Clinical trial NCT05268341: Neuroimaging Reveals Treatment-related Changes in DLD
Official title: Neuroimaging Reveals Treatment-related Changes in DLD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Developmental Language Disorder
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: Children's Hospital Medical Center, Cincinnati
name: University of Toronto
First posted: 2022-03-07
Enrollment: 184
Sex: ALL
Minimum age (years): 48
Maximum age (years): 71
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Children with developmental language disorders (DLD, aka specific language impairment), a prevalent pediatric disorder, experience hallmark grammar deficits with life-long impacts on educational and occupational outcomes. While effective and early interventions can mitigate the impact of DLD, not enough is known about the neural basis of DLD in young children, yet is needed to inform the design of more individualized interventions. This project uses neuroimaging, along with behavioral methods, with the goal of better understanding the memory-language mechanisms that underlie grammar learning and impairment, while also considering their association to treatment-related changes in preschoolers with DLD.

Detailed description: Although the impact of developmental language disorder (DLD), a prevalent preschool disorder, can be mitigated through evidence-based and early interventions, little is known about the neural basis of DLD, especially in young children, yet is useful in the design of efficacious treatments. While much of the evidence has been furnished by studies examining domain-specific processes (language network), domain-general processes relating memory and language also offer valuable testing ground and present the opportunity to advance the current knowledge base. The Procedural circuit Deficit Hypothesis (PDH) posits that grammar deficits are explained by an impairment of procedural memory (rule learning, "knowing how"). This impairment is associated with structural abnormalities in connections between frontal brain regions and basal ganglia, with corresponding underactivation and reduced functional connectivity. However, the declarative memory system (semantic, "knowing what"), supported by cortical and subcortical regions in the temporal lobes, including hippocampus, is spared, acting as a compensatory mechanism to offset grammar deficits.

This proposed research will use neuroimaging (functional MRI and diffusion imaging) to describe the neural basis (functional and structural connectivity) of grammar learning and treatment-related change by way of the PDH. The investigators will gather critical data regarding grammar learning in preschoolers with DLD before, after, and following a break in intervention (computer-assisted treatment: DLD treatment; "business as usual": DLD no treatment) as part of a randomized controlled trial. The investigators will also include typically developing (TD) peers to inform development vs disorder. Our central hypothesis is that treatment designed to improve grammar learning will normalize the procedural learning network in association with increases in language function and that the degree of improvement may be associated with the underlying neurobiology of baseline grammar deficits.

Building on a robust history of recruitment and treatment of preschoolers with DLD, the investigators will enroll 184 preschoolers, 100 with DLD (n=50 treatment; n=50 no treatment controls) and 84 TD. Aim 1 will establish the relationship between functional and structural connectivity for preschoolers with DLD and their TD peers between regions in the procedural learning and declarative networks. In Aim 2, the investigators will establish the neurobiological basis of treatment-related changes in DLD only. The investigators examine potential changes in functional and structural connectivity between regions of the procedural learning and declarative memory networks, and investigate whether treatment-related changes occur into the typical range (DLD and TD). To meet our scientific goals, the investigators pair behavioral tools (traditional grammar tools) with neuroimaging to describe co-occurring behavioral performance underlying learning and outcome. This research will contribute novel insights into mechanisms underlying learning and impairment to help advance the evidence-based management of DLD.

Eligibility criteria: Inclusion Criteria:

* ages 48-71 months
* average nonverbal intelligence quotient (IQ)
* enrolled in participating center
* typically developing (receptive and expressive language, social, articulation, other)
* DLD for expressive grammar
* typical oral motor function
* typical social/pragmatics skills
* average hearing thresholds
* monolingual and native Standard English speakers
* does not have any uncorrected vision challenges

Exclusion Criteria:

* receiving co-occurring speech-language or other intervention for communication
* not MRI safe
* special education placement of child based on ability or behavior

Primary outcomes:
measure: Functional connectivity data (time 1) from typical and DLD preschoolers
timeFrame: Time 1 (pre)
measure: Functional connectivity data DLD preschoolers only to assess changes with treatment
timeFrame: Pre-to-post (up to 14 weeks), post-to-followup (at 27 to 28 weeks)
measure: Functional connectivity data for typically developing and DLD preschoolers to assess changes in development
timeFrame: pre-to-follow-up (up to 28 weeks)
Secondary outcomes:
measure: Structural connectivity data for typically developing and DLD preschoolers
timeFrame: Pre/Time 1 (up to 3-weeks)
measure: Structural connectivity data for DLD preschoolers only to assess changes with treatment
timeFrame: pre-to-post (up to 14-weeks) and post-to-follow-up (at 27 to 28 weeks)
measure: Structural connectivity data for typically developing and DLD preschoolers to assess development and disorder over time.
timeFrame: pre-to-followup (up to 28-weeks)
measure: Percent correct on a grammar task for typically developing and DLD preschoolers to assess development and disorder.
timeFrame: Pre/Time 1 (up to 3-weeks)
measure: Raw score on the SPELT-3 for typically developing and DLD preschoolers to assess development
timeFrame: Pre/Time 1 (up to 3-weeks)
measure: Raw score on the DSS for typically developing and DLD preschoolers to assess development
timeFrame: Pre/Time 1 (up to 3-weeks)
measure: Percent correct on a grammar screener for DLD preschoolers only to identify treatment targets
timeFrame: Pre/Time 1 (up to 3-weeks)
measure: Percent correct on a grammar task for DLD preschoolers only
timeFrame: Pre-to-post (up to 14 weeks), post-to-followup (at 27 to 28 weeks)
measure: Raw score on the SPELT-3 for DLD preschoolers only to assess change with treatment
timeFrame: Pre-to-post (up to 14 weeks), post-to-followup (at 27 to 28 weeks)
measure: Raw score on the DSS for DLD preschoolers only to assess change with treatment
timeFrame: Pre-to-post (up to 14 weeks), post-to-followup (at 27 to 28 weeks)
measure: Percent correct on a grammar task for typically developing and DLD preschoolers to assess development and disorder.
timeFrame: pre-to-followup (up to 28-weeks)
measure: Raw score on the SPELT-3 for typically developing and DLD preschoolers to assess development
timeFrame: pre-to-followup (up to 28-weeks)
measure: Raw score on the DSS for typically developing and DLD preschoolers to assess development
timeFrame: pre-to-followup (up to 28-weeks)
Other outcomes:
Locations:
city: Cincinati
country: United States
facility: New Horizon Childcare
state: Ohio
city: Cincinnati
country: United States
facility: Empower Learn Create INC
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: CWFF CHild Development Center
state: Ohio
city: Cincinnati
country: United States
facility: Wesley Education Center for Children and Families
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Karla N Washington, PhD
role: PRINCIPAL_INVESTIGATOR
References: