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Dysarthria in Parkinsons Disease and Ataxia

ASHA, 2011 John J. Sidtis


Director, Brain and Behavior Laboratory The Nathan Kline Institute for Psychiatric Research Professor, NYU School of Medicine

john.sidtis@nyu.edu

Dysarthria in Parkinsons Disease and Ataxia


The ability to speak clearly involves a complex brain system that is not fully understood. Parkinson's disease and the ataxias interfere with this ability.

Dysarthria in Parkinsons Disease and Ataxia


The ability to speak clearly involves a complex brain system that is not fully understood. Parkinson's Disease and the ataxias interfere with this ability. Our Laboratory explores this speech control system with a combination of studies on the effects of speech tasks and functional brain imaging with PET. We have been particularly interested in the role of cortical-subcortical interactions during speech.

Dysarthria in Parkinsons Disease and Ataxia


How do we begin to understand this complex brain system?
Clinically informed behavioral studies: perceptual ratings intelligibility acoustic analysis

Dysarthria in Parkinsons Disease and Ataxia


How do we begin to understand this complex brain system?
Clinically informed behavioral studies: perceptual ratings intelligibility acoustic analysis Clinically informed functional imaging: disease relevant tasks performance-based analysis

Dysarthria in Parkinsons Disease and Ataxia


How do we begin to understand this complex brain system?
Clinically informed behavioral studies: perceptual ratings intelligibility acoustic analysis Clinically informed functional imaging: clinically relevant tasks performance-based analysis Take advantage of advances in neurobiology, genetics, and neuroscience.

Taking advantage of advances in neurobiology, genetics, and neuroscience


The genetics of hereditary, spino-cerebellar ataxia (SCA)

Normal cerebellum

SCA5 pure ataxia chromosome 11 spectrin mutation

SCA6 pure ataxia chromosome 19 CAG repeat

SCA1 mixed ataxia chromosome 6 CAG repeat

The genetics of SCA


Using perceptual ratings, are there genotypic differences in the speech produced by subjects with SCA1, SCA5, and SCA6?

Speech samples were rated on the following primary dimensions: articulation, rate, rhythm, and prosody. When a primary dimension was rated abnormal, secondary dimensions were rated as well. These included articulatory and voice dimensions.

Sidtis JJ, Ahn JS, Gomez C, Sidtis D. Speech characteristic associated with three genotypes of ataxia. Journal of Communication Disorders 44: 478-492, 2011.

The genetics of SCA

Primary Dimensions
There were significant task differences. Diadochokinesis produced the most consistent ratings across genotypes. There were also significant dimension differences. Articulation was the most Impaired primary dimension.

Sidtis JJ, Ahn JS, Gomez C, Sidtis D. Speech characteristic associated with three genotypes of ataxia. Journal of Communication Disorders 44: 478-492, 2011.

The genetics of SCA

Secondary Dimensions
Picture description was most effective in eliciting abnormal secondary dimensions. Voice dimensions showed greater differences across SCA types than articulation.

Sidtis JJ, Ahn JS, Gomez C, Sidtis D. Speech characteristic associated with three genotypes of ataxia. Journal of Communication Disorders 44: 478-492, 2011.

The genetics of SCA


Articulation is the most impaired primary dimension across SCA types. This corresponds to a core dimension described by Zeplin and Kent. Syllable repetition was the most effective task for the primary features of ataxic dysarthria (Kent et al, 1997; Ziegler, 2002). Voice subgroups have been reported in the ataxic dysarthrias (Grmy et al. 1967; Joanette & Dudley, 1980). Spontaneous speech (picture description) is more effective than repetition in characterizing problems in normal communicative settings (Kempler & Van Lancker, 2002; D. Sidtis et al., 2010).
Zeplin & Kent (1996). In Robin, Yorkston, Beukelman, (Eds.), Disorders of motor speech. Baltimore: Brookes. Kent et al. (1997). Folia Phoniatrica et Logopaedica, 49, 63-82. Ziegler (2002). Brain and Language, 80, 556-575. Grmy et al. (1967). Revue Neurologique (Paris), 116(5), 401-426. Joanette & Dudley (1980). Brain and Language, 10, 3950. Kempler & Van Lancker (2002). Brain and Language, 80, 449-464. D. Sidtis et al., (2010) JSLHR, 53, 1167-1177.

Taking advantage of advances in neurobiology, genetics, and neuroscience.


The ability to map brain activity with functional imaging.

PET measures the concentration of isotope paired with a biologically active substance (e.g., water, drug).

fMRI measures the signals produced by nuclear particles as they respond to magnetic pulses. The BOLD signal is based on the differences in signal produced by oxygenated and de-oxygenated blood.

The ability to map brain activity with functional imaging


Currently, the most common approach is to use fMRI to Identify areas of activation in the BOLD signal. Activation is a significant signal increase when two or more conditions are contrasted. We have argued that alternative approaches may be more suitable for a systems approach to studying the neurological systems for speech motor control.

The ability to map brain activity with functional imaging Performance-based analysis:
is an alternative to activation approaches. does not require contrasting two or more conditions. does not remove brain areas that do not activate from further analysis. simply seeks to determine if there is a linear combination of brain areas in which activity predicts performance on the task done during scanning (e.g., repetition of /pa-ta-ka/).

Mapping brain activity with performance-based analysis.

Although speech and language are strongly lateralized, functional images typically show bilateral signals. Performance-based analysis using multiple linear regression allows us to predict syllable rate during the repetition of /pa-ta-ka/. Although the images are bilaterally symmetrical, the performancebased analysis identifies an inverse relationship between the left inferior frontal region (Brocas area) and the right caudate nucleus.

Sidtis JJ, Strother SC, Rottenberg DA. Predicting performance from functional imaging data: Methods matter. NeuroImage 20(2): 615-624, 2003. Sidtis JJ. Some problems for representations of brain organization based on activation. Brain and Language 102(2): 130-140, 2007.

Mapping brain activity with performance-based analysis.


/pa,ta,ka/ repetition

INFERIOR FRONTAL REGION 1.6 ns

vnrCBF

1.4

SPEECH RATE PREDICTORS: Predicting normal rate


1.2

NORMALS 5.0
LEFT IFG

1.0 LEFT RIGHT


CAUDATE NUCLEUS 1.8 ns

Regression Weight

2.5 0.0 -2.5


RIGHT CAUDATE

vnrCBF

1.6

Performance Based Analysis

1.4

-5.0
1.2 LEFT RIGHT

Sidtis JJ, Strother SC, Rottenberg DA. Predicting performance from functional imaging data: Methods matter. NeuroImage 20(2): 615-624, 2003.

Mapping brain activity with performance-based analysis.


/pa,ta,ka/ repetition

INFERIOR FRONTAL REGION

vnrCBF (speech-rest)

0.10 0.08 0.06 0.04 0.02 0.00 LEFT RIGHT p = 0.002

CAUDATE NUCLEUS

No Solution
Performance Based Analysis

vnrCBF (speech-rest)

0.05 0.03 0.01 -0.01 -0.03 -0.05 LEFT RIGHT ns

Sidtis JJ, Strother SC, Rottenberg DA. Predicting performance from functional imaging data: Methods matter. NeuroImage 20(2): 615-624, 2003.

Performance-based connectivity analysis.


The original performance-based analysis establishes primary relationships between brain regions and performance (e.g., rate). This was expanded to explore a larger system of functional connectivity using partial correlation. This expanded analysis determines the relationship between each primary predictor region and other brain regions, controlling for the correlation between the primary predictor and its contralateral homologous region (e.g., relationships with the left inferior frontal region are determined controlling for the influence of the right inferior frontal region).

Sidtis JJ. Performance-Based Connectivity Analysis: A Path to Convergence with Clinical Studies. NeuroImage 2011, doi:10.1016/j.neuroimage.2011.09.037.

Performance-based connectivity analysis.


PRIMARY RELATIONSHIPS WITH RATE PRIMARY AND SECONDARY RELATIONSHIPS WITH RATE

Increased speech rate is predicted by a linear combination of increased contribution by the left inferior frontal region and decrease by the right caudate. Secondary relationships present a pattern consistent with clinical evidence.
GREEN = POSITIVE ASSOCIATION RED = NEGATIVE ASSOCIATION

Sidtis JJ. Performance-Based Connectivity Analysis: A Path to Convergence with Clinical Studies. NeuroImage (2011), doi:10.1016/j.neuroimage.2011.09.037.

Performance-based connectivity analysis.


Performance-based analysis captures:
left hemisphere motor control; thalamic involvement in speech rate; auditory suppression during speech.

Sidtis JJ. Performance-Based Connectivity Analysis: A Path to Convergence with Clinical Studies. NeuroImage (2011), doi:10.1016/j.neuroimage.2011.09.037.

Performance-based connectivity analysis.


Performance-based analysis captures:
left hemisphere motor control; thalamic involvement in speech rate; auditory suppression during speech.

Important to note:
both positive and negative relationships are significant; regions that do not activate (e.g., the caudate) play a significant role in predicting speech rate.

Mapping the ataxic brain during speech.

How does brain function in ataxia compare to normal brain function during speech?

Mapping the ataxic brain during speech.

SPEECH RATE PREDICTORS: Predicting ataxic rate ATAXIA 5.0


LEFT IFG RIGHT INFERIOR CEREBELLUM

Regression Weight

2.5 0.0 -2.5


RIGHT CAUDATE

INFERIOR FRONTAL REGION 1.6

1.4 ns 1.2

Performance Based Analysis

vnrCBF

-5.0

LEFT TRANSVERSE TEM PORAL

Brain Regions
1.0 LEFT RIGHT

Ataxic mean flow values

Sidtis JJ, Gomez C, Naoum A, Strother SC, Rottenberg DA. Mapping cerebral blood flow during speech production in hereditary ataxia. NeuroImage 31: 246-254, 2006.

Mapping the ataxic brain during speech.


In a combined group of SCAs, performance-based analysis:
replicated the normal inverse cortical-subcortical relationship with speech rate; identified a role for the right cerebellum; identified a role for an auditory area in the left temporal lobe.

Sidtis JJ, Gomez C, Naoum A, Strother SC, Rottenberg DA. Mapping cerebral blood flow during speech production in hereditary ataxia. NeuroImage 31: 246-254, 2006.

Mapping the ataxic brain during speech.


In a combined group of SCAs, performance-based analysis:
replicated the normal inverse cortical-subcortical relationship with speech rate; identified a role for the right cerebellum; identified a role for an auditory area in the left temporal lobe.

Can genotypic differences be identified?

Sidtis JJ, Gomez C, Naoum A, Strother SC, Rottenberg DA. Mapping cerebral blood flow during speech production in hereditary ataxia. NeuroImage 31: 246-254, 2006.

Genotypic Differences in Functional Connectivity of Predictor Regions SCA 1 SCA 5 SCA 6

INFERIOR FRONTAL REGION

CAUDATE NUCLEUS

GREEN = POSITIVE ASSOCIATION

RED = NEGATIVE ASSOCIATION

Performance-based connectivity analysis identified genotypic differences among the ataxias


SCA5, with least affected speech, has generalized positive relationships with speech rate associated with the left inferior frontal region and negative relationships associated with the right caudate nucleus; SCA6, with the greatest speech impairment, had no identifiable secondary associations with the right caudate; The two pure ataxias did not have similar functional connectivity; The two trinucleotide repeat ataxias appeared more similar to each other than to the spectrin based pathology; Molecular pathophysiology may be more important than gross pathology These results, together with the results of listening studies, suggest that neurobiological advances will contribute to a better understanding of the complex systems underlying articulatory and vocal control.

Take advantage of advances in neurobiology, genetics, and neuroscience.


The ability to study the effects of stimulating basal ganglia structures in the treatment of Parkinsons Disease (Deep brain stimulation or DBS)
High frequency, repetitive electrical stimulation of certain brain areas improves some of the symptoms of movement disorders, including Parkinsons Disease (PD). Originally, DBS was conceived of as a reversible lesion. DBS is now seen as changing firing patterns of nuclei in the basal ganglia. Side effects are produced by stimulation of adjacent pyramidal tracts.

Take advantage of advances in neurobiology, genetics, and neuroscience.


The subthalamic nucleus (STN), part of the basal ganglia, is the most common target in PD. STN-DBS is effective at controlling tremor and rigidity. Continuous STN-DBS reduces the on-off effects of PD medication. STN-DBS also allows a reduction in PD medication. Our studies are investigating how DBS affects speech and brain activity as a function of speaking task.

MRI showing the placement of bilateral stimulating electrodes in the STN (Alterman).

Take advantage of advances in neurobiology, genetics, and neuroscience.


Dysfluencies are greater during conversation compared to conversation-repetition. There is a tendency for greater dysfluency with DBS on during conversation.

Sidtis D, RogersT, Godier V, Tagliati M, Sidtis JJ. Voice and fluency changes as a function of speech task and deep brain stimulation. JSLHR 53(5): 1167-77, 2010. Sidtis, D, Cameron K, Bonura L, Sidtis JJ. Speech intelligibility by listening in Parkinson speech with and without deep brain stimulation: Task effects. Journal of Neurolinguistics, In press.

Take advantage of advances in neurobiology, genetics, and neuroscience.

HNR improved with DBS during conversation. The DBS effect on HNR is comparable to the effect of repetition.

Sidtis D, RogersT, Godier V, Tagliati M, Sidtis JJ. Voice and fluency changes as a function of speech task and deep brain stimulation. JSLHR 53(5): 1167-77, 2010. Sidtis, D, Cameron K, Bonura L, Sidtis JJ. Speech intelligibility by listening in Parkinson speech with and without deep brain stimulation: Task effects. Journal of Neurolinguistics, In press.

Take advantage of advances in neurobiology, genetics, and neuroscience.

Voice abnormalities are reduced with DBS during conversation. The effect of repetition on voice quality is greater than the effects of DBS.

Sidtis D, RogersT, Godier V, Tagliati M, Sidtis JJ. Voice and fluency changes as a function of speech task and deep brain stimulation. JSLHR 53(5): 1167-77, 2010. Sidtis, D, Cameron K, Bonura L, Sidtis JJ. Speech intelligibility by listening in Parkinson speech with and without deep brain stimulation: Task effects. Journal of Neurolinguistics, In press.

Take advantage of advances in neurobiology, genetics, and neuroscience.

During conversational speech, DBS improves voice but tends to reduce articulatory performance. The effects of DBS are comparable to, or slightly less effective than the effects of repetition. Providing an external model (repetition) appears to reduce the burden on the basal ganglia during conversational speech. Can we learn more about these effects using functional imaging?

Take advantage of advances in neurobiology, genetics, and neuroscience.

Performance-based analysis identified an inverse cortical-subcortical relationship with speech rate.

Take advantage of advances in neurobiology, genetics, and neuroscience.

Performance-based analysis identified an inverse cortical-subcortical relationship with speech rate.

In PD, these same brain regions predicted speech rate, but the weighting for the inferior frontal region is inverted. For the PD analyses, data for three repetition tasks were used.

Take advantage of advances in neurobiology, genetics, and neuroscience.

LEFT

RIGHT

With DBS, the inverse cortical-subcortical relationship with rate observed in normal and ataxic speakers is restored, but is now bilateral.

Take advantage of advances in neurobiology, genetics, and neuroscience.

With DBS off, the inferior frontal region is lost and the right caudate is inverted. Short term cessation of DBS does not reflect PD, and may reflect a temporally unstable state.

LEFT

RIGHT

Take advantage of advances in neurobiology, genetics, and neuroscience.


The study of the effects of DBS on different speech tasks promises to provide insights into basal ganglia function and the ways in which these structures interact with the rest of the brain. As with molecular genetics in the spino-cerebellar ataxias, the DBS manipulation is biologically complex and not fully understood. Using DBS to better understand motor speech control, we will also have to better understand the neurobiology of DBS. For example, in studying cerebral blood flow during speech in DBS, we discovered a previously unknown effect: a significant increase in global blood flow (Sidtis et al., 2011). In spite of the unknowns, the advances in neuroscience will lead to a more sophisticated understanding of motor speech control.
Sidtis JJ et al. Therapeutic high frequency stimulation of the subthalamic nucleus in Parkinsons Disease produces global increases cerebral blood flow. J Cerebral Blood Flow and Metabolism, doi:10.1038/jcbfm.2011.135

Take advantage of advances in neurobiology, genetics, and neuroscience.


When advances in neurobiology, genetics, and neuroscience are incorporated into research on the dysarthrias, do we replicate what we already know (or think we know)? Can we use these advances to learn more about the neurology of speech motor control? Advances in neurobiology, genetics, and neuroscience should be viewed as providing potential tools to pursue questions raised by clinical experience, and never as replacements for that experience.

Regards from Diana Sidtis, Associate Director, who was unable to attend after breaking her arm at the German Aphasia Conference.

Acknowledgments
NIH R01 NS37211

Brain and Behavior Laboratory


Diana Sidtis, Associate Director
Students:
Danielle Acerno Nicole Acquafredda Ji Sook Ahn Amy Alken Bettina Armstrong Maria Anderson Katie Barnes Sara-Jean Bartky Pelinsu Belut Kathy Bih Lisa Bonura Kelly Bridges Tarun Calidas Krista Cameron* Claudia Cerulli Liz Dovlatyan* Violette Godier* Ariana Gluck Aly Hoffman Hae Su Kang Dora Katsnelson Kathy Kougentakis Nina Lisitsa Jennifer Melgarejo Raz Meltzer Jeon Moon Holly Pralgever Tiffany Rogers Robert Sidtis Liz Sweeting* Elana Winters Theresa Yang Lisa Yeung Judy Yuen Victoria Zeldin

Cerebellar Ataxia
Christopher Gomez, University of Chicago David Rottenberg, University of Minnesota Stephen Strother, University of Toronto

Parkinsons Disease
Michele Tagliati, Ron Alterman, Cathy Cho Fiona Gupta, Tyler Chung Mount Sinai Medical School David Eidelberg, Vijay Dhawan Feinstein Institute, North Shore University Hospital

Image Processing
Babak Ardekani, Ali Tabash, Khadija Figarsky Nathan Kline Institute for Psychiatric Research

* Served as Laboratory Manager