Cortical thinning of temporal pole and orbitofrontal cortex in medication-naïve children and adolescents with ADHD

Highlights

• A MRI study was conducted in 50 medication-näive ADHD patients and 50 controls.

• Cortical thickness analysis focused on prefrontal cortex and temporal lobe areas.

• Patients exhibited cortical thinning in the right temporal pole relative to controls.

• Patients exhibited cortical thinning in the orbitofrontal cortex relative to controls.

• Results suggest that temporal pole and OFC are important in the neuropathology of ADHD.

Abstract

Structural and functional brain studies on attention deficit/hyperactivity disorder (ADHD) have primarily examined anatomical abnormalities in the prefronto-striatal circuitry (especially, dorsal and lateral areas of the prefrontal cortex and dorsal striatum). There is, however, increased evidence that several temporal lobe regions could play an important role in ADHD. The present study used MRI-based measurements of cortical thickness to examine possible differences in both prefrontal and temporal lobe regions between medication-näive patients with ADHD (N=50) and age- and sex-matched typically developing controls (N=50). Subjects with ADHD exhibited significantly decreased cortical thickness in the right temporal pole and orbitofrontal cortex (OFC) relative to healthy comparison subjects. These differences remained significant after controlling for confounding effects of age, overall mean cortical thickness and comorbid externalizing conditions, such as oppositional defiant and conduct disorders. These results point to the involvement of the temporal pole and OFC in the neuropathology of ADHD. Moreover, present findings add evidence to the assumption that multiple brain regions and psychological processes are associated with ADHD.

Introduction

Structural neuroimaging studies on attention deficit/hyperactivity disorder (ADHD) have focused primarily on anatomical alterations in prefronto-striatal circuitry (Seidman et al., 2005, Valera et al., 2007). Functional and structural brain abnormalities in prefrontal cortex (primarily, dorsolateral and ventrolateral regions) and dorsal striatum have been strongly linked with response inhibition, one of the most consistently implicated deficits in ADHD (Hart et al., 2013). Other executive control processes that mainly rely on prefrontal cortex, such as conflict monitoring and error processing, have also been related to the disorder (Liotti et al., 2005). Recent evidence, however, indicates that executive dysfunction is not present among all patients with ADHD and cannot explain alone the great heterogeneity of the disorder (Willcutt et al., 2005). Other brain regions beyond the prefronto-striatal circuitry and other psychological processes beyond inhibitory control underlie ADHD (Castellanos and Proal, 2012).

Within this context, results from several studies suggest that some temporal lobe areas might be important in ADHD (Kobel et al., 2010, Rubia et al., 2007). Structurally, it has been found reduced gray matter volume and cortical thickness in predominantly right but also left temporal regions (Carmona et al., 2005, Kobel et al., 2010, Shaw et al., 2006, Sowell et al., 2003). Remarkably, Shaw et al. (2006) found a prominent thinning in the right anterior portion of the temporal lobe in a large sample of children and adolescents with ADHD (more than one hundred) when they were compared cross-sectionally with healthy comparison controls. This finding suggests that this particular region of the temporal lobe may play a key role in the pathophysiology of ADHD. However, other temporal lobe regions, such as inferior and middle temporal gyri, have also been associated with ADHD (Kobel et al., 2010, Sowell et al., 2003). Moreover, functionally abnormal activation in several temporal lobe regions (primarily, in the right side) has been observed while ADHD patients performed different cognitive paradigms (Kobel et al., 2010, Rubia et al., 2007, Smith et al., 2006). For instance, patients ADHD displayed reduced temporal lobe activation in tasks examining the allocation of attention to target and novel stimuli (Rubia et al., 2007, Shafritz et al., 2004; Stevens et al., 2007), attentional and response set switching (Smith et al., 2006), working memory (Kobel et al., 2010) and post-error behavioral (Spinelli et al., 2011). However, probably because structural and functional temporal lobe anomalies are less expected, they have been little discussed and further examined in subsequent experiments.

The temporal lobe is an heterogeneous brain area subserving a broad array of cognitive and emotional functions. Much like the prefrontal cortex, several regions of the temporal lobe, including the temporal pole and the temporo-parietal junction, are considered to be heteromodal associative areas that integrate inputs coming from multiple sensory modalities (vision, audition or smell) with internal sensations (Blaizot et al., 2010, Olson et al., 2007). Furthermore, these associative regions are thought to subserve various high-level cognitive and socioemotional processes, including attention, memory, emotion recognition, emotion regulation and empathy (Blaizot et al., 2010, Olson et al., 2007). Some of these processes have been reported to be affected in ADHD (Kobel et al., 2010, Rubia et al., 2007, Sjöwall et al., 2013, Sobanski et al., 2010). Therefore, together with prefrontal cortex, several temporal regions could play an important role in ADHD.

Based on these factors of interest, and the absence of previous structural studies focused on the examination of temporal lobe regions, the present study aimed to perform a detailed analysis of possible anatomical abnormalities not only in the prefrontal cortex but also in the temporal lobe in a large sample of medication-näive children and adolescents with ADHD. Given that cortical thickness has been shown a particularly sensitive metric for detecting anatomic changes that can provide complementary information to other structural measures, we used MRI-based measurements of cortical thickness to quantify anatomical differences between ADHD and healthy comparison subjects. Based on the findings discussed above, we predicted that patients with ADHD would show cortical thinning not only in prefrontal but also in temporal lobe regions (especially in integrative associative areas) compared to healthy comparison subjects.