Building an adaptive brain across development: targets for neurorehabilitation must begin in infancy

Much progress has been made toward behavioural and pharmacological intervention in intellectual disability, which was once thought too difficult to treat. Down syndrome research has shown rapid advances, and clinical trials are currently underway, with more on the horizon. Here, we review the literature on the emergent profile of cognitive development in Down syndrome, emphasizing that treatment approaches must consider how some “end state” impairments, such as language deficits, may develop from early alterations in neural systems beginning in infancy. Specifically, we highlight evidence suggesting that there are pre- and early postnatal alterations in brain structure and function in Down syndrome, resulting in disturbed network function across development. We stress that these early alterations are likely amplified by Alzheimer’s disease progression and poor sleep. Focusing on three network hubs (prefrontal cortex, hippocampus, and cerebellum), we discuss how these regions may relate to evolving deficits in cognitive function in individuals with Down syndrome, and to their language profile in particular

Seeing can be remembering: interactions between memory and perception in typical and atypical development

Recent work suggests that memory representations may guide basic perceptual functions, such as figure-ground perception. In three studies we assessed top-down contributions to figure-ground perception in typical development and in two developmental disorders: Down syndrome (DS) and autism (ASD). We investigated how figure-ground segregation is modulated by high-level cues (i.e., memory representations) and low-level cues (i.e., convexity and surface integration). Study 1 results showed that both high-level and low-level contributions to figure-ground perception are functional by the age of 4 years. In Study 2, individuals with DS exhibited intact figure-ground segregation based on low level cues when compared with mental age–matched participants, but they showed attenuated effects of high-level memory cues on figure-ground assignment. In Study 3, individuals with ASD showed intact effects of both high-level and low-level cues on figure-ground perception, counter to previous suggestions that high-level influences on perception are usually impaired in ASD.</jats:p

Everyday executive functions in Down syndrome from early childhood to young adulthood: evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY)

Executive functions (EF) are thought to be impaired in Down syndrome (DS) and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X). However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a) compared everyday EF difficulties in youth with DS, +1X, and typical development (TD); and (b) examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF) in DS (n=30), +1X (n=30), and a TD group (n=30), ages 5-18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2’s findings for DS by examining age-EF relations in a large independent sample of youth with DS (n=85) and TD (n=43), ages 4-24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups

Assessment of cognitive scales to examine memory, executive function and language in individuals with Down syndrome: implications of a 6-month observational study

Down syndrome (DS) is the most commonly identifiable genetic form of intellectual disability. Individuals with DS have considerable deficits in intellectual functioning (i.e., low intellectual quotient, delayed learning and/or impaired language development) and adaptive behavior. Previous pharmacological studies in this population have been limited by a lack of appropriate endpoints that accurately measured change in cognitive and functional abilities. Therefore, the current longitudinal observational study assessed the suitability and reliability of existing cognitive scales to determine which tools would be the most effective in future interventional clinical studies. Subtests of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Cambridge Neuropsychological Test Automated Battery (CANTAB), and Clinical Evaluation of Language Fundamentals-Preschool-2 (CELF-P-2), and the Observer Memory Questionnaire-Parent Form (OMQ-PF), Behavior Rating Inventory of Executive Function®–Preschool Version (BRIEF-P) and Leiter International Performance Scale-Revised were assessed. The results reported here have contributed to the optimization of trial design and endpoint selection for the Phase 2 study of a new selective negative allosteric modulator of the GABAA receptor α5-subtype (Basmisanil), and can be applied to other studies in the DS population