حجم منزوی کاهش یافته در اختلال نقص توجه بیش فعالی

The aim of this study was to evaluate whether structural differences in the insula and anterior cingulate cortex (ACC), two critical areas of the “salience network,” co-exist in adolescents with attention deficit hyperactivity disorder (ADHD) compared with healthy controls (HC). In addition we aimed to determine if structural changes within these regions correlate with attention and inhibitory function. Nineteen adolescents with ADHD and 25 HC received MRI scans on a 3 T magnet. Morphometric analysis was performed with FreeSurfer. Youths with ADHD were found to have a bilateral reduction in anterior insular (AIC) gray matter volumes compared to HC. Furthermore, the left AIC was found to positively correlate with oppositional symptoms, while the right AIC was found to associate with both attention problems and inhibition. To our knowledge this is the first report of a bilateral reduction in AIC volumes in ADHD. Our findings suggest a role for the insula in modulating attention and inhibitory capacity in ADHD.

Inattention, impulsivity and hyperactivity are the core symptoms of attention-deficit hyperactivity disorder (ADHD) (American Psychiatric Association, 2000a). The anterior cingulate cortex (ACC) has been shown to play a critical role in attention, emotion and cognitive processing, and the integrity of this region has been extensively evaluated in youths with ADHD (Adler et al., 2005, Bush et al., 2000, Makris et al., 2007, Narr et al., 2009 and Shaw et al., 2006). Morphometrically, reduced cortical thickness in the ACC has been reported both in children and adults with ADHD (Makris et al., 2007, Narr et al., 2009, Seidman et al., 2011, Seidman et al., 2006 and Shaw et al., 2006). Task-based functional magnetic resonance imaging (fMRI) studies in ADHD have reported atypical activation patterns, primarily hypoactivation, in the ACC on a variety of attention and executive functioning tasks (Bush et al., 1999, Ernst et al., 2003, Konrad et al., 2006 and Smith et al., 2008). Finally, studies examining functional connectivity in youths with ADHD have reported abnormal functional connections of the ACC to other brain regions, including the insula (Tian et al., 2006 and Zang et al., 2007). These findings, in combination with the hypothesized role of the ACC in attention and cognition, suggest that the ACC is a central brain structure involved in the pathophysiology of ADHD. Interestingly, the ACC and insula have been found to co-activate on numerous functional imaging studies including those involved in goal-directed attention and emotion, and both are crucial structures in the salience network (Craig, 2009, Medford and Critchley, 2010 and Menon and Uddin, 2010). The salience network has been proposed to detect and segregate incoming internal and external stimuli. It provides this information to other brain regions in order to guide appropriate behavioral responses to those stimuli and includes the bilateral anterior insula (AIC) and ACC (Menon and Uddin, 2010, Seeley et al., 2007 and Sridharan et al., 2008). The proposed role of the AIC in the salience network is in the detection and segregation of important information from insignificant stimuli, while the ACC modulates responses in the sensory, motor and association cortices based on the information provided by the AIC (Menon and Uddin, 2010). Furthermore, the salience network may engage in the recruitment of the appropriate brain regions for the processing of current stimuli and the down-regulation of formerly engaged networks (Palaniyappan and Liddle, 2012). The right AIC has been proposed to play a critical role in switching between two major brain networks, the default mode network (DMN) and the central executive network, which have competitive interactions during cognitive information processing (Sridharan et al., 2008). The insula has also been associated with attention, decision-making, cognitive control, performance monitoring, body movement, emotional awareness, risk uncertainty and anticipation (Craig, 2009). Despite the wide array of cognitive functions associated with the insula, few studies to date have evaluated the morphology of the insula in ADHD, and the reports thus far have been negative (Filipek et al., 1997 and Hynd et al., 1993). For instance, Hynd et al. (1993) examined the length of the right and left insula in 10 youths with ADHD and did not find a significant difference compared to 10 age-matched controls. A subsequent study by Filipek et al. (1997) did not find differences in left or right total insular volumes when they compared 15 healthy control (HC) youths and 15 youths with ADHD. More recently, advanced imaging techniques have found insular abnormalities in several neuropsychiatric illnesses. For example, in a voxel-based morphometry analysis, Sterzer et al. (2007) found reductions in bilateral insular gray matter volumes in youths with conduct disorder (CD) compared to HC. Furthermore, a study of children with Smith–Magenis syndrome, which is associated with aggression, hyperactivity, and attention deficits, also noted bilateral anterior insular gray matter reductions (Boddaert et al., 2004). Reductions in insular volumes have also been reported in other neuropsychiatric disorders including pervasive developmental disorder (Kosaka et al., 2010), bipolar disorder (Ellison-Wright and Bullmore, 2010) and schizophrenia (Ellison-Wright and Bullmore, 2010 and Makris et al., 2006), suggesting that insular abnormalities are not specific to ADHD and may represent a common neurodevelopmental biological marker of attentional and inhibitory function across disorders. In addition, increased anterior insula activity has been reported during risky decision-making tasks in HC (Lee et al., 2008 and Paulus et al., 2003). In an fMRI study utilizing a task-switching paradigm, adults with ADHD had greater activation in the dorsal ACC (dACC) and insula, while controls displayed more activation in brain regions, which included DMN regions (Dibbets et al., 2010). Furthermore, a recent study by Tian et al. (2006), which compared the resting-state dACC functional connectivity patterns in adolescents with and without ADHD, found that ADHD patients had stronger connections with the bilateral dACC and bilateral insula, as compared to HC. Given that the ACC and insula have been found to co-activate on numerous functional imaging studies and that the connectivity of the ACC and insula has been shown to be different in ADHD, structural investigations of the insula and ACC, two critical areas of the “salience network,” are warranted in ADHD. Both ACC subregions were included in the “salience network” as the rostral or “affective” ACC subregion has been linked to the assessment of the salience of emotional and motivational information while the caudal ACC or “cognitive” region has been found to mediate attention and executive functions (Bush et al., 2000, Laurens et al., 2003 and Margulies et al., 2007). Therefore, the aim of this study was to evaluate whether gray matter volumes in the anterior and posterior insula and rostral and caudal ACC differed between adolescents with ADHD and HC compared to healthy controls (HC). The Child Behavior Checklist (CBCL) has been utilized frequently to assess internalizing and externalizing symptoms in children with psychiatric illnesses (Achenbach and Rescorla, 2001). The Connors Parent Rating Scale – Revised – Long Version (CPRS) (Conners, 2008) and the Continuous Performance Test (CPT) (Conners, 2000) were utilized to assess attention and impulsivity. We predicted that gray matter volumetric reductions would be present in the ACC and AIC in youths with ADHD and that these reductions would correlate with measures of attention and impulsivity.