EATING DISORDERS (E ATTIA, SECTION EDITOR)

What can Cognitive Neuroscience Teachus about Anorexia Nervosa?

Amelia Kidd & Joanna Steinglass

Published online: 2 June 2012# Springer Science+Business Media, LLC 2012

Abstract Anorexia nervosa (AN) is a complex illness andhighly challenging to treat. One promising approach tosignificantly advance our understanding of the underlyingpathophysiology of AN involves developing a cognitiveneuroscience model of illness. Cognitive neuroscience usesprobes such as neuropsychological tasks and neuroimagingtechniques to identify the neural underpinnings of behavior.With this approach, advances have been made in identifyinghigher-order cognitive processes that likely mediate symp-tom expression in AN. Identification of related neuropathol-ogy is beginning. Such findings led to the development ofcomplex neurobehavioral models that aim to explain theetiology and persistence of AN. Future research will usethese advanced tools to test and refine hypotheses about theunderlying mechanisms of AN.

Keywords Anorexia nervosa . AN . Neuropsychology .

Neuroimaging . Cognitive neuroscience . Cognitiveflexibility . Set-shifting . Central coherence . Reward .

Corticostriatal systems . Insula

Introduction

Anorexia nervosa (AN) is a serious psychiatric illness de-fined by maintenance of an inappropriately low body weightand overimportance of shape and weight in identity. AN has

a mortality rate among the highest of any psychiatric illness[1] and is associated with the highest mortality rate amongeating disorders, with a mortality rate almost six times thatexpected among young women [2]. Current treatmentapproaches are often ineffective, and many individuals suf-fer with symptoms for years. In part, the difficulty in iden-tifying more effective treatments stems from the lack ofclarity about the etiology and pathophysiology of AN. Onepathway toward understanding this multifaceted illness hasbeen through characterization of cognitive features. Amongthe many psychological and behavioral features of AN,obsessionality, rigidity, and perfectionism are often de-scribed. Most challenging are patients’ firmly held beliefsabout foods and their concern with a “thin ideal.” Evenwhen they have expressed a desire for change in treatment,patients struggle to alter their thinking.

Cognitive involvement in AN has long been noted,and many propose that this illness includes a neuropsy-chological component. There is a moderately large bodyof research describing cognitive abnormalities in the ANpopulation. Some of these studies rely on neuropsycho-logical tasks that have been well validated in otherclinical populations. Others employ measures that havebeen used to characterize underlying neural activity inhealthy populations. These methods allow for develop-ment and testing of hypotheses about the neural under-pinnings of AN. These hypotheses, in turn, can betested more directly in neuroimaging studies that exam-ine neural activity or systems. Efforts to draw connec-tions between patterns of cognition and potentialunderlying neuropathology led to the development of modelsof illness and thus the opportunities to test these models. Thisarticle discusses some advances in neuropsychology and neu-roimaging that hold promise for improving the understandingof the mechanisms of AN.

A. Kidd : J. Steinglass (*)New York State Psychiatric Institute, Columbia University,1051 Riverside Drive, Unit 98,New York, NY 10032, USAe-mail: Js1124@columbia.edu

A. Kidde-mail: ak2500@columbia.edu

Curr Psychiatry Rep (2012) 14:415–420DOI 10.1007/s11920-012-0285-8

Neuropsychology: Advances in Understandingthe Clinical Characteristics of AN

Classic Neuropsychology

Neuropsychology is the study of brain pathology and itsrelationship to behavior. Neuropsychological tasks are stan-dardized measures of cognitive functioning across a range ofdomains. These cognitive domains are not discrete entities,as each depends significantly on the other, but they arereliably differentiated and have become standard in the field.In AN, clinical observations regarding distorted thinkingand difficulty incorporating treatment recommendationshave often raised questions about whether cognitive pro-cessing deficits are prevalent in this population. However,neuropsychological studies using classic assessment bat-teries have not always supported these hypotheses. Forexample, initial hypotheses that AN was an illness of highintellectual quotient (IQ) were not borne out in communitystudies, which demonstrated a mean IQ within the normalrange [3]. Similarly, body-image distortions that are a diag-nostic criterion for AN led many researchers to wonderwhether visual perception was altered in this population.The program of research designed to answer this questionfound that there is no visual perceptual deficit in AN andthat shape and weight abnormality is best demonstrated inthe affective evaluation of the body [4, 5]. Individuals withAN can accurately perceive their size, but the degree ofdissatisfaction with their body is extreme and differs fromhealthy peers.

Neuropsychological findings are inconsistent across stud-ies, likely stemming from small sample sizes and varyingexperimental methodologies. Studies commonly administera large battery of tasks that evaluate across multiple cogni-tive domains. Whereas studies may evaluate comparabledomains, specific tasks within a particular battery varybetween studies. For example, although the majority ofstudies suggest that attention is impaired in underweightAN, this is not a universal finding. Similarly, short-termmemory is commonly—but not universally—impaired inthe underweight state. One fairly consistent finding is thatwhereas aspects of attention and memory may be abnormalin the acute state, there is improvement with weight resto-ration [6–9]. This suggests that these are manifestations ofstarvation and are not intrinsic to the illness.

Visuospatial processing has emerged empirically as anarea of interest in AN. Visuospatial deficits appear withsome consistency in studies of underweight individuals[6], persist after weight restoration [10], and have emergedin factor analyses even when individual task performancevaried [11]. These studies suggest that individuals with ANhave difficulty replicating complex visual designs, a taskthat uses a combination of spatial memory and processing,

as well as processing complex designs where individualshapes are embedded in a background. Interestingly,patients with AN may be skilled at identifying the detailswithin a visual task at the cost of processing the entire image[9, 12, 13]. This cognitive process is termed “central coher-ence” and is the subject of investigation. In short, individu-als with AN show deficits on tasks that require globalprocessing, showing a preference for local processing[13–15]. These studies link a neuropsychological findingwith a common clinical observation that individuals withAN tend to focus on details and neglect the larger picture.

Some investigators questioned whether cognitive deficitsin AN may be amplified in syndrome-specific domains: thatis, do individuals with AN have cognitive deficits primarilywhen food or shape and weight are concerned? Classicneuropsychological tasks such as the Color-Word Stroop[16] have been adapted to incorporate illness-relevant stim-uli. In these tasks, the color words are replaced with wordsrelated to food or body image. These studies, too, yieldedmixed results but tend to suggest that attention is impaired inAN when the task stimulus is illness related [17–19]. Thisidea is compelling, as selective attention to body imageinformation may contribute to the persistence of an eatingdisorder in a culture saturated with messages emphasizingdieting and thinness. Women with AN may pay particularattention to such cues. If true, training patients to mitigatetheir selective attention to messages about food and bodysize and attend to other, non-eating-disorder-related, stimuliin their environments may be a new strategy for treatment,akin to new treatments for social phobia [20]. Adaptationsof tasks with relevant stimuli show promise in better char-acterizing some of the most salient neuropsychological def-icits in AN.

Executive Functioning

Evaluation of executive functioning, defined as higher-orderprocessing primarily mediated by the frontal lobe, furtherhighlights neuropsychological abnormalities that relate toclinical phenomena in AN. Two interesting trends emergedfrom this body of research: First, individuals with AN showdeficits in cognitive flexibility, or difficulty adapting tochanging environmental cues. Second, patients with ANprocess and respond abnormally to rewards. Cognitive flex-ibility is operationalized in set-shifting tasks in which par-ticipants are required to quickly and accurately modify theirbehavior in response to a change in task demand. Excessiveerrors in these tasks, and perseverative errors in particular,have been shown among individuals acutely ill with AN[21–23] and those with weight-restored or recovered AN[24]. Attenuated deficits have been found among unaffectedsiblings [24]. These findings seem to relate to theentrenched nature of AN symptoms; that is, patients persist

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in dieting behavior even when environmental cures shouldindicate a need to change strategies. Patients have difficultydeveloping healthy strategies even when they ostensiblyseek change.

Neuropsychological findings support to some degree thespeculation that patients with AN may approach rewardsdifferently than healthy controls. A hallmark feature of AN,dietary restriction, could be considered as altered rewardprocessing: patients with AN delay or avoid the inherentreward of food. There are many potential ways to under-stand this phenomenon. One possibility is a difference infeedback-based learning, or how to respond to positive andnegative feedback. In a decision-making task in which par-ticipants must learn to avoid the “risky” choices in order tocollect the maximal monetary reward, a number of studiesdemonstrate that acutely ill AN patients do not learn theoptimal response, suggesting inability to incorporate thereward-based feedback during the task [22, 25, 26]. Anotherpossibility is that these patients differ in their response to areward, even if the valuation of reward is not different. Thatis, patients with AN are able to override the reward of food.Preliminary investigation of delayed gratification usingmeasures developed by the field of behavioral economicssupports the hypothesis that AN patients are prone to over-riding immediate rewards in favor of delayed rewards, evenwhen the reward is monetary [27].

Together these data suggest that the rigid and restrictiveeating patterns that promote the persistence of AN may bemediated by cognitive processes that are known to be in-volved in behavior and decision making. These findingshelp refine models of illness and can contribute to a clini-cian’s understanding of patients with AN.

Neuroimaging: Determining the Neural Mechanismsof AN

Despite decades of research, the neurobiology of AN is notwell understood. Many neuroimaging techniques have beenused to characterize potential structural and functional ab-normalities in AN patients (for comprehensive review, seeKaye [28•] or Fuglset [29•]). To date, these studies have notelucidated a clear and coherent pathophysiology of AN.Findings are often inconsistent, and large, definitive studiesare lacking. Despite the variability across studies, intriguingtrends have emerged, and several of these ideas are notedbelow.

Structural studies, primarily using computed tomography(CT) scans, consistently identify decreased brain volumes,including gray and white matter in underweight patients.Brain volume improves considerably with weight restora-tion and in some but not all studies normalizes completely[30, 31]. Neurotransmitter abnormalities in AN have been

identified using positron emission tomography (PET) scan-ning, with demonstrated abnormalities in both serotonin anddopamine systems. Receptor-density abnormalities havebeen found for both those neurotransmitters in the striatum,for example [32–34]. Patterns of cerebral blood flow iden-tified by single-photon-emission CT (SPECT) studies sug-gest altered cerebral metabolism in cortical and subcorticalregions [35] that may persist after weight restoration [36].As methodologies vary considerably, and many were pilotinvestigations, no clear regions of interest have emerged.These studies have been successful at hypothesis generation,if not for definitive testing.

Functional magnetic resonance imaging (fMRI) para-digms aim to further evaluate these hypotheses by examin-ing regional activity with the expectation of identifyingneural systems that underlie AN. Both symptom-provocation and cognitive-activation designs have been in-corporated in fMRI paradigms used to examine AN.Symptom-provocation studies aim to identify neural regionsthat may underlie specific acute symptoms by identifyingneural activity as the patient expresses a relevant symptom.In cognitive-activation designs, cognitive tasks are admin-istered that are known to activate particular systems inhealthy individuals, and activation patterns are thencompared.

In AN, symptom-provocation studies primarily relyon measuring neural responses to stimuli that wouldbe expected to be more salient for patients with ANthan for their healthy peers. As expected, individualswith AN have a differential pattern of activation inresponse to pictures of food [37–40] and images ofbodies [41–43]. Given the variations in procedures, itis perhaps not surprising that the findings in thesestudies do not consistently identify activation-patternabnormalities the same regions, but common areas ofhyperactivation include subcortical regions such as theamygdala, as well as a range of cortical areas. Nosingle neural system has emerged.

Cognitive-activation paradigms aim to test the integ-rity of targeted neural systems and can evaluate an apriori hypothesis about neurocognitive abnormalities inAN patients. At this time, there is a relatively smallamount of literature reporting the use of this approach.One group probed reward systems in AN patients andidentified abnormalities in neural regions, such as ven-tral striatum [44] and insula [45]. Another study sug-gested that abnormalities in set shifting may bemediated by corticostriatal and frontoparietal systems[46]. In one study, the Stroop task was modified forAN patients, and relevant stimuli also showed abnormalactivation patterns in frontal cortex regions [47]. Takentogether, these disparate studies suggest frontostriatalsystem abnormalities that may underlie AN.

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Cognitive Neuroscience Provides the Tools for TestingModels of AN

AN is a devastating illness that all too often becomes chron-ic. Current treatments are inadequate, and no pharmacologicagents have proven effective [48]. Development of newtreatments requires a better understanding of the neuropa-thology of AN. The neuropsychological and neuroimagingfindings summarized above support the development ofneurobehavioral models that link salient clinical character-istics of AN with likely underlying neural systems. Onesuch model proposes that excessive fear of weight gain inAN may be mediated by a predisposition to fear learning,with neurobiological and genetic underpinnings [49]. Arelated model, proposed by our group, emphasized height-ened anxiety and obsessionality in AN and proposed that theneurobiology may be similar to obsessive compulsive dis-order, with abnormal functioning in corticostriatal systems[50]. In this model, limbic-system abnormalities are thoughtto mediate heightened anxiety and that corticostriatal-system abnormalities underlie heightened obsessionality,which interact with each other to produce the rigid, avoidantdieting behaviors that promote the underweight state that, inturn impacts, the underlying neuropathology [51]. Similarly,Marsh et al. proposed that corticostriatal systems, thought tomediate self-regulatory control, may be dysfunctional dur-ing adolescence in some individuals in a way that createsparticular vulnerability to the development of AN [52]. In adifferent approach, Nunn et al. proposed that dysregulationof neural activity in the insula may account for a range ofsymptoms present in AN, as the insula may integrate manyperceptual and somatosensory disturbances observed in AN[53]. Whereas these models differ in their specific neuralhypotheses, they share a common approach: neural media-tion of behavioral phenomena that can be tested empirically.

Conclusions

Neuropsychology has progressed from characterizing thecognitive profile of individuals with AN to developingspecific neurocognitive hypotheses, suggesting that cogni-tive dysfunction may in fact mediate the disorder. With thisprogression has come several advances for studying andtreating AN. First, neuropsychological evaluation can con-tinue to help clinicians in treating individual patients; forexample, an individual’s neuropsychological deficits mayyield information about prognosis. One study reported thatpatients with AN who manifest two or more neuropsycho-logical deficits after weight restoration had more difficulttime maintaining health at 1-year follow-up [54]. Second,clarification of executive functioning deficits that seem to becharacteristic of the illness led to a new idea for an

adjunctive treatment for AN: cognitive remediation therapy(CRT) [55]. This treatment aims to improve cognitive flex-ibility, in particular through repeated practice with skillssuch as set shifting. Currently, this treatment is being inves-tigated for its potential to enhance success with other longer-term psychotherapy, such as cognitive behavioral therapy.Third, refinement of neuropsychological tasks led to thedevelopment of cognitive probes for the underlying neuralsystems. These tasks can then be used to begin to test eachproposed model of AN. For example, if corticostriatal dys-function mediates AN, then this patient population would beexpected to perform poorly on tasks of self-regulatory con-trol, even after acute weight restoration. Advances in neuro-imaging allow for further hypotheses testing and refining.Each imaging modality contributes a piece to the puzzle aswe progress from identifying structural changes, to neuro-transmitter and neurohormonal changes, to functional activ-ity abnormalities. As cognitive neuroscience evolves,paradigms become increasingly sophisticated in testing neu-ral underpinnings of cognition and the relationship betweencognition and behavior. These methods can be applied to thestudy of AN, with the promise of identifying neural mech-anisms that can explain this enigmatic and dangerousillness.

Disclosure Ms. Kidd: noneDr. Steinglass: received research funding from Klarman Family

Foundation, NARSAD, National Institutes of Health (NIH), and Na-tional Institute of Mental Health (NIMH).

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