSP Amplitude (mv) mv 100 ms LTP Normalized EPSP Amplitude n=48 EPSP Amplitude (mv) EPSP Amplitude (mv) 10 mv ms mv ms 10 No Effect LTD Normalized EPSP Amplitude Normalized EPSP Amplitude n= n= EPSP Amplitude (mv) EPSP Amplitude (mv) 10 mv ms mv No Effect LTD ms 10 Normalized EPSP Amplitude Normalized EPSP Amplitude n= n= Time (min) Time (min) Time (min) Time (min)

9 Different sets of synapses on the same neuron can undergo opposite polarities of synaptic plasticity in response to a common learning experience the synapse as the computational learning unit Pixel # Scan # It s the local calcium signals that matter for how the synapses respond Fitch and Friedlander, unpublished Neuronal network activity enhancement accentuating task start - end with over-training and habit formation Pennartz et al., J. Neurosci., 2009 Repetition causes efficient activation of learning gated signaling pathways that facilitate longer term memory formation and access to utilization of learned information Kandel, ER, Science, 2001

10 Spaced vs. mass activation is more efficient at inducing biological substrates of memory formation Scharf, MT et al., J. Neurophysiol., 2002 Scaling up - non-invasively monitoring activity in the intact human brain fmri and MEG fmri makes a movie of microscopic blood flow changes in the brain proxy for localized neural activity while performing a task or thinking Repetitively spaced activation requires protein synthesis for longer term plasticity to manifest Practice really works getting started early is good but not essential

11 Neural enhancement induced by repetitive recall active re-visiting what was learned by the learner Teruo Hashimoto., T. et al., Neurobiology of Learning and Memory, , no. 2, Consolidation during sleep promotes qualitative and quantitative enhancement of memories Diekelmann and Born, Nat. Rev Neurosci., Spaced learning enhances subsequent recognition memory by reducing neural repetition suppression. Xue G, et al.. J Cogn Neurosci Jul;23(7): Memory replay of learned information during rest Ji and Wilson, 2007

12 Emotionally significant experiences are well remembered but chronic stress is destructive to the biological processes that underlie long term memory formation Roozendaal et al., Nat Rev Neurosci., 2009 High levels of stress inhibit learning induced synaptic plasticity and retention of learned information Kim et al., PNAS 2007 Neural circuitry that contributes to the formation of new memories is richly invested with the signaling pathways for mediating stress responses The Influence of selective attention on the mnemonic binding of contextual information Uncapher MR and Rugg, MD, J. Neuroscience, 29: 2009 McEwen, Physiol Rev., 2007

13 . Interference of working memory load with long-term memory formation. Axmacher N, et al., J Eur J Neurosci Apr;29(7): Growing new neurons throughout life - neurogenesis, Van Prag et al (Gage lab), J. Neuroscience, 2005 Group interactions dynamically modulate cognitive performance and capacity Adult born neurons integrate into hippocampal circuitry C. Zhao Kishida, K., Montague, P.R., et al., 2012, Philosop. Trans of the Royal Society B. S. Jessberger

14 Social interactions facilitate biological substrates of learning including adult neurogenesis Neural signatures of cognitive variability between individuals for accomplishing approximate quantification tasks with different strategies Gandini D et al. Brain Research, 2008 isolation group environment Stranahan et al, Nature Neuroscience, 2006 Downar J, Bhatt M, Montague PR. PLoS One. 2011;6(11):e27768 Neural correlates of effective learning in experienced medical decision-makers. Positive reinforcement through the brain s reward pathways rewards can be externally or internally generated Fields et al., types of medical learners

15 Reward signaling activity patterns in the young vs. older brain Dreher et al, PNAS, 2008 Neural substrates of self control processes that can value delayed rewards over more immediately available incentives Luo et al., J. Neurosci., 2009 Cabeza et al., Nat Rev Neurosci, 2008 Visual imagery or mental rehearsal can activate higher order brain regions Kaas A., et al., Neiuroimage, 49: 2010 During episodic retrieval, VPC activity increases as a function of recollection and confidence

16 Observed effector-independent motor learning by observing. Williams A, Gribble PL J Neurophysiol Mar;107(6): Neural activation with motor imagery vs. observation of action Munzert et al., by American Physiological Society Vividness of mental imagery: Individual variability can be measured objectively Cui X., et al., Vision Research, 47: Writing affects the brain network of reading in Chinese: A functional magnetic resonance imaging study. Cao F, et al., Hum Brain Mapp Feb 29.

17 . Learning by doing and learning by thinking: an FMRI study of combining motor and mental training Olsson CJ, et al., Front Hum Neurosci. 2008;2:5. Epub 2008 Jun 18. What we know Repetition works; Spacing is important (drink from the fire hose with breaks); Reward is key to learning (rewards can come in many forms and can be delayed); Visualization, mental imagery, practice all engage the brain s learning machinery; Active learning works the learner should engage and have responsibility; attention Group dynamics affect learning and capacity; Social interactions affect biological changes in learning circuitry; Stress (in its many forms) is not a bad thing for enhancing learning (in fact it is useful) but chronic stress is destructive to learning and memory; Mental rehearsal/imagery engage neural circuitry for learning; Rest/sleep helps consolidation of memories; fatigue is disruptive to learning; There are individual differences in learning strategies and mechanisms. Neural system for abstraction of commonalities across multiple related experiences giving rise to network of conceptual knowledge Kumaran et al., Neuron, 2009 What we don t know What are the most effective repetition rates and epochs How often should information be revisited for most effective retention What is the optimal mix of factual and conceptual information to allow the learner to go deep and to be able to locate the additional necessary information on their own

18 THANKS! QUESTIONS?