Rewards and Challenges of Cognitive Neuroscience Studies of Persons With Intellectual and Developmental Disabilities
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Rewards and Challenges of Cognitive NeuroscienceStudies of Persons With Intellectual andDevelopmental DisabilitiesDOI: 10.1352/1944-7558-115.2.79
It is with great pleasure that I write an editorialfor this special issue of the American Journal onIntellectual and Developmental Disabilities (AJIDD)on Cognitive Neuroscience Studies of PersonsWith Intellectual and Developmental Disabilities,just as it was to accept Len Abbedutos invitation tojoin the journal as an associate editor. His charge tome, as part of that invitation, was to increase therepresentation in the Journal of first class cognitiveneuroscience studies of children and adults withintellectual and developmental disabilities. I ac-cepted both invitations enthusiastically for tworeasons. One was that as a developmental cognitiveneuroscientist studying children with neurodevel-opmental disorders, I know firsthand how fewreally appropriate journals exist for this ratheryoung and emerging field of clinical and transla-tional research. The other reason was that it wasobvious to me how appropriate it is that AJIDD,with its long history of communicating the cuttingedge of research and practice about individualswith intellectual impairments and cognitive dis-ability, should become a leader in this discipline. Ihope that, as Abbeduto stated in a recent editorial,the appearance of this special issue does indeedmark the beginning of a whole new era forAJIDD (Editorial, 2010, p. 2).
To explain the motivation for this specialissue, I think it is worth reprising some of themain points made in our Call for Papers (2008).There we made the following statements.
The now well-established field of cognitive neuroscience hasmade significant progress in elucidating the neural substratesand cognitive processing underpinnings of a wide range ofcognitive functions. However, its focus has been predomi-nantly on typical adult function; much less attention has beengiven to typical and atypical development. (p. 322)
We also stated that
cognitive neuroscientific methods hold considerable promisefor significantly advancing explanations for the basis for many
conditions that produce intellectual and developmentaldisabilities. Also, because of their neurobiological andmechanistic strengths, these methods are likely to lead torapid progress towards a range of interventions. (p. 322)
However, the application of cognitive neuro-science methods to the study of atypicallydeveloping individuals is not one of simpletranslation of established techniques to a newstudy population. In general, in cognitive neuro-science studies of typical adults and, morerecently, children, researchers tend to focus onidentifying the mental representation and algo-rithmic processing and/or neural underpinningsof a particular cognitive function or domain.Although these are also crucial goals in cognitiveneuroscience studies of atypical development,investigators generally aim to go further bygenerating causal mechanistic explanations forparticular domains of impairment, and they alsotry to account for the etiology and developmentalprogression of the observed disorder. Frequently,this is done because a longer term goal is todevelop therapeutic interventions.
These goals make the task more difficultbecause one must interpret atypical development(whether in children or adults) entirely differentlyfrom typical development. This is especially truewhen attempting to make mappings of impairedcognitive functions and their underlying substratein the atypically developing brain. This is notonly because they change over the course ofdevelopment, as in the typical case, but alsobecause, in the atypical brain, the mappings arelikely to be different from typical ones and changein atypical ways. These methodological concernshave been discussed in detail, most particularly byKarmiloff-Smith and her colleagues (Johnson,Halit, Grice, & Karmiloff-Smith, 2002; Karmil-off-Smith, 1998; Scerif & Karmiloff-Smith, 2005)In brief, the issue can be understood as follows.
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All other things being equal, most typicallydeveloping people experience a somewhat similarneurodevelopmental environment throughouttheir lives. Thus, in Westernized cultures at least,one would expect, and can observe, a good deal ofconvergence in the mental representations andprocesses individuals acquire and the neuralsubstrates that are gradually specialized for thosefunctions even while significant individual differ-ences exist. However, in atypically developingindividuals, especially those with congenitalrather than acquired disorders, there is quite likelyto be an entirely different developmental trajec-tory towards a mature, if not ever stable,neurocognitive state that begins even before birth.The genetic and associated environmental impactcreated by such disorders will significantly influ-ence the nature of the developing neurocognitivemachinery so that what information can beacquired, represented, processed, and transformedis atypical throughout these individuals entirelives. One could argue, then, that the leastreasonable assumption one might make is thattheir neurocognitive state, at any point duringdevelopment, would or even should be the sameas that of a typically developing person of similarchronological or even mental age. This makeshypothesizing, predicting, and interpreting thenature and course of neurocognitive functioningand growth, particularly challenging and prone tosignificant error if one makes the oversimplisticassumption that the minds and brains of theseindividuals should be generally like those of theirtypical counterparts but are damaged or al-tered in some way (Johnson et al., 2002). Inreality, the challenge is more one of trying todetermine just what entirely different neurocog-nitive solution such individuals have created inresponse to their altered world and how that isstructurally and functionally configured.
All of this means that, more than anything, itis critical for researchers conducting studies ofatypical development to focus on the delineationof an endophenotype of the domain of functionof interest. An endophenotype, according toGottesman and Gould (2003), consists of mea-sureable components unseen by the unaided eyealong the pathway between disease and distalgenotype [that] may be neurophysiological,biochemical, endocrinological, neuroanatomical in nature (p. 636). An endophenotype neednot be genetically heritable in the sense thatGottesman and Gould envisaged, but it should
aid the process of explicating genotypepheno-type relationships by identifying tractable levels ofanalyses at which scientists can explain not justhow but also why the behavior and abilities ofatypically developing children or adults differsfrom their typically developing peers. Once suchexplanations exist, it is likely that scientists willbegin to identify targeted questions about howsubstrates or processes might be changed by arange of interventions such that different out-comes may be possible.
In this special issue, we present a set of articlesthat begin that process by identifying atypicalitiesin a range of cognitive functions and in severalneurodevelopmental disorders. Some characterizedifferences in genetic type and expression; othersfocus on changes affecting cognitive processingand the mental representations on which itdepends. Another set characterizes differences interms of neural responses to cognitive taskdemands. In each case the authors seek to explainhow atypically developing individuals differ fromtheir typical peers and expect that, if theirhypotheses are supported by replications in theirown labs and those of others, these differencescould one day become targets for interventionsthat may vary as widely as gene therapy topharmacological agents to cognitive and behav-ioral training.
In all six papers in this issue, the authorsapproach the endophenotyping issue in slightlydifferent but related ways. Four papers are focusedon two very heavily studied neurodevelopmentaldisorders of known genetic etiology, namelyWilliams and Down syndromes. Elsabbagh et al.explored how (mostly) adults with Williamssyndrome represent and computationally processauditory information by examining how it isstructured in mental representations and thenprocessed for coherence and relationships amongunits. Their research was motivated in part byattempting to explain how and why individualswith Williams syndrome have apparent strengthsin domains involving auditory information, suchas music and language. For them, the key to thesestrengths lies in the fact that for both kinds ofinformation, accessing and working with internalstructure of the auditory information are neces-sary to comprehend its content.
In other words, there may be commonunderlying processes neither explicitly musicalor linguistic in nature that explain how thesehigher level competencies work. In a series of
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experiments, Elsabbagh et al. required participantsto determine which elements in a stream ofauditory input should be grouped together tomake meaningful units and which should besegregated from one another to create boundariesbetween those units. They found that adults withWilliams syndrome could segment unfamiliarmelodies as effectively as could typical controlson the basis of pitch. These authors also reportedthat despite their often vaunted linguistic andmusical strengths, individuals with Williamssyndrome could not take advantage of furthercues involving the contour of the elements in theauditory stream to more effectively segment them,whereas typical controls were able to use the extrainformation. In this way, Elsabbagh et al.discovered the different ways in which those withWilliams syndrome can perform as well as typicalindividuals and how and why they fail to do so indifferent kinds of tasks. The timeliness of thistopic is shown by the fact that it is accompaniedby a second paper on auditory processing inindividuals with Williams syndrome by Thorton-Wells and colleagues, who focused more onmusical aspects. Their results, obtained usingfunctional MRI (fMRI), offer a further insightinto how and why such individuals so often showa relative strength for musical cognition. Usingmusical and nonmusical stimuli, in a series ofexperiments, they found that adults with Williamssyndrome differed from similarly aged typicalcontrols in that they tended to activate brain areastypically associated with visual and emotionalinformation processing much more than didcontrol participants. These results represent novelinformation about the possible cross modalmanner in which those with Williams syndromerepresent and process auditory information thatmight bear some resemblance to the phenome-mon of synesthesia or the blending of multiplesenses when processing sensory or even concep-tual information. Of course, bearing in mind theinterpretive caveats mentioned earlier, the resultsmight also indicate that for those with Williamssyndrome, some parts of visual cortex come toprocess different kinds of information than dotypically developing brains or that they are able toprocess the same information in a different way.They may even operate more flexibly to process,and possibly then blend, a wider range of sensoryinformation. A series of future experiments isclearly indicated to clarify these fascinating andimportant questions.
In another functional imaging study, Virji-Babul and colleagues examined the neural corre-lates of action execution and observation inindividuals with Down syndrome because under-standing of the physical and social world requiresthe ability to perceive and interpret the actions ofothers. Furthermore, in recent studies of what hasbeen termed the mirror neuron system (Cattaneo &Rizzolatti, 2009), researchers have pointed to therole of mental and physical imitation in bothcomprehension and learning. Understanding thefunctioning of such a system may help usunderstand as well as remediate common motorand perceptual impairments seen in people withDown syndrome. Using magnoencephalographyto measure electrical signaling in the brain, Virji-Babul and her colleagues found that, unlike theirtypically developing peers, adults with Downsyndrome did not show strongly lateralized neuralactivations when executing motor movementsand that when observing the movements ofothers, they did not appear to activate the areasof motor cortex that were seen in the typicalparticipants in the same condition. The authorsinterpreted the apparent discontinuity in theirfindings between execution and observation inthe Down syndrome group as evidence that themirror neuron system is dysfunctional in theindividuals whom they studied. Such findingsmight lead to an explanation of why motorlearning can be hard for individuals with Downsyndrome and could point to interventions toimprove that weakness either by finding ways tostrengthen the functioning of the mirror neuronsystem or to discover methods of teaching andlearning that compensates for its weakness.
In a very different paper, Rachidi andcolleagues reviewed work on the molecular andcellular basis of cognitive impairments in Downsyndrome, much of it in the form of studiescarried out with mouse models that allow genes inthe critical regions of chromosome 21 associatedwith Down syndrome to be directly manipulated.Identification of possible explanations for cogni-tive dysfunctions in terms of anomalies in theCalcineurin and NFATc pathways and theregulation and expression of neurotransmitterssuch as NMDA and GABA may lead in the futureto pharmacological and genetic therapies thatcould significantly alter the neurodevelopmentaltrajectory of those with Down syndrome andenhance their intellectual, functional, and adap-tive outcomes.
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Beaton and colleagues also used fMRI todetermine whether girls with Turner syndromeprocess spatiotemporal information differentlyfrom typically developing controls, primarilybecause this information could help us under-stand their problems when processing informa-tion about space, time and numbers, and learningarithmetic. Using a dynamic object tracking task,Beaton et al. found that, girls with Turnersyndrome activated some of the same areas seenin the typically developing group in response tothe task but also activated many different parts oftheir brains that did not respond compared withtypically developing girls. This was true evenwhen performance between the two groups washeld constant and, therefore, could not beexplained by errors, suggesting that girls withTurner syndrome cannot develop the sameneurocognitive solution to the problem ofspatiotemporal informa...