title: Symbolic sequence learning is associated with cognitive-affective profiles in female FMR1 premutation carriers.
abstract: This study examines implicit sequence learning impairments that may indicate at-risk cerebellar profiles proposed to underlie some aspects of subtle cognitive and affective dysfunctions found among female fragile X mental retardation 1 (FMR1) premutation (PM)-carriers. A total of 34 female PM-carriers and 33 age- and intelligence-matched controls completed an implicit symbolically primed serial reaction time task (SRTT) previously shown to be sensitive to cerebellar involvement. Implicit learning scores indicated a preservation of learning in both groups; however, PM-carriers demonstrated poorer learning through significantly elevated response latencies overall and at each specific block within the symbolic SRTT. Group comparisons also revealed a core deficit in response inhibition, alongside elevated inattentive symptoms in female PM-carriers. Finally, strong and significant associations were observed between poor symbolic SRTT performance and executive, visuospatial and affective deficits in the PM-carrier group. These associations remained strong even after controlling motor speed, and were not observed in age- and intelligence quotient-matched participants. The findings implicate cerebellar non-motor networks subserving the implicit sequencing of responses in cognitive-affective phenotypes previously observed in female PM-carriers. We contend that symbolic SRTT performance may offer clinical utility in future pharmaceutical interventions in female PM-carriers.
authors: School of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University.
authors: C M
authors: CM
authors: Kraan
authors: D R
authors: DR
authors: Hocking
authors: J L
authors: JL
authors: Bradshaw
authors: N
authors: N
authors: Georgiou-Karistianis
authors: S A
authors: SA
authors: Metcalfe
authors: A D
authors: AD
authors: Archibald
authors: J
authors: J
authors: Fielding
authors: J
authors: J
authors: Trollor
authors: J
authors: J
authors: Cohen
authors: K M
authors: KM
authors: Cornish
mesh_terms: D000328:Adult; D000483:Alleles; D001288:Attention; D016022:Case-Control Studies; D002526:Cerebellar Diseases / Q000235:genetics* / Q000503:physiopathology; D003071:Cognition; D056344:Executive Function; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D007858:Learning; D008875:Middle Aged; D011930:Reaction Time
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: Cerebellar cognitive affective syndrome; FMR1 gene; FMRP; FXTAS; cortico-cerebellar networks; phenotype; premutation carrier