University:
Boston University
Course:
CAS BI 107 | Biology 1
Academic year:

2020
Views:

67

Pages:

42
Author:

Jaxon Hanna

Recent advances in our understanding of Neuroplasticity of Language Recovery Outline q Epochs of recovery qNeurophysiological changes underlying recovery q Anatomical and physiological substrates of recovery q Patterns of reorganization of language qAcute Stage qSub-acute stage qChronic stage q Language recovery after rehabilitation q A network approach to language rehabilitation q Promoting reorganization in the brain- What can the clinician do? 3 Epochs of recovery (Cramer, 2008) Acute injury ◦ initial hours after a stroke ◦ numerous profound changes evolve in blood flow, edema, metabolism, inflammatory state, and diaschisis Repair ◦ first days after stroke onset, and lasts several weeks ◦ most spontaneous behavioral recovery ◦ endogenous repair-related events (BDNF, synaptogenesis, neuronal sprouting) reach peak levels Chronic ◦ weeks to months after stroke ◦ spontaneous behavioral gains have generally reached a plateau ◦ stable but still modifiable 4 Neurophysiological changes Edema Reduction in cerebral blood flow Abnormal concentration /release of neurotransmitters Denervation Transneuronal degeneration Diaschisis 5 Neurophysiological changes in early recovery Neurophysiological changes occur in the brain for a period of time following cerebral insult Edema ◦ Like any other wound, brain damage causes edema ◦ Occurs 2-3 days post onset ◦ affects remote parts of the brain ◦ shift of midline structures ◦ behavioral deficits may be diffuse ◦ diminishes about 1 week post onset ◦ dead tissue removed by macrophages ◦ distortions disappear ◦ lesion becomes circumscribed 6 Neurophysiological changes in early recovery Reduction in cerebral blood flow (hypoperfusion) ◦ Widespread ¯ function related to ¯ blood flow/metabolism of oxygen and glucose ◦ may last several months/longer 7 Neurophysiological changes in early recovery Abnormal concentration /release of neurotransmitters ◦ occurs immediately after infarction ◦ Due to activation/ inhibition after damage to other parts of network ◦ Neurons release glutamate onto nearby neurons which become excited, overloaded with calcium and die Denervation Cell B Cell B Cell A Cell A ◦ Decreased nerve supply ◦ Cells become really hypersensitive to neurotransmitters Transneuronal degeneration ◦ Neurons or nerve cells may atrophy when they don’t have normal inputs ◦ Cell A---Cell B ◦ Over time B dies without input from A 8 Excitotoxicity 9 Neurophysiological changes in early recovery Diaschisis (Von Monakow, 1914) “shocked throughout” ◦ ¯ responsiveness and dysfunction of intact neurons remote from damaged area ◦ May be related to ¯ in blood flow /metabolism and or abnormal neurotransmitter release ◦ Damaged area no longer sends signals to intact area Flint et al., 2005 10 Summary: Neurophysiological changes Edema Reduction in cerebral blood flow Abnormal concentration /release of neurotransmitters Denervation Transneuronal degeneration Diaschisis 11 Repair Neuronal regeneration ◦ Axons and dendrites can regenerate if cell body has remained Synaptogenesis ◦ Formation of new synapses ◦ Cells that fire together wire together Promoting repair ◦ BDNF ◦ Stimulation 12 In order for recovery of function to be restored to the infarcted hemisphere, its structural, functional and physiological integrity will need to be at optimal operationality to sustain such recovery Kiran, 2012; ISRN 13 What are the patterns of reorganization of language? • Acute phase - reperfusion of tissue • Sub-acute phase –resolution of diaschisis • Chronic phase- the role of the ipsilesional hemisphere 14 Acute phase - reperfusion of tissue Hillis et al., 2001 Language recovery in the acute phase (typically in the first few weeks after the infarct) is mostly determined by the extent of successful reperfusion of the infarcted tissue in order to restore language function. FIG. DWI and PWI scans before treatment (top two rows) and during treatment (lower two rows) for patients who showed improved lexical-semantics with treatment. Arrows point to BA 22. 15 Sub-acute phase –resolution of diaschisis Reperfusion can only salvage the ischemic penumbra for the first few days following ischemia and eventually, the hypo-perfused area often progresses to infarction (Chen & Yi-Cheng, 2012; Guadagno et al., 2008; Hillis et al., 2004). Nonetheless, language recovery continues to occur in the ensuing months following the stroke. 16 Sub-acute phase –resolution of diaschisis Saur et al., 2006; Brain 17 Restoration of language function to the left hemisphere over time that corresponded with improvements in language function Saur et al., 2006; Brain 18 Slide courtesy- Erin Meier What constitutes neural recovery in aphasia? Hillis & Heidler, 2002; Saur et al., 2006 College of Health & Rehabilitation Sciences: Sargent College 19 Neural correlates of language recovery in PWA Slide courtesy- Jeff Johnson § Evidence that the right hemisphere supports language recovery and/or is recruited via language treatment 1Gold & Kertesz, 2000 (NT) et al., 2005 (T) 3Meinzer et al., 2006 (T) 4Vitali et al., 2007 (T) 5Raboyeau et al., 2008 (T) 6Fridriksson et al., 2009 (NT) 7Mohr et al., 2014 (T) 8Skipper-Kallal et al., 2017 (NT) 2Crosson T = Treatment Study NT = Non-treatment Study College of Health & Rehabilitation Sciences: Sargent College 20 Slide courtesy- Jeff Johnson Neural correlates of language recovery in PWA § Evidence that better recovery and treatment outcomes are achieved when activation returns to the left hemisphere 1Cao et al., 1999 (NT) et al., 2002 (T) 3Perani et al., 2003 (NT) 4Fernandez et al., 2004 (NT) 5Crosson et al., 2005 (T) 6Saur et al., 2006 (NT) 7Vitali et al., 2007 (T) 8Meinzer et al., 2008 (T) 9Fridriksson, 2010 (T) 10Fridriksson et al., 2010 (NT) 11Rochon et al., 2010 (T) 12Van Oers et al., 2010 (NT) 13Sebastian & Kiran, 2011 (NT) 14Szaflarski et al., 2011 (NT) 15Allendorfer et al., 2012 (NT) 16Szaflarski et al., 2013 (NT) 17Van Hees et al., 2014 (T) 18Sims et al., 2016 (NT) 2Leger T = Treatment Study NT = Non-treatment Study College of Health & Rehabilitation Sciences: Sargent College 21 Neural correlates of language functions in PWA § Studies linking behavioral recovery to increased activation in regions in both hemispheres Slide courtesy- Jeff Johnson 1Cardebat et al., 2003 (NT) Boissezon et al., 2005 (NT) 3Davis et al., 2006 (T) 4Fridriksson et al., 2006 (T) 5Fridriksson et al., 2007 (T) 6Menke et al., 20096 (T) 7Kiran et al., 2015 (T) 2De T = Treatment Study NT = Non-treatment Study College of Health & Rehabilitation Sciences: Sargent College 22 So when language areas are damaged, releases inhibition from other areas capable of taking over language function Adjacent areas assume function RH participation in language after LH infarction College of Health & Rehabilitation Sciences: Sargent College 23 • Semantic word judgment (a)- perilesional left frontal activation • Picture Naming (b)- perilesional LH activation, but also RH activation • Depending on task demands, may see LH or bilateral activation 24 Understanding language recovery-where we are.. A network of regions in LH and RH Traditional Language Regions Homologous Right Hemisphere Regions Domain general regions Upregulate to compensate Downregulate as they become more efficient College of Health & Rehabilitation Sciences: Sargent College 25 Traditional view of recovery Network view to recovery College of Health & Rehabilitation Sciences: Sargent College 26 §Typical activity patterns & language abilities are not always restored by the chronic phase of recovery § Model of recovery in chronic aphasia: 1. Optimal (possibly complete) behavioral recovery: minor damage to left hemisphere (LH) regions not central to language 2. Satisfactory (but incomplete) behavioral recovery: damage to core LH language regions but LH perilesional tissue remains functional 3. Poor behavioral recovery: extensive damage to entire LH; only homotopic RH regions remain for language 27 Specific patterns of activation may inform regions that may changebut not necessarily how they are modulated within a network. Understanding changes in activation and changes in network connectivity will provide a better understanding of the dynamics of language recovery. 28 For both patients, more connections that were strengthened appeared during trained items than during untrained items. Patient with the larger lesion had more connections strengthened in RH Patient with the smaller lesion had more connections strengthened in LH 29 LIFG was the most consistently active VOI in the pre- and post-rehabilitation scans and the most consistently significantly modulated region as a function of rehabilitation Next, LPCG and RIFG also consistently modulated regions RIFG-RMFG and LIFG-LPCG most consistently modulated connections 30 Changes in BOLD signal from pre- to post-treatment for abstract and concrete words at the group level. LH regions show changes in activation for abstract items as a function of abstract treatment. Different regions show changes for concrete items. 31 The region with the highest node degree in the trained abstract difference network is the left inferior frontal gyrus pars triangularis (L IFGtri) The regions with the highest node degree in the generalized concrete difference network were L SupMed and R IFGtri. The regions with the highest node degree in the non-generalized concrete difference network were L MFG and R IFGorb. The size of each sphere represents the number of participants who show significant increases in connectivity for that region, while the color of the sphere represents the average node degree. Higher values are more purple, lower values are more turquoise. The bar graphs highlight the regions with the highest node degree for the majority (at least 2/3) of participants. PWA Controls Warm colors = significant positive connections Cool colors = significant negative connections Connections are significant at p < .05 after FDR College of Health & Rehabilitation Sciences: Sargent College 33 Warm colors = significantly stronger in controls than PWA Cool colors = significantly stronger in PWA than controls 34 Warm colors = significantly stronger in controls than PWA Cool colors = significantly stronger in PWA than controls Sims et al. 2016, Neuropsychologia • Functional Connectivity is reduced in PWA relative to controls, in the language network • This altered network includes bilateral fronto-temporal regions 35 A ‘Revised” Summary of fMRI studies Restoration of undamaged language dedicated regions in the left hemisphere is the most likely to result in long-term positive outcomes. A less efficient but secondary mechanism involves compensation by intrahemispheric neighboring regions in the left hemisphere. Finally, if damage to the left hemisphere is substantial, then homotopic regions in the contralateral (right) hemisphere are engaged in language recovery A combination of TRADITIONAL LANGUAGE REGIONS & DOMAIN GENERAL REGIONS- also participate in recovery 36 Promoting reorganization 1. Use it or lose it Fridriksson et al. (2007); Neuropsychologia 38 2. Use it and improve it Sandberg et al; 2015, Brain and Language Abel et al., 2015, Brain 3. Specificity, 4. Repetition 3. Specificity ◦ Changes in the brain specific to what is trained- not diffuse effects Vitali et al., 2010, Neurocase 4. Repetition matters ◦ Single or few trials not sufficient to promote facilitate long term potentiation/learning 40 5. Intensity, 6. Time 5. Intensity matters ◦ In chronic aphasia, Persad and colleagues reviewed outcomes from rehabilitation centers that provide intensive comprehensive aphasia treatment and reported positive outcomes Persad et al. (2013). Topics in Stroke Rehabilitation. 6. Time matters ◦ Godecke et al., 2012 found that initiating daily aphasia therapy within first 4 weeks post-stroke resulted in better outcomes than usual care. Godecke, et al. (2012). International journal of stroke. 41 7. Salience, 8. Age, 9. Transference, 10. Interference 7. Salience matters ◦ Attention, motivation, meaning, reward, emotion 8. Age matters ◦ Neurogenic response is reduced with age ◦ Exercise increases neurotrophic factors 42 7. Salience, 8. Age, 9. Transference, 10. Interference 7. Salience matters ◦ Attention, motivation, meaning, reward, emotion 8. Age matters ◦ Neurogenic response is reduced with age ◦ Exercise increases neurotrophic factors 9. Transference ◦ Successful and unsuccessful generalization has different consequences in the brain (Sandberg et al., 2015) 10. Interference ◦ Maladaptive compensatory strategies (RH) ◦ (Rehme et al., Neuroimage 2011) Sandberg et al; 2015, Brain and Language 43

Principles of Neuroplasticity of Language Recovery

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