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hyperactivity disorder
Psychiatry Research 188 (2011) 406–410
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Psychiatry Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / p s yc h r e s
Cognitive control in adults with attention-deficit/hyperactivity disorder Margaretha Dramsdahl a,b,⁎, René Westerhausen c, Jan Haavik a,d,e, Kenneth Hugdahl a,c,e, Kerstin J. Plessen e,f,g a
Division of Psychiatry, Haukeland University Hospital, Bergen, Norway Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Norway Department of Biological and Medical Psychology, University of Bergen, Norway d Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Norway e K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Norway f Center for Child and Adolescent Psychiatry, Bispebjerg Hospital Copenhagen, Denmark g Institute for Neurology, Psychiatry, and Sensory Sciences, University of Copenhagen, Denmark b c
a r t i c l e
i n f o
Article history: Received 21 April 2010 Received in revised form 28 March 2011 Accepted 12 April 2011 Keywords: ADHD Dichotic listening Cognitive processes Executive functions Attentional networks
a b s t r a c t The objective of the present study was to investigate the ability of adults with Attention-Deficit/Hyperactivity Disorder (ADHD) to direct their attention and exert cognitive control in a forced instruction dichotic listening (DL) task. The performance of 29 adults with ADHD was compared with 58 matched controls from the Bergen Dichotic Listening Database (N N 1500). Participants in the Bergen DL task listen to and report from conflicting consonant–vowel combinations (two different syllables presented simultaneously, one to each ear). They are asked to report the syllable they hear (non-forced condition), or to focus and report either the right- or leftear syllable (forced-right and forced-left condition). This procedure is presumed to tap distinct cognitive processes: perception (non-forced condition), orienting of attention (forced-right condition), and cognitive control (forced-left condition). Adults with ADHD did not show significant impairment in the conditions tapping perception and attention orientation, but were significantly impaired in their ability to report the leftear syllable during the forced-left instruction condition, whereas the control group showed the expected leftear advantage in this condition. This supports the hypothesis of a deficit in cognitive control in the ADHD group, presumably mediated by a deficit in a prefrontal neuronal circuitry. Our results may have implications for psychosocial adjustment for persons with ADHD in educational and work environments. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Attention-Deficit/Hyperactivity Disorder (ADHD) is a disorder with three different clinical subtypes grouped according to their dominant symptoms; the inattentive, the hyperactive/impulsive, and the combined type (American Psychiatric Association, 2000). The estimated worldwide-pooled prevalence in children and adolescents with ADHD is 5.3% (Polanczyk et al., 2007). Although ADHD is primarily diagnosed in childhood the majority of children affected shows persistent symptoms which cause severe functional impairment into adulthood (Biederman and Faraone, 2005; Faraone et al., 2006). Typical symptoms that interfere with daily life are difficulties to maintain attention-span during longer periods of time or to keep attention focused despite distractions, problems in following instructions and to complete activities that demand cognitive focus.
⁎ Corresponding author at: Division of Psychiatry, Haukeland University Hospital, Jonas Liesvei 65, N-5021 Bergen, Norway. Tel.: + 47 958354; fax: + 47 55975146. E-mail address: [email protected] (M. Dramsdahl). 0165-1781/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2011.04.014
Several causal models have been presented that attempt to explain the symptoms of ADHD (e.g. Sergeant et al., 2003; Nigg, 2006). Earlier models have stressed the dysfunction in a few core domains, such as problems with impaired executive functions (EF) and response inhibition (Pennington and Ozonoff, 1996; Barkley, 1997). ADHD is, however, likely to be a neuropsychologically heterogeneous disorder (Nigg and Casey, 2005; Willcutt et al., 2005; Doyle, 2006; SonugaBarke et al., 2010), reflected by the recently described multiple pathways models (Sergeant et al., 2003; Sonuga-Barke, 2005; Castellanos et al., 2006), which highlight other domains than merely EF as problematic, e.g. state regulation (Sanders, 1983; Sergeant, 2005) or delay aversion (Sonuga-Barke et al., 1992). Deficits in EF or in cognitive control are, however, considered key impairments in ADHD in most of the existing models. Although not exclusive (Jurado and Rosselli, 2007), cognitive abilities often included into the concept of EF are working memory, response inhibition, set-shifting, planning and fluency (Pennington and Ozonoff, 1996; Sergeant et al., 2003). We will in the following use EF and cognitive control as synonym concepts, both defined by the ability to cope with disturbances and conflict situations, where bottom-up, automatic
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responses interfere with the given instructions requiring top-down control. As recently suggested, dichotic listening (DL) to repeated presentations of consonant-vowel (CV) syllables may represent a way of studying orienting of attention and cognitive control processes (Hugdahl et al., 2009; Westerhausen et al., 2009; Arciuli et al., 2010; see also Carlsson et al., 1994, studying clinical samples). Confronted with two CV-syllables presented dichotically, i.e. one presented to the right and a different presented simultaneously to the left ear, participants more often correctly report the stimulus presented to the right compared with the left ear. Neuronal wiring of the auditory pathways and lateralization of speech sound processing to the left temporal lobe favor stimuli presented to the right ear, and this results in a right-ear advantage (REA) (Kimura, 1967). The REA may thus be regarded as a bottom-up automatic response tendency to presentations of CV-syllables that are reported by the participant. Instructing the participants to attend to one ear and explicitly report only the syllable presented to that ear, however, will modulate the REA. Healthy participants, when asked to selectively report the right-ear stimulus (forced-right (FR) condition), show an increased REA as compared to the free report (non-forced (NF)) instruction condition. Conversely, when asked to focus attention on the left-ear stimulus (forced-left (FL) condition), the participants typically report more correct stimuli from the left ear, which results in a left-ear advantage (LEA) (Bryden et al., 1983; Hugdahl and Andersson, 1986). The FR and the FL condition may at the outset appear to reflect the same underlying attentional processes, but asking a participant to focus on and report only the right- or left-ear stimulus may create two different experimental conditions that rely on different cognitive functions (Hugdahl et al., 2009). The FR condition requires to focus attention on the stronger, or more salient stimulus (referred to as “orienting” by Posner and Rothbart, 2007), whereas the FL condition specifically requires the ability to resolve a conflict between the bottom-up stronger tendency to report the right-ear stimulus and the top-down instruction to report the weaker left-ear stimulus (Hugdahl et al., 2009). The ability to resolve a conflict is one of the most fundamental aspects of cognitive control (Miller and Cohen, 2001; Fan et al., 2005; Posner and Rothbart, 2007). The DL task may thus explore three distinct aspects of perception and cognition: bottom-up perception in the NF condition, an orienting process with a synergic bottom-up and a top-down effect in the FR condition, and a cognitive control process with a conflicting top-down effect that needs to override the automatic response in the FL condition. Although the auditory stimuli are identical across all three instruction conditions, the different instructions in this paradigm may hypothetically allow to tease apart the processes of perception, orienting and cognitive control (Hugdahl et al., 2009). In fact, the single experimental manipulation that differentiates the FR and FL instruction conditions is one word within the instruction ("right" versus "left"), whereas all other parameters are kept identical between the two conditions. The NF instruction is in this context a baseline condition to against which to evaluate the effects in the FR and FL conditions. During the past decade, researchers have started to explore the specific neuropsychological deficits in adults with ADHD (Hervey et al., 2004; Boonstra et al., 2005), whereas prior research has focused mainly on children and adolescents. Profiles generated in samples of children with ADHD are not consistently overlapping with those stemming from adults (Doyle, 2006). In comparison to children with ADHD, adults have had the opportunity to develop different cognitive strategies to cope with cognitive conflicts and response inhibition. We expected that applying a new paradigm with rigorous experimental control could reveal new aspects of cognitive deficits in ADHD. The objective of the present study was thus to investigate the performance in the forced instruction DL tasks in adults with ADHD. We predicted that individuals with ADHD compared with sex- and handedness-
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matched controls would show impaired cognitive control during FL condition. 2. Methods 2.1. Participants The sample consisted of 29 participants with ADHD, 15 men and 14 women. The patients were recruited from the Norwegian ADHD-project in Bergen, and further details of the procedure for recruitment are accessible in other publications (Johansson et al., 2008; Halleland et al., 2009; Halmoy et al., 2009). Exclusion criteria were current serious psychiatric disturbance or substance abuse, epilepsy or other neurological or physical disease that significantly impair neurocognitive function, a lifetime history of developmental delay, premature birth before 34 weeks of gestational age, or an IQ below 70, as measured by the Wechsler Abbreviated Scale of Intelligence (WASI). Audiometry was performed for the frequencies 500, 1000, 2000, and 3000 Hz prior to the DL task. We excluded participants with hearing deficits (more than 35 dB hearing loss) on one of the ears in any of the above mentioned frequencies, and individuals that had more than 10 dB differences in hearing between the two ears in two or more frequencies. Applying these criteria, five out of 34 individuals originally recruited from the Norwegian ADHD-project, were not eligible for the present study. All patients had been diagnosed according to ICD-10 or DSM-IV criteria for hyperkinetic disorder/ADHD by a psychiatrist or psychologist before the inclusion in the project. One of the participants had received a diagnosis of bipolar disorder several years ago, but that diagnosis was not confirmed as prior or present diagnosis during the clinical diagnostic interview. An experienced psychiatrist (M.D.) used the ADHD module of the K-SADS (Kaufman et al., 1997) adjusted to adults to validate the diagnoses and determine the subtype of ADHD. Current ADHD symptoms were determined with the Adult ADHD Self-Report Scale (ASRS-18) (Kessler et al., 2005). The profile of symptoms reported in childhood determined the ADHD-subtype, resulting in 19 participants with a combined type, seven with an inattentive type, and three with a hyperactive/impulsive type. The mean age in the ADHD group was 32.9 years (S.D. = 7.1, age range 21– 48 years), and mean IQ was 110.6 (S.D. = 14.3, IQ range 78–128). Sixteen patients were medicated with stimulants or atomoxetine. Patients were instructed to withhold medication 48 h prior to testing, and nine did this, whereas two continued their ordinary medication and five reduced the dosage during the last 48 h prior to the examination. Thirteen of the patients had not used stimulants or atomoxetine during the past 6 months. Handedness was determined by the hand the participant preferred to draw and write with. Using this definition, 23 of the patients were right-handed, and six were left-handed. Participants in the control group were selected from the Bergen Dichotic Listening Database, which consists of data from more than 1500 healthy participants, and which all have been tested using the same version of the DL test as used in the present study (described below; see also Hugdahl, 2003). Controls were randomly selected after matching for gender and handedness. Two controls were selected for each participant with ADHD, resulting in 58 controls, 30 men and 28 women, with 46 participants being right-handed and 12 left-handed. The database consists of controls in the following categories of age: b8 years, 9 years, 10–15 years, 16–30 years, 31–49 years, 50– 70 years, and controls in corresponding age groups to the participants with ADHD, were selected. Exact age in years and IQ measures were not available for the control group.
2.2. The Dichotic Listening paradigm The Bergen Dichotic Listening paradigm (Hugdahl, 2003) consists of consonantvowel (CV) stimuli/ba/,/da/,/ga/,/pa/,/ta/, and/ka/with dichotic stimuli pairs originating from 30 possible (heteronym) combinations of two different stimuli (e.g.,/ba/–/da/,/ ba/-/ga/). Homonym pairs, such as/ba/–/ba/, were not presented in the present study. The syllables were read by a male voice in Norwegian with constant intonation and intensity. Each CV syllable lasted between 400 and 450 ms, and the interstimulus interval between two consecutive presentations was about 4 s. Participants were shown the six syllables printed on a piece of paper before the test. Stimulus presentation was performed using headphones, and the stimulus administration and response collection were controlled using E-Prime (Psychology Software Tools Inc., Pittsburgh, PA, USA). The 30 dichotic CV-pairs were presented three times with three different randomizations, one for each attention instruction condition, thus giving a total of 90 presentations. In the first condition, the NF condition, the participants were instructed to report the syllable they heard best without any specific instruction concerning the focus of attention. In the two remaining conditions the participants were instructed to focus attention on and report the syllable heard either in the right ear, the FR condition, or in the left ear, the FL condition. The NF condition was always presented first, whereas the FR and FL conditions alternated (counterbalanced across participants), being presented second or third. The numbers of correct reports from left and right ear, respectively, were scored with a maximum score of 30 for each ear and condition (NF, FR, FL). The experimenter scored the response on-line on the same PC that controlled the stimulus presentations.
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2.3. Statistical analysis The data were analyzed using a four-way analysis of variance (ANOVA) including the two between-subject factors Group (with two levels: ADHD and control) and Sex (two levels: males, females), and the two within-subject factors Condition (three levels: NF, FR, FL) and Ear (two levels: left and right ear). The number of correct responses served as dependent variable. Significant interaction- and main effects were followed-up by lower-order ANOVAs or appropriate t-tests (for dependent or independent measures). The level of significance was set to α = 0.05 for the post-hoc tests, and no correction for multiple comparisons was performed in order to retain statistical power (Cohen, 1988). All post-hoc tests that were calculated separately for the two groups, differed in their statistical power, because ADHD and control group were of different sample size (n = 29 versus n = 58). Hence, in those cases the interpretation of the post-hoc test results was not only based on statistical probability, but in addition on effect size measures, which account for differences in sample size (Cohen, 1988). The effect size was determined as proportion of explained variance (η2) for main and interaction effects. The effect-size measures Cohen's d and d′ were calculated for pair-wise comparisons of independent or dependent measures, respectively (using the G*Power 3 software package; Faul et al., 2007).
3. Results The four-way ANOVA revealed a significant interaction of the factors Condition and Ear (Table 1) indicating a significant REA (p b 0.05 in posthoc paired t-test) in the NF (d′ = 0.74) and FR (d′ = 1.36) condition and no significant difference between left- and right-ear responses (p = 0.30) in the FL condition (d′ = 0.10). However, a significant three-way interaction of Group, Condition, and Ear (Table 1, Fig. 1) also indicated that the interaction effect of Condition and Ear differed between the ADHD and the control group. Further analyzing the three-way interaction effect by calculating separate post-hoc two-way ANOVAs for the ADHD and the control group, revealed a significant interaction of Condition and Ear in both groups (ADHD: F(2,56) = 10.96; p b 0.0001; control: F(2,114) = 52.06; p b 0.0001). The analysis of the effect size showed, however, that the interaction of Condition and Ear explained more variance in the control (η2 = 0.53) than in the ADHD group (η2 = 0.18), indicating a stronger top-down attention modulation of the ear advantage in the control group. This group difference in the interaction effect was mainly driven by the FL condition (Fig. 1) and was confirmed in post-hoc paired t-tests. Here, the control group showed a significant LEA (p = 0.03; d′ = −0.3), whereas the ADHD group showed more correct right- than left-ear responses, (p = 0.22; d′ = 0.19). The group difference in the FL condition was further confirmed by the between-group post-hoc t-tests, revealing a significantly larger number of correct left-ear responses in the control group compared with the ADHD group (p = 0.02; d = 0.53), and a trend toward smaller numbers of correct right ear responses in the control Table 1 Main and interaction effects of the four-way analysis of variance (ANOVA) including the factors Group (ADHD, Control), Sex (males, females), Condition (Cond; NF, FR, FL), and Ear (left ear, right ear). Effect
F-value
d.f.effect
d.f.error
p
η2
Group Sex Cond Ear Group × Sex Cond × Group Cond × Sex Cond × Group × Sex Ear × Group Ear × Sex Ear × Group × Sex Cond × Ear Cond × Ear × Group Cond × Ear × Sex Cond × Ear × Group × Sex
2.89 0.22 8.30 71.81 5.70 2.45 0.54 0.57 0.64 2.90 2.16 45.87 4.63 0.06 2.37
1 1 2 1 1 2 2 2 1 1 1 2 2 2 2
83 83 166 83 83 166 166 166 83 83 83 166 166 166 166
0.09 0.64 b 0.01 b 0.01 0.02 0.09 0.59 0.57 0.43 0.09 0.15 b 0.01 0.01 0.95 0.10
0.00 0.00 0.01* 0.46* 0.01* 0.00 0.00 0.00 0.00 0.02 0.01 0.32* 0.03* 0.00 0.02
Notes: d.f.: degrees of freedom; p: empirical probability; η2: effect size, proportion of explained variance; significant effects (p b 0.05) are additionally marked with an asterisk “*”.
Fig. 1. Mean correct reports of stimuli presented to the right (RE) or the left ear (LE) split for the ADHD and the control group, and presented separately for the non-forced (NF), forced-right (FR), and forced-left (FL) attention condition. Vertical bars denote 95% confidence intervals.
compared with the ADHD group (p = 0.051; d = −0.43). During the FL condition 33 of the 58 controls reported a LEA, 22 reported a REA, and three reported a non-ear advantage (NEA), whereas the 29 participants with ADHD reported as follows: nine LEA, 17 REA, and three NEA (Table S1 in the Supplementary material). In the NF and FR conditions both groups showed a significant REA (all p b 0.001) with the control group showing a stronger effect than the ADHD group in both conditions (NF ADHD: d′ = 0.80; NF control: d′ = 0.87; FR ADHD: d′ = 1.08; FR control: d′ = 1.50). No significant post-hoc comparison was found neither for the NF nor FR condition, when testing for differences between the two groups concerning the rate of correct left- and right-ear responses, respectively (all p N 0. 17, all |d| b 0.31). The three subgroups of adults with ADHD, the combined (n = 19), the inattentive (n = 7), and the hyperactive/impulsive (n = 3), did all share the same pattern in the DL task, with a clear deviation in the FL condition. There were significant main effects of Condition (post-hoc test: FR N NF, whereas FR = FL and NF = FL) and Ear (more correct rightthan left-ear responses) and a significant interaction of Sex and Group. Post-hoc t-tests showed that this interaction was due to an overall (independent of Condition and Ear) significantly higher number of correct reports in control women as compared to ADHD women (p b 0.05, d = 1.08), whereas no other pair-wise group comparisons were significant. No other main or interaction effects were statistically significant (Table 1). Leaving out sex as a variable in the ANOVA, making it a three-way omnibus ANOVA, results in largely the same findings, apart from the absence of a significant sex-by-group interaction. 4. Discussion Adults with ADHD were impaired in their ability to correctly report the stimulus from the left ear during the FL instruction condition, resulting in a REA, whereas the control group showed the expected LEA. The FL condition is considered a measure of cognitive control (Hugdahl et al., 2009; Westerhausen et al., 2009), and the results thus support the hypothesis of deficit in cognitive control in individuals with ADHD, using a well-controlled experimental task. Adults with ADHD performed comparable to and equally well as the controls during the NF and FR conditions, thus revealing normal abilities of perception and orienting of attention in the ADHD group. The results of this study thus indicate that adults with ADHD have more deficits in cognitive control than in orienting attention. The reported differences
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are, however, demonstrated on a group level, and it is not possible to conclude on an individual level. Sub-grouping of the ADHD participants into the combined, the inattentive, and the hyperactive/ impulsive types, resulted in small samples that were not amenable to rigorous statistical analyses. Impairment of cognitive control in an experimental condition where the participants had to override an automatic drive with help of top-down control processes, has implications for the understanding of ADHD in adults with regard to e.g. the importance of the environment in education and work and of training procedures. For example, in everyday life, coping with an open-office work environment with its continuous distractions challenging is likely to fail, whereas training in cognitive skills may be important. Studies of computer-based training of working memory and sustained attention in children have revealed promising results (Klingberg et al., 2005; Shalev et al., 2007; Beck et al., 2010), a topic almost neglected in adults (White and Shah, 2006; Virta et al., 2010). The current results may point to the possibility of implementing new training procedures, by e.g. applying a simple routine for daily practice to overcome the problem of focusing attention on the left ear stimulus in the FL condition in the presence of a distracting right ear stimulus. Alternative explanations to impaired cognitive control in the ADHD group during the FL condition, could be abnormalities in the left temporal lobe in adults with ADHD, which would primarily affect processing of the left ear stimulus. Alternatively, abnormalities in the corpus callosum in individuals with ADHD (Valera et al., 2007; Schnoebelen et al., 2010) may explain reduced transfer of stimuli from the left ear, and thus result in problems with LEA during FL condition. Functional brain imaging studies, however, support the notion of separate cognitive processes during DL with forced conditions. The cingulate gyrus is activated during all three conditions in DL, but the extent of the activated clusters increases with the cognitive load (Thomsen et al., 2004). The activation in the NF condition in the cingulate gyrus is small and present only in the left hemisphere, whereas bilateral activation is present during FR and FL conditions. During FL condition the activation of the cingulate gyrus stretches further out, also including the dorsal cognitive part of the anterior cingulate cortex (ACC; Bush et al., 2000; Hugdahl et al., 2009). Cognitive control depends on top-down instructions from the prefrontal cortex (Braver and Barch, 2002; Braver and Bongiolatti, 2002), which the ACC is an essential part of (Bush et al., 2000). The attention process triggered by the FR condition is comparable to orienting of attention, as defined in the attentional networks model (Fan et al., 2005; Posner and Rothbart, 2007; Fan et al., 2009), whereas the cognitive control process during the FL condition presumably taps the executive control network (Fan et al., 2005; Posner and Rothbart, 2007). Our results may indicate an impaired executive control network as the main cognitive dysfunction in adults with ADHD, whereas the orienting network functions normally in those adults with ADHD. The executive control network is associated with the ACC and lateral prefrontal cortex (LPFC; Fan et al., 2005) in which the ACC plays a crucial role when monitoring conflicts, whereas LPFC may have a more strategic role in resolving conflicts (Kerns et al., 2004; Sohn et al., 2007). Brain imaging studies have described dysfunctional neurocircuits involving these areas in individuals with ADHD (Bush, 2010; Makris et al., 2009). No functional brain imaging studies to date have yet compared these different attentional networks in individuals with ADHD, and it would be relevant to compare brain activation in these networks during tasks that involve the orienting and cognitive control functions. Some limitations need consideration when interpreting the results. First, we compared individuals with ADHD to healthy individuals in a database without full documentation of the IQ in every participant in the database. The relatively high IQ in the ADHD group (mean total IQ of 110), however, suggests that the IQ difference probably cannot explain the problems with cognitive control in the
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ADHD group. Second, we cannot exclude a selection bias, although we tried to recruit participants with ADHD as representative as possible. Clinical research often implicates selected groups, because participating in a comprehensive study requires motivation, the ability to meet to assessments, and to cooperate with the researchers in the study. Third, a high degree of comorbidity and medication are common challenges when studying adults with ADHD, and it is necessary to balance these potential confounders with the aim to examine representative groups. We have thus excluded participants with disorders that have a clearly documented influence on cognitive functions, but included participants with minor comorbid disorders. Although the participants were instructed to withhold medication 48 h prior to testing, some of the patients did not, resulting in a heterogeneous group with respect to current medication. Analyses comparing the ADHD participants with and without medication, did not reveal any effect of the medication (Figs. S1 and S2 in the Supplementary material). In summary, the results show that adults with ADHD have a normal ability to direct attention, whereas they show less ability to override a more automatic reaction and thus a deficit in cognitive control in a conflict situation, when the perceptually less salient leftear stimulus should be reported in the FL situation. The findings therefore contribute to our understanding of problems that emerge for adults with ADHD in everyday situations involving potential cognitive conflicts, and thus highlight the functional deficits caused by this disorder. Although highly developed compensatory strategies in adults with ADHD may conceal some of the dysfunctions, the results have implications for psychosocial adjustment in educational and work environment. Supplementary materials related to this article can be found online at doi:10.1016/j.psychres.2011.04.014. Acknowledgments The research was supported by grants from Division of Psychiatry, Haukeland University Hospital, the Research Council of Norway, Western Norway Regional Health Authority, and the National Resource Unit for AD/HD, Tourette Syndrome and Narcolepsy. We would like to thank Liv Karin Heldal, Anne Halmøy, Astri Johansen Lundervold, and Helene Halleland for their contributions to the study.
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Psychiatry Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / p s yc h r e s
Cognitive control in adults with attention-deficit/hyperactivity disorder Margaretha Dramsdahl a,b,⁎, René Westerhausen c, Jan Haavik a,d,e, Kenneth Hugdahl a,c,e, Kerstin J. Plessen e,f,g a
Division of Psychiatry, Haukeland University Hospital, Bergen, Norway Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Norway Department of Biological and Medical Psychology, University of Bergen, Norway d Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Norway e K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Norway f Center for Child and Adolescent Psychiatry, Bispebjerg Hospital Copenhagen, Denmark g Institute for Neurology, Psychiatry, and Sensory Sciences, University of Copenhagen, Denmark b c
a r t i c l e
i n f o
Article history: Received 21 April 2010 Received in revised form 28 March 2011 Accepted 12 April 2011 Keywords: ADHD Dichotic listening Cognitive processes Executive functions Attentional networks
a b s t r a c t The objective of the present study was to investigate the ability of adults with Attention-Deficit/Hyperactivity Disorder (ADHD) to direct their attention and exert cognitive control in a forced instruction dichotic listening (DL) task. The performance of 29 adults with ADHD was compared with 58 matched controls from the Bergen Dichotic Listening Database (N N 1500). Participants in the Bergen DL task listen to and report from conflicting consonant–vowel combinations (two different syllables presented simultaneously, one to each ear). They are asked to report the syllable they hear (non-forced condition), or to focus and report either the right- or leftear syllable (forced-right and forced-left condition). This procedure is presumed to tap distinct cognitive processes: perception (non-forced condition), orienting of attention (forced-right condition), and cognitive control (forced-left condition). Adults with ADHD did not show significant impairment in the conditions tapping perception and attention orientation, but were significantly impaired in their ability to report the leftear syllable during the forced-left instruction condition, whereas the control group showed the expected leftear advantage in this condition. This supports the hypothesis of a deficit in cognitive control in the ADHD group, presumably mediated by a deficit in a prefrontal neuronal circuitry. Our results may have implications for psychosocial adjustment for persons with ADHD in educational and work environments. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Attention-Deficit/Hyperactivity Disorder (ADHD) is a disorder with three different clinical subtypes grouped according to their dominant symptoms; the inattentive, the hyperactive/impulsive, and the combined type (American Psychiatric Association, 2000). The estimated worldwide-pooled prevalence in children and adolescents with ADHD is 5.3% (Polanczyk et al., 2007). Although ADHD is primarily diagnosed in childhood the majority of children affected shows persistent symptoms which cause severe functional impairment into adulthood (Biederman and Faraone, 2005; Faraone et al., 2006). Typical symptoms that interfere with daily life are difficulties to maintain attention-span during longer periods of time or to keep attention focused despite distractions, problems in following instructions and to complete activities that demand cognitive focus.
⁎ Corresponding author at: Division of Psychiatry, Haukeland University Hospital, Jonas Liesvei 65, N-5021 Bergen, Norway. Tel.: + 47 958354; fax: + 47 55975146. E-mail address: [email protected] (M. Dramsdahl). 0165-1781/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2011.04.014
Several causal models have been presented that attempt to explain the symptoms of ADHD (e.g. Sergeant et al., 2003; Nigg, 2006). Earlier models have stressed the dysfunction in a few core domains, such as problems with impaired executive functions (EF) and response inhibition (Pennington and Ozonoff, 1996; Barkley, 1997). ADHD is, however, likely to be a neuropsychologically heterogeneous disorder (Nigg and Casey, 2005; Willcutt et al., 2005; Doyle, 2006; SonugaBarke et al., 2010), reflected by the recently described multiple pathways models (Sergeant et al., 2003; Sonuga-Barke, 2005; Castellanos et al., 2006), which highlight other domains than merely EF as problematic, e.g. state regulation (Sanders, 1983; Sergeant, 2005) or delay aversion (Sonuga-Barke et al., 1992). Deficits in EF or in cognitive control are, however, considered key impairments in ADHD in most of the existing models. Although not exclusive (Jurado and Rosselli, 2007), cognitive abilities often included into the concept of EF are working memory, response inhibition, set-shifting, planning and fluency (Pennington and Ozonoff, 1996; Sergeant et al., 2003). We will in the following use EF and cognitive control as synonym concepts, both defined by the ability to cope with disturbances and conflict situations, where bottom-up, automatic
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responses interfere with the given instructions requiring top-down control. As recently suggested, dichotic listening (DL) to repeated presentations of consonant-vowel (CV) syllables may represent a way of studying orienting of attention and cognitive control processes (Hugdahl et al., 2009; Westerhausen et al., 2009; Arciuli et al., 2010; see also Carlsson et al., 1994, studying clinical samples). Confronted with two CV-syllables presented dichotically, i.e. one presented to the right and a different presented simultaneously to the left ear, participants more often correctly report the stimulus presented to the right compared with the left ear. Neuronal wiring of the auditory pathways and lateralization of speech sound processing to the left temporal lobe favor stimuli presented to the right ear, and this results in a right-ear advantage (REA) (Kimura, 1967). The REA may thus be regarded as a bottom-up automatic response tendency to presentations of CV-syllables that are reported by the participant. Instructing the participants to attend to one ear and explicitly report only the syllable presented to that ear, however, will modulate the REA. Healthy participants, when asked to selectively report the right-ear stimulus (forced-right (FR) condition), show an increased REA as compared to the free report (non-forced (NF)) instruction condition. Conversely, when asked to focus attention on the left-ear stimulus (forced-left (FL) condition), the participants typically report more correct stimuli from the left ear, which results in a left-ear advantage (LEA) (Bryden et al., 1983; Hugdahl and Andersson, 1986). The FR and the FL condition may at the outset appear to reflect the same underlying attentional processes, but asking a participant to focus on and report only the right- or left-ear stimulus may create two different experimental conditions that rely on different cognitive functions (Hugdahl et al., 2009). The FR condition requires to focus attention on the stronger, or more salient stimulus (referred to as “orienting” by Posner and Rothbart, 2007), whereas the FL condition specifically requires the ability to resolve a conflict between the bottom-up stronger tendency to report the right-ear stimulus and the top-down instruction to report the weaker left-ear stimulus (Hugdahl et al., 2009). The ability to resolve a conflict is one of the most fundamental aspects of cognitive control (Miller and Cohen, 2001; Fan et al., 2005; Posner and Rothbart, 2007). The DL task may thus explore three distinct aspects of perception and cognition: bottom-up perception in the NF condition, an orienting process with a synergic bottom-up and a top-down effect in the FR condition, and a cognitive control process with a conflicting top-down effect that needs to override the automatic response in the FL condition. Although the auditory stimuli are identical across all three instruction conditions, the different instructions in this paradigm may hypothetically allow to tease apart the processes of perception, orienting and cognitive control (Hugdahl et al., 2009). In fact, the single experimental manipulation that differentiates the FR and FL instruction conditions is one word within the instruction ("right" versus "left"), whereas all other parameters are kept identical between the two conditions. The NF instruction is in this context a baseline condition to against which to evaluate the effects in the FR and FL conditions. During the past decade, researchers have started to explore the specific neuropsychological deficits in adults with ADHD (Hervey et al., 2004; Boonstra et al., 2005), whereas prior research has focused mainly on children and adolescents. Profiles generated in samples of children with ADHD are not consistently overlapping with those stemming from adults (Doyle, 2006). In comparison to children with ADHD, adults have had the opportunity to develop different cognitive strategies to cope with cognitive conflicts and response inhibition. We expected that applying a new paradigm with rigorous experimental control could reveal new aspects of cognitive deficits in ADHD. The objective of the present study was thus to investigate the performance in the forced instruction DL tasks in adults with ADHD. We predicted that individuals with ADHD compared with sex- and handedness-
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matched controls would show impaired cognitive control during FL condition. 2. Methods 2.1. Participants The sample consisted of 29 participants with ADHD, 15 men and 14 women. The patients were recruited from the Norwegian ADHD-project in Bergen, and further details of the procedure for recruitment are accessible in other publications (Johansson et al., 2008; Halleland et al., 2009; Halmoy et al., 2009). Exclusion criteria were current serious psychiatric disturbance or substance abuse, epilepsy or other neurological or physical disease that significantly impair neurocognitive function, a lifetime history of developmental delay, premature birth before 34 weeks of gestational age, or an IQ below 70, as measured by the Wechsler Abbreviated Scale of Intelligence (WASI). Audiometry was performed for the frequencies 500, 1000, 2000, and 3000 Hz prior to the DL task. We excluded participants with hearing deficits (more than 35 dB hearing loss) on one of the ears in any of the above mentioned frequencies, and individuals that had more than 10 dB differences in hearing between the two ears in two or more frequencies. Applying these criteria, five out of 34 individuals originally recruited from the Norwegian ADHD-project, were not eligible for the present study. All patients had been diagnosed according to ICD-10 or DSM-IV criteria for hyperkinetic disorder/ADHD by a psychiatrist or psychologist before the inclusion in the project. One of the participants had received a diagnosis of bipolar disorder several years ago, but that diagnosis was not confirmed as prior or present diagnosis during the clinical diagnostic interview. An experienced psychiatrist (M.D.) used the ADHD module of the K-SADS (Kaufman et al., 1997) adjusted to adults to validate the diagnoses and determine the subtype of ADHD. Current ADHD symptoms were determined with the Adult ADHD Self-Report Scale (ASRS-18) (Kessler et al., 2005). The profile of symptoms reported in childhood determined the ADHD-subtype, resulting in 19 participants with a combined type, seven with an inattentive type, and three with a hyperactive/impulsive type. The mean age in the ADHD group was 32.9 years (S.D. = 7.1, age range 21– 48 years), and mean IQ was 110.6 (S.D. = 14.3, IQ range 78–128). Sixteen patients were medicated with stimulants or atomoxetine. Patients were instructed to withhold medication 48 h prior to testing, and nine did this, whereas two continued their ordinary medication and five reduced the dosage during the last 48 h prior to the examination. Thirteen of the patients had not used stimulants or atomoxetine during the past 6 months. Handedness was determined by the hand the participant preferred to draw and write with. Using this definition, 23 of the patients were right-handed, and six were left-handed. Participants in the control group were selected from the Bergen Dichotic Listening Database, which consists of data from more than 1500 healthy participants, and which all have been tested using the same version of the DL test as used in the present study (described below; see also Hugdahl, 2003). Controls were randomly selected after matching for gender and handedness. Two controls were selected for each participant with ADHD, resulting in 58 controls, 30 men and 28 women, with 46 participants being right-handed and 12 left-handed. The database consists of controls in the following categories of age: b8 years, 9 years, 10–15 years, 16–30 years, 31–49 years, 50– 70 years, and controls in corresponding age groups to the participants with ADHD, were selected. Exact age in years and IQ measures were not available for the control group.
2.2. The Dichotic Listening paradigm The Bergen Dichotic Listening paradigm (Hugdahl, 2003) consists of consonantvowel (CV) stimuli/ba/,/da/,/ga/,/pa/,/ta/, and/ka/with dichotic stimuli pairs originating from 30 possible (heteronym) combinations of two different stimuli (e.g.,/ba/–/da/,/ ba/-/ga/). Homonym pairs, such as/ba/–/ba/, were not presented in the present study. The syllables were read by a male voice in Norwegian with constant intonation and intensity. Each CV syllable lasted between 400 and 450 ms, and the interstimulus interval between two consecutive presentations was about 4 s. Participants were shown the six syllables printed on a piece of paper before the test. Stimulus presentation was performed using headphones, and the stimulus administration and response collection were controlled using E-Prime (Psychology Software Tools Inc., Pittsburgh, PA, USA). The 30 dichotic CV-pairs were presented three times with three different randomizations, one for each attention instruction condition, thus giving a total of 90 presentations. In the first condition, the NF condition, the participants were instructed to report the syllable they heard best without any specific instruction concerning the focus of attention. In the two remaining conditions the participants were instructed to focus attention on and report the syllable heard either in the right ear, the FR condition, or in the left ear, the FL condition. The NF condition was always presented first, whereas the FR and FL conditions alternated (counterbalanced across participants), being presented second or third. The numbers of correct reports from left and right ear, respectively, were scored with a maximum score of 30 for each ear and condition (NF, FR, FL). The experimenter scored the response on-line on the same PC that controlled the stimulus presentations.
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2.3. Statistical analysis The data were analyzed using a four-way analysis of variance (ANOVA) including the two between-subject factors Group (with two levels: ADHD and control) and Sex (two levels: males, females), and the two within-subject factors Condition (three levels: NF, FR, FL) and Ear (two levels: left and right ear). The number of correct responses served as dependent variable. Significant interaction- and main effects were followed-up by lower-order ANOVAs or appropriate t-tests (for dependent or independent measures). The level of significance was set to α = 0.05 for the post-hoc tests, and no correction for multiple comparisons was performed in order to retain statistical power (Cohen, 1988). All post-hoc tests that were calculated separately for the two groups, differed in their statistical power, because ADHD and control group were of different sample size (n = 29 versus n = 58). Hence, in those cases the interpretation of the post-hoc test results was not only based on statistical probability, but in addition on effect size measures, which account for differences in sample size (Cohen, 1988). The effect size was determined as proportion of explained variance (η2) for main and interaction effects. The effect-size measures Cohen's d and d′ were calculated for pair-wise comparisons of independent or dependent measures, respectively (using the G*Power 3 software package; Faul et al., 2007).
3. Results The four-way ANOVA revealed a significant interaction of the factors Condition and Ear (Table 1) indicating a significant REA (p b 0.05 in posthoc paired t-test) in the NF (d′ = 0.74) and FR (d′ = 1.36) condition and no significant difference between left- and right-ear responses (p = 0.30) in the FL condition (d′ = 0.10). However, a significant three-way interaction of Group, Condition, and Ear (Table 1, Fig. 1) also indicated that the interaction effect of Condition and Ear differed between the ADHD and the control group. Further analyzing the three-way interaction effect by calculating separate post-hoc two-way ANOVAs for the ADHD and the control group, revealed a significant interaction of Condition and Ear in both groups (ADHD: F(2,56) = 10.96; p b 0.0001; control: F(2,114) = 52.06; p b 0.0001). The analysis of the effect size showed, however, that the interaction of Condition and Ear explained more variance in the control (η2 = 0.53) than in the ADHD group (η2 = 0.18), indicating a stronger top-down attention modulation of the ear advantage in the control group. This group difference in the interaction effect was mainly driven by the FL condition (Fig. 1) and was confirmed in post-hoc paired t-tests. Here, the control group showed a significant LEA (p = 0.03; d′ = −0.3), whereas the ADHD group showed more correct right- than left-ear responses, (p = 0.22; d′ = 0.19). The group difference in the FL condition was further confirmed by the between-group post-hoc t-tests, revealing a significantly larger number of correct left-ear responses in the control group compared with the ADHD group (p = 0.02; d = 0.53), and a trend toward smaller numbers of correct right ear responses in the control Table 1 Main and interaction effects of the four-way analysis of variance (ANOVA) including the factors Group (ADHD, Control), Sex (males, females), Condition (Cond; NF, FR, FL), and Ear (left ear, right ear). Effect
F-value
d.f.effect
d.f.error
p
η2
Group Sex Cond Ear Group × Sex Cond × Group Cond × Sex Cond × Group × Sex Ear × Group Ear × Sex Ear × Group × Sex Cond × Ear Cond × Ear × Group Cond × Ear × Sex Cond × Ear × Group × Sex
2.89 0.22 8.30 71.81 5.70 2.45 0.54 0.57 0.64 2.90 2.16 45.87 4.63 0.06 2.37
1 1 2 1 1 2 2 2 1 1 1 2 2 2 2
83 83 166 83 83 166 166 166 83 83 83 166 166 166 166
0.09 0.64 b 0.01 b 0.01 0.02 0.09 0.59 0.57 0.43 0.09 0.15 b 0.01 0.01 0.95 0.10
0.00 0.00 0.01* 0.46* 0.01* 0.00 0.00 0.00 0.00 0.02 0.01 0.32* 0.03* 0.00 0.02
Notes: d.f.: degrees of freedom; p: empirical probability; η2: effect size, proportion of explained variance; significant effects (p b 0.05) are additionally marked with an asterisk “*”.
Fig. 1. Mean correct reports of stimuli presented to the right (RE) or the left ear (LE) split for the ADHD and the control group, and presented separately for the non-forced (NF), forced-right (FR), and forced-left (FL) attention condition. Vertical bars denote 95% confidence intervals.
compared with the ADHD group (p = 0.051; d = −0.43). During the FL condition 33 of the 58 controls reported a LEA, 22 reported a REA, and three reported a non-ear advantage (NEA), whereas the 29 participants with ADHD reported as follows: nine LEA, 17 REA, and three NEA (Table S1 in the Supplementary material). In the NF and FR conditions both groups showed a significant REA (all p b 0.001) with the control group showing a stronger effect than the ADHD group in both conditions (NF ADHD: d′ = 0.80; NF control: d′ = 0.87; FR ADHD: d′ = 1.08; FR control: d′ = 1.50). No significant post-hoc comparison was found neither for the NF nor FR condition, when testing for differences between the two groups concerning the rate of correct left- and right-ear responses, respectively (all p N 0. 17, all |d| b 0.31). The three subgroups of adults with ADHD, the combined (n = 19), the inattentive (n = 7), and the hyperactive/impulsive (n = 3), did all share the same pattern in the DL task, with a clear deviation in the FL condition. There were significant main effects of Condition (post-hoc test: FR N NF, whereas FR = FL and NF = FL) and Ear (more correct rightthan left-ear responses) and a significant interaction of Sex and Group. Post-hoc t-tests showed that this interaction was due to an overall (independent of Condition and Ear) significantly higher number of correct reports in control women as compared to ADHD women (p b 0.05, d = 1.08), whereas no other pair-wise group comparisons were significant. No other main or interaction effects were statistically significant (Table 1). Leaving out sex as a variable in the ANOVA, making it a three-way omnibus ANOVA, results in largely the same findings, apart from the absence of a significant sex-by-group interaction. 4. Discussion Adults with ADHD were impaired in their ability to correctly report the stimulus from the left ear during the FL instruction condition, resulting in a REA, whereas the control group showed the expected LEA. The FL condition is considered a measure of cognitive control (Hugdahl et al., 2009; Westerhausen et al., 2009), and the results thus support the hypothesis of deficit in cognitive control in individuals with ADHD, using a well-controlled experimental task. Adults with ADHD performed comparable to and equally well as the controls during the NF and FR conditions, thus revealing normal abilities of perception and orienting of attention in the ADHD group. The results of this study thus indicate that adults with ADHD have more deficits in cognitive control than in orienting attention. The reported differences
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are, however, demonstrated on a group level, and it is not possible to conclude on an individual level. Sub-grouping of the ADHD participants into the combined, the inattentive, and the hyperactive/ impulsive types, resulted in small samples that were not amenable to rigorous statistical analyses. Impairment of cognitive control in an experimental condition where the participants had to override an automatic drive with help of top-down control processes, has implications for the understanding of ADHD in adults with regard to e.g. the importance of the environment in education and work and of training procedures. For example, in everyday life, coping with an open-office work environment with its continuous distractions challenging is likely to fail, whereas training in cognitive skills may be important. Studies of computer-based training of working memory and sustained attention in children have revealed promising results (Klingberg et al., 2005; Shalev et al., 2007; Beck et al., 2010), a topic almost neglected in adults (White and Shah, 2006; Virta et al., 2010). The current results may point to the possibility of implementing new training procedures, by e.g. applying a simple routine for daily practice to overcome the problem of focusing attention on the left ear stimulus in the FL condition in the presence of a distracting right ear stimulus. Alternative explanations to impaired cognitive control in the ADHD group during the FL condition, could be abnormalities in the left temporal lobe in adults with ADHD, which would primarily affect processing of the left ear stimulus. Alternatively, abnormalities in the corpus callosum in individuals with ADHD (Valera et al., 2007; Schnoebelen et al., 2010) may explain reduced transfer of stimuli from the left ear, and thus result in problems with LEA during FL condition. Functional brain imaging studies, however, support the notion of separate cognitive processes during DL with forced conditions. The cingulate gyrus is activated during all three conditions in DL, but the extent of the activated clusters increases with the cognitive load (Thomsen et al., 2004). The activation in the NF condition in the cingulate gyrus is small and present only in the left hemisphere, whereas bilateral activation is present during FR and FL conditions. During FL condition the activation of the cingulate gyrus stretches further out, also including the dorsal cognitive part of the anterior cingulate cortex (ACC; Bush et al., 2000; Hugdahl et al., 2009). Cognitive control depends on top-down instructions from the prefrontal cortex (Braver and Barch, 2002; Braver and Bongiolatti, 2002), which the ACC is an essential part of (Bush et al., 2000). The attention process triggered by the FR condition is comparable to orienting of attention, as defined in the attentional networks model (Fan et al., 2005; Posner and Rothbart, 2007; Fan et al., 2009), whereas the cognitive control process during the FL condition presumably taps the executive control network (Fan et al., 2005; Posner and Rothbart, 2007). Our results may indicate an impaired executive control network as the main cognitive dysfunction in adults with ADHD, whereas the orienting network functions normally in those adults with ADHD. The executive control network is associated with the ACC and lateral prefrontal cortex (LPFC; Fan et al., 2005) in which the ACC plays a crucial role when monitoring conflicts, whereas LPFC may have a more strategic role in resolving conflicts (Kerns et al., 2004; Sohn et al., 2007). Brain imaging studies have described dysfunctional neurocircuits involving these areas in individuals with ADHD (Bush, 2010; Makris et al., 2009). No functional brain imaging studies to date have yet compared these different attentional networks in individuals with ADHD, and it would be relevant to compare brain activation in these networks during tasks that involve the orienting and cognitive control functions. Some limitations need consideration when interpreting the results. First, we compared individuals with ADHD to healthy individuals in a database without full documentation of the IQ in every participant in the database. The relatively high IQ in the ADHD group (mean total IQ of 110), however, suggests that the IQ difference probably cannot explain the problems with cognitive control in the
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ADHD group. Second, we cannot exclude a selection bias, although we tried to recruit participants with ADHD as representative as possible. Clinical research often implicates selected groups, because participating in a comprehensive study requires motivation, the ability to meet to assessments, and to cooperate with the researchers in the study. Third, a high degree of comorbidity and medication are common challenges when studying adults with ADHD, and it is necessary to balance these potential confounders with the aim to examine representative groups. We have thus excluded participants with disorders that have a clearly documented influence on cognitive functions, but included participants with minor comorbid disorders. Although the participants were instructed to withhold medication 48 h prior to testing, some of the patients did not, resulting in a heterogeneous group with respect to current medication. Analyses comparing the ADHD participants with and without medication, did not reveal any effect of the medication (Figs. S1 and S2 in the Supplementary material). In summary, the results show that adults with ADHD have a normal ability to direct attention, whereas they show less ability to override a more automatic reaction and thus a deficit in cognitive control in a conflict situation, when the perceptually less salient leftear stimulus should be reported in the FL situation. The findings therefore contribute to our understanding of problems that emerge for adults with ADHD in everyday situations involving potential cognitive conflicts, and thus highlight the functional deficits caused by this disorder. Although highly developed compensatory strategies in adults with ADHD may conceal some of the dysfunctions, the results have implications for psychosocial adjustment in educational and work environment. Supplementary materials related to this article can be found online at doi:10.1016/j.psychres.2011.04.014. Acknowledgments The research was supported by grants from Division of Psychiatry, Haukeland University Hospital, the Research Council of Norway, Western Norway Regional Health Authority, and the National Resource Unit for AD/HD, Tourette Syndrome and Narcolepsy. We would like to thank Liv Karin Heldal, Anne Halmøy, Astri Johansen Lundervold, and Helene Halleland for their contributions to the study.
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