Effect of Working Memory Training on ADHD Brain Function

There is evidence both that computer-administered cognitive training can improve ADHD working memory deficits and that this type of training in non-ADHD enhances normal working memory ability by altering brain activity in prefrontal cortex and the parietal lobe. However, no study has characterized brain activity changes following working memory training in ADHD to understand what neural changes occur when cognitive deficits are remedied. This R21 exploratory study will examine the neural basis of cognitive training treatment gains in working memory, ADHD symptoms, and various other executive abilities. We will test the hypothesis that working memory training increases frontoparietal brain activation and examine other regions to see if there is any evidence for "neural compensation" (i.e., engagement of brain regions after training that are not normally recruited for task performance).

Study Overview

• Status: Completed
• Conditions: Attention-Deficit/Hyperactivity Disorder (Combined-subtype)
• Intervention / Treatment: Behavioral: Working memory training; Device: Functional magnetic resonance imaging (fMRI)

Detailed Description

There is evidence both that computer-administered cognitive training can improve ADHD working memory deficits and that this type of training in non-ADHD enhances normal working memory ability by altering brain activity in prefrontal cortex and the parietal lobe. However, no study has characterized brain activity changes following working memory training in ADHD to understand what neural changes occur when cognitive deficits are remedied. This R21 exploratory study will examine the neural basis of cognitive training treatment gains in working memory, ADHD symptoms, and various other executive abilities. The study will compare n=21 ADHD adolescents with evidence for baseline deficits in working memory (i.e., <1.5 SD below normative ratings at baseline) before and after working memory training. Participants will undergo baseline neuropsychological and fMRI imaging with verbal and visuospatial Sternberg fMRI working memory tasks, 5 weeks of daily computerized working memory training, and then endpoint fMRI and cognitive evaluation of neural and behavioral changes. Training will utilize commercially-available Cogmed software (http://www.cogmed.com) as it has a well-developed set of computerized tools, with numerous practical advantages for this study. Our analyses will identify which brain regions in ADHD adolescents are affected by working memory treatment and characterize patterns of activation change between baseline and endpoint. We will examine post-treatment differences in the extent of activation and functional connectivity among activated brain regions to test hypotheses about possible neural mechanisms underlying treatment gains. Finally, we will conduct a series of analyses to determine what changes in brain function underlie a generalized effect of working memory training on ADHD symptoms and other 'executive' abilities. By identifying the neural correlates any such effect, this study could yield invaluable information about what the neural targets of any effective ADHD treatment must be. The key accomplishment of this exploratory study will be to characterize the neural basis of treatment gains in ADHD by testing theoretically-guided hypotheses about possible neuroplastic changes. The results will support larger, future studies aimed at better understanding the neural basis of this alternative treatment for ADHD, identifying biological or genetic factors that might denote the presence of a remediable working memory deficit, and ultimately achieving a better understanding of the etiology of ADHD working memory deficits.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Olin Neurospychiatry Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants will be 13-17 years old and >6th grade English reading level to complete self-report evaluations (most are only available in English). ADHD-C participants must meet DSM-IV criteria (314.01).

Exclusion Criteria:

• Head injury sufficient to have caused >30 minutes lost consciousness; past or current CNS disease (e.g. stroke, MS, epilepsy or any repeated seizure history, tumor, etc) or brain lesion identified by MR (structural MR scans will be reviewed by a radiologist for the presence of clinical neuropathology that may affect cognitive task performance); Axis I DSM-IV lifetime history Bipolar disorder, psychotic disorder, OCD, PTSD, Tourette's disorder, Pervasive developmental disorder (e.g., Autistic disorder, PDD NOS, etc.); current DSM-IV substance dependence, Major Depressive Disorder or anxiety disorder; hypertension or juvenile-onset diabetes (current treatment with antihypertensives or insulin); current pregnancy (menstruating females will be tested); IQ estimate <80; left-handedness; psychotropic medication other than common psychostimulants that act primarily on dopamine neurotransmission systems. For instance, ADHD-C medications such as Wellbutrin (Buproprion), Strattera (Atomoxetine HCl), Cylert (Pemoline), or Provigil (Modafinil) will exclude participation; report of psychotic illness in first degree relative. Note, current DSM-IV disorders serve as exclusionary criteria to avoid the possibility of acute brain activity differences related more greatly to these disorders than ADHD. These stringent exclusion criteria are an advantage over many previous ADHD studies. However, given the frequent comorbidity and suspected biological liability among ADHD, substance, mood, and anxiety disorders, a lifetime history of mood or anxiety disorders will not exclude participation. Likewise, the frequent occurrence of CD/ODD and specific learning disabilities will not exclude participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cogmed Working Memory Training; Cogmed (TM) working memory training following standard, recommended administration procedures	Behavioral: Working memory training; Device: Functional magnetic resonance imaging (fMRI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional magnetic resonance imaging (fMRI)	fMRI assessment of working memory-related brain function	5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Working memory neuropsychological test performance	Several tests of working memory abillity	5 weeks
ADHD clinical dysfunction	Parent- and self-reported ADHD symptom severity, ADHD-related problems, and role impairment at home	5 weeks

Collaborators and Investigators

• Sponsor: Hartford Hospital
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Michael C. Stevens, Ph.D., Hartford Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: May 28, 2014
• First Submitted That Met QC Criteria: May 29, 2014
• First Posted (Estimate): May 30, 2014

Study Record Updates

• Last Update Posted (Estimate): May 30, 2014
• Last Update Submitted That Met QC Criteria: May 29, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: ADHD, hyperactivity, inattention, working memory
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis
• Other Study ID Numbers: R21HD061915 (U.S. NIH Grant/Contract)