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Reduced Activation in Lateral Prefrontal Cortex and Anterior Cingulate during Attention and Cognitive Control Functions in Medication-Naive Adolescents with Depression Compared to Controls

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Title: Reduced Activation in Lateral Prefrontal Cortex and Anterior Cingulate during Attention and Cognitive Control Functions in Medication-Naive Adolescents with Depression Compared to Controls
Language: English
Authors: Halari, Rozmin, Simic, Mima, Pariante, Carmine M.
Source: Journal of Child Psychology and Psychiatry. Mar 2009 50(3):307-316.
Availability: Blackwell Publishing. 350 Main Street, Malden, MA 02148. Tel: 800-835-6770; Tel: 781-388-8599; Fax: 781-388-8232; e-mail: customerservices@blackwellpublishing.com; Web site: http://www.blackwellpublishing.com/jnl_default.asp
Peer Reviewed: Y
Physical Description: PDF
Page Count: 10
Publication Date: 2009
Document Type: Journal Articles
Reports - Research
Descriptors: Negative Attitudes, Attention, Pathology, Adolescents, Brain, Depression (Psychology), Brain Hemisphere Functions, Cognitive Processes, Neurological Organization, Child Health, Diagnostic Tests, Comparative Analysis, Responses
DOI: 10.1111/j.1469-7610.2008.01972.x
ISSN: 0021-9630
Abstract: Background: There is increasing recognition of major depressive disorder (MDD) in adolescence. In adult MDD, abnormalities of fronto-striatal and fronto-cingulate circuitries mediating cognitive control functions have been implicated in the pathogenesis and been related to problems with controlling negative thoughts. No neuroimaging studies of cognitive control functions, however, exist in paediatric depression. This study investigated whether medication-naive adolescents with MDD show abnormal brain activation of fronto-striatal and fronto-cingulate networks when performing tasks of attentional and cognitive control. Methods: Event-related functional magnetic resonance imaging was used to compare brain activation between 21 medication-naive adolescents with a first-episode of MDD aged 14-17 years and 21 healthy adolescents, matched for handedness, age, sex, demographics and IQ. Activation paradigms were tasks of selective attention (Simon task), attentional switching (Switch task), and motor response inhibition and error detection (Stop task). Results: In all three tasks, adolescents with depression compared to healthy controls demonstrated reduced activation in task-relevant right dorsolateral (DLPFC), inferior prefrontal cortex (IFC) and anterior cingulate gyrus (ACG). Additional areas of relatively reduced activation were in the parietal lobes during the Stop and Switch tasks, putamen, insula and temporal lobes during the Switch task and precuneus during the Simon task. Conclusions: This study shows first evidence that medication-naive adolescents with MDD are characterised by abnormal function in ACG and right lateral prefrontal cortex during tasks of attention and performance monitoring, suggesting an early pathogenesis of these functional abnormalities attributed to MDD.
Abstractor: As Provided
Entry Date: 2009
Accession Number: EJ832583
Database: ERIC
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  Value: <anid>AN0036880247;jyy01mar.09;2024Jun04.07:35;v2.2.500</anid> <title id="AN0036880247-1">Reduced activation in lateral prefrontal cortex and anterior cingulate during attention and cognitive control functions in medication-naïve adolescents with depression compared to controls. </title> <p>Background:  There is increasing recognition of major depressive disorder (MDD) in adolescence. In adult MDD, abnormalities of fronto‐striatal and fronto‐cingulate circuitries mediating cognitive control functions have been implicated in the pathogenesis and been related to problems with controlling negative thoughts. No neuroimaging studies of cognitive control functions, however, exist in paediatric depression. This study investigated whether medication‐naïve adolescents with MDD show abnormal brain activation of fronto‐striatal and fronto‐cingulate networks when performing tasks of attentional and cognitive control. Methods:  Event‐related functional magnetic resonance imaging was used to compare brain activation between 21 medication‐naïve adolescents with a first‐episode of MDD aged 14–17 years and 21 healthy adolescents, matched for handedness, age, sex, demographics and IQ. Activation paradigms were tasks of selective attention (Simon task), attentional switching (Switch task), and motor response inhibition and error detection (Stop task). Results:  In all three tasks, adolescents with depression compared to healthy controls demonstrated reduced activation in task‐relevant right dorsolateral (DLPFC), inferior prefrontal cortex (IFC) and anterior cingulate gyrus (ACG). Additional areas of relatively reduced activation were in the parietal lobes during the Stop and Switch tasks, putamen, insula and temporal lobes during the Switch task and precuneus during the Simon task. Conclusions:  This study shows first evidence that medication‐naïve adolescents with MDD are characterised by abnormal function in ACG and right lateral prefrontal cortex during tasks of attention and performance monitoring, suggesting an early pathogenesis of these functional abnormalities attributed to MDD.</p> <p>Keywords: adolescent; FMRI; cognitive control; executive functions; Depression</p> <p>MDD is characterised by anhedonia, poor concentration and diminished positive affectivity ([<reflink idref="bib1" id="ref1">1</reflink>]). It is a leading cause of disability across the lifespan, is increasingly recognised in adolescence and expected to increase in adults and adolescence worldwide ([<reflink idref="bib19" id="ref2">19</reflink>]).</p> <p>Neuropsychological deficits have been reported in executive functions (EF), measured in tasks that are effortful and depend on access to limited capacity cognitive processes ([<reflink idref="bib26" id="ref3">26</reflink>]). Children with MDD show deficits in EF tasks, including sustained and selective attention, working memory, decision‐making, interference inhibition, cognitive flexibility and motor response inhibition ([<reflink idref="bib9" id="ref4">9</reflink>]; [<reflink idref="bib12" id="ref5">12</reflink>]; [<reflink idref="bib14" id="ref6">14</reflink>]).</p> <p>Cognitive deficits observed in early life depression might be precipitated by the various putative causes of depression in young people, including biological factors and psychosocial factors such as loss, interpersonal conflicts, family breakdown, and role transitions ([<reflink idref="bib5" id="ref7">5</reflink>]), as well as reduced positive affect and poor motivation which can impact upon cognitive functions ([<reflink idref="bib8" id="ref8">8</reflink>]). In adult MDD, deficits in cognitive control functions have been related to the behavioural difficulties with inhibiting inappropriate negative thoughts and rumination ([<reflink idref="bib22" id="ref9">22</reflink>]). Enhancing control over negative cognitions is therefore at the core of psychotherapeutic intervention for the disorder ([<reflink idref="bib8" id="ref10">8</reflink>]).</p> <p>Neuroimaging studies of adult MDD have found abnormalities in fronto‐striatal, cingulate and temporal brain regions that mediate motivation and affect regulation ([<reflink idref="bib26" id="ref11">26</reflink>]), but also play a crucial role in cognitive control functions ([<reflink idref="bib29" id="ref12">29</reflink>]; [<reflink idref="bib31" id="ref13">31</reflink>]). In paediatric MDD, structural abnormalities have been reported in the frontal lobes ([<reflink idref="bib20" id="ref14">20</reflink>]), amygdala, hippocampus ([<reflink idref="bib18" id="ref15">18</reflink>]), and the pituitary gland ([<reflink idref="bib17" id="ref16">17</reflink>]), and metabolic abnormalities in caudate and anterior cingulate ([<reflink idref="bib10" id="ref17">10</reflink>]; [<reflink idref="bib27" id="ref18">27</reflink>])<bold>.</bold> Hardly any functional imaging studies, however, exist in paediatric MDD. A study using evoked‐potentials found reduced fronto‐temporal activation in relation to attentional distractibility in children with MDD ([<reflink idref="bib15" id="ref19">15</reflink>]). The few fMRI studies in paediatric depression have found reduced activation in the amygdala in response to fearful faces ([<reflink idref="bib34" id="ref20">34</reflink>]) and increased amygdala activity during face encoding ([<reflink idref="bib25" id="ref21">25</reflink>]). Reduced activation has also been reported in orbitofrontal cortex, anterior cingulate, and amygdala during reward‐related decision‐making and reward evaluation ([<reflink idref="bib7" id="ref22">7</reflink>]). Thus, despite evidence for neuropsychological impairment in EF tasks and structural and metabolic deficits in brain regions that mediate EF, no fMRI studies have as yet investigated brain activation during pure, non‐reward related tasks of attention and cognitive control in paediatric depression. The examination of the neural abnormalities during cognitive control processes in paediatric MDD can provide targets for both pharmacological and psychosocial intervention.</p> <p>This study used event‐related fMRI to examine brain function in first‐episode medication‐naïve adolescents with MDD compared healthy controls during three tasks of attention and cognitive control: 1) the Simon task, that measures selective‐attention and interference inhibition, and activates DLPFC, striatal and temporal brain regions in healthy adolescents ([<reflink idref="bib31" id="ref23">31</reflink>]; [<reflink idref="bib32" id="ref24">32</reflink>]), 2) the Switch task, an attentional switching paradigm, that measures cognitive flexibility, and activates IFC, parietal and striatal brain areas ([<reflink idref="bib31" id="ref25">31</reflink>]; [<reflink idref="bib32" id="ref26">32</reflink>]), and 3) the Stop task, an individually adjusted tracking stop task, that measures motor response inhibition and inhibition failure/error detection, and activates right IFC, caudate and ACG ([<reflink idref="bib29" id="ref27">29</reflink>]).</p> <p>Most previous studies on depression are confounded by medication effects ([<reflink idref="bib26" id="ref28">26</reflink>]). We investigated young medication‐naïve patients with first‐episode MDD to avoid potentially confounding factors such as behavioural and pharmacological treatments, and minimise others such as illness duration and potential long‐term environmental stressors.</p> <p>Based on previous imaging findings in paediatric MDD during attention and decision‐making ([<reflink idref="bib15" id="ref29">15</reflink>]; [<reflink idref="bib7" id="ref30">7</reflink>]), we hypothesised that medication‐naïve adolescents with depression compared to healthy control adolescents would show reduced brain activation in task‐relevant prefrontal, cingulate and striatal brain regions. Additionally, in order to control for the confound of potentially different cortisol responses to an environmental stressor in paediatric depression ([<reflink idref="bib16" id="ref31">16</reflink>]), in this case functional imaging, we also measured salivary cortisol levels pre and post scan.</p> <hd id="AN0036880247-2">Methods</hd> <p></p> <hd id="AN0036880247-3">Subjects</hd> <p>Twenty‐one dextral (Edinburgh Handedness Inventory) ([<reflink idref="bib21" id="ref32">21</reflink>]) adolescent outpatients (11 girls, 10 boys), aged between 14 and 17 years were recruited from London clinics. Patients had a DSM‐IV ([<reflink idref="bib1" id="ref33">1</reflink>]) diagnosis of first‐episode MDD, which was assessed by an experienced child psychiatrist (M.S.) using the Schedule for Affective Disorders and Schizophrenia for School‐Age Children‐Present and Lifetime Version (K‐SADS‐PL; [<reflink idref="bib13" id="ref34">13</reflink>]), and the Beck Depression Inventory (BDI‐II; [<reflink idref="bib2" id="ref35">2</reflink>]). Comorbidity with other major psychiatric disorders was excluded. Participants also completed the Rosenberg Self Esteem Scale (RSES) ([<reflink idref="bib28" id="ref36">28</reflink>]) and the Stressful Life Events Schedule (SLES) for children and adolescents ([<reflink idref="bib35" id="ref37">35</reflink>]). All participants were medication‐naïve and not undergoing any psychological therapy.</p> <p>Controls were 21 healthy adolescents, matched for age, sex, and IQ (Table 1). They were recruited via advertisements at local schools and had no history or presence of a mental disorder, assessed by a trained research psychologist (R.H.) using the K‐SADS‐PL and the BDI‐II.</p> <p>1  Sample characteristics and salivary cortisol levels (nmoles/litre) for adolescents with and without depression</p> <p> <ephtml> <table><thead valign="bottom"><tr><th valign="bottom"> </th><th>Mean (SD)</th><th valign="bottom"><italic>t</italic> (df)</th><th valign="bottom"><italic>p</italic>‐value</th></tr><tr><th>Patients</th><th>Controls</th></tr></thead><tbody valign="top"><tr><td>Age (years)</td><td>16.2 (.83)</td><td>16.3 (1.1)</td><td>.501 (40)</td><td>n.s</td></tr><tr><td>Age females (years)</td><td>16.1 (.87)</td><td>16.0 (1.0)</td><td>.518 (22)</td><td>n.s</td></tr><tr><td>Age males (years)</td><td>16.2 (.82)</td><td>16.6 (1.0)</td><td>1.394 (16)</td><td>n.s</td></tr><tr><td>Performance IQ</td><td>96.4 (12.3)
(range: 76–125)</td><td> 97.1 (13)
(range: 81–119)</td><td>.689 (40)</td><td>n.s</td></tr><tr><td>BDI‐II</td><td>35.4 (7.7)</td><td>4.12 (3.3)</td><td>8.124 (40)</td><td><.001</td></tr><tr><td>Pre scan cortisol (nmol/L)</td><td>4.2 (2.7)</td><td>4.5 (3)</td><td>.740 (34)</td><td>n.s</td></tr><tr><td>Post scan cortisol (nmol/L)</td><td>3.2 (1.9)</td><td>3.8 (4)</td><td>.556 (34)</td><td>n.s</td></tr><tr><td>RSES</td><td>22.1 (2.4)</td><td> </td><td> </td><td /></tr><tr><td>SLES</td><td>40.4 (19.1)</td><td> </td><td> </td><td /></tr></tbody></table> </ephtml> </p> <p>1 <emph>Note</emph>: IQ equivalents of the scaled scores from the Ravens SPM based on the Wechsler's Intelligence Scale for Children (1991); BDI‐II = Beck Depression Inventory RSES = Rosenberg Self Esteem Scale; SLES = Stressful Life Events Scale.</p> <p>All participants completed the Raven's Standard Progressive Matrices Intelligence test ([<reflink idref="bib24" id="ref38">24</reflink>]). A history of substance abuse was an exclusion criterion for all subjects.</p> <p>Equal numbers of boys and girls were recruited to test for potential sex by group interactions.</p> <p>Written informed consent/assent was obtained from all participants and the study was approved by the local Ethics Committee. All participants were paid £30. One control participant did not complete the stop task (due to technical difficulties) and results for this task are presented for 20 controls and 21 patients.</p> <hd id="AN0036880247-4">Salivary cortisol levels</hd> <p>Salivary samples were obtained from each participant before and after the fMRI scan, an hour apart, using plain Salivettes (Sarstedt, UK). All participants were scanned at the same time of day (1600–1700 hrs) and had been fasting for at least two hours prior to the fMRI scan. Saliva was extracted from salivettes by centrifugation and stored at −40 C until further analysis. Saliva cortisol was quantified by time resolved fluoro‐immunoassay (TR‐FIA) as described earlier ([<reflink idref="bib23" id="ref39">23</reflink>]), using cortisol antibody batch B930818 (Biogenesis, Poole, Dorset, UK). Differences in cortisol levels between groups were investigated using a repeated‐measures multivariate analysis of variance (MANOVA) with group as the between‐subjects factor and cortisol values in nanomoles/litre (nmol/L) pre and post‐scan as the repeated measures.</p> <hd id="AN0036880247-5">FMRI activation paradigms</hd> <p>Mixed trial, rapid event‐related fMRI was used for all tasks of 6‐minute duration with jittered inter‐stimulus intervals (Stop, Simon tasks) and randomised presentation to optimise statistical efficiency. The tasks were presented in a fixed order: Simon, Switch and Stop. All subjects practised the tasks once before scanning.</p> <p> <bold>Simon task. </bold> The fMRI adaptation of the Simon task involves a stimulus–response incompatibility effect measuring interference inhibition and selective attention. Subjects have to press a left/right button depending on whether an arrow stimulus of 300ms duration points either to the left or right side of the screen (ITI: 1.8 s). In 77% of congruent trials (184 trials), the arrow pointing left (right) appears on the left (right) side of the screen. In 11.5% (24 trials) of incongruent trials, arrows appear on the opposite side of where they point. There were also 11.5% of oddball trials (slightly slanted congruent arrows) (see Figure 1). The spatial information (side of screen) is predominant over the iconic information (arrow side) and subjects have to inhibit the tendency to make an incorrect response, triggered by the interfering, prepotent spatial information (see [<reflink idref="bib31" id="ref40">31</reflink>]; [<reflink idref="bib32" id="ref41">32</reflink>]).</p> <p>Graph: 1 Display of fMRI activation tasks. (a) Simon task (b) Switch task (c) Stop task</p> <p>Performance variables are errors to congruent and incongruent trials and the Simon effect, which is the difference between typically slower reaction times to incongruent trials and those to congruent trials (MRT incongruent – MRT congruent). The event‐related fMRI analysis subtracts the successfully performed congruent trials from the successfully performed incongruent trials.</p> <p> <bold>Switch task. </bold> This task measures attentional set shifting/cognitive flexibility. A target dot appears in one of the 4 corners of a grid with an arrow in the middle of the grid ((ITI) = 2.4 s). If the central arrow is horizontal, the subject has to indicate whether the target is on the left or right side of the grid (left or right button); if the central arrow is vertical, subjects have to indicate whether the target is in the lower or upper half of the grid (up or down button). During the 32 switch trials (21%), the central arrow changes position, which occurs after every 4–6 of the 120 repeat trials (79%) (See Figure 1b) ([<reflink idref="bib31" id="ref42">31</reflink>]; [<reflink idref="bib32" id="ref43">32</reflink>]). Dependent variables are errors to Switch trials and the Switch cost, which is the difference between typically slower reaction time to switch trials and reaction time to repeat‐trials (MRT Switch – MRT repeat). The event‐related analysis subtracts activation associated with successful repeat‐trials from activation associated with successful switch trials.</p> <p> <bold>Stop task. </bold> The fMRI adaptation of the tracking stop task measures the ability to suppress unexpectedly and unpredictably an already triggered motor response. Arrows of 300ms duration pointing either left or right appear on the screen centre with a mean ITI of 1.8 s (156 trials, 80%). Subjects are instructed to make a button response with their left or right thumb corresponding to the arrow direction. In the unpredictable, infrequent stop trials (40 trials, 20%), the arrows are followed (about 250ms later) by arrows pointing upwards (stop signals), and subjects have to inhibit their motor responses. A tracking algorithm changes the time‐interval of 250ms between go‐signal and stop‐signal onsets in steps of 50ms according to each subject's performance, making sure the task is equally challenging and difficult for each individual, providing 50% successful and 50% failed inhibition trials. (See Figure 1c; [<reflink idref="bib30" id="ref44">30</reflink>], [<reflink idref="bib29" id="ref45">29</reflink>].) The dependent variable is the speed of the stopping process, the Stop signal reaction time (SSRT), calculated as the difference between MRT to go trials and the average delay of the stop signal (SSD). In the event‐related fMRI analysis, brain activation to the 50% successful stop trials are contrasted with the 50% of failed stop trials in order to control for attentional effects of the low frequency appearance of stop trials. Activation to successful go‐response trials is subtracted from activation to failed stop trials in order to control for brain activation related to motor response execution.</p> <p>Performance data were analysed using <emph>t</emph>‐tests.</p> <hd id="AN0036880247-6">fMRI image acquisition and analysis</hd> <p>Gradient‐echoplanar MR imaging (EPI) data were acquired on a GE Signa 1.5T Horizon LX System (General; Electric, Milwaukee, WI, USA) at the Maudsley Hospital, London. A quadrature birdcage headcoil was used for RF transmission and reception. In each of 16 non‐contiguous planes parallel to the anterior‐posterior commissure, 208 (Simon task), 152 (Switch task) and 196 (Stop task), T<subs>2</subs>*‐weighted MR images depicting BOLD (Blood Oxygen Level Dependent) contrast covering the whole brain were acquired with TE = 40ms, TR = 1.8 s for Simon and Stop tasks, 2.4 s for Switch task, flip angle = 90°, in‐plane resolution = 3.1 mm, slice thickness = 7 mm, slice‐skip = .7 mm.</p> <p>The method of analysis used, XBAM (Brain Activation Mapping; [<reflink idref="bib3" id="ref46">3</reflink>]; [<reflink idref="bib4" id="ref47">4</reflink>]; http://www.brainmap.co.uk), makes no normality assumptions as it uses median statistics to control outlier effects and permutation rather than normal theory‐based inference.</p> <p>After realignment to minimise motion‐related artefacts and smoothing using a Gaussian filter (FWHM 7.2 mm), responses to the experimental paradigms were then detected by time‐series analysis carried out for each individual subject, based on a wavelet‐based data resampling method for functional MRI data ([<reflink idref="bib4" id="ref48">4</reflink>]). Using rigid body and affine transformation, the individual maps were registered into Talairach standard space ([<reflink idref="bib33" id="ref49">33</reflink>]). A group brain activation map (GBAM) was then produced for each experimental condition and hypothesis testing was carried out at the cluster level, shown to give excellent cluster‐wise type I error control in structural and functional fMRI analysis ([<reflink idref="bib3" id="ref50">3</reflink>]; [<reflink idref="bib4" id="ref51">4</reflink>]). For each task, <1 false positive activated clusters was expected at a <emph>p</emph>‐value of <.05 at the voxel‐level and <.075 at the cluster‐level. ANOVA analysis for between‐group differences was calculated using randomisation‐based test for voxel or cluster‐wise differences as described in detail previously ([<reflink idref="bib4" id="ref52">4</reflink>]). For this particular group comparison, less than 1 false activated cluster was expected at a <emph>p</emph>‐value of <emph>p </emph>< .05 for voxel and <emph>p </emph>< .01 for cluster comparisons.</p> <hd id="AN0036880247-7">Results</hd> <p></p> <hd id="AN0036880247-8">Sample characteristics</hd> <p>There were no significant between‐group differences in age and performance IQ. As expected, there were significant group differences on the BDI‐II (Table 1).</p> <hd id="AN0036880247-9">Task performance</hd> <p>There were no significant group differences in any of the main task variables (Table 2).</p> <p>2  Performance data for adolescents with and without depression</p> <p> <ephtml> <table><thead valign="bottom"><tr><th>Task/Measure</th><th>Patients</th><th>Controls</th><th><italic>t</italic> (df)</th><th><italic>p</italic>‐value</th><th>Effect size</th></tr></thead><tbody valign="top"><tr><td>Simon task</td></tr><tr><td> Simon effect (ms)</td><td>97 (56)</td><td>94 (53)</td><td>−.180 (40)</td><td>.85</td><td>.05</td></tr><tr><td> Errors to Simon trials (%) </td><td>28 (15)</td><td>23 (14)</td><td>−1.169 (40)</td><td>.25</td><td>.33</td></tr><tr><td> Errors to congruent trials (%)</td><td>2 (2)</td><td>2 (2)</td><td>.642 (40)</td><td>.52</td><td>0</td></tr><tr><td>Switch task</td></tr><tr><td> Switch cost (ms)</td><td>75 (62)</td><td>110 (81)</td><td>1.580 (40)</td><td>.12</td><td>.49</td></tr><tr><td> Errors to switch trials (%)</td><td>6 (8)</td><td>4 (4)</td><td>−1.451 (40)</td><td>.15</td><td>.32</td></tr><tr><td>Stop task</td></tr><tr><td> Probability of inhibition (%)</td><td>50.6 (3)</td><td>50.5 (5)</td><td>−.023 (39)</td><td>.98</td><td>.02</td></tr><tr><td> SSRT (ms)</td><td>164 (110)</td><td>159 (57)</td><td>−.618 (39)</td><td>.93</td><td>.04</td></tr><tr><td> MRT (go) (ms)</td><td>525 (120)</td><td>669 (231)</td><td>2.531 (39)</td><td>.15</td><td>.78</td></tr></tbody></table> </ephtml> </p> <p>2 <emph>Note</emph>: Independent samples 2‐tailed <emph>t</emph>‐test for between‐group comparisons for the main task variables of the three tasks. <emph>P</emph>‐values were adjusted using the FDR.</p> <hd id="AN0036880247-10">Brain activation</hd> <p>All subjects were within acceptable limits for head movement (below 1.5 mm), and no significant group differences were observed in the extent of 3‐dimensional motion for the x,y,z rotation and translation during task performance.</p> <p>Within‐group brain activation clusters for the contrast of (a) incongruent–congruent trials for the Simon task, (b) switch‐repeat trials for the switch task, and (c) successful–failed stop trials and failed stop trials–go trials are reported in Table 3a–c.</p> <p>3  Brain areas of within‐group activations in patients and controls and of between‐group differences in activation for the relevant contrasts for the (a) Simon, (b) Switch and (c) Stop tasks</p> <p> <ephtml> <table><thead valign="bottom"><tr><th>Talairach coordinates</th><th valign="bottom">Brain region</th><th valign="bottom">BA</th><th valign="bottom">N<sup>o</sup> of Voxels</th><th valign="bottom"><italic>p</italic>‐value</th></tr><tr><th>x</th><th>y</th><th>z</th></tr></thead><tbody valign="top"><tr><td><bold>a) Simon: incongruent–congruent trials</bold></td></tr><tr><td><bold>Controls </bold></td></tr><tr><td>47</td><td>−60</td><td>−13</td><td>R temporal/ fusiform gyrus</td><td>37</td><td>90</td><td>.004</td></tr><tr><td>−50</td><td>7</td><td>−2</td><td>Left medial/ superior temporal gyrus</td><td>21/22</td><td>176</td><td>.001</td></tr><tr><td> 36</td><td>22</td><td>−2</td><td>R inferior frontal gyrus/insula/medial temporal gyrus</td><td>47/21/22</td><td>242</td><td>.000</td></tr><tr><td> 40</td><td>−74</td><td>20</td><td>R medial/inferior temporal gyrus, posterior cingulate</td><td>18/19/31</td><td>876</td><td>.000</td></tr><tr><td> 18</td><td>−63</td><td>42</td><td>Precuneus</td><td> 7</td><td>94</td><td>.000</td></tr><tr><td>−14</td><td>−81</td><td>−18</td><td>L cerebellum</td><td> </td><td>75</td><td>.000</td></tr><tr><td><bold>Patients</bold></td></tr><tr><td> 43</td><td>−52</td><td>−2</td><td>R inferior temporal gyrus</td><td>19</td><td>109</td><td>.001</td></tr><tr><td>−47</td><td>14</td><td>−2</td><td>L inferior frontal/ insula</td><td>22/47</td><td>91</td><td>.003</td></tr><tr><td>−36</td><td>−63</td><td>−24</td><td>L cerebellum/middle temporal gyrus</td><td>39</td><td>699</td><td>.000</td></tr><tr><td>  0</td><td>15</td><td>31</td><td>ACG</td><td>24/32</td><td>106</td><td>.000</td></tr><tr><td>−32</td><td>−51</td><td>42</td><td>L inferior parietal lobe</td><td>40</td><td>220</td><td>.000</td></tr><tr><td>  7</td><td>−70</td><td>−13</td><td>R cerebellum</td><td> </td><td>55</td><td>.000</td></tr><tr><td>  4</td><td>4</td><td>4</td><td>R caudate</td><td> </td><td>52</td><td>.000</td></tr><tr><td>  7</td><td>−7</td><td>9</td><td>Thalamus</td><td> </td><td>40</td><td>.000</td></tr><tr><td> 18</td><td>15</td><td>−2</td><td>Putamen</td><td> </td><td>37</td><td>.000</td></tr><tr><td><bold>Controls</bold><italic> </italic>> <bold>Patients</bold></td></tr><tr><td>50</td><td>11</td><td>31</td><td>R dorsolateral/inferior frontal gyrus</td><td> 9/44</td><td>67</td><td>.007</td></tr><tr><td>−7</td><td>−70</td><td>20</td><td>L & R Precuneus /Cuneus</td><td>31/18</td><td>169</td><td>.001</td></tr><tr><td>−22</td><td>−78</td><td>−13</td><td>L occipital lobe/cerebellum</td><td>19</td><td>73</td><td>.004</td></tr><tr><td><bold>b) Switch: Switch–repeat trials </bold></td></tr><tr><td><bold>Controls </bold></td></tr><tr><td>−36</td><td>−33</td><td>48</td><td>L inferior/superior parietal lobe</td><td> 7/40</td><td>257</td><td>.006</td></tr><tr><td>43</td><td>−26</td><td>42</td><td>R inferior parietal lobe/postcentral gyrus</td><td>40/2</td><td>213</td><td>.000</td></tr><tr><td>0</td><td>7</td><td>42</td><td>R ACG</td><td>24/32</td><td>86</td><td>.001</td></tr><tr><td>−4</td><td>−70</td><td>−2</td><td>L lingual gyrus</td><td>18</td><td>56</td><td>.006</td></tr><tr><td>−25</td><td>−4</td><td>4</td><td>L thalamus</td><td> </td><td>18</td><td>.041</td></tr><tr><td>25</td><td>4</td><td>−7</td><td>R putamen</td><td> </td><td>13</td><td>.040</td></tr><tr><td>−50</td><td>0</td><td>26</td><td>L inferior frontal gyrus/insula</td><td> 6/44</td><td>11</td><td>.030</td></tr><tr><td>4</td><td>−67</td><td>−13</td><td>R cerebellum</td><td> </td><td>28</td><td>.000</td></tr><tr><td><bold>Patients</bold></td></tr><tr><td>−40</td><td>−37</td><td>48</td><td>L inferior parietal lobe</td><td>40</td><td>177</td><td>.000</td></tr><tr><td>43</td><td>−26</td><td>37</td><td>R postcentral gyrus</td><td> </td><td>48</td><td>.004</td></tr><tr><td>4</td><td>−59</td><td>−2</td><td>R Cerebellum</td><td> </td><td>25</td><td>.027</td></tr><tr><td>−54</td><td>−22</td><td>20</td><td>L postcentral gyrus</td><td>40</td><td>27</td><td>.004</td></tr><tr><td>−18</td><td>−67</td><td>53</td><td>L precuneus/superior parietal lobe</td><td> 7</td><td>21</td><td>.018</td></tr><tr><td><bold>Controls</bold><italic> </italic>> <bold>Patients</bold></td></tr><tr><td>36</td><td>26</td><td>−2</td><td>R inferior frontal/insula/putamen/ superior temporal/parietal</td><td>45/47/22/40</td><td>243</td><td>.001</td></tr><tr><td>−7</td><td>−11</td><td>48</td><td>L ACG/SMA</td><td>24/32/6</td><td>134</td><td>.001</td></tr><tr><td>−40</td><td>15</td><td>−24</td><td>L superior temporal gyrus/insula/putamen</td><td>38</td><td>84</td><td>.009</td></tr><tr><td><bold>c) Stop task</bold></td></tr><tr><td><bold>Successful–failed inhibition trials</bold></td></tr><tr><td>Controls</td></tr><tr><td>43</td><td>26</td><td>26</td><td>R mesial/dorsolateral/inferior frontal cortex</td><td> 9/46</td><td>53</td><td>.000</td></tr><tr><td>−40</td><td>−63</td><td>−7</td><td>L medial occipital gyrus</td><td>19/37</td><td>16</td><td>.002</td></tr><tr><td>11</td><td>−14</td><td>9</td><td>R thalamus</td><td> </td><td>23</td><td>.001</td></tr><tr><td>40</td><td>44</td><td>15</td><td>DLPFC</td><td>46</td><td>12</td><td>.003</td></tr><tr><td>43</td><td>−40</td><td>9</td><td>R superior temporal gyrus</td><td>22</td><td>23</td><td>.001</td></tr><tr><td>46</td><td>−51</td><td>42</td><td>R inferior parietal lobe</td><td>40</td><td>13</td><td>.008</td></tr><tr><td>14</td><td>55</td><td>20</td><td>R medial frontal gyris</td><td>10</td><td>10</td><td>.007</td></tr><tr><td><bold>Patients</bold></td></tr><tr><td>−36</td><td>−59</td><td>−24</td><td>L cerebellum</td><td> </td><td>29</td><td>.000</td></tr><tr><td>43</td><td>7</td><td>37</td><td>R DLPFC/insula</td><td> 9</td><td>19</td><td>.002</td></tr><tr><td>18</td><td>11</td><td>−18</td><td>R inferior frontal gyrus</td><td>47</td><td>18</td><td>.009</td></tr><tr><td>43</td><td>−48</td><td>42</td><td>R inferior parietal lobe</td><td>40</td><td>17</td><td>.004</td></tr><tr><td>7</td><td>−37</td><td>4</td><td>R thalamus</td><td> </td><td>12</td><td>.005</td></tr><tr><td><bold>Controls</bold><italic> </italic>> <bold>Patients</bold></td></tr><tr><td>43</td><td>30</td><td>26</td><td>R DLPFC</td><td> 9/46</td><td>26</td><td>.008</td></tr><tr><td>25</td><td>−60</td><td>48</td><td>R Superior parietal lobe</td><td> 7</td><td>24</td><td>.008</td></tr><tr><td><bold>Failed inhibition–go trials </bold></td></tr><tr><td><bold>Controls </bold></td></tr><tr><td>−54</td><td>−37</td><td>31</td><td>L inferior parietal lobe</td><td>40</td><td>419</td><td>.000</td></tr><tr><td>0</td><td>30</td><td>26</td><td>ACG/mesial frontal cortex</td><td>24/32/9/10</td><td>374</td><td>.000</td></tr><tr><td>47</td><td>−63</td><td>−7</td><td>R medial temporal,/medial occipital gyri</td><td>21/37/19</td><td>317</td><td>.000</td></tr><tr><td>43</td><td>26</td><td>−13</td><td>R inferior/dorsolateral frontal gyrus</td><td>47</td><td>253</td><td>.000</td></tr><tr><td>−36</td><td>18</td><td>4</td><td>L insula</td><td> </td><td>161</td><td>.001</td></tr><tr><td>29</td><td>−67</td><td>−40</td><td>Cerebellum</td><td> </td><td>110</td><td>.004</td></tr><tr><td><bold>Patients</bold></td></tr><tr><td>0</td><td>22</td><td>31</td><td>ACG/mesial frontal gyrus</td><td>32/9</td><td>363</td><td>.000</td></tr><tr><td>54</td><td>−48</td><td>15</td><td>R superior temporal gyrus</td><td>22</td><td>122</td><td>.002</td></tr><tr><td>−47</td><td>18</td><td>−13</td><td>L inferior frontal gyrus</td><t d>47</td><td>103</td><td>.001</td></tr><tr><td>47</td><td>18</td><td>−13</td><td>R inferior frontal gyrus</td><td>47</td><td>101</td><td>.001</td></tr><tr><td>−50</td><td>−48</td><td>26</td><td>L inferior parietal lobe</td><td>40</td><td>88</td><td>.000</td></tr><tr><td>−25</td><td>48</td><td>26</td><td>Mesial frontal gyrus/insula</td><td> 9/10</td><td>73</td><td>.003</td></tr><tr><td><bold>Controls</bold><italic> </italic>> <bold>Depression</bold></td></tr><tr><td>Stop: Failed inhibition–go trials</td><td /></tr><tr><td>0</td><td>33</td><td>20</td><td>Anterior cingulate/mesial frontal </td><td>24/32/8</td><td>59</td><td>.004</td></tr><tr><td>Depression<italic> </italic>> Controls</td><td /></tr><tr><td>No significant differences in any condition</td><td /></tr></tbody></table> </ephtml> </p> <p>3 ANOVAS for between‐group comparisons were conducted at <emph>p </emph>< .05 for voxel and <emph>p </emph>< .01 for cluster comparisons.</p> <p> <bold>Simon task. </bold> ANOVA revealed significantly reduced activation in patients compared to controls in right DLPFC reaching into inferior frontal gyrus, left and right precuneus and cuneus and in the left occipital lobe bordering the cerebellum (Table 3a, Figures 2a and 3a).</p> <p>Graph: 2 Schematic illustration of the (a) Simon, (b) Switch task and (c) Stop task. Brain regions of significant increased activation in control adolescents compared to adolescents with MDD (at a cluster‐level comparison of p < .01) for the (a) Simon (b) Switch (c) Stop task (for successful inhibition and inhibition failure). Talairach coordinates are indicated for slice distance (in mm) from the intercomissural line. The right side of the image corresponds to the right side of the brain</p> <p>Graph: 3 The magnitude of the BOLD response for adolescents with MDD and controls in the brain activation clusters of ANOVA group differences for the (a) Simon, (b) Switch and (c) Stop task: (For successful inhibition and inhibition failures)</p> <p> <bold>Switch task. </bold> ANOVA showed reduced brain activation in patients compared to controls bilaterally in clusters of inferior and ventrolateral prefrontal cortex reaching in both sides into the superior temporal lobe and deep into the insula and putamen. In the right hemisphere the cluster included inferior parietal cortex. Further reduced activation in patients compared to controls was observed in ACG, reaching caudally into the supplementary motor cortex (SMA) (Table 3b, Figures 2b, 3b).</p> <p> <bold>Stop task. </bold> ANOVA comparison for the contrast of successful stop–failed stop trials showed reduced brain activation in patients compared to controls in right DLPFC bordering IFC and in right superior parietal lobe (Table 3c, Figures 2c, 3c).</p> <p>ANOVA for the contrast of failed stop trials–go trials showed reduced activation in patients compared to controls in ACG, reaching dorsally into mesial frontal cortex (Table 3c, Figures 2c, 3c).</p> <p>There were no areas of increased brain activation in depressed patients compared to the control participants on any of the tasks.</p> <p> <bold>Gender effects. </bold> There was no significant group by gender interaction effects on any of the brain activation differences.</p> <hd id="AN0036880247-11">Cortisol secretion</hd> <p>There were no significant group differences in pre‐ and post‐scan salivary cortisol levels (Table 1) and in the delta cortisol increase (used as a measure of stress reactivity) between pre‐ and post scan (<emph>F</emph> = 2.207, df = 1,34, <emph>p </emph>> .05).</p> <hd id="AN0036880247-12">Discussion</hd> <p>Consistent with our hypothesis, medication‐naïve adolescents with a first‐episode of depression, compared to controls, demonstrated reduced brain activation in task‐relevant areas of lateral IFC, DLPFC, ACG and striatal brain regions during three tasks of EF, suggestive of abnormalities in task‐specific fronto‐striatal and fronto‐cingulate pathways. Further reductions in patients compared to controls were observed in parietal (Switch, Stop) and temporal brain areas (Switch).</p> <p>Task performance in patients was comparable to that of controls, which is consistent with some previous neuropsychological studies on paediatric MDD ([<reflink idref="bib6" id="ref53">6</reflink>]; [<reflink idref="bib11" id="ref54">11</reflink>]) but not others ([<reflink idref="bib14" id="ref55">14</reflink>]). However, patients made slightly more errors in the Simon and Switch tasks, with low to medium effect sizes (see Table 2), suggesting that larger sample sizes might potentially have resulted in behavioural differences. Our findings of brain activation differences, despite intact behavioural performance, suggest that brain function in paediatric MDD is more sensitive to reveal abnormalities than neuropsychological performance. The superior sensitivity of fMRI to capture physiological change not manifested in behavioural performance has been reported in other child psychiatric imaging studies (e.g., [<reflink idref="bib30" id="ref56">30</reflink>]; [<reflink idref="bib32" id="ref57">32</reflink>]).</p> <p>In all three tasks, adolescents with depression showed reduced activation compared to controls in right IFC and DLPFC. In the Stop and Simon tasks, the location was in DLPFC, bordering caudally IFC, an area of typical activation in these tasks in adolescents ([<reflink idref="bib29" id="ref58">29</reflink>]; [<reflink idref="bib31" id="ref59">31</reflink>]; [<reflink idref="bib32" id="ref60">32</reflink>]). In the Switch task, which elicits bilateral orbito‐frontal, striatal and temporal activation in adolescents ([<reflink idref="bib31" id="ref61">31</reflink>]; [<reflink idref="bib32" id="ref62">32</reflink>]), the under‐activation was more ventral, reaching from lateral orbital to IFC. In addition, there was reduced activation in patients compared to controls in bilateral temporal regions that reached deep into insula and putamen in both hemispheres. These findings suggest that paediatric MDD is associated with abnormal function in lateral prefrontal cortex and ACG and potentially interconnected striatal and temporo‐parietal regions during tasks of EF. The exact localisation in the prefrontal cortex, however, appears to be task‐dependent.</p> <p>The findings of abnormalities in lateral prefrontal function are in line with evidence for prefrontal structural abnormalities in paediatric MDD ([<reflink idref="bib20" id="ref63">20</reflink>]) and structural, metabolic and functional abnormalities in lateral prefrontal regions in adult MDD ([<reflink idref="bib26" id="ref64">26</reflink>]). During the Switch task, activation differences were also observed in the orbitofrontal cortex. The orbitofrontal cortex has previously been reported to be reduced in activation in paediatric depression during a reward‐related decision‐making task, tapping into 'hot', reward‐related motivational EF ([<reflink idref="bib7" id="ref65">7</reflink>]). The orbitofrontal cortex is part of the paralimbic system that controls motivation and emotions and a functional abnormality in this region may underlie both poor top‐down emotional and cognitive control in paediatric MDD.</p> <p>The reduced activation in patients in the putamen during the Switch task, in addition to the fronto‐cingulate abnormality, supports our hypothesis of fronto‐striatal abnormalities in paediatric MDD during tasks of EF. Functional and metabolic reductions have been found in paediatric MDD in the basal ganglia, albeit in the caudate during rest ([<reflink idref="bib10" id="ref66">10</reflink>]) and during reward‐related decision making ([<reflink idref="bib7" id="ref67">7</reflink>]). Our findings thus extend the evidence for basal ganglia abnormalities in paediatric MDD. Different parts of the basal ganglia may be abnormal in paediatric MDD depending on the type of cognitive control required.</p> <p>In the Stop task, activation in the more cognitive rostral, pregenual part of ACG was reduced in patients compared to controls, while activity in the caudal part was reduced in the Switch task. ACG is consistently activated during EF tasks in healthy adults and adolescents and has been suggested to play a role in cognitive control, performance monitoring, and error‐detection ([<reflink idref="bib29" id="ref68">29</reflink>]; [<reflink idref="bib31" id="ref69">31</reflink>]). The reduced activation of ACG in paediatric MDD during inhibition failures, in particular, suggests abnormalities in the neural correlates of error‐detection and performance monitoring. Reduced ACG activation has previously been observed in paediatric MDD during reward outcome evaluation, suggesting a lack of interest for outcomes associated with low motivation ([<reflink idref="bib7" id="ref70">7</reflink>]). The ACG is a key area of abnormality, metabolically, structurally and functionally in paediatric MDD ([<reflink idref="bib7" id="ref71">7</reflink>]). Findings of ACG abnormalities in paediatric MDD in the context of cognitive control could be the neural basis for the poor cognitive control over negative affect and motivation.</p> <p>During the Stop and Simon tasks, we observed additional abnormalities in temporal (Switch) and superior and inferior parietal lobes (Stop, Switch). Abnormal structure of the temporal lobes has been reported in paediatric MDD ([<reflink idref="bib18" id="ref72">18</reflink>]). The reduced inferior fronto‐parietal activation during the Stop and Simon tasks is in line with findings of reduced ERPs in the inferior frontal‐temporo‐parietal regions during increased sensitivity to interference from distraction in children with MDD ([<reflink idref="bib15" id="ref73">15</reflink>]). The parietal lobes form important integrative parts of fronto‐striato‐parietal networks for attention control and the reduced activation could be the neural basis for attention deficits observed in behaviour and cognition in paediatric MDD ([<reflink idref="bib14" id="ref74">14</reflink>]).</p> <p>In our study, prefrontal abnormalities were right hemispheric with, however, bilateral temporal, insula and striatal abnormalities. Given that inhibitory functions are lateralised to the right frontal lobes ([<reflink idref="bib29" id="ref75">29</reflink>]; [<reflink idref="bib31" id="ref76">31</reflink>]), supported in our study by a predominantly right hemispheric frontal activation in controls in most tasks, the laterality findings may suggest that abnormalities in MDD are task‐specific and dependent on the laterality (and location) of activation triggered by the task, rather than being a disorder‐specific lateralisation of abnormalities in one hemisphere.</p> <p>We found no group differences in stress‐related effects of fMRI procedures, as indicated by salivary cortisol levels, demonstrating that the functional brain abnormalities observed in this patient group are not confounded by group differences in stress levels.</p> <p>For all paradigms, activation to target functions was contrasted with that to lower‐level cognitive rather than resting conditions. fMRI contrasts are relative, and we cannot exclude that group differences at the lower‐level cognitive conditions could have influenced the findings.</p> <p>No sex by group interaction effects were observed. The recruitment of equal numbers of boys and girls for this study, however, may have limited external validity given that depression is reported to be more common in females during adolescence ([<reflink idref="bib5" id="ref77">5</reflink>]).</p> <p>This study shows for the first time that medication‐naïve adolescents with MDD have functional abnormalities in task‐specific frontal, striatal, cingulate and temporo‐parietal brain regions during tasks of cognitive control. The findings suggest that functional abnormalities in these brain regions observed in adult MDD are likely to develop early in childhood and are inherent to the pathogenesis of MDD.</p> <hd id="AN0036880247-13">Acknowledgements</hd> <p>This work was supported by a grant of the PPP Foundation to K.R. 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  Label: Title
  Group: Ti
  Data: Reduced Activation in Lateral Prefrontal Cortex and Anterior Cingulate during Attention and Cognitive Control Functions in Medication-Naive Adolescents with Depression Compared to Controls
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  Label: Language
  Group: Lang
  Data: English
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Halari%2C+Rozmin%22">Halari, Rozmin</searchLink><br /><searchLink fieldCode="AR" term="%22Simic%2C+Mima%22">Simic, Mima</searchLink><br /><searchLink fieldCode="AR" term="%22Pariante%2C+Carmine+M%2E%22">Pariante, Carmine M.</searchLink>
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  Label: Source
  Group: Src
  Data: <searchLink fieldCode="SO" term="%22Journal+of+Child+Psychology+and+Psychiatry%22"><i>Journal of Child Psychology and Psychiatry</i></searchLink>. Mar 2009 50(3):307-316.
– Name: Avail
  Label: Availability
  Group: Avail
  Data: Blackwell Publishing. 350 Main Street, Malden, MA 02148. Tel: 800-835-6770; Tel: 781-388-8599; Fax: 781-388-8232; e-mail: customerservices@blackwellpublishing.com; Web site: http://www.blackwellpublishing.com/jnl_default.asp
– Name: PeerReviewed
  Label: Peer Reviewed
  Group: SrcInfo
  Data: Y
– Name: PhysDesc
  Label: Physical Description
  Group: PhysDesc
  Data: PDF
– Name: Pages
  Label: Page Count
  Group: Src
  Data: 10
– Name: DatePubCY
  Label: Publication Date
  Group: Date
  Data: 2009
– Name: TypeDocument
  Label: Document Type
  Group: TypDoc
  Data: Journal Articles<br />Reports - Research
– Name: Subject
  Label: Descriptors
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Negative+Attitudes%22">Negative Attitudes</searchLink><br /><searchLink fieldCode="DE" term="%22Attention%22">Attention</searchLink><br /><searchLink fieldCode="DE" term="%22Pathology%22">Pathology</searchLink><br /><searchLink fieldCode="DE" term="%22Adolescents%22">Adolescents</searchLink><br /><searchLink fieldCode="DE" term="%22Brain%22">Brain</searchLink><br /><searchLink fieldCode="DE" term="%22Depression+%28Psychology%29%22">Depression (Psychology)</searchLink><br /><searchLink fieldCode="DE" term="%22Brain+Hemisphere+Functions%22">Brain Hemisphere Functions</searchLink><br /><searchLink fieldCode="DE" term="%22Cognitive+Processes%22">Cognitive Processes</searchLink><br /><searchLink fieldCode="DE" term="%22Neurological+Organization%22">Neurological Organization</searchLink><br /><searchLink fieldCode="DE" term="%22Child+Health%22">Child Health</searchLink><br /><searchLink fieldCode="DE" term="%22Diagnostic+Tests%22">Diagnostic Tests</searchLink><br /><searchLink fieldCode="DE" term="%22Comparative+Analysis%22">Comparative Analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Responses%22">Responses</searchLink>
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1111/j.1469-7610.2008.01972.x
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 0021-9630
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: There is increasing recognition of major depressive disorder (MDD) in adolescence. In adult MDD, abnormalities of fronto-striatal and fronto-cingulate circuitries mediating cognitive control functions have been implicated in the pathogenesis and been related to problems with controlling negative thoughts. No neuroimaging studies of cognitive control functions, however, exist in paediatric depression. This study investigated whether medication-naive adolescents with MDD show abnormal brain activation of fronto-striatal and fronto-cingulate networks when performing tasks of attentional and cognitive control. Methods: Event-related functional magnetic resonance imaging was used to compare brain activation between 21 medication-naive adolescents with a first-episode of MDD aged 14-17 years and 21 healthy adolescents, matched for handedness, age, sex, demographics and IQ. Activation paradigms were tasks of selective attention (Simon task), attentional switching (Switch task), and motor response inhibition and error detection (Stop task). Results: In all three tasks, adolescents with depression compared to healthy controls demonstrated reduced activation in task-relevant right dorsolateral (DLPFC), inferior prefrontal cortex (IFC) and anterior cingulate gyrus (ACG). Additional areas of relatively reduced activation were in the parietal lobes during the Stop and Switch tasks, putamen, insula and temporal lobes during the Switch task and precuneus during the Simon task. Conclusions: This study shows first evidence that medication-naive adolescents with MDD are characterised by abnormal function in ACG and right lateral prefrontal cortex during tasks of attention and performance monitoring, suggesting an early pathogenesis of these functional abnormalities attributed to MDD.
– Name: AbstractInfo
  Label: Abstractor
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  Data: As Provided
– Name: DateEntry
  Label: Entry Date
  Group: Date
  Data: 2009
– Name: AN
  Label: Accession Number
  Group: ID
  Data: EJ832583
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=eric&AN=EJ832583
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1111/j.1469-7610.2008.01972.x
    Languages:
      – Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 10
        StartPage: 307
    Subjects:
      – SubjectFull: Negative Attitudes
        Type: general
      – SubjectFull: Attention
        Type: general
      – SubjectFull: Pathology
        Type: general
      – SubjectFull: Adolescents
        Type: general
      – SubjectFull: Brain
        Type: general
      – SubjectFull: Depression (Psychology)
        Type: general
      – SubjectFull: Brain Hemisphere Functions
        Type: general
      – SubjectFull: Cognitive Processes
        Type: general
      – SubjectFull: Neurological Organization
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      – SubjectFull: Child Health
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      – SubjectFull: Diagnostic Tests
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      – SubjectFull: Comparative Analysis
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      – SubjectFull: Responses
        Type: general
    Titles:
      – TitleFull: Reduced Activation in Lateral Prefrontal Cortex and Anterior Cingulate during Attention and Cognitive Control Functions in Medication-Naive Adolescents with Depression Compared to Controls
        Type: main
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            NameFull: Halari, Rozmin
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            NameFull: Simic, Mima
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            NameFull: Pariante, Carmine M.
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              Type: published
              Y: 2009
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              Value: 50
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              Value: 3
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            – TitleFull: Journal of Child Psychology and Psychiatry
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