Study Notes on Reduced Perfusion in Broca’s Area in Developmental Stuttering

Study Notes on Reduced Perfusion in Broca’s Area in Developmental Stuttering

Authors and Affiliations

  • Jay Desai: Division of Neurology, Children’s Hospital Los Angeles, California

  • Yuankai Huo: Department of Psychiatry, Columbia University, New York, New York

  • Zhishun Wang: Department of Psychiatry, Columbia University, New York, New York

  • Ravi Bansal: Keck School of Medicine at the University of Southern California, Los Angeles, California; Institute for the Developing Mind, Children’s Hospital, Los Angeles, California

  • Steven C. R. Williams: Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College, London, United Kingdom

  • David Lythgoe: Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College, London, United Kingdom

  • Fernando O. Zelaya: Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College, London, United Kingdom

  • Bradley S. Peterson: Keck School of Medicine at the University of Southern California, Los Angeles, California; Institute for the Developing Mind, Children’s Hospital, Los Angeles, California (Corresponding Author)

Abstract

Objective

  • Study resting cerebral blood flow in children and adults with developmental stuttering.

Methods

  • Participants: 26 with stuttering, 36 healthy controls.

  • Imaging Data: Acquired pulsed arterial spin labeling magnetic resonance imaging data.

  • Adjustments: Covaried for age, sex, and IQ.

  • Comparison: Voxel-wise across diagnostic groups.

  • Correlation Assessment: Perfusion with stuttering severity within stuttering group and motor speed in both groups.

Results

  • Findings:

    • Lower regional cerebral blood flow (rCBF) at rest in the stuttering group compared to controls in:

    • Broca’s area (bilaterally)

    • Superior frontal gyrus

    • Correlation of rCBF in Broca’s area with stuttering severity; more severe stuttering is associated with greater reduction in rCBF.

    • Increased rCBF in:

    • Cerebellar nuclei

    • Parietal cortex in stuttering group compared to controls.

  • Results remained consistent in child-only analyses and excluding participants with comorbidity or medication.

Conclusions

  • rCBF is reduced in Broca’s region in individuals who stutter.

  • Greater severity in stuttering correlates with greater reductions in rCBF, indicating common pathophysiology throughout the language loop.

Introduction

Overview of Stuttering

  • Definition: Disorder of speech fluency characterized by repetition, prolongation, or inability to produce speech.

  • Incidence: Approximately 5% over a lifespan; average prevalence around 1%. Onset typically occurs in early childhood, with 25% of cases persisting into adulthood.

Neuroimaging Studies

  • Previous studies using anatomical MRI, task-based fMRI, and resting-state fMRI have shown widespread abnormalities in brain regions associated with stuttering.

  • Limitations of Task-Based fMRI:

    • Only measures specific brain regions implicated in the task itself.

    • Task performance may differ by participant age, affecting results.

    • rCBF as a surrogate measure of brain activity is independent of task performance, allowing data from all brain regions at rest.

Hypotheses

  • Hypothesized reduced perfusion in regions related to:

    • Speech production

    • Sensory feedback

    • Phonological encoding

    • Motor planning and programming.

Methods

Participants

  • Sample Size: 26 participants with developmental stuttering, recruited via advertisements.

  • Diagnosis: Conducted by licensed speech-language pathologists.

  • Comorbidities: Diagnosed using Kiddie-Schedule for Affective Disorders and Schizophrenia for minors and Structured Clinical Interview for DSM-IV-TR for adults.

  • Severity of Stuttering: Assessed using the Assessment of the Child’s Experience of Stuttering for children and Overall Assessment of the Speaker’s Experience of Stuttering for adults.

  • Control Group: 36 fluent controls selected to match age and sex, screened for Axis I disorders and language disorders.

Neuropsychological Assessments

  • IQ assessed via Wechsler Abbreviated Scale of Intelligence.

  • Handedness measured using Edinburgh Inventory.

  • Socioeconomic status calculated via Hollingshead’s index.

  • Additional tasks: Finger tapping, line bisection, and Purdue pegboard test.

MRI Scanning

  • Equipment: GE Signa 3T HDx system.

  • Imaging Technique: Optimized Pulsed Arterial Spin Labeling (PASL) sequence used to measure perfusion; pulse sequences detailed including tagging slab placements and control image acquisitions.

Image Analysis

  • Voxel-wise rCBF map construction:

    1. Pair-wise subtraction of control images from labeled images.

    2. rCBF calculated using equation: rCBF=DI−M<em>0racT1</em>BT1<em>Ae−racTI</em>2T1BrCBF = DI - M<em>0 rac{T1</em>B}{T1<em>A} e^{- rac{TI</em>2}{T1_B}}

    • Where DI represents image difference,

    • M0 estimates, and tagging efficiency set to default.

  • Statistical Analysis:

    • Used Statistical Parametric Mapping (SPM-8) for analyses; performed corrections for multiple comparisons using Monte Carlo simulations.

Results

Sample Characteristics

  • General matching characteristics noted regarding age, sex, socioeconomic status, ethnicity, and handedness; slight IQ difference noted, favoring controls.

Group Comparison of rCBF Values

  • Significant findings:

    • Lower rCBF in Broca’s area and superior frontal gyrus.

    • Higher rCBF in cerebellar nuclei and parietal cortex among stutterers.

    • Within-group correlation analysis showed that decreased rCBF in Broca’s area correlated with increased severity of stuttering.

Neuropsychological Measures

  • Positive correlations between finger tapping speed and rCBF noted, particularly in language areas.

    • Inverse correlations also significant in bilateral sensorimotor areas.

Discussion

Summary of Key Findings

  • First use of perfusion MRI in relation to stuttering differences; consistently reduced rCBF in Broca’s area noted.

  • Strong inverse relationships between rCBF and stuttering severity suggest critical disruptions in motor planning and phonological processes.

Anatomical and Functional Implications

  • Insights into speech production issues based on Broca’s functional role - essential for fine motor planning in speech.

  • Inverse correlation extending to areas associated with the arcuate fasciculus and Wernicke’s area highlights dysfunction in broader language networks.

Compensatory Mechanisms

  • Increased rCBF in cerebellar regions and parietal cortex may reflect compensatory mechanisms due to disrupted speech processing.

Limitations

  • Wide age range of participants considered, although analyses remained consistent.

  • Imaging studies were conducted at rest, potentially limiting functional insights under task conditions.

  • Future studies should employ sequences that minimize localized signal dropouts and incorporate objective measures of dysfluency.

Acknowledgments

  • Research supported by multiple funding sources, notably Milhiser Family fund and NIMH grant K02 74677.

Contributions to the Study

  • Roles identified for each author in experiment design, data collection, and analysis tasks.

Disclosure of Financial Relationships

  • Detailed disclosures of financial interests among authors, including those with grants and editorial board positions.