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Rosemary Varley Division of Psychology & Language Sciences

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1 Building therapies on neurobiological principles Word-level therapy for apraxia of speech
Rosemary Varley Division of Psychology & Language Sciences University College London

2 Collaborators Sandra Whiteside & Patricia Cowell (HCS, Sheffield)
Core research team Lucy Dyson; Lesley Inglis; Abigail Roper Additional assistance from: Andrew Harbottle; Jenny Ryder; Vitor Zimmerer Additional collaborators SLTs across South Yorkshire, & in particular Rotherham NHS Catrin Blank (Clinical Neurology, NHS Sheffield) Tracey Young (ScHaRR, Health Economics, Sheffield) Funders The Health Foundation; BUPA Foundation: University of Sheffield/HEIF4 knowledge transfer grants

3 Conflict of Interest Statement Sword Software
Software program is commercially available ‘Inventors’ Varley, Whiteside & Cookmartin receive share of royalties from sales

4 Post-Stroke Speech Production Impairments
Anomia Lexical-semantic Apraxia (AOS) Phonology-phonetic Dysarthria Phonetic

5 Generative-Computational Models of Speech & Language
Minimise storage, maximise computation ‘Elegant’, ‘Parsimonious’ Phonology: store small number of units (phonemes, distinctive features e.g. [+ voice]) & large combinatorial mechanism to create syllables e.g., Shattuck-Hufnagel’s (1979) slots and fillers model

6 Slots & Fillers Abstract phonological representation is ‘scanned’ /k æ t/ Slots (syllable frame determined): _ _ _ Fillers: Mechanism locates segments/phones corresponding to phonemes [k] [æ] [t] Fillers inserted into slots [k æ t]

7 Apraxia of Speech (AOS)
Under C-G view, underlying impairment: Inaccessible segmental plans Impairment of allocating segment to slot Classical apraxia therapy: microstructural (also articulatory-kinematic or sound production therapy) Rebuilding segmental plans Practice in generating cohesive syllables through combination of segmental plans i.e., subcomponents & generative mechanism

8 Example AOS & Microstructural Therapy
Articulatory errors; Altered durational characteristics; Loss of speech automaticity; non-fluent, effortful, struggle & groping.

9 Evidence-Base for Microstructural Therapy
Wambaugh, J. et al. (2006). J. Medical Speech-Language Pathology, 14(2), xv-xxxiii Treatment Guidelines for Acquired Apraxia of Speech: A Synthesis and Evaluation of the Evidence Majority of research on articulatory therapies Learning of targeted gesture/syllable Poor generalisation of learning Expensive Cochrane Review (2009): “No evidence was found for the treatment of AOS.” Therapists view as hard-to-treat condition.

10 Generative Models Under Attack
At all levels of structural linguistic processing (phonology, morphology, syntax) generative-computational models under attack Syntax: I + am + go + ing + to + ____ vs. Morphology: un + fortunate + ly Phonology y+e+s+t+er+d+ay Neurocognitive implausibility “human memory capacity is quite large” Bybee (2006: 717) I’m going to ____ unfortunately yesterday

11 Alternative Model Usage/frequency-mediated models of processing
Sequences which are frequently repeated become stored as complete units (complete words/ phrases/clauses)

12 Shattuck-Hufnagel’s puzzle & Levelt’s and paradox
Shattuck-Hufnagel (1979): “perhaps [the] most puzzling aspect is the question of why a mechanism is proposed for the one-at-a-time serial ordering of phonemes when their order is already specified in the lexicon.” Levelt (1992) : “Why would a speaker go through the trouble of first generating an empty skeleton for the word, and then filling it with segments? In some way or another both must proceed from a stored phonological representation, the word’s phonological code in the lexicon. Isn’t it wasteful of processing resources to pull these apart first, and then to combine them again (at the risk of creating a slip).”

13 Re-thinking AOS via Frequency-mediated Account
High frequency constructions stored as complete plans. Speech control (Crompton, 1982; Whiteside & Varley, 1998; Varley & Whiteside, 2001): frequently used output stored as complete phonetic plans. Biologically more plausible, and capable of delivering fast, cohesive and error-free movements.

14 Building Therapies on Neurobiological Principles (Varley 2011. Int. J
Building Therapies on Neurobiological Principles (Varley Int. J. SLP) Frequency-mediated vs. computational Therapy focuses on whole words Procedural vs. declarative learning Interconnectivity of processing systems Errorless learning/error-reducing strategies Therapy intensity (‘Dose’) - Illustrate with reference to AOS therapy

15 Procedural vs. Declarative Learning ‘Doing vs. Talking about doing’
Some speech/language interventions involve giving patient explicit knowledge of how (we think) speech/language systems operate i.e., metalinguistic knowledge Assumption that patient will assimilate this explicit knowledge & ‘re-boot’ the automatic/procedural systems that govern listening & talking In the case of AOS, clinician shares explicit knowledge of articulatory phonetics – patient becomes patient becomes a ‘mini-phonetician’. But notice, most healthy speakers produce speech fluently without any awareness of phonetics

16 Procedural vs. Declarative Learning ‘Doing vs. Talking about doing’
Some speech/language interventions involve giving patient explicit knowledge of how (we think) speech/language systems operate i.e., metalinguistic knowledge Assumption that patient will assimilate this explicit knowledge & ‘re-boot’ the automatic/procedural systems that govern listening & talking In the case of AOS, clinician shares explicit knowledge of articulatory phonetics – patient becomes patient becomes a ‘mini-phonetician’. But notice, most healthy speakers produce speech fluently without any awareness of phonetics

17 Procedural vs. Declarative Learning ‘Doing vs. Talking about doing’
Wulf et al (2001) Quarterly J Expt. Psych. Internal focus of attention leads to less automaticity in complex motor skill learning. Ballard et al (2011) Motor Control. Poorer retention of a novel speech movement in healthy speakers within kinematic feedback, than those without constant kinematic feedback. Possible link to learned misuse & constraint therapies: by making patient consciously aware of articulatory movements may result in learned non-use of usual automatic/procedural mechanisms of fluent speech control.

18 Interconnected of sensory-motor systems
AOS therapy often uses nonsense syllables & pure production therapy (modules/autonomy) Observing movement results in sensory-perceptual activation, and ‘mirror’ activation in motor cortex (‘mirror neurons’, e.g. Wilson et al NatNeurosci). Fridriksson et al (2009, Stroke): therapy consisting of word-picture match + observing video of mouth resulted in improved word production in non-fluent aphasia.

19 Sword (Sheffield Word)


21 Therapy Structure Sensory-perceptual phase: 6 modules
Computer models errorless spoken word-picture matching Computer models errorless spoken-written word matching Participant performs spoken word-picture matching task Participant performs spoken-written word matching task Computer models errorless spoken lexical decision task Participant performs spoken lexical decision task

22 Errorless Learning/Error-reduction Strategies (Whiteside et al. 2012
Errorless Learning/Error-reduction Strategies (Whiteside et al JNeuroRehab.) Errorful vs. Errorless/error reduction techniques. Errorless learning may be particularly important in procedural/motor learning. Errors prevent formation of stable movement memories. Therapy designed to minimise errors : Priming output via sensory-perceptual phase Imagined movement (Page et al. 2005) Immediate – Delayed Repetition – Independent production

23 Therapy Structure (Output: 7 modules)
Observe video of speaker saying target word Imagined production of words Immediate repetition of words delayed repetition Repetition with audio-recording & playback Practise of target words in sentence frames Production of word in isolation, with cue support if needed


25 Therapy Dose Pulvermüller & Berthier, 2008. Aphasiology.
Neuronal plasticity & Hebbian learning Hebb (1949) described how connections between synapses alter as a result of learning: “any two cells or systems of cells that are repeatedly active at the same time will tend to be become ‘associated’, so that activity in one facilitates activity in the other.” (1949, p. 70). Computer therapy cost-effective means of achieving necessary ‘dose’.

26 Therapy Study Therapy based on neurocognitive principles
Computer therapy, allowing participants to self-administer intervention with potential to achieve high dose Advised to use program regularly for short periods (‘little and often’) Program records user interactions 50 participants with single therapy protocol Speech intervention contrasted to sham/placebo computer intervention

27 Visual Sham Intervention

28 Participants 50 participants with AOS (+ aphasia) recruited;
25 female: 25 male Mean age = 65 years >5 months post-LH-stroke (Mean = 22 months) 44 participants completed study Varying levels of computer experience (novice to expert). Participants randomly assigned to: Speech first (speech program – sham program) or, Sham first (sham program – speech program) No significant differences at baseline between two groups

29 Study Design Two period cross-over design (Cowell, et al. 2010
Study Design Two period cross-over design (Cowell, et al Frontiers in Human Neuroscience) Baselines 1-2 3-4 weeks Period 1 Treatment 1 6 weeks Rest 4 weeks Period 2 Treatment 2 6 weeks Maintenance 8 weeks Rest Maintenance Sham-First SHAM SPEECH Speech-First SPEECH SHAM

30 Measures of Behaviour Word Production (35 in each set) Treated: ‘dog’ Phonetically-matched, untreated: ‘door’ Frequency-matched, untreated: ‘game’ Performance measured in naming & repetition Also collected spontaneous speech samples at baseline & maintenance Untreated behaviours Written word-picture matching (PALPA 48, Kay et al., 1992) Spoken sentence-picture matching (CAT, Swinburn et al., 2004) Health Economic Assessment

31 Speech Analysis Word-level
Repetition accuracy (0-7 scale) & word duration (fluency, cohesiveness of articulatory routines) 7 = error-free, response latency <2 sec; normal word duration 6 = error-free, response latency >2sec or slowed duration 4 = one segment error 2 = two segment error + groping 0 = no response or off-target Naming communicative adequacy (0/1) (would a naive listener understand the intended meaning?)

32 Blinding ‘Open-label’ trial as not possible to blind clinician or participant to treatment being administered. Rater for word-level outcome measures blind to randomisation to speech-first/sham-first allocation. Inter-rater reliability check by further rater blinded to phase & rater 1 measurement (10% data). Measure Correlation Repetition accuracy Spearman r=.892, p<.001 Repetition duration Pearson r=.956, p<.001 Naming Spearman r=.912, p<.001

33 Results

34 Compliance with ‘little and often recommendation’
Program use (hours:mins in 42 day period) Speech program: 3:32 – 50:29; M=16:48 Sham program: 0:41 – 50:09; M=14:54 No significant difference between sham/speech-first groups in level of use of either program 11 participants completed entire speech program; 33 completed word-level production tasks. 50 hours = 8 hours/week

35 Outcomes Summary Baseline behaviour was stable
Untreated behaviours showed no significant change over course of study Spoken sentence-picture match (t(43)=-0.113, p=.911) Written word-picture match (t(42)=-1.017, p=.315) No spontaneous change in behaviour Sham program had no influence on word production scores. Any treatment effect was not placebo

36 Results Format Sham-First Speech-First Post-Tx1 Baselines Post-Tx2

37 * Sham-First * Speech-First
Naming Communicative Adequacy (Treated Words) * Sham-First Speech vs. Sham program F(1,39)=14.486, p=0.0001) Treatment X Sequence interaction approached significance F(1,39)=4.006, p=0.052 * Y axis: speech first 65% accuracy at baseline to 78% accuracy after speech intervention , 75% at maintenance. Speech-First

38 Repetition Accuracy - Treated
* Speech>Sham program F(1,39)=4.562, p= No interaction with sequence * Speech first average score at baseline 5.3, post speech 6, maintenance 5.9.

39 Correct/Fluent scores across word sets (repetition)
ns * Treated ‘dog’ ns * ns Frequency-matched ‘game’ Phonetically-matched ‘door’

40 Error/Struggle scores across word sets (repetition)
* ns Treated ‘dog’ ns ns Frequency-matched ‘game’ Phonetically-matched ‘door’

41 High users (over 25 hours)
Delta/change scores Baseline = 0 Post-tx = 7 Delta 0 – 7 = -7 High users (over 25 hours) Low users (under 10 hours) Low – under 10 hours: AOS hours High – over 25 hours: 35 & 41 – 81 hours in total

42 Results Summary (1) Group level: significant improvement in naming & repetition accuracy of treated words following speech program, & improvements maintained weeks after withdrawal of therapy. Evidence of generalisation to phonetically-matched words. Pattern of response of speech-first group generally better than that of sham-first.

43 Results Summary (2) Individual differences in response
Some high users showed improvement on both treated and untreated words Other high users responded but little generalisation Some lower users showed good response (‘super learners’)

44 Participants’ Attitudes
Generally positive regarding model of service delivery, when combined with therapist support. Those with family members who could support use of computer were more positive. Many found the repetitive stimulation ‘boring’ & likely to be factor in low compliance in some participants Positive responses from carers: “I felt I could leave him, knowing he had something useful to get on with.” “I got more gardening done that summer.”

45 Why impairment therapies sometimes don’t work (Varley, 2011. IntJSLP)
Based on biologically implausible computational models Low dose. Focus on conscious, metalinguistic, declarative knowledge vs. Implicit/procedural knowledge. Insufficient practice of ‘getting it right’. Focus on isolated level (module/level of representation) & ignore interconnectedness of information processing & neural system.

46 Summary & Conclusions Intervention study with larger sample of patients, administered single treatment protocol. Self-administered, IT-based therapy may represent cost-effective way of resolving dosage problem. Word-level therapy for AOS is effective. Effects most evident on treated word forms, with maintenance of therapy gains. Unlike microstructural therapies, evidence of generalisation to untreated words if phonetically similar. Sub-groups may provide insight into those individuals who benefit most from therapy

47 Thank you

48 Macrostructural Therapy for AOS
Macrostructural (whole word/utterance) therapies used in AOS e.g. Key word therapy (Square-Storer, 1989) & Melodic Intonation Therapy. Intervention study: whole words, self-administered computer therapy. Self-administered computer therapy allows users to deliver intervention at times/locations convenient to them & without therapist being present. Potential to achieve high dose therapy. Computers ideal for delivering repeated stimulation necessary to stimulation reorganisation of damaged neural system (Bhogal et al., 2003; Pulvermüller & Berthier, 2008; Varley, 2011).

49 Word Duration (Treated)

50 Segments & Speech Control
Segmental models built upon evidence of switch errors (Jeremy Hunt, the culture secretary). But these errors rare in novice users of speech production mechanism (appearing after 7 yrs Stemberger, 1989), & rare in acquired speech disorders (Varley & Whiteside, 2001). Influenced by word frequency, occurring on lower frequency words.

51 Background Assessments
Screens for: Prognostic indicators Severity of aphasia Auditory processing Dysarthria Non-word repetition Presence of oral apraxia Repetition priming Severity of AOS Cloze/isolated production Health economic assessment Psycholinguistic battery

52 Data Analysis (Cowell, et al. 2010. Frontiers in Human Neuroscience).
Cross-over designs typical in drug trials. Small number in cog-behavioural interventions (e.g. Fillingham, 2005; Raymer et al, 2010). Avoids ‘resentful demoralisation’ of randomisation to sham in open-label RCT. But semi-permanence of successful cog-behav. therapy creates statistical problem: setting of new baselines across phases. Use of delta scores; lambda statistic to determine if possible to join 2 phases of trial. Accuracy score: Test 1 20/35; Test 2 30/35; delta =-10 Word duration: Test 1 400ms; Test 2 300ms; delta = +100

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