Methodological considerations and intervention implications
Deborah J. Fidler, Lisa A. Daunhauer, Elizabeth A. Will & Emily Schworer
Diagnostic features
Down syndrome is the most common chromosomal cause of intellectual disability (Parker et al., 2010) and predisposes individuals to a range of biomedical risks (e.g.
sleep disturbance, congenital heart defects, gastrointestinal defects). Researchers have characterized areas of relative competence (social relatedness; receptive language) and areas of relative weakness (expressive language; Executive Functioning) in individuals with Down syndrome (for a review see Daunhauer & Fidler, 2011;
Edgin, 2013) that impact adaptation and function in home, school, and community environments. Global cognitive impairments are evidenced throughout the lifespan in Down syndrome, however, individuals with Down syndrome also show difficulties in distinct areas of cognition, with poorer than anticipated performances in specific aspects of memory, and in particular, Working Memory.
While research on the broader domain of Executive Functioning in Down syndrome has recently gained momentum, Working Memory has been the focus of research attention for several decades (Costanzo, Varuzza, Menghini, Addona, Gianesini, & Vicari, 2013; Edgin, Pennington, & Mervis, 2010; Pennington, Moon, Edgin, Stedron, & Nadel, 2003; Vicari, Carlesimo, & Caltagirone, 1995;
Yang, Conners, & Merrill, 2014). However, the complex impact of Down syndrome on development can pose researchers with study design and psychometric challenges. In this chapter, we review the various methodological issues that researchers have faced in assessing Working Memory in individuals with Down syndrome, including valid assessment, appropriate comparison groups, and under - standing Working Memory in relation to overall developmental status. We then
synthesize the current state of knowledge regarding Working Memory abilities in Down syndrome, their relationship to real-world, adaptive outcomes and academic achievement, and intervention-related findings.
Impact of Down syndrome on daily functioning
The majority of cases of Down syndrome are associated with a diagnosis of intellectual disability, with a range of outcomes in severity of impairment from borderline or mild intellectual disability (IQs ranging from 70–85) to severe levels of intellectual disability (IQs below 40; for an overview of outcomes in DS, see Daunhauer & Fidler, 2011). Within the domain of information processing, individuals with Down syndrome tend to show relatively stronger visual than verbal processing, though not all aspects of visual processing are stronger (Yang, Conners
& Merrill, 2014). Many individuals show emerging competencies in aspects of social relatedness during early development, though these strengths become less evident as the social–cognitive demands associated with perspective taking and theory of mind become more critical later in childhood. Language acquisition in DS tends to follow a pattern wherein receptive language skills are stronger than expressive language skills, a developmental profile that has great relevance for academic and intervention planning. Individuals with Down syndrome are also predisposed to patterns of strength and challenge in the area of adaptive behavior that includes relatively stronger socialization skills than daily living skills and adaptive motor skills (Fidler, Hepburn, & Rogers, 2006). These difficulties with adaptation have been linked to challenges in aspects of Executive Function in DS (Daunhauer, Gerlach-McDonald, Will, & Fidler, in press; Will, Fidler, Daunhauer, & Gerlach- McDonald, 2016).
Working Memory (WM) and related Executive Function (EF) deficits
Valid assessment of Working Memory in Down syndrome
The Working Memory profile associated with Down syndrome has been studied in the larger context of “behavioral phenotype” research in neurogenetic syndromes. Researchers with a behavioral phenotype perspective argue for the importance of syndrome-specific outcomes, and that individuals with a particular neurogenetic syndrome have a higher probability of demonstrating certain developmental or behavioral characteristics than those without the disorder (Dykens, 1995). Within this approach, Working Memory research has sought to identify specific patterns of functioning for individuals with Down syndrome when compared to other developmentally matched individuals, often with the end goal of identifying targets for intervention and education planning. The probabilistic nature of this work also allows for degrees of within-syndrome variability on
a given phenotypic dimension. Therefore, not every individual with a particular syndrome is expected to demonstrate all aspects of a syndrome’s phenotype.
Indeed, a newer focus within behavioral phenotype research relates to sources of within-syndrome variability and the extent to which some pathways can be strengthened in anticipatory ways for individuals with a given syndrome (Fidler, Daunhauer, Will, Gerlach-McDonald, & Schworer, 2016).
Critical to our understanding of Working Memory in Down syndrome are sound assessment approaches that accurately capture the construct of interest (i.e. construct validity; Coaley, 2014). Evaluating construct validity involves identifying whether and how much a specific assessment elicits responses that represent the construct of interest, in this case, Working Memory, while minimizing confounds from irrelevant domains. For assessment in Down syndrome, the issue of construct validity is highly relevant, as confounding developmental presentations may compromise the measurement validity of memory and other aspects of cognition. For example, a core feature of the Down syndrome behavioral phenotype involves a profile of stronger receptive than expressive language skills (for a review see Daunhauer &
Fidler, 2011). Because of this, Working Memory assessments that require verbal responses are likely to produce compromised data, as task performances can be confounded by the expressive modality required to generate a response. Even visual tasks can require a high verbal processing load related to the task instructions, which could mask underlying competencies in this area. Early development in Down syndrome is also associated with delays in achieving gross and fine motor milestones (Fidler, Hepburn, Mankin, & Rogers 2005; Palisano et al., 2001). Thus, Working Memory assessments that require a great deal of motor proficiency or motor planning may demonstrate similar compromises to construct validity. Although efforts to adapt tasks to account for phenotype-related confounds are underway, a review of existing Working Memory research in Down syndrome should be interpreted with this important issue in mind.
Down syndrome and verbal Working Memory measures
Verbal Working Memory requires the temporary storage and manipulation of verbal information. Backwards digit span (Orsini, Grossi, Captani, Laiacona, Papagno, & Vallar, 1987) is a widely used measure of verbal Working Memory (Costanzo et al., 2013; Rowe, Lavender, & Turk, 2006), wherein a list of numbers is read to the participant, and the participant is required to repeat them in reverse order. The reversal component, or manipulation of verbal information, involves more executive engagement, tapping into Working Memory. As discussed above, these tasks depend upon expressive language responses, and such confounds should play a role in interpretation of patterns of performance for individuals with Down syndrome.
Alternatives used to measure Working Memory in Down syndrome have included tasks that require the temporary storage of verbal information paired with
non-reversal recall (Carney, Brown, & Henry, 2013; Lanfranchi, Cornoldi, &
Vianello, 2004; Lanfranchi, Carretti, Spanò, & Cornoldi, 2009a; Lanfranchi, Jerman, & Vianello, 2009b; Lanfranchi, Jerman, DalPont, Alberti, & Vianello, 2010).
For example, Carney and colleagues used a listening span task in which participants with Down syndrome (10 to 18 years old) listened as an examiner read sentences aloud. They were then asked to judge the veracity of the sentence prior to recalling the final single syllable word of each sentence. The spans became progressively longer as the task proceeded. Lanfranchi and colleagues used a similar approach across a series of studies on verbal Working Memory abilities in Down syndrome (Lanfranchi et al., 2004; Lanfranchi et al., 2009a; Lanfranchi et al., 2009b;
Lanfranchi, Jerman, Dal Point, Alberti, & Vianello, 2010). These verbal Working Memory tasks were designed to increase in difficulty by placing greater demands on executive control as the level of the task progressed (Lanfranchi et al., 2004).
The simplest level was a forward word recall, measuring short-term memory, which then progressed to backwards word recall (similar to backwards digit span), tapping into verbal Working Memory with the manipulation (i.e., reversal) of the word list. The next level of the task required selective word recall, for which participants were required to repeat only the first word in a list of words read by the examiner.
Finally, the most complex level of the task, requiring the greatest demands on executive verbal Working Memory, was a dual request word recall that required participants to recall the first word in the list and also tap on the table when the word “ball” was read (Lanfranchi et al., 2004). The latter two levels of this task place increasing demands on verbal Working Memory abilities as participants must retain multiple sets of information, including rules and word lists, while manipu - lating information in a progressively more complex way. Importantly, these latter approaches reduce the expressive language demands to a short verbal response, or a short verbal response with an accompanying motor act.
Although several of these tasks are derived from widely accepted measures of Working Memory, they present challenges for use with individuals with Down syndrome related to floor effects. Across the majority of these studies, verbal Working Memory tasks were administered to older children and adolescents with Down syndrome, ages 7 to 18. However, Rowe and colleagues (2006) tested back - wards digit span tasks in adult participants with Down syndrome between the ages of 23 and 40 years old, and found considerable floor effects even in adulthood.
Based on these floor effects, Rowe and colleagues elected to measure the most foundational aspect of the Working Memory model, short-term memory, using a forward span task instead. Whether this underscores a fundamental deficit in verbal Working Memory abilities for individuals with Down syndrome or a lack of valid memory measures for this population is unclear. Although verbal Working Memory is generally more impaired in Down syndrome relative to visuospatial Working Memory (discussed in greater detail below), additional work is necessary to identify adequate and reliable verbal Working Memory measures for Down syndrome, particularly young children with Down syndrome.
Down syndrome and visuospatial Working Memory measures
Visuospatial Working Memory requires the temporary storage and manipulation of visuospatial information (Baddeley & Jarrold, 2007). Similar to verbal Working Memory measures, backwards versions of classic visuospatial short-term Working Memory measures (e.g. Corsi block tasks; Corsi, 1972; Orsini et al., 1987) have been utilized as visuospatial Working Memory measures for individuals with Down syndrome (Costanzo et al., 2013; Edgin et al., 2010; Vicari et al., 1995;
Yang et al., 2014). Corsi span and related tasks require participants to observe an examiner tapping a sequence of blocks, and then immediately perform the sequence in reverse order. Adaptations related to modality and complexity of this task have been used to measure visuospatial Working Memory in Down syndrome (Lanfranchi et al., 2004; Lanfranchi et al., 2009b; Lanfranchi et al., 2010; Lanfranchi, Baddeley, Gathercole, & Vianello, 2012; Pennington et al., 2003; Visu-Petra, Benga,
& Miclea, 2007). For example, Lanfranchi and colleagues designed a visuospatial Working Memory task that becomes gradually more complex as the task progresses (Lanfranchi et al., 2004). As with their verbal Working Memory task (Lanfranchi et al., 2004), their visuospatial task also began with foundational short-term memory tasks, which in this case included memory for positions and pathway forwards (i.e., modified Corsi block task). The task then progressed in complexity, recruiting visuospatial Working Memory, using a modified version of the reverse Corsi block task (Lanfranchi et al., 2004). In this task, the examiner moved a toy frog along a certain path on a chess board, and the participant was required to repeat the pathway in reverse order. The advanced levels of this task required participants to remember the frog’s starting position and then tap on the table when the frog jumped on a red square in addition to remembering the frog’s initial position. Lanfranchi and colleagues have used this task or isolated levels of this task across studies with individuals with Down syndrome ranging in age from 7 (Lanfranchi et al., 2004) to 23 years (Lanfranchi et al., 2012). Although no floor effects or age-related performance issues were reported for these studies, it is possible that for the younger participants, as well as children with Down syndrome below the age of 7 years old, the verbal instruction load could potentially confound performance.
The self-ordered pointing task (SOP; Petrides & Milner, 1982) is another visuospatial Working Memory task that has been used in individuals with Down syndrome (Landry, Russo, Dawkins, Zelazo, & Burack, 2012). This task presents three pictured items on a single board, and the participant is asked to choose one of the items. This is then repeated for subsequent trials with the items in a different arrangement, and the participant is instructed to select a different item than previously selected items, for up to 9 objects (Landry et al., 2012). Visual Working Memory is required in this task because participants must mentally maintain which items they had previously selected, while updating this information each time they made a new selection. This particular study implemented this task with individuals with Down syndrome between the ages of 9 and 21 years. The CANTAB Spatial
Working Memory test (Cardoso-Martins et al., 2009; Pennington et al., 2003; Visu- Petra et al., 2007) similarly requires participants to remember the location of a token after it is placed in a box. Upon locating the token on the first trial, participants are instructed that the token must be found in a different location than previously found tokens. This element requires participants to maintain information regard- ing found locations in their temporary store, while also updating that information each time a new token is found, tapping into Working Memory. It has been used in individuals with Down syndrome between the ages of 8 and 21 years (Visu-Petra et al., 2007), as well as 11 to 19 years (Cardoso-Martins et al., 2009;
Pennington et al., 2003), but may present challenges in assessing visuospatial Working Memory in younger children with Down syndrome given the complexity of verbal instructions.
Measurement considerations
While a variety of approaches have been taken to assessing visuospatial and verbal Working Memory in Down syndrome, several critical issues may impact the interpretation of findings. As discussed, phenotype-related confounds may be embedded in the nature of a task. For example, Rowe and colleagues (2006) determined that complex Working Memory tasks involving reversal of either visual or verbal information resulted in significant floor effects across both their group of adults with Down syndrome, as well as their comparison group of adults with other ID. However, these types of tasks have been used in other studies including younger individuals with Down syndrome with no reported floor effects, many of which draw comparison to TD individuals. Although this allows for potentially accurate conclusions regarding performance on these tasks across groups and may also be indicative of cognitive decline in older individuals with Down syndrome, there is also potential that these tasks are in fact less appropriate for individuals with Down syndrome due to other factors associated with their phenotype, such as inherent language difficulties (Yang et al., 2014).
Furthermore, as tasks become adapted from traditional Working Memory tasks, the nature of these adaptations may confound measurement. For example, Vicari and colleagues (1995) found participants with Down syndrome to perform significantly worse on backwards Corsi block task than a matched typically developing comparison group, whereas Lanfranchi and colleagues (2004) found no difference between Down syndrome and matched typically developing participants on an adapted version of this task that involved a jumping frog. This inconsistency in findings may be the result of the use of a more engaging task (i.e., the frog task; Yang et al., 2014), or the result of different matching procedures of nonverbal mental age using the Leiter (Vicari et al., 1995) and logical operations (Lanfranchi et al., 2004).
Task impurity
In addition, because Working Memory is considered to be a component process contributing to the larger domain of Executive Function, other Executive Function processes may impact Working Memory, including inhibition, cognitive flexibility, and the higher-order concept of planning. The level of dissociability among these constructs is unclear, and they have collectively been referred to as unitary, yet dissociable (Miyake & Friedman, 2012). Task impurity issues further add to the measurement complexity of assessing a single Executive Functioning construct such as Working Memory. For example, a Working Memory task used in children with Down syndrome known as Pony/Gator (Will et al., 2016) that was adapted from the original Bear/Dragontask used to measure Executive Functioning in typically developing children (Carlson, 2005; Carlson, Mandell, & Williams., 2004) also includes a component of inhibition. In this task, the participant is introduced to two puppets: a “nice” pony, and a “gruff” gator. Each puppet delivers an instruction to the participant, such as “touch your nose,” and the participant is instructed to respond to the pony, but ignore the gator. This task recruits Working Memory abilities through the maintenance of the task rules while manipulating information related to the motor response, and it also requires inhibition of motor responses to the gator (Will et al., 2016).
Another example of a non-dissociable task that taps into Working Memory is the Modified Dots task, which has been used in individuals with Down syndrome from ages 7 to 38 years (Edgin et al., 2010). This task requires participants to press a button below a cat on a computer touch screen when it appears to the right or left side in the first task phase. In the second phase, participants are required to touch the button on the opposite side when a frog appears. In the final phase, they must respond to randomly alternated trials of the first two phases. This task requires Working Memory through maintenance of the rule, manipulating information to respond, and updating the rule as it changes. In addition, the second and third phases require an inhibition component when participants must refrain from making a pre-potent response learned on previous trials. Moving forward, these phenotype and construct validity questions should continue to be examined closely to produce even more innovative and psychometrically valid approaches to Working Memory assessment in this population.
Developmental status and chronological age
Down syndrome is associated with widespread developmental delays, and as such, Working Memory performances are expected to track with overall developmental status and less so with chronological age. However, more precise scientific questions can be asked regarding whether Working Memory difficulties are simply in line with overall developmental status in Down syndrome, or whether there are more pronounced difficulties in this domain than would be expected based on global level of developmental delay. This particular, more nuanced, question may offer
an additional level of insight into intervention planning, as a specific area of more pronounced deficit can or should be supported in more concerted ways throughout intervention and educational experiences. At present, there is some existing research characterizing Working Memory in individuals with Down syndrome at different mental and chronological ages, which may help to identify the ways that broader development and Working Memory interact.
Age groupings
A wide range of chronological ages have been included in Working Memory research in Down syndrome, with participants as young as 5 years (Will et al., 2016; Caretti & Lanfranchi, 2010) and adults as old as 72 years (Ball, Holland, Treppner, Watson, & Huppert, 2008). In many studies, broad age ranges have been grouped together with mean performances reported for the group. Among these studies, children as young as 8 years old have been grouped with adolescents or adults up to age 23 (Lanfranchi et al., 2012). Although some studies have selected narrower age ranges of participants with Down syndrome (i.e. specific studies on a particular developmental period), most commonly, mean ages are within early adolescence and studies generally group school-aged children and young adults together (Carney et al., 2013; Costanzo et al., 2013; Lanfranchi et al., 2009a; b).
Age ranges are important to consider given the changes in Working Memory that are observed in typical populations from ages 5 to 19 years (Alloway & Alloway, 2013). When wide chronological age ranges are used to compare individuals with Down syndrome to developmentally matched groups, overall mean differences may mask important developmental trends, points of vulnerability, and other age- dependent features. However, one potential justification for the use of wide chronological age ranges is variability in overall developmental status among individuals with Down syndrome. For example, one study that included 8–19- year-olds with Down syndrome reported a mental age range of 4–7 years (Lanfranchi et al., 2009b), a much narrower developmental window.
Among the studies including broader chronological age ranges, general trends have emerged. In a foundational study examining both verbal and spatial Working Memory tasks, Pennington and colleagues (2003) reported similar performances in their sample of children and adolescents with Down syndrome (11–19 years) and a group of typically developing children matched for developmental level (3–6 years). This suggests that the children and adolescents with Down syndrome showed pronounced delays, but their performances are in line with anticipated performances based on developmental status. However, this “no difference” finding has not been replicated in other studies. Subsequent studies spanning middle childhood through early adulthood have frequently reported significant Working Memory challenges in individuals with Down syndrome, specifically in verbal Working Memory (Belacchi, Passolunghi, Brentan, Dante, Perso, & Cornoldi, 2014;
Carney et al., 2013; Costanzo et al., 2013). A combination of verbal and visuospatial