Brain imaging and stuttering: An update for researchers and clinicians

Size: px

Start display at page:

Download "Brain imaging and stuttering: An update for researchers and clinicians"

Bonnie Richards
5 years ago
Views:

1 Brain imaging and stuttering: An update for researchers and clinicians Luc De Nil, Ph.D. University of Toronto ASHA November 2011

2 Number of brain imaging publications (excluding review articles, etc.)

3 Meta-analysis: Neural signatures of developmental stuttering (Brown et al., 2005) Overactivation of frontal operculum/anterior insula Decreased activity in bilateral auditory cortex Overactivation of lobule III of the cerebellum

5 overactivation De Nil, et al., 2000

6 Fox, et al., 1996 Other recent studies: Lu et al (picture naming - PWS showed RH>LH) Chang, et al (bilateral overactivation for speech as well as nonspeech oral tasks)

7 Laterality differences Fox, et al., 1996 OP 4 is densely connected to the PCG and the frontal cortex (note: Broca s and PMC but appears stronger connections in animals than humans) and may consequently play a role in sensorymotor integration processes, such as incorporating sensory feedback into motor actions Eickhoff, et al Chang, et al. 2009

8 Relation to stuttering severity Chang, et al., 2009 Other recent studies: Kell, et al. 2009: Positive correlation with severity for right insula, right rolandic operculum, and bilateral striatum; Negative correlation with right orbitofrontal and bilateral medial frontal gyrus No relationship to recovery from stuttering Giraud, et al., 2008

9 Speech vs. Nonspeech Speech Nonspeech Chang, et al. 2009

10 Overactivation of Cerebellum Silent Reading Chang, et al., 2011 The cerebellum is the brain structure most critically involved in reflex adjustments and the acquisition of fine and sequential motor control. (Glickstein, et al., 2009) Oral Reading The overall task of the cerebellum may be the ability to provide correct predictions about the relationship between sensory stimuli in both sequence and associative learning. There is increasing evidence that predictive control is a major function of the cerebellum in motor control and learning (Timmann, et al. 2010) Verb Generation De Nil et al., 2001

11 Overactivation increases with intensive motor-skill focused treatment PNS PWS - pre PreTx PostTx 2 yr follow-up PWS -post PWS -fup De Nil et al., 2000 Neumann et al., 2003

12 Deficit compensation? Effort? Motor learning? Motor task approach?.

13 Walter Moore (1984) right hemisphere compensates for deficient left hemisphere function William Webster (1990) deficient gating between RH activation and LH speech motor functions resulting in interference Kell, et al. (2009) How the brain repairs stuttering

14 Chang, et al increased activation during production but not during perception or planning could reflect effort Kell, et al., Correlations with stuttering severity may indicate greater effort De Nil, 1999, De Nil, et al Effort as a result of greater voluntary control and less automaticity Packmann, et al. (2007) Vmodel of stuttering (effort related to syllable stress variability is trigger of stuttering)

15 Effort in nonstuttering adults f..f..f..flower

16 Learning to play a melody Chen, et al., in press

17 Dual task interference effects Breaking news: Beal, et al. ASHA 2011 Bauerly, et al., submitted

18 Semantic/phonology Working memory Emotional behaviour/empathy Fine motor control Based on meta-analysis of 485 neuroimaging studies of the Inferior Frontal Gyrus (G. Liakakis et al., 2011)

Fox, et al. 1996 Other recent studies: Lu et al.

20 Fox, et al Other recent studies: Lu et al. 2010: Decreased activation in left ASTG (but not right) Chang, et al 2009: Increased right STG and decreased left STG

21 Auditory inhibition animal studies Neural silence when vocalizing Neural activation when listening

22 Stuttering adults listening to the vowel /i/ Stuttering adults saying the vowel /i/ Beal et al., 2010

23 Auditory inhibition CWS Beal et al., 2011 The greater the severity, the lower the amplitude of the signal in auditory cortex indicating a possible role of effort

24 Brown, et al. 2005

25 Kikuchi, et al 2011 In NS sensory gating was more dominant in LH than in RH; No such difference was present in PWS - they may not be able to gate out ignorable auditory inputs which may cause auditory error signals Defective auditory motor integration the causes of stuttering Beal, et al CWS demonstrate longer bilateral latency in M50 during a listen and speak task (vowel), but similar latencies during a listen to tone task This may reflect a deficiency in integrating auditory and speech motor processes The difference may be compensatory in nature (related to severity and effort)

27 Structural imaging Gray Matter Voxel based morphometry (adults) a b L. Inferior frontal g. L. temporal pole L R L. and R. superior temporal g. c d R. insula P A L. middle temporal g. Beal et al., 2007

28 PDS subjects showed a small but significant increase in both the number of sulci connecting with the second segment of the right Sylvian fissure and in the number of suprasylvian gyral banks (of sulci) along this segment Cykowski et al., 2008

supramarginal g. Recovered > Persistent posterior cingulate cerebellar inferior frontal g.

29 Structural imaging in CWS Group differences in Gray Matter Fluent > Stuttering inferior, middle, superior frontal g. medial frontal g. pre- post central g. anterior cingulate middle temporal g. supramarginal g. Recovered > Persistent posterior cingulate cerebellar inferior frontal g. Chang et al Persistent > Recovered cerebellum precentral Inferior parietal superior temporal g. middle frontal g.

30 Structural imaging in CWS Red: Green: Yellow: CWS < control for grey matter CWS < control for white matter CWS > control for grey Beal, et al. - submitted

31 Other recent studies Lu, et al more gray matter in left MFG, bilateral PCG, bilateral cingulate gyrus and left Putamen less in left SFG, bilateral medial FG, left STG and right cerebellum Kikuchi, et al more gray matter in right frontal gyrus, right temporal gyrus, right insula, and supramarginal gyrus less gray matter in left precentral gyrus, left middle frontal gyrus and left insula Kell, et al 2009 Less gray matter in left IFG negative correlation with severity

Structural imaging White Matter Diffusion Tensor Imaging (DTI) PWS: less dense white matter underlying the motor cortex, especially in laryngeal

32 Structural imaging White Matter Diffusion Tensor Imaging (DTI) PWS: less dense white matter underlying the motor cortex, especially in laryngeal and tongue areas in left hemisphere may point to deficient timing of speech motor processes RH activation may point to compensation Sommer et al., 2001

33 Other recent studies Cykowski, et al reduced white matter in left forceps minor extending into the left superior longitudinal fasciculus, including deep into BA 44 reduced white matter in Corpus Callosum Lu, et al 2010; WM (VBM) reduced white matter in right PCG, left STG and bilateral cerebellum increased right SFG, right Inferior and Superior TG and left cerebellum Watkins, et al reduced white matter in left hemisphere reduced connections between cortical and between cortical-subcortical structures

Structural imaging associated with neural activation? Fig. 3 Structural and functional abnormalities in the premotor cortex and underlying white matter in people who stutter.

34 Structural imaging associated with neural activation? Fig. 3 Structural and functional abnormalities in the premotor cortex and underlying white matter in people who stutter. The skeleton (green) is overlaid onto the average FA image of the subjects studied. Blue indicates areas where PWS had significantly less activity than Controls during speech production, across the three feedback conditions (see Fig. 1 for details). Pink indicates areas where PWS had lower FA than Controls (see Fig. 2 for details). Sagittal image in the top right of figure shows the position of the axial and coronal slices shown below (a^ d). For axial and coronal slices the left side of the brain is shown on the left. vpmc=ventral premotor cortex; cop=central operculum. Watkins, et al. 2008

35 Trait difference? Cykowski, et al deficient myelogenesis but no evidence of tissue damage (thus disfunction rather than deficit) Lu, et al deficient timing of motor plan: A disruption of timing in presma and posterior temporal cortex resulting in a disruption of timing control of speech production Chang, et al 2011 functional and structural connectivity differences between PWS and NS in left inferior frontal to premotor connections, but only functional differences in thalamocortical connections. The latter could reflect compensatory or reactive change. Lu et al (2010) connectivity from left IFG to left PMA is weaker in PWS than in NS; similarly between right IFG and left motor cortex deficiency in the connection may be a result of deficient connections between BG and IFG, and between cerebellum and PWM there is increased connectivity between the motor cortex and cerebellum in PWS, but not in NS Structural differences as a result of stuttering history?

37 tml

38 A case study: Parkinson Disease Oliver Sacks (2007). Musicophilia. Tales of Music and the Brain chapter 20

Neurogenic stuttering Ludlow, et al. (1987) 8 of the 10 patients they examined who had acquired stuttering incurred symptoms after injury to the striatum or cortico-striatal connections. Theys, et al.

39 Neurogenic stuttering Ludlow, et al. (1987) 8 of the 10 patients they examined who had acquired stuttering incurred symptoms after injury to the striatum or cortico-striatal connections. Theys, et al. (submitted) the following brain areas differentiate between stroke patients with and without neurogenic stuttering: left inferior frontal gyrus and sulcus superior temporal sulcus ascending limb of inferior temporal sulcus intraparietal sulcus basal ganglia superior longitudinal fasciculus internal capsule

Drug treatment of developmental stuttering Exploratory Randomized Clinical Study of Pagoclone in Persistent Developmental Stuttering: The EXamining Pagoclone for persistent developmental Stuttering

40 Drug treatment of developmental stuttering Exploratory Randomized Clinical Study of Pagoclone in Persistent Developmental Stuttering: The EXamining Pagoclone for persistent developmental Stuttering Study. Maguire, Gerald; Franklin, David; PsyD, MHA; Vatakis, Nick; Morgenshtern, Elena; Denko, Timothey; Yaruss, J; Scott PhD, CCC SLP; Spotts, Crystal; Davis, Larry; Davis, Aaron; Fox, Peter; Soni, Poonam; Blomgren, Michael; PhD, CCC SLP; Silverman, Andrew; Riley, Glyndon Journal of Clinical Psychopharmacology. 30(1):48 56, February DOI: /JCP.0b013e3181caebbe FIGURE 2. Average (+/ SE) percent change from pretreatment to on treatment in percentage of syllables stuttered ITT (LOCF) double blind and open label treatment periods (open label data include only patients who completed the 12 month open label study visit) Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2

41 Alm (2004) There are strong indications that the basal ganglia-thalamocortical motor circuit, through the putamen to the SMA, plays an important role in the pathophysiology of stuttering. The core dysfunction in stuttering is suggested to be impaired ability of the basal ganglia to produce timing cues. Some of the conditions that temporarily alleviate stuttering are proposed to be effective by providing compensatory timing information. This pertains to the rhythm effect, chorus speech, and singing. The adaptation effect is mainly based on an improvement of the basal ganglia timing cues resulting from practice of a specific speech sequence.

42 Other explanations: Indirect influence of BG on intra-cortical communication and coordination Watkins, 2011: influence of BG complex on intra-cortical communication as a result of reduced WM in left hemisphere and reduced connections between cortical areas and between cortical-subcortical structures Lu et al. 2010: Weaker connectivity from left IFG to left PMA in PWS than in NS; also between right IFG and left motor cortex. The deficiency in cortical connections may be the result of deficient connections between BG and IFG, as well as between cerebellum and PMC Atypical activity in BG or in areas receiving efferent output from basal ganglia nuclei contributes to a system dysfunction that interferes with rapid and dynamic speech processing for production (Ludlow & Loucks, 2003) Point to deficit in sequence learning and automatization (Smits- Bandstra & De Nil, 2007)

43 Differential role of Basal Ganglia and Cerebellum in Learning For motor sequence learning skills, it is proposed that the long-term retention of this type of skill is dependent upon activity maintained in the cortico-striatal system, whereas for motor adaptation skills, the longlasting representation of this form of learning is mediated through the cortico-cerebellar system. Doyon, et al., 2009 Basal Ganglia circuits are intimately involved in and necessary for new skill learning, but are of far less importance in the retention and recall of well-learned motor skills. Turner & Desmurget, 2010

44 Synthesis and Conclusion PWS and NS differ in activation of brain regions involved in speech production Increased activation, especially in structures involved in speech motor control (frontal cortex, basal ganglia and cerebellum) Primarily right hemisphere but also bilateral Reduced activation in auditory cortex Bilateral or left hemisphere PWS and NS show structural differences in cortical regions Differences in gray matter Differences in white matter these are becoming increasingly consistent and important Underlying frontal premotor and motor cortex Between motor cortex and auditory cortex Between motor cortex and subcortical structures (Basal Ganglia and Cerebellum) Regions of functional and structural differences are also evident in neurogenic stuttering Important role of basal ganglia and cerebellum in regulating and modulating the inter-region neural communication Functional and structural differences may point to timing disruptions of sensorimotor coordination required for speech

45 Sensorimotor dysfunction Reduced ability for articulatory coordination cognition temperament Temperament Linguistic Weaker ability to acquire new motor skills. Stuttering Chronic stuttering Weaker ability to automatize new motor skills Maturation Recovery experiences conditioning

46 Therapy Fluency shaping?? Stutter modification Ability for motor learning Recovery or relapse Automatization

Stuttering Research. Vincent Gracco, PhD Haskins Laboratories

Stuttering Research. Vincent Gracco, PhD Haskins Laboratories Stuttering Research Vincent Gracco, PhD Haskins Laboratories Stuttering Developmental disorder occurs in 5% of children Spontaneous remission in approximately 70% of cases Approximately 1% of adults with