Agenda. Selected References. Learning Objectives. Selected References (continued) 5/14/2013

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1 Agenda What s New in Neuroscience? Martha S. Burns, Ph.D. May, 2013 New neurophysiology research on connectomes and their relevance to clinical practice in neurorehabilitation language, attention memory, and executive functions New research neuromodulators upregulated during language, cognition and motorpanning therapy that drive neuroplasticity: Acetylcholine clinical methodology that drives arousal setting the brain up to reorganize Facilitating selective attention Maintaining attention to task Norepinephrine clinical methodology that drives excitability of neural pathways for maintaining attention and building new connections The neuromodulator equivalent of an adrenalin rush The power of novelty in treatment Common drugs used for norepinephrine enhancement Dopamine and the reward network The reward network in adolescents versus adults The importance and value of timely reward in clinical practice Questions and answers 1 I am an employee of Scientific Learning Corporation. I have no financial or nonfinancial interest or related personal interest of bias in other organizations whose products or services are described, reviewed, evaluated or compared in the presentation.. Selected References Barr WB, Prichep LS, Chabot R, Powell MR, McCrea M. (2012) Measuring brain electrical activity to track recovery from sport-related concussion. Brain Inj. 26(1):58-66 Bassett, D., Wymbs, N.,Porter, M., Mucha, P., Carlson, J., Grafton, S. (2011) Dynamic reconfiguration of human brain networks during learning. PNAS, 108, 18, Blake, M.L., Frymark, T., Venediktov, R., (2012) An Evidence-Based Systematic Review on Communication Treatments for Individuals with Right Hemisphere Brain Damage. AJSLP, August 9, Bonnelle, V. et al. (2012) Default Mode Network Connectivity Predicts Sustained Attention Deficits after TBI. Journal of Neuroscience. Sept. 21, Buckholtz, J. and Meyer-Lindenberg, A. (2012) Psychopathology and the Human Connectome: Toward a Transdiagnostic Model of Risk For Mental Illness. Neuron (74) June 21, Learning Objectives Apply new research on neural connectomes to differential diagnosis of disorders of language, cognition and motor planning. Develop comprehensive treatment plans based on neuroscience principles that drive maximal neuroplastic change. Utilize new neuroplasticity research to develop evidence-based goals and methodology for rehabilitation of language, cognition and motor planning. Selected References (continued) Caeyenberghs, K. et al. (2012) Graph Analysis of Functional Brain Networks for Cognitive Control of Action in TBI. Brain April 1, Cicerone, K., Dams-O Connor, K., Eberlie, R., Langenbahn, D., Shapiro-Rosenbaum, A. (2012) Cognitive Rehabilitation Manual: Translating Evidence-Based Recommendations into Practice. Reston, Virginia: American Congress of Medicine. Davidson, R & McEwen, B (2012) Social influences on neuroplasticity: stress and interventions to promote wellbeing. Nature Neuroscience 15(5) Irimia, A. et al (2012) Patient-Tailored connectomics visualization for the assessment of white matter atrophy in in TBI. Frontiers in Neurology. 3, article 10. 1

2 Selected References (continued) Kleim, J. and Jones, T.A. (2008) Principles of experiencedependent neural plasticity. JSHR 51(1), S225-S239 Lomber, S., and Eggermont, J (2006) Reprogramming the Cerebral Cortex: Plasticity following central and peripheral lesions. Oxford: Oxford University Press. Mc Crea,M, Prichep L, Powell MR, Chabot R, Barr WB.J (2010) Acute effects and recovery after sport-related concussion: a neurocognitive and quantitative brain electrical activity study. Head Trauma Rehabil. Jul-Aug;25(4): Nature Reviews Neuroscience. Schacter, D. et al. The Future of Memory: Remembering, Imagining, and the Brain, Neuron, 76 (4) Reference Source for Chemistry and Rehabilitation aspects of neuroplasticity Neuron (2012) 76(1) Reviews on Neuromodulatory Mechanisms Chapman, Sandra Bond (2013) Make Your Brain Smarter. New York: Free Press, Chapter 11. Chen, A. et al. (2011) Training of goal-directed attention regulation enhances control over neural processing for individuals with brain injury. Brain 134, Kim, Y-H et al. (2009) Plasticity of the Attentional Network after Brain Injury and Cognitive Rehabilitation. Neurorehabilitation and Neural Repair (23) Patel, R. Spreng, RN & Turner, F. (2012) Functional Brain Changes Following Cognitive and Motor Skills Training: A Quantitative Meta-Analysis. Neurorehabilitation and Neural Repair Oct. 23. Vas, A., Chapman, S. et al. (2011) Higher Order Reasoning Training Years After Traumatic Brain Injury in Adults. Journal of Head Trauma Rehabilitation 26(3) Selected References (continued) Neuron (2012) 76(1) Reviews on Neuromodulatory Mechanisms Chapman, Sandra Bond (2013) Make Your Brain Smarter. New York: Free Press, Chapter 11. Chen, A. et al. (2011) Training of goal-directed attention regulation enhances control over neural processing for individuals with brain injury. Brain 134, Hovington, C., & Brouwer, B., (2010) Guided Motor Imagery in Healthy Adults and Stroke: Does Strategy Matter? Neurorehabilitation and Neural Repair 24, Kim, Y-H et al. (2009) Plasticity of the Attentional Network after Brain Injury and Cognitive Rehabilitation. Neurorehabilitation and Neural Repair (23) Patel, R. Spreng, RN & Turner, F. (2012) Functional Brain Changes Following Cognitive and Motor Skills Training: A Quantitative Meta- Analysis. Neurorehabilitation and Neural Repair Oct. 23. Reference Access To get access to any of the articles in the reference list or referred to during the presentation or to purchase books in the reference list. Go to Google Scholar (not Google) Type in the first author s last name and a few major words from the article or topic of interest. Eg. Galaburda dyslexia genes You can purchase the article through Science Direct (link on the left) or go to right links if available and download at no cost from the funding agency or supporting research center. Selected References (continued) Let s Start from the Beginning Turner, G., & Levin, B. (2008) Augmented neural activity during executive control processing following diffuse axonal injury. American Society of Neurorehabilitation 71. Vas, A., Chapman, S. et al. (2011) Higher Order Reasoning Training Years After Traumatic Brain Injury in Adults. Journal of Head Trauma Rehabilitation 26(3) Westerberg, H. et al., (2007) Computerized working memory training after stroke A pilot study. Brain Injury 21, No. 1, Pages Wymbs, N., Bassett, D., Mucha, P., Porter, M., Grafton, S. (2012) Differential Recruitment of the Sensorimotor Putamen and Frontoparietal Cortex during Motor Chunking in Humans. Neuron 74,

3 Brodmann s area map and colored outlines by process the search for modularity Hickock and Poeppel (2007) Progressed to Network Theory Network theory was an expansion of connectionistic theory that: Was proposed after early neuroimaging results (PET and MEG scanning) revealed that distributed cortical regions fire in parallel and simultaneously during standard cognitive tasks like language processing. Based on Hebbian stance that neurons that fire together wire together. New Technologies Expand Understanding Diffusion Tensor Imaging Measures diffusion (motion) of protons in water molecules.. The linear structure of fiber tracts constrains proton diffusion and produces anisotropy. Provides clearly defined images of white matter tracts Tracts mature at different rates Lebel et al.,

4 Cortical module mapping also progresses Typical brain function Disorders Fig. 3 Localization of fmri responses, depth electrodes, and neural generators N. T. Sahin et al., Science 326, (2009) Published by AAAS How Maps of Modules and Fiber Tracts Intersect Turken and Dronkers (2011) 4

5 Turken and Dronkers (2011) motor speech planning, fluency and grammar pathways Huth, et al. (2012) Continuous Semantic Space Study Design Turken and Dronkers (2011) White Matter tracts underlying auditory speech processing Huth, et al. (2012) Continuous Semantic Space voxel organization Combined methodologies yield insight into therapeutic processes Huth, H., Shinji N., Vu, A. & Gallant, J. (2012) A Continuous Semantic Space Describes the Representation of Thousands of Object and Action Categories across the Human Brain. Neuron (76) December 20, gallantlab.org/semanticmovies/ - This is a great interactive site where you can manipulate the information on semantic space Huth, et al. (2012) Continuous Semantic Space Cortical Surface Comparison of group semantic space across subjects 5

6 Potential treatment applications Better understanding of how the brain is organized for different types of cognitive processing Hierarchically as in semantic organization which supports research showing that semantic categories provide an effective way to treat word recall. Economically understanding connections that underlie working memory for example may help determine which cognitive tasks to select to underlie processing efficiency. So what is the Default Mode Network (DMF)? Two views of brain function Marcus E. Raichle (2010) Trends in Cognitive Sciences 14, 4, Clinical Takeaways Most neurological disorders may best be understood by a combination of modular and connection maps (connectomes). Differential diagnosis may be much easier once the connectome differences are corroborated see issues with DSM-5 NYTimes, May 7, Treatment hierarchies can be developed using information from these combined constructs. Some developmental disorders of connectome organization and progressive dementias may be partially preventable or amenable to cognitive interventions that enable more efficient brain processing. Figure 2. Performance of a wide variety of tasks has called attention to a group of brain areas (a) that decrease their activity during task performance (data adapted from [31]). These areas are often referred to as the brain s DMN [32]. If one records the spontaneous fmri BOLD signal activity in these areas in the resting state (arrows, a) what emerges is a remarkable similarity in the behavior of the signals between areas (b), a phenomenon originally described by Biswaland colleagues in the somatomotorcortex [147] and later in the DMN by Greiciusand colleagues [38]. Using these fluctuations to analyze the network as a whole reveals a level of functional organization (c) that parallels that seen in the taskrelated activity decreases (a). Raichle, 2010 Understanding the Default Mode Network DMN as the mind wandering network Shown are six major brain networks analyzed in this way: visual, sensorimotor, auditory, default mode, dorsal attention and executive control. (Raichle, 2010) Raichle,

7 Bonnelle et al (2011) The greater the Selective Attention impairment the greater the DMN activity Human Connectome Project Which takes us to Connectomes Bullmore& Sporns, 2012 How do these modular systems integrate through the white matter fiber tracts for brain efficiency and plasticity FROM THE JANUARY-FEBRUARY 2013 ISSUE of Discover Magazine: New Project Maps the Wiring of the Mind Project to trace all the brain's main neural pathways begins its first human imaging. By Kat McGowan Wednesday, January 23, 2013 a. Network connections shortest path connections are called hubs b. network modules color coded based on membership in major modules (Bulmore and Sporns, 2012) 7

8 Color-coded FreeSurfer parcelation of sample brain from which Connectograms were developed. Central section is the pial surface and bottom section is the inflated surface Irimia, A. et al (2012) Connector hubs are regions of multimodal association cortex (Bullmore and Sporns, 2012) So where is this taking us clinically? Understanding long term consequences of acquired neuropathology in terms of atrophy of fiber tracts will allow us to prioritize processing systems to stimulate For example, Irimia, et al, Understanding developmental and degenerative disorders in terms of neurophysiological patterns of disturbance rather than symptoms For example - Bullmore and Sporns, Understanding attentional and memory processes and effective interventions For example, Buckholtz and Meyer-Lindenberg (2012). Connectogram atrophy profile of patient 2 from Irimia, A et al (2012). Links displayed indicate connections that suffered large atrophy from the acute baseline in the chronic followup time point. Moving from fmri to connectograms for understanding effect of lesion(s) and outcome of treatment (Irimia, A. et al 2012) Default Mode Network and Connectome Research Applications Cognitive processing networks Developmental neuropathologies Autism Schizophrenia 8

9 With application to understanding disorders like Schizophrenia and Autism Buckholtz and Meyer-Lindenberg (2012) Connectomes patterns with developmental disorders - ADD Bullmore and Sporns (2012) Attentional Networks (Connectomes) Attention as a core component of cognitive control deficits as distractibility and impulsivity Wide distributed networks with frontal lobe providing top-down control. Two primary attentional networks: Frontal parietal ignoring distractions and working memory. Frontal striatal lack of flexibility and impulsivity. Sustained Attention predicted by the Default Mode Network. Schacter et al. (2012) Visual spatial versus autobiographical planning and the default network Extended view Attention as a core component of Cognitive Control. Inhibition/distractibility Holding information in mind while inhibiting a prepotent response Day-night Tapping ( When I tap once you tap twice) Appearance-reality (clouds) /technology/ distraction-filteringdemo.html?th&emc=th 9

10 Response inhibition Stroop-like test Changes in Attention and Executive Function Scores for Subjects (A) in attention training group (B) educational group (Chen et al, 2011) Response inhibition Stroop-like Test Neural mechanisms of selective auditory attention are enhanced by computerized training: Electrophysiological evidence from language-impaired and typically developing children Courtney Stevens, Jessica Fanning, Donna Coch, Lisa Sandersa, Helen Neville B R A I N R E S E A R C H ( ) Frontoparietal network reorganization Chen et al, 2011 Used computerized goal directed attention regulation task. 12 patients with chronic acquired brain injury. randomized to receive either the goals training intervention or education during the first 5-week study period. The participants then switched over to the alternative condition forthe second 5-week study period. Of the 12 participants, five started with goals training and seven started with education. Behavioural and ERP attention effect for the FFW-LI, FFW-TD, and NoTx control groups, separately for pre- and post-testing 10

11 M. Balter Science 328, (2010) Published by AAAS Interactive therapeutic activities for working memory training See esp. Jaeggi, et al., Proceedings of the National Academy of Sciences May, 2008 Improving fluid intelligence with training on working memory Susanne M. Jaeggi, Martin Buschkuehl, John Jonides, and Walter J. Perrig Studies with normal adults Jolles et al (2010) Practice effects in brains: changes in cerebral activation after working memory practice depend on task demands. Neuroimage 52, Kondo et al (2005) Changes in brain activation associated with use of a memory strategy: a functional MRI study. Neuroimage 24, Working memory training improves reading processes in typically developing children. Sandra V. Loosli Martin Buschkuehl Walter J. Perrig Susanne M. Jaeggi Volume 18, Issue 1,

12 Buckholtz and Meyer-Lindenberg (2012) Connectomes patterns with developmental disorders Buckholtz and Meyer-Lindenberg (2012) Connectomes patterns with developmental disorders Task Switching Card sorting Go/no-go (Simon says) Can increase complexity to increase task switching 6/07/technology/ task-switchingdemo.html Maximizing Neuroplastic Change through what you do in therapy New principals and guidelines derived from neuroscience research help in selection of tasks Maximizing neuromoduation of neuroplasticity helps in selecting methodology New research Clinical takeaways Buckholtz and Meyer-Lindenberg (2012) Connectomes patterns with developmental disorders 1. Balance Brain Stimulation Chapman (2013) Active mental stimulation is required to improve or recover lost cognitive functions 80% rule (Merzenich & Jenkins) Too low challenge creates boredom Too high challenge creates frustration agitation Tasks need to be ratcheted up a notch to constantly achieve brain wiring 12

13 Zone of Proximal Development New concepts/skills are maximally learnable/processed because they should be just difficult enough to engage the client/patient yet easy enough to maintain high spirits 4. & 5. Stay Informed and Modify Based on New Research Chapman (2013) Expect new breakthroughs each year in neuroscience of plasticity and rehabilitation especially with new connectome research Never let your client give up the brain can rewire for the rest of our lives 2. Strengthen Strategic Attention Chapman (2013) See especially research by Kim et al (2012); Bonnell et al (2012); Chen et al (2011) Goal Directed Attention Keep background stimulation as low as possible The brain has to work harder to process input while blocking out extraneous distractions The processing impaired/injured brain tires faster when there are extraneous stimuli Therapist can gradually add distractions during tasks to build tolerance Maximizing Plastic Change in Therapy by How You Do It! 3. Practice Integrated Reasoning Chapman (2013) Start with higher-order processing Build in working memory exercises for all levels of processing difficulties Continue on to higher level reasoning tasks such as analogies, problem solving, pattern analysis Neurochemistry of Neuroplasticity - Explaining the How of Therapy 13

14 Different dimensions of adult cortical plasticity are enabled by the behaviorallycontext-dependent release of: acetylcholine (focused attention/reward) (Kilgard, Bao) dopamine (reward, novelty) (Bao) norepinephrine (novelty) (Bollinger) serotonin (Bollinger) et alia In infants, exposure-based plasticity is relatively uniform. In older children, learning-induced changes are complexly nuanced by differences in behavioral context that result in the differential release of 6 or 7 modulatory neurotransmitters. Take away from Picciotto, Higley and Mineur (2012) ACh is an arousal neuromodulator both excitatory and inhibitory it enhances the salience of the primary signal and decreases attention to less important things going on in the environment To upregulate ACh in therapy think TV commercials (they are louder and grab you with color and quick relevance) Put the client in charge of when information is presented ( signal [or tell me] when you are ready ) Use Movement and activity in the sessions to keep arousal high (why I wish I was an OT or PT), establish eye contact frequently with non-attending clients, use bells and whistles Picciotto, Higley and Mineur (2012) Acetylcholine (ACh) as a neuromodulator: Cholinergic Signally Shapes Nervous System Function and Behavior. Neuron, 76, October ACh increases behaviors that are environmentally adaptive ACh decreases responses to ongoing stimuli that don t require immediate action Sara and Bouret (2012) Orienting and Reorienting: The Locus Coeruleus Mediates Cognition through Arousal. Neuron, 76, October 4, 2012 Norepinephrine [noradrenalin (NA)] regulates mood, motivation and arousal NA drives a reallocation of neural resources toward regions involved in attention, vigilant perception, and behavior control Picciotto, Higley and Mineur (2012) Acetylcholine The environmental attention modulator Figure 3. Effects of Acetylcholine on Activity of Cortical Neurons Salient cues induce acetylcholine release onto interneurons targeting the apical dendrites of cortical pyramidal neurons, resulting in rapid inhibition of pyramidal cells. Activation enhances stimulation of pyramidal neuron firing from the environment Acetylcholine also suppresses corticocortical transmission through reducing distraction while preserving attention to an environmental stimulus Sara and Bouret (2012) Figure 4. Schematic Overview of the Proposed Mechanisms Underlying Norephinephrine Activation and Its Function Norephinephrine the environmental adaptor chemical A salient stimulus release of noradrenaline in its numerous target regions (blue arrows), including cerebral cortices, limbic structures, thalamus, cerebellum, brainstem, and spinal cord. Surge of NA facilitates sensory and motor processing reorganizing distributed functional networks & promoting behavioral adaptation. 14

15 Take away from Sara and Bouret (2012) Making content of sessions emotionally relevant is the key to increased norepinephrine. The ah hah moment. The wow that is cool response to information. Similar dopamine (coming up) novelty works well. Try presenting the information several different ways. This is where the creativity of a clinician and engaging materials really come into play. Take away from Tritsch and Sabitini (2012) Continued REWARD, REWARD, REWARD Reward meaningfully and frequently Know what is and is not rewarding for each person you work with Provide good personal examples of why and how that session applies to real situations Be careful about rewards (saying the same thing every time, like nice try or good is not rewarding Dopaminergic Modulation of Synaptic Transmission in Cortex and Striatum Nicolas X. Tritsch and Bernardo L. Sabatini Neuron 76, October 4, 2012 Lesch and Waider (2012) Serotonin in the Modulation of Neural Plasticity and Networks: Implications for Neurodevelopmental Disorders. Neuron, 76, October 4, 2012 Serotonin (5-HT) shapes brain development influencing social cognition and emotional learning. 5-HT and brain development are highly affected by genetics and environmental influences. Tritsch and Sabitini (2012) The prefrontal cortex is the major cortical recipient of Dopaminergic inputs Dopamine (DA) is believed to play a critical role in several cognitive processes conducted by Pre Frontal Cortex networks, including working memory, attention, and decision making Take Away from Lesch and Waider (2012) and Kravitz et al (2012) The environment of the clinic should be safe and non-threatening The goal of discipline should be to reward correct responses and keep materials at an appropriate level for 80% correct Withholding reward is preferable to punishment (adverse outcomes) this is very important with adolescents 15

16 Q & A 16