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4/6/2016

Selected Neuroscience Bibliography Cognitive Function in • Anderson, Morris, Amaral, Bliss, and O’Keefe( 2007) The Cerebrovascular Accident (CVA) & Hippocampus Book. Oxford: Oxford University Press. Traumatic Injury (TBI) – MSHA • Burke, Sara and Barnes, C.A. (2006) Neural Plasticity in the Ageing Brain. Nature Reviews Neuroscience. 7;1, 30-40 Part One • Cowan,N(2008) What are the differences between long-term, short-term, and working ? Progress in Brain Research, Volume 169, 2008, Pages 323-338 Martha S. Burns Ph.D. • Devinsky and D’Esposito (2004) of Cognitive and Joint Appointment Professor Behavioral Disorders, Oxford University Press • Healey, M.K.,Campbell, KL, Hasher, L (2008) Cognitive aging and increased Northwestern University distractibility: Costs and potential benefits Progress in Brain April 2016 Research, Volume 169, 2008, Pages 353-363

Neuroscience Bibliograpgy (continued) Overview References

• Jaeggi, S., Buschkuehl, M.,Jonides, J., & Perig, W. (2008) • Anderson, P., Morris, R., Amaral, D., Bliss, T., O’Keefe, J. (2007) Improving fluid Intelligence with training on . PNAS, May 2008 The Hippocampus Book. Oxford: Oxford University Press. • Klingberg, et al. (2005) Computerized training of working • Buzsaki, G. (2006) Rhythms of the Brain. Oxford: Oxford memory in children with ADHD – a randomized controlled University Press trial. J. Am. Acad. Child Adolesc. ,;44(2):177–186. • Devinsky, O and D’Exposito (2004) Neurology of Cognitive and • LaBar, K and Cabeza, R. (2006) Cognitive Neuroscience of Behavioral Disorders. Oxford: Oxford University Press. emotional memory. Nature Reviews Neuroscience. 7;1, 54- 65 • Hillis, A. (2002) The Handbook of Adult Language Disorders: • Mattson, M.P. and Magnus, Tim (2006) Ageing and Integrating Cognitive , Neurology, and neuronal vulnerability. Nature Reviews Neuroscience. 7;4, Rehabilitation. New York: Psychology Press 278-290 • Mesulam, M-Marsel (2000) Principles of Behavioral and • Sossin, W., Lacaille, J., Castellucci, V. & Belleville, S. (2008) Progress in Brain Research. Elsevier Cognitive Neurology. Oxford: Oxford University Press

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References Pediatric Focus References Pediatric Focus

• Galaburda, A., LoTurco, F., Fitch, R.H., and Rosen, G. (2006) • Miller, M. (2006) Brain Development: Normal Processes and From genes to behavior in developmental dyslexia. Nature Effects of Alcohol and Nicotine. Oxford: Oxford University Neuroscience, 9(10). Press • Huttenlocher, P (2002) Neural Plasticity: The effects of the • environment on the Development of the Cerebral Cortex. Nature Reviews Neuroscience. www.nature.com/reviews Oxford: Oxford University Press • Stuss, D. and Knight, D. (2002) Principles of Frontal Lobe • Kadis, D et al. (2013) Cortical Thickness in Children Receiving Function. Oxford: Oxford University Press. Intensive Therapy for Idiopathic of Speech. Brain • Van Hemmen, J.L. and Sejnowski, T.J. (2006) 23 Problems in Topography:A Journal of Cerebral Function and Dynamics Systems Neuroscience. Oxford: Oxford University Press • Lomber, S., and Eggermont, J (2006) Reprogramming the Cerebral Cortex: Plasticity following central and peripheral lesions. Oxford: Oxford University Press. • Mesulam, M-Marsel (2000) Principles of Behavioral and Cognitive Neurology. Oxford: Oxford University Press

Selected Recent Overview References References cited on Diet and Oncology and

• Craig CD, Monk BJ, Farley J, Chase DM (2013) Cognitive Impairment in Gynecologic • Enzinger C, Fazekas F, Matthews PM, et al. Risk factors for progression of brain Cancers: A Systematic Review of Current Approaches to Diagnosis and Treatment. J atrophy in aging. Neurology. 2005;64:1704-1711. Abstract Palliative Care Med 3: 144 • Crane PK, Walker R, Hubbard RA, et al. Glucose levels and risk of dementia. N Engl • Ferguson RJ et al (2012) Development of CBT for chemotherapy-related -cognitive J Med. 2013;369:540-548.Abstract change: results of a waitlist control trial. Psycho-Oncology, 21,2: 76-186. • Roberts RO, Roberts LA, Geda YE, et al. Relative intake of macronutrients impacts risk of mild cognitive impairment or dementia. J Alzheimers Dis. 2012;32:329- • Gehring, Karin, Roukema, Jan Anne, & Sitskoorn, Margriet M. Review of recent 339. Abstract studies on interventions for cognitive deficits in patients with cancer. Expert • Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer's Reviews (2012); 12(2): 255-269. disease prevalence. Lancet Neurol. 2011;10:819-828. Abstract • Jim, H et al. (2012) Meta-Analysis of Cognitive Functioning in Breast Cancer • Fasano A. Zonulin and its regulation of intestinal barrier function: the biological Survivors Previously Treated With Standard-Dose Chemotherapy. Journal of Clinical door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011;91:151- Oncology. VOLUME 30 NUMBER 29 175. Abstract • Mattson & Magnus (2006) Ageing and Neuronal Vulnerability. Nature Reviews • Sapone A, Bai JC, Ciacci C, et al. Spectrum of gluten-related disorders: consensus Neuroscience 7, 278–294 on new nomenclature and classification. BMC Medicine. 2012;10:13. • McNeil, C. (2012) Treating Chemobrain: Rehabilitation Therapies Emerge. • Hadjivassiliou M, Grunewald RA, Davies-Jones GA. Gluten sensitivity as a neurological illness. J Neurol Neurosurg Psychiatry. 2002;72:560-563. Abstract JNCI,104, 22. November 21, 1691-1692. • Sherling, C. & Smith, A. (2013) Opening up the Window into “Chemobrain”: A Neuroimaging Review. Sensors, 13, 3169-3203

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Selected References and Selected References Attention and Memory Intervention (2011-2015) Memory Intervention (continued) • Anguera, J. A. et al. Video game training enhances • Melby-Lervag, M. & Hulme, C. Is working memory cognitive control in older adults. Nature 501, 97–101 training effective? A meta-analytic review. Dev. (2013). Psychol. 49, 270–291 (2013). • Amso, D. & Scerif, G. (2015) The attentive brain: • Merzenich, MM, Van Vleet, T., and Nahum, M (2014) insights from developmental cognitive neuroscience. Nature Reviews Neuroscience. Vol.16:12. October 2015 Brain Plasticity Based Therapeutics. Front Hum • Bavelier, D., Green, C.S., Hyun D., Perry, H., Renshaw, Neurosci. 8: 385. F.,Merzenich, M.M. and Gentile, D.A. (2011) on • Munakata, Y. et al (2012) A unified framework for Video Games. Nature Reviews Neuroscience. 12:12 inhibitory control Trends Cogn Sci. 2011 October ; • Gazzaley, A. & Mobre, A.C. (2012) Top-down modulation: bridging selective attention and working 15(10): 453–459. memory. Trends in .Feb;16(2):129-35 • Shipstead, Z., Redick, T. S. & Engle, R. W. (2012) Is working memory training effective? Psychol. Bull. 138, 628–654

Selected References Attentiona and Overview of Cognitive Processes Memory Intervention (continued) • Vinogradav, S. , Fisher, M., and de Villers-Sidani , E. (2012) • Attention Cognitive Training for Impaired Neural Systems in Neuropsychiatric Illness. Neuropsychopharmacology REVIEWS • Memory 37, 43–76 • Executive Functions • Van Vleet, TM & DeGutis, JM (2013) Cross-training in hemispatial neglect: auditory sustained attention training ameliorates visual attention deficits. Cortex Mar;49(3):679-90. • Wass, S. V., Scerif, G. & Johnson, M. H. Training attentional control and working memory — is younger, better? Dev. Rev. 32, 360–387 (2012). • Wass, Sam (2015) Applying cognitive training to target executive functions during early development. Child Neuropsychol. Mar 4; 21(2): 150–166.

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Sohlberg and Mateer (APT, 1989)) Model • Sustained Attention • Alternating Attention • Selective Attention • Divided Attention

DeHaene, 2009

Neurons that fire together wire together in networks Neuronal Communication System

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Diffusion Tensor Imaging BRAIN MATURATION is EXPERIENCE DEPENDENT

• Nodes in a network become mapped, first – To perceive world around us - LANGUAGE • Measures diffusion (motion) of protons in water molecules. – To act on the world around us – talk, read, do • Direction of proton motion within a voxel can be described by math problems a “tensor”. • Proton diffusion tends to be relatively isotropic in gray matter. • Later to plan, prioritize, solve novel • The linear structure of fiber tracts constrains proton diffusion problems and produces anisotropy.

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Fiber Tract Development Observable with DTI (from Hermoye et al., 2006)

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Understanding the development of the Brain’s Superhighway Different dimensions of adult cortical plasticity are enabled by system, Lebel, 2008 the behaviorally-context-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.

Attention Assessment – usually Attention (2) conducted by • Immediate span of attention • Sustained Attention – Forward and backward digit span – Conners Continuous Performance Test (Conners & • Focused Attention Multi-Health Systems Staff, 1995; Test of Variables – Cancellation Tasks of Attention, Greenberg, 1998). – • Part A – randomly distributed numbers that must be connected in ascending order (dot to dot) • Part B – set shifting and some degree of divided attention (performance closely related to tests of timed executive function)

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Attention (3) Inhibition (Davidson, et al., 2004)

• Divided Attention • Cognitive Control (Executive Functions) – • Response Inhibition – Stroop Test Inhibition – Inhibition – inhibiting distractions selective and sustained attention – Inhibiting a strong behavioral inclination makes a change possible as well as social politeness – External stimuli and engrained behavioral tendencies exert strong influences on our behavior – inhibition allows us to act otherwise

Response inhibition – Stroop-like test Response inhibition – Stroop-like Test

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Are medications necessary?

• Neuroscientists hope to eventually provide effective interventions that would decrease the necessity for medication to treat attentional disorders • Evidence-based neuroscience approaches can enhance Working memory attentional skills in all children – Technological approaches: • Fast ForWord The bridge to executive function? • CogMed • Brain HQ (adolescents) • TEVO • Educators can help as well

Proceedings of the National Academy of Sciences May, 2008

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Assessments

• Objective – isolate deficient processes and guide rehabilitation • Most Frequently Used (usually by Educational Psychologists) Include: – Set-shifting – Wisconsin Sort Test (WCST) – Planning – Trail Making Test, Part B – Fluency tasks • Shown to be related to focal DLPFC lesions

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Task Switching Activation Regulating Functions

• Card sorting • Damage to left or right medial frontal regions • Go/no-go (Simon says) – Can increase complexity to increase task switching results in poor capacity to generate or • http://www.nytimes.com/interactive/2010/06 maintain actions or mental processes /07/technology/20100607-task-switching- • Fluency tasks demo.html • STROOP Test – problems maintaining a selected target – Sensitive to DLPFC and VMPFC lesions

Other Assessments used in research that can be Dots mixed task applied for clinical use • Dots incongruent vs. dots congruent • Object or picture sorting where the sorting rule is switched

In the congruent condition, the correct response is to press the dot on the same side as the stimulus. In the incongruent condition, the response and stimulus are on opposite sides. In the mixed condition, equal numbers of congruent and incongruent trials are randomly intermixed.

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Assessment and Treatment of Inhibition/distractibility Cognitive Disorders in Adults – Holding information in mind while inhibiting a prepotent response • Day-night • Tapping ( When I tap once you tap twice) • Appearance-reality (clouds) – http://www.nytimes.com/interactive/2010/06/07/ technology/20100607-distraction-filtering- demo.html?th&emc=th

Etiologies of Cognitive Disorders in Focal Lesions Adults • RH CVA – CVA represents a disruption of the cerebral vascular system – Problems with attention • Hemispatial Neglect - Usually to the left side of space • Simultagnosia - Global attention (often viewed more as a perceptual impairment) – TOM

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TBI and penetrating head injury mechanisms • Coup and contrecoup injuries - contusions • Hemorrhages – ruptured vessels – Epidural – Subdural Bigler, E. (2007) Anterior and Middle Cranial Fossa in : Relevant Neuroanatomy and Neuropathology in the Study of – Intracerbral Neuropsychological Outcome • Infarction of vessels caused by swelling MECHANISMS OF TRAUMATIC • Shearing stains – diffuse axonal injury BRAIN INJURY

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Degenerative Neuropathies

• – Progressive – Degenerative – Disease processes

Chemotherapy Related Cognitive Impairments (CRCI) Figure 3. Cortical hubs are associated with multiple distinct networks based on published research

Buckner, R. L. et al. J. Neurosci. 2009;29:1860-1873 Jim, H et al. (2012) Meta-Analysis of Cognitive Functioning in Breast Cancer Survivors Previously Treated With Standard-Dose Chemotherapy. Journal of Clinical Oncology.

Copyright ©2009 Society for Neuroscience VOLUME 30 NUMBER 29

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Other acquired neuropathies that Pre-frontal Lobes cause Cognitive Impairment • Toxic encephalopathy • Ventromedial – includes anterior limbic system – Theory of mind (mentalizing) (with R TPJ) • Anoxia/hypoxia – Self-perception – Motor monitoring • Tumors – Self-monitoring – Important in delayed gratification • Radiation necrosis of white matter tracts – Empathy • Dorsolateral – Executive functions (cognitive control) – Organization, planning, flexibility – Task switching – Inhibitory control – Working memory – Processing speed

Commonly used Neuropsych Batteries and Product Summary Auditory Continuous Performance Overview Test (ACPT) Assessments Author(s): Robert W. Keith, Ph.D. Screen for auditory attention Adults - Working memory Determine if an attention problem is deficits – At a Glance: one of the underlying factors – Digits Forward Test Administration: 10 minutes contributing an individual’s learning – Point Digit Span Scores: Pass/Fall criterion score problems. – Letter Span Audio Available: Yes •Pass/Fail criterion scores indicate – Recurring Figures Test Qualification level: B-Level whether performance matches that – Picture Scanning of Behavioral Publication Date: 1994 of individuals with normal attention – Inattention Test Ages / Grades: 6:0 through 11:11 skills – Wechsler Memory Scale -III Family Pictures

• Listens to single words presented – Weschler Memory Scale-III on the tape and raises a thumb when – Hopkins Verbal Learning Test - Revised the target word is heard. – Four Unrelated Words •Written by the author of SCAN-3: – Benson Bedside Memory Test Tests for Auditory Processing – Auditory-Verbal Learning Test Disorders – Wechsler Memory Scale, Logical Memory – Memory Assessment Scales

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Commonly used Neuropsych Batteries Acute Care v. Outpatient Tests for SLP’s and Assessments Adults - Executive Functions (cognitive control) (RT • Acute Care Processing speed) in adults on: – Cognistat – HI-LAB (?) – Organization, planning, flexibility – – Task switching if the patient does have a hx of dementia: • Car Sort • SLUMS or • Trailmaking Test • MoCA. – Inhibitory control – Stroop Test • For the outpatient setting Adults - Critical thinking – RBANS – BURNS – Luria’s Neuropsychological Investigation – CLQT – Wechsler Adult Intelligence Scale - – For RH patients – RICE-3 – III Digit Symbol-Coding – TrailMaking A&B – Digit Symbol Substitution – RIPA – Symbol Digit Modalities Test – – Category Test (HCT) – Object Sorting Test

Cognistat Administration Webinar

Rapidly assesses neurocognitive functioning in... 3 general areas: • http://www.cognistat.com/node/41 Level of Consciousness Orientation Attention (Digit Span) 5 major ability areas: Language (Comprehension, Repetition, Naming) Constructional Ability (Drawing from Memory, Arranging Tiles) Memory Calculation Skills Executive Skills (Reasoning, Judgment) Normative Data: Adolescents from 12 to 17 years of age and Adults 18 years of age and older Time to Administer: 15-20 minutes for cognitively intact individuals and 20-30 minutes for those who are cognitively impaired

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SLUMS Download MoCA Download

• http://medschool.slu.edu/agingsuccessfully/p • https://pdbp.ninds.nih.gov/assets/crfs/Montr dfsurveys/slumsexam_05.pdf eal%20Cognitive%20Assessment%20(MoCA)7 _1.pdf

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Repeatable Battery for the Assessment of Neuropsychological Status (RBANS™)Christopher Burns Brief Inventory of Communication Randolph and Cognition (Burns Inventory) • 30 minutes adult assessment Author(s): Martha S. Burns, Ph.D., CCC- • RBANS can be used a variety of SLP ways including: Identify – • As a stand-alone "core" battery communication and for the detection and cognitive deficits characterization of dementia in the elderly – • As a neuropsychological "screening battery Administration: 30 minutes • RBANS has two parallel forms, Scores: Criterion-Referenced Scores ideal for measuring change in the Audio Available: Yes client's neuropsychological status Qualification level: B,Q1,Q2-Level over time. Publication Date: 1997 Ages / Grades: 18 through 80 years Norms: Criterion referenced to identify moderate level impairment

• The Cognitive Linguistic Quick Test (CLQT) assists you in quickly identifying Test Purpose strengths and weaknesses in five Use the SCCAN to: cognitive domains (attention, memory, identify patients with neurocognitive and executive functions, language, and communicative impairment visuospatial skills) of adults with determine the severity of the impairment neurological impairment due to , help plan treatment head injury, or dementia. measure changes in patient functioning over • Quick Screener time • Administered in 15 to 30 minutes Subtests • Scored in 10 to 15 minutes (cut scores, The test contents relate to daily activities adults no normative data) would be expected to perform for independent • Can be administered at a table or living. The SCCAN has eight scales: bedside (as long as patient can sit up Oral Expression and use a pen) Orientation Memory • Available in both English and Spanish Speech Comprehension • Useful for screening a full range of Reading Comprehension cognitive processes with patients who Writing may have decreased language skills Attention Problem Solving

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Understanding RH problems with Behavioural Assessment of the Dysexecutive Syndrome (BADS) Attention including Neglect Wilson, Alderman, Burgess et al., 1996 Behavioural Assessment of the Dysexecutive Syndrome (BADS)C For children

Administration: 35 to 45 minutes Qualification level: B-Level

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Attention and Attentional disorders Left Neglect Syndrome

• Functional attentional networks • Reduction of neural resources that can be mobilized – Diffuse network – arousal and alterting – By sensory events located on the left • Awakens, surveys internal mileau and extrapersonal space for – By motor plans directed to the left relevant novel or changing stimuli • Acetylcholine and norephinephrine • Patient may behave as if one-half of the universe has • Disorder - delirium abruptly ceased to exist – Mixed cortical-subcortical – orientation to stimuli • Often multimodal • Disorders – progressive supranuclear palsy – impaired visual orientation and visually guided behavior • May co-exist with but not caused by hemianopia, • Posterior parietal cortex lesions – hyperattention to ipsilateral cues hemihypesthesia, or hemiparesis – Cortical network – mediates selective attention • Disorders - neglect

Clinical characteristics - severe Clinical characteristics - mild

• May shave, groom, dress only right side of body • May not show obvious deficits except on • May fail to eat food on left side of plate or tray testing • May omit left side of words on a page – May fail to observe left side of road while driving • May fail to copy detail on left side of drawing – May tend to ignore objects in left pocket • May leave wide left margin when writing – May forget to scan desk for notes or items on the • May display a tonic rotation to the right left side of desk or room

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Representational (perceptual) Assessment component • Bilateral simultaneous stimulation • More obvious when competing events are present • Cancellation tasks on the right – Probed with tests of extinction, • Drawing of a clock • Demonstration • It is not a disorder of seeing, , or • Distinguish from hemianopia – line bisection moving but one of looking, detecting, • Mark midpoint of horizontal line listening, and exploring • Hemianopics tend to be left of center (compensation) – covert attentional shifts

Patient Demo Motor exploratory aspects of neglect

• George – drawing of a clock • A pervasive reluctance to scan and explore left hemispace – Lack of interest in the left side – Rightward bias • Seen in cancellation tasks where pt starts at the right and moves left • Rightward bias seen in tasks where pt asked to erase targets (rather than cancel) as right targets decrease left sided attention increases

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Neglect dyslexia Exploratory deficit & hypokinesia

• Fail to read words on the left or letters on the • Also see problems with manual exploration left side of a word (tactile search) – May show confabulatory completions of left side – Blindfolded searches of objects of word or sentence • Hypokinesia – general impairment of leftward movements • Intentional neglect – reluctance to direct movements to the left

Motivational aspects Mesulam’s neglect model • Damage to the RH results in the left hemisphere • Patients with left neglect devalue the left and pushing toward the right (neglecting the left) assume nothing of importance could be

occurring on the left Shift focus, – May be related to motivation explore

– Ie., very hungry patient may explore the left side R>>L R = L of tray better than less hungry one Self salience, Map targets

Left Hemisphere Right hemisphere attends to R side attends to both or space sides of space

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Anatomy of neglect Comorbidity

• Right inferior parietal lobe damage results in • Unilateral neglect commonly occurs in neglect conjunction with – Once called a “parietal sign” – • However, frontal lobes, cingulate, thalamus, Anosognosia – denial of illness (correlation = .46) temporo-occipito-parietal area and striatum – Constructional deficits (correlation = .4) also contribute – Dressing difficulty (apraxia) (Correlation = .64) • All these areas form an interconnected network • Better term maybe “attentional network syndrome”

Causes Saxe, 2006

• Focal right hemisphere lesions • The developmental trajectory from attending to: • During seizures – Human faces and bodies (infants), • Toxic-metabolic encephalopathy, subdural – to understanding goal-directed actions (toddlers), hematoma, or head injury may give rise to unilateral – to the uniquely human representational theory of mind neglect (preschoolers), • Recovery after CVA varies from 9 to 43 weeks • is reflected in the functional profiles of three regions • Persistent cases caused by large lesions that extend in lateral occipitotemporo-parietal cortex to subcortical structures

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Right Parietal Junction

• Research of Rebecca Saxe on the importance of the Right Parietal Junction in thinking about another person’s thoughts – We have been attributing theory of mind to pre-frontal lobe function but……. – Saxe’s research points to the importance of the RPJ in Theory of Mind and Social Cognition in general • Since children develop social skills early – see new research on intention and affiliation as early as nine months old (Bloom, Wynn, etc.) – this may be the precursor to full TOM skills that later emerge with other areas

Miyashita Science, 306, 5695, Oct.15, Disorders of memory in adults 2004

– Brief review of Types of memory – Memory disturbances associated with head injury and – Memory disturbances associated with oncological cancer treatments

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Organization of Memory (Mesulam, 2000) Organization of Memory

• The memorization process - short term • Memorization – short term memory Impairments memory- depends on the limbic system – Holding Attentional disorders – Working memory TBI • The storing process -learned material that is – Acquiring – encoded Anterograde reconstructed, reassembled and consolidated • – learning/explicit Amnesia for permanent memory traces - explicit – – Episodic • Remembering – recognition Agnosia v. Aphasia • The remembering process – Implicit – , , skills – Explicit – scanning and retrieval

Short term memory Short-term memory span

• Holding – • STM = 7 + 2 items – Boutla, Spulla, Newport and Bavelier (2004) Short-term memory span: insights from sign • Working memory language. Nature Neuroscience 7, 997-1002. • But in American Sign Language it is 5+1 – Authors demonstrate that this cannot be due to phonologic factors, item duration or reduced memory capacity in deaf individuals – 7+ may be due to reliance of speakers on auditory-based rather than visually based representations

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What is learning and memory?

• The job of the brain is to detect and change based on relevant events in the environment – can only fire or not fire – So, neurons must fire preferentially for relevant events and experiences of value – Grand Loop – Ignore or fire less regularly for irrelevant events – Then “save” the relevant synapses and discard the irrelevant synapses Tononi, G. and – Cirrelli, C. (2014) This is the neural plasticity of memory and During wake the brain interacts with the environment (grand loop) and samples a learning limited number of inputs dictated by current events (current sampling, here represented by a new acquaintance).High levels of neuromodulators, such as noradrenaline released by the locus coeruleus(LC), ensure that suspicious coincidences related to the current sampling percolate through the brain and lead to synaptic potentiation.

To understand how our patients learn The “fit” brain - from us we need to know • Preferentially strengthens (hence prioritized • The WHAT of Memory - What are the types of for saving) synapses that are: ? E.g.. • – Sustained by repetition – statistically recurring or Events – important for Orientation e.g. • Facts – SLP world – semantic knowledge coinciding more frequently • Motor skills – OT and PT world – ADL’s, transfers, gait – Better integrated with older memories • The HOW of Memory – All therapists have this • Importance of functionality in treatment in common • Relationship to past in treatment • Value of repetition and practice • Weaker synapses will be subject to decay and • Value of past knowledge, interest discarded • Factors that aid retention – fitness of the brain

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Components of Memory and Learning– Components memory and learning – THE WHAT OF MEMORY (Historical View) The HOW of Memory part 1 (see especially Tononi and Cirelli, 2014) • Short Term Working Memory and Acquisition • Short Term (Working) Memory – Acquisition – relies on short term working – Top down – pre-frontal memory – “OK, I think I’ve got it. Heel toe away • Long Term we go” – Declarative (explicit) – Consolidation – during wake, probably highly related to selective attention and prioritization • Episodic (events) – largely hippocampus based on previous knowledge (Early Hippocampal) • Semantic (facts) – widely dispersed through cortex • Support and sustain synapses related to – Procedural (implicit) relevant memories – “That makes sense! If I • Skills and motor learning – largely striatal once don’t hold on the hand rail I might fall” overlearned • Suppress weak synapses or those less • Conditioning – largely striatal integrated with previous memories “What’s that man’s name again?”

Components of Memory and Learning Components memory and learning – – The How of Memory part 2 The How Of memory - part 3 (after Tononi and Cirelli, 2014) • Long Term Memory - Learning • Disregarding and Discarding – – Matching – High levels of neuromodulators in wake maintain the “grand loop” with the environment to enable learning “Oh yes, I – Protection from interference – likely dependent remember now, we did that yesterday” – Gist Extraction – forming more enduring memories of high-level on neurotransmitters like Glutamate – Importance invariants, such as faces, places, or even maps, than low-level details of a non-distracting environment and limiting and unique instances of a specific encounter – “So this is what I have to know to climb any steps!” emotional distractions – Integration (see Nere et al., 2013 for computer simulation) – – essential for dealing efficiently with • new material is better learned if it fits with previously learned schemas “I play tennis – core and balance are important there inevitable accumulation of unimportant details – also” Essential role of SLOW WAVE SLEEP • Incorporated with an organized body of old memories – “I remember from dance lessons – try to avoid looking down at your feet”

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Working memory, Cowan 2008 Short Term Memory Acquisition (requires working • Working memory defined in three different, memory) slightly discrepant ways: – short-term memory applied to cognitive tasks – as a multi-component system that holds and manipulates information in short-term memory, – And, as the use of attention to manage short-term memory

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, 658-668 • Kondo et al (2005) Changes in brain activation associated with use of a memory strategy: a functional MRI study. Neuroimage 24, 1154- 1163

M. Balter Science 328, 160-163 (2010)

Published by AAAS

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Short Term Memory Short term - Early Hippocampal • Holding • Support and sustain synapses related to relevant memories – • Working memory –repetition • Acquiring - encoding – integration with past knowledge • Suppress weak synapses or those less integrated with previous memories –Inhibition of irrelevant or interfering information »Maladaptive patterns or associations »Recurrent utterances

Retrograde and Anterograde Medial temporal lobes

• Associated with traumatic head injuries • Hippocampal formation – Temporal gradient where – Input is largely excitatory • the time before the injury (retrograde) can be days, – Inhibitory input arises from contralateral hippocampus months, even years) – Strong dopaminergic, noradrenergic and serotonergic • the time after the injury (anterograde) can last for inputs years but may be less severe over time – Exquisite sensitivity to hypoxia • Contrast this to remote memory impairment • Parahippocampal gyrus seen in dementia where there is a loss of • Amygdala memory from the distant past

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Hippocampal formation 3. To posterior cingulate • Likely builds directories/address books to bind and find fragments of experience

– Once learned, memory representations are 2.To anterior nucleus of distributed throughout the neocortex thalamus • Both episodic and semantic – They continue to consolidate over time – Establishes initially sparse and fragile linkages,

nurturing them and inserting them into a matrix 4. Back to of existing knowledge

1. Thru fornix to mamillary bodies Hippocampal circuit

Pure Amnesia Amygdala

• Inability to learn anything new • Bilateral damage does not cause significant – Due to bilateral hippocampal damage memory impairment in – – Can hold information in attention Probably critical in forming long-term emotional memories – Working memory is ok as long as attention is not – Bonds a stimulus with its emotional connotation distracted – Mediates the influence of emotional valence on – Cannot remember anything after being distracted learning – Encodes the emotional valance of an experience

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Amygdala Long term memory

• Deep posterior cerebral arteries/ECT may affect this • Storage region specifically • Remembering • Emotionally based memory - past experiences that triggered emotional responses may fail to now - or emotions may not fit situation • Disconnection lesions may result in emotion recorded in the autonomic NS with no conscious awareness

Recent vs. remote memory (Frankland and The storing process Bontempi, Nature Reviews Neuroscience,6, 119-130 (2005)

• - unique, personally – Medial temporal lobe damage causes temporally experienced events (note: these are the graded with sparing of remote hardest to recall and most easy to alter of memory • Experience is initially encoded in parallel in change through suggestion) hippocampal and cortical networks • Semantic memory - general principles, facts, • Replay of hippocampal cortical networks strengthens associations, - parietal lobe the cortical-cortical connections • This eventually allows memories to become independent of the hippocampus

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Long term memory The remembering process

• Declarative(explicit) • Explicit retrieval and scanning to choose the correct – Facts (semantic) traces are involved in accurate recall is a symptom of inability to correctly scan and retrieve – Events (episodic) • Implicit memories are not consciously remembered but traces can be demonstrated to exist. Consist of procedural memory for motor skills and priming effects from previously learned but forgotten information

Semantic Memory Everyday memory

• Input into the matrix of knowledge through limbic • - the capacity to connections remember to do things – after consolidation become independent of limbic connections • it does rely on some of the same structures as – Episodic memories for personal experience remain episodic memory and is drastically impaired in tethered to limbic areas • Pick’s disease is an example of patients with good amnesic syndrome language and cognition in the face of poor • Rivermead Behavioral Memory Test has performance on tasks requiring intact semantic proved to be sensitive to and correlate with knowledge lapses of everyday memory

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Autobiograhical Memory Long Term Memory

• Recollection of early life events • The implicit-explicit distinction • Role of memory in the concept of self • Implicit learning – demonstrated in amnesics who showed enhanced performance without being able • Confabulation to recollect the experience of learning (late 1970’s) • How we evaluate the veracity of our • Procedural/declarative distinction (mid 1980’s) – memories procedural=skills, declarative=facts • Pattern across life-span • Vivid and flashbulb memories

Short Term to Long Term Memory Long Term Memory – All Therapies

• Is not always gradual • Matching – • There are different strength levels based on – Grand loop – many varied but similar experiences with information – How widely distributed the memory is – Potentiation over progressive wake/sleep cycles – How strong the synapses are • Gist Extraction – (main idea) • As clinicians – our job is to drive wide – highly sleep dependent distribution and synapse strength as early in – Becomes widely dispersed [default mode the process as possible network] • Integration

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Progressive matching over repeated Matching sleep/wake cycles (Tononi & Cirelli, 2014) • The “grand loop” • Leads to • This favors retention of statistical regularities – Transfer in the environment (as opposed to imagined – Transformation or trivial experiences) – Integration • This is the principal upon which most intensive computerized interventions depend

Integration – What we know without Gist Extraction effortful retrieval • Forming more enduring memories of high-level •New material is better learned if invariants, such as faces, places, or even maps, it fits with previously learned “the big picture” than low-level details and schemas unique instances of a specific encounter - –Importance of functionality essential for generalization and carry over –ADL’s • Benefits of sleep (Stickgold and Walker, 2013) for – Gaining insight of a hidden rule •Incorporated with an organized – Enhancing the extraction of second-order interactions body of old memories

– Helping abstraction in language learning

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Procedural memory Intervention

• Skill learning • Evidence-based interventions for memory and • Difficult to access consciously cognitive impairments in adults • and cerebellar functions – Spaced retrieval and errorless learning • Often a dramatic dissociation with episodic • In patients with severe memory disturbances and/or semantic memory • for memory intervention as applications for perceptual impairments • Common etiologies include – Parkinson’s – disease, Huntington’s chorea, cerebellar Memory strategies for higher level patients lesions • Developing memory strategies • Memory training

Mahncke et al

Memory enhancement in healthy older adults using a brain plasticity-based training program: A randomized, controlled study Mahncke, H. et al. PNAS August 15, 2006 vol. 103 no. 33 12523–12528

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Cognitive Training: The Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) Subject and Cognitive Training Design • Community-dwelling seniors – recent study • 6 metropolitan centers - included 2802 – 10 years after 5-6 weeks of cognitive training participants – experienced significantly improved reasoning and speed of – average age of 73.6 years processing skills, – no significant cognitive dysfunction. – as well as better activities of daily living – compared with those who didn't get such training. • randomly assigned to 1 of 3 interventions — a • Main results after 5 years published in JAMA in 2006, memory, a reasoning, or a speed-of- – first large-scale randomized trial processing or no-contact control group. – showed that cognitive training improves cognitive function • Training was conducted in small groups in ten in noninstitutionalized persons 60- to 75-minute sessions over 5 to 6 weeks. – Training is transferable to daily function.

Tasks Conclusions on function

• The speed-of-processing training is now • Short period of training available through PositScience – Brain HQ – enhanced all of the cognitive abilities • Although the other 2 training programs are – and functional skills — the primary outcome of the not yet commercially available, Dr. Rebok and study – And lasted 10 years! his colleagues have a grant from the National Institute on Aging (NIA) to develop a Web- • “After 10 years of participation, 60% to 70% of the participants said they were as well as, or based version of the ACTIVE memory training. better off than, when they started the study in terms of their everyday activities," said Dr. Rebok.

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But, this research is on normal aging Take away for Clinicians and Nursing adults • The value of “Brain Fitness” is not limited to • Computerized cognitive training is available now typical brains – Posit Science exercises (those used in the ACTIVE trial) – The aging process has many similarities to specific are available and inexpensive neuropathologies whether MCI, early stage – Working memory exercises for children and adults are dementias, even Parkinson’s Disease available and inexpensive – Just as physical fitness enhances effects of physical – The training is highly evidence based for enhancing training, research now indicates enhancing memory and maintaining memory and other cognitive skills processes (and reasoning and processing speed) is beneficial to all individuals even with neurological • Computerized memory, reasoning, and injury processing speed exercises can be included as • an adjunct to any and all treatment programs The CogMed and much motor learning research with memory impaired individuals has included stroke patients

Task-Specific Training (Naoyuki Takeuchi and Enriched Environment (Naoyuki Takeuchi and Shin-Ichi Izumi, 2013) Shin-Ichi Izumi, 2013) • All training after stroke should be targeted to goals that • Enriched environments are relevant to the functional needs of the patient – Those that provide greater opportunity for physical • Task-specific training to facilitate activities of daily activity and motivation living or other relevant motor tasks is a well-accepted – a well coordinated multidisciplinary team can provide principle of stroke rehabilitation an enriched environment – – Patient involvement in patient-centered Task-specific training can effectively recover a wide array interdisciplinary goal setting has been shown to of motor behaviors involving the upper limbs, lower limbs, encourage their motivation and engagement in sit-to-stand movements, and gait after stroke therapy – Compared to traditional stroke rehabilitation approaches such as simple motor exercises, task-specific training • Reported benefits of multidisciplinary care induces long-lasting motor learning and associated cortical extend to patients of all ages and to patients with reorganization varying stroke severity

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Preventing Maladaptive Plasticity Evidence-Based Research for Cognitive (Naoyuki Takeuchi and Shin-Ichi Izumi, 2013) Rehabilitation • From a PT and OT perspective maladaptive plasticity that weakens motor function and limits recovery • From a speech perspective – maladaptive plasticity results in recurrent utterances and hyperfluent neologisms in aphasic patients • From a nursing and family perspective – maladaptive plasticity results in repetitive habits that interfere with re-acclimation in the home, community or vocational setting

Most effective for individuals with Interventions in the manual severe memory impairments • The interventions described can be readily • Use of external compensations with direct used by occupational therapists, speech and application to functional activities is language therapists, psychologists, and other recommended for people with severe memory rehabilitation professionals. deficits after TBI or stroke. • Guidelines adapted into step-by- • Practice Guideline step procedures that can be used by clinicians who treat individuals with brain injury.

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Memory Interventions discussed in the Cognitive Memory Interventions discussed in the Cognitive Rehabilitation Rehabilitation Manual and Reviewed by Cicerone et al. 2011 Manual and Reviewed by Cicerone et al. 2011 Level of Intervention Recommendation Intervention Level of Recommendation For people with severe Memory strategy training is memory impairments recommended for mild memory after TBI, errorless impairments from TBI, including the Practice Standard learning techniques use of internalized strategies (eg, may be effective for visual imagery) and external memory learning specific skills compensations (eg, notebooks). or knowledge, with limited transfer to Use of external compensations with novel tasks or direct application to functional reduction in overall activities is recommended for people Practice Guideline Practice Option functional memory with severe memory deficits after TBI problems. or stroke.

Group-based interventions may be considered for remediation of memory deficits after TBI.

Practice Option

Compensatory Strategy Training Memory Interventions discussed in the Cognitive Rehabilitation Manual and Reviewed by Cicerone et al. 2005, (Cicerone, et al 2011 review) 2001 • 4-week structured, group format memory • Errorless learning and Spaced Retrieval training program – Ehlhardt, L., Sohlberg, M.M. et al. (2008). Evidence-based Practice Guidelines for Instructing Individuals with Acquired Memory • Results indicated that frequency and intensity Impairments: What Have We Learned in the Past 20 Years? of memory training were critical in improving Neuropsychological Rehabilitation, 18 (3), 300-342 memory performance. • Focus - minimizing errors during delivery of • Also demonstrated increased knowledge of memory instruction: strategies and use of memory aids: • Errorless learning – reduced behaviors indicative of memory impairment, and • Spaced retrieval – improved performance on neuropsychologic assessment of memory • Most helpful for individuals with more severe cognitive impairments.

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Strategic Memory and Reasoning Training (SMART) • Sandra Bond Chapman – Director of the Center for Brain Health at The University of Texas at Dallas • SMART teaches how – to think strategically enabling deeper understanding – to imagine potential problems, identify multiple solutions, create novel directions, and view issues from diverse perspectives.

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