title: Adaptive working memory training improved brain function in human immunodeficiency virus-seropositive patients.
abstract: OBJECTIVE
  We aimed to evaluate the effectiveness of an adaptive working memory (WM) training (WMT) program, the corresponding neural correlates, and LMX1A-rs4657412 polymorphism on the adaptive WMT, in human immunodeficiency virus (HIV) participants compared to seronegative (SN) controls.
  
  
  METHODS
  A total of 201 of 206 qualified participants completed baseline assessments before randomization to 25 sessions of adaptive WMT or nonadaptive WMT. A total of 74 of 76 (34 HIV, 42 SN) completed adaptive WMT and all 40 completed nonadaptive WMT (20 HIV, 20 SN) and were assessed after 1 month, and 55 adaptive WMT participants were also assessed after 6 months. Nontrained near-transfer WM tests (Digit-Span, Spatial-Span), self-reported executive functioning, and functional magnetic resonance images during 1-back and 2-back tasks were performed at baseline and each follow-up visit, and LMX1A-rs4657412 was genotyped in all participants.
  
  
  RESULTS
  Although HIV participants had slightly lower cognitive performance and start index than SN at baseline, both groups improved on improvement index (>30%; false discovery rate [FDR] corrected p < 0.0008) and nontrained WM tests after adaptive WMT (FDR corrected, p ≤ 0.001), but not after nonadaptive WMT (training by training type corrected, p = 0.01 to p = 0.05) 1 month later. HIV participants (especially LMX1A-G carriers) also had poorer self-reported executive functioning than SN, but both groups reported improvements after adaptive WMT (Global: training FDR corrected, p = 0.004), and only HIV participants improved after nonadaptive WMT. HIV participants also had greater frontal activation than SN at baseline, but brain activation decreased in both groups at 1 and 6 months after adaptive WMT (FDR corrected, p < 0.0001), with normalization of brain activation in HIV participants, especially the LMX1A-AA carriers (LMX1A genotype by HIV status, cluster-corrected-p < 0.0001).
  
  
  CONCLUSIONS
  Adaptive WMT, but not nonadaptive WMT, improved WM performance in both SN and HIV participants, and the accompanied decreased or normalized brain activation suggest improved neural efficiency, especially in HIV-LMX1A-AA carriers who might have greater dopaminergic reserve. These findings suggest that adaptive WMT may be an effective adjunctive therapy for WM deficits in HIV participants. ANN NEUROL 2017;81:17-34.
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI.|The Queen's Medical Center, Honolulu, HI.
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI.|Department of Child Neurology and Rehabilitation (HABU-A), Sørlandet Sykehus HF, HABU, Arendal, Norway, and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, MTFS, Trondheim, Norway.
authors.forename: Gro C
authors.initials: GC
authors.lastname: Løhaugen
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI.
authors.forename: Tamara
authors.initials: T
authors.lastname: Andres
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Jiang
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Douet
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI.
authors.forename: Naomi
authors.initials: N
authors.lastname: Tanizaki
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI.
authors.forename: Christina
authors.initials: C
authors.lastname: Walker
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI.
authors.forename: Deborrah
authors.initials: D
authors.lastname: Castillo
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI.
authors.forename: Ahnate
authors.initials: A
authors.lastname: Lim
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI.|Department of Child Neurology and Rehabilitation (HABU-A), Sørlandet Sykehus HF, HABU, Arendal, Norway, and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, MTFS, Trondheim, Norway.
authors.forename: Jon
authors.initials: J
authors.lastname: Skranes
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI.
authors.forename: Chad
authors.initials: C
authors.lastname: Otoshi
authors.affiliation: Department of Psychiatry, University of California, Los Angeles, CA.
authors.forename: Eric N
authors.initials: EN
authors.lastname: Miller
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Ernst
mesh_terms: D056344:Executive Function; D005260:Female; D005625:Frontal Lobe / Q000502:physiology*; D005838:Genotype; D006679:HIV Seropositivity / Q000503:physiopathology* / Q000523:psychology*; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000235:genetics; D007858:Learning / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D014157:Transcription Factors / Q000235:genetics
chemical_list: D060850:LIM-Homeodomain Proteins; C078021:LMX1A protein, human; D014157:Transcription Factors