Mariana Rovira

Global and regional gray matter reductions in ADHD: A voxel-based morphometric study

Attention deficit hyperactivity disorder (ADHD) is a developmental disorder characterized by inattentiveness, motor hyperactivity and impulsivity. According to neuroimaging data, the neural substrate underlying ADHD seems to involve fronto-striatal circuits and the cerebellum. However, there are important discrepancies between various studies, probably due to the use of different techniques. The aim of this study is to examine cerebral gray (GM) and white (WM) matter abnormalities in a group of ADHD children using a voxel-based morphometry protocol. The sample consisted of 25 children/adolescents with DSM-IV TR diagnosis of ADHD (medicated, aged 6-16 years) who were compared with 25 healthy volunteer children/adolescents. ADHD brains on an average showed a global volume decrease of 5.4% as compared to controls. Additionally, there were regionally specific effects in the left fronto-parietal areas (left motor, premotor and somatosensory cortex), left cingulate cortex (anterior/middle/posterior cingulate), parietal lobe (precuneus bilaterally), temporal cortices (right middle temporal gyrus, left parahippocampal gyrus), and the cerebellum (bilateral posterior). There were no differences in WM volume between ADHD children and control subjects. The results are consistent with previous studies that used different techniques, and may represent a possible neural basis for some of the motor and attentional deficits commonly found in ADHD.

Pediatric OCD structural brain deficits in conflict monitoring circuits : A voxel-based morphometry study

The aim of this study is to use a voxel-based morphometry protocol to compare the brains of 18 children with obsessive-compulsive disorder (OCD) with those of a healthy group matched for gender and handedness. Images were acquired with a 1.5-T MRI scanner, spatially normalized, and segmented with an optimized voxel-based morphometry protocol. OCD children presented a 5.93% reduction of gray matter (GM) total volume in comparison with control brains. We identified OCD brain volume reductions in regions that have been extensively related to action monitoring and error signaling processes. Specifically, we found decreased bilateral GM in frontal (significant after Family Wise Error (FEW), multiple comparisons correction) and cingulate regions as well as decreased white matter (WM) in bilateral frontal and right parietal (p<0.001 uncorrected). Additionally, we found a negative correlation between symptom severity and bilateral hippocampal GM-volume (p<0.001uncorrected) as well as a positive correlation between age and GM left caudate volume (p=0.037 FWE small volume corrected) in the OCD group. As a conclusion, our results point to conflict monitoring structural brain regions as primary deficits in pediatric OCD, and to striatal abnormalities as age-related deficits.

Ventro-Striatal Reductions Underpin Symptoms of Hyperactivity and Impulsivity in Attention-Deficit/Hyperactivity Disorder

BACKGROUND Models of attention-deficit/hyperactivity disorder (ADHD) classically emphasize the relevance of executive processes and, recently, reward circuits. The neural bases of reward processes have barely been explored in relation to this disorder, in contrast to extensive neuroimaging studies that examine executive functions in patients with ADHD. To our knowledge, no previous studies have analyzed the volume of the ventral striatum, a key region for reward processes in ADHD children. METHODS We used a manual region-of-interest approach to examine whether there were volumetric differences in the ventral striatum of ADHD children. Forty-two children/adolescents with ADHD (ages 6-18), and 42 healthy control subjects matched on age, gender, and handedness were selected for the study. RESULTS The ADHD children presented significant reductions in both right and left ventro-striatal volumes (t = 3.290, p = .001; and t = 3.486, p = .001, respectively). In addition, we found that the volume of the right ventral striatum negatively correlated with maternal ratings of hyperactivity/impulsivity (r = -.503, p = .003). CONCLUSIONS Our study provides neuroanatomical evidence of alterations in the ventral striatum of ADHD children. These findings coincide with previous explicative models as well as with recent reports in behavioral and functional neuroimaging studies. Furthermore, the negative correlations we observed strongly uphold the relation between the ventral striatum and symptoms of hyperactivity/impulsivity.

An independent components and functional connectivity analysis of resting state fMRI data points to neural network dysregulation in adult ADHD

Spontaneous fluctuations can be measured in the brain that reflect dissociable functional networks oscillating at synchronized frequencies, such as the default mode network (DMN). In contrast to its diametrically opposed task‐positive counterpart, the DMN predominantly signals during a state of rest, and inappropriate regulation of this network has been associated with inattention, a core characteristic of attention‐deficit/hyperactivity disorder (ADHD). To examine whether abnormalities can be identified in the DMN component of patients with ADHD, we applied an independent components analysis to resting state functional magnetic resonance imaging data acquired from 22 male medication‐naïve adults with ADHD and 23 neurotypical individuals. We observed a stronger coherence of the left dorsolateral prefrontal cortex (dlPFC) with the DMN component in patients with ADHD which correlated with measures of selective attention. The increased left dlPFC‐DMN coherence also surfaced in a whole‐brain replication analysis involving an independent sample of 9 medication‐naïve adult patients and 9 controls. In addition, a post hoc seed‐to‐voxel functional connectivity analysis using the dlPFC as a seed region to further examine this regions suggested connectivity differences uncovered a higher temporal coherence with various other neural networks and confirmed a reduced anticorrelation with the DMN. These results point to a more diffuse connectivity between functional networks in patients with ADHD. Moreover, our findings suggest that state‐inappropriate neural activity in ADHD is not confined to DMN intrusion during attention‐demanding contexts, but also surfaces as an insufficient suppression of dlPFC signaling in relation to DMN activity during rest. Together with previous findings, these results point to a general dysfunction in the orthogonality of functional networks. Hum Brain Mapp 35:1261–1272, 2014.

Response inhibition and reward anticipation in medication-naïve adults with attention-deficit/hyperactivity disorder: a within-subject case-control neuroimaging study.

Background: Previous research suggests that ADHD patients are characterized by both reduced activity in the inferior frontal gyrus (IFG) during response inhibition tasks (such as the Go‐NoGo task), and reduced activity in the ventral striatum during reward anticipation tasks (such as the Monetary‐Incentive‐Delay [MID] task). However, no prior research has applied either of these paradigms in medication‐naïve adults with ADHD, nor have these been implemented in an intrasubject manner. Methods: The sample consisted of 19 medication‐naïve adults with ADHD and 19 control subjects. Main group analyses were based on individually defined regions of interest: the IFG and the VStr for the Go‐NoGo and the MID task respectively. In addition, we analyzed the correlation between the two measures, as well as between these measures and the clinical symptoms of ADHD. Results: We observed reduced bilateral VStr activity in adults with ADHD during reward anticipation. No differences were detected in IFG activation on the Go‐NoGo paradigm. Correlation analyses suggest that the two tasks are independent at a neural level, but are related behaviorally in terms of the variability of the performance reaction time. Activity in the bilateral VStr but not in the IFG was associated negatively with symptoms of hyperactivity/impulsivity. Conclusions: Results underline the implication of the reward system in ADHD adult pathophysiology and suggest that frontal abnormalities during response inhibition performance may not be such a pivotal aspect of the phenotype in adulthood. In addition, our findings point toward response variability as a core feature of the disorder. Hum Brain Mapp 33:2350–2361, 2012.

Gray matter volume deficits and correlation with insight and negative symptoms in first-psychotic-episode subjects

Bergé D, Carmona S, Rovira M, Bulbena A, Salgado P, Vilarroya O. Gray matter volume deficits and correlation with insight and negative symptoms in first‐psychotic‐episode subjects.

Neural correlates of impaired emotional discrimination in borderline personality disorder: An fMRI study

A common approach to study neuronal aspects of emotional reactivity of borderline personality disorder (BPD) is to study the brain response to emotional faces with functional magnetic resonance imaging (fMRI). 10 BPD patients and 10 matched controls were submitted to an emotional discrimination task in which subjects had to identify an emotional face from a neutral face while fMRI data was acquired. BPD patients made more mistakes than controls in the discrimination task when negative faces were involved. The emotional discrimination task activated brain areas that are known to participate in processing of emotional faces (fusiform gyrus, insula and amygdala) regardless of the psychiatric condition. Additionally, BPD showed higher activation than controls in the middle and inferior temporal cortical areas, brain areas that participate in the processing of face features that carry emotional value. Furthermore, activity at this site correlated with impulsivity score in the Zuckerman-Kuhlman Personality Questionnaire. Our findings may be related to cognitive impairment that may be characteristic of the disorder.

Enhanced neural activity in frontal and cerebellar circuits after cognitive training in children with attention-deficit/hyperactivity disorder.

The brain is a plastic entity that can undergo dynamic changes throughout the lifespan as a result of training. Attention‐deficit/hyperactivity disorder (ADHD) is commonly treated with psychostimulant medication, and the prevalence of ADHD medication prescription is a topic of heated scientific debate. In addition, cognitive training is frequently provided to patients with ADHD. Although psychostimulant effects have been thoroughly investigated, no previous studies have assessed the neural effects of cognitive training in ADHD. We applied fMRI‐paradigms of response inhibition and selective attention to chart the effects of a 10‐day cognitive training program in 19 unmedicated ADHD children receiving either cognitive or control training. The two resulting longitudinal datasets were analyzed using whole‐brain random‐effects general linear models. Although we observed no increases of activity in the control group, both fMRI‐datasets revealed enhanced activity after cognitive training in neural structures closely related to ADHD pathophysiology. On the inhibition paradigm, our results indicated increases in orbitofrontal, superior frontal, middle temporal, and inferior frontal cortex. The attentional task was characterized by increased activity in the cerebellum, which correlated with improvement on in‐scanner measures of attention. Our findings provide preliminary evidence that cognitive training enhances activity in neural structures typically affected by the disorder. Similar results have been obtained following methylphenidate administration, suggesting that training of cognitive functions may mimic the effects of psychostimulant medication on the brain. These findings postulate a neural account for the potency of cognitive training in ADHD, and hold clinical implications, supporting the inclusion of training programs in standard ADHD‐treatment. Hum Brain Mapp, 2010.

The functional neuroanatomy of blood-injection-injury phobia: a comparison with spider phobics and healthy controls

BACKGROUND Most neuroimaging studies of specific phobia have investigated the animal subtype. The blood-injection-injury (BII) subtype is characterized by a unique biphasic psychophysiological response, which could suggest a distinct neural substrate, but direct comparisons between phobia types are lacking. METHOD This study compared the neural responses during the presentation of phobia-specific stimuli in 12 BII phobics, 14 spider (SP) phobics and 14 healthy controls using functional magnetic resonance imaging (fMRI). RESULTS Subjective ratings showed that the experimental paradigm produced the desired symptom-specific effects. As in many previous studies, when viewing spider-related stimuli, SP phobics showed increased activation in dorsal anterior cingulate and anterior insula, compared to BII phobics and healthy controls. However, when viewing images of blood-injection-injuries, participants with BII phobia mainly showed increased activation in the thalamus and visual/attention areas (occipito-temporo-parietal cortex), compared with the other two groups. The degree of provoked anxiety and disgust by phobia-relevant images was strongly associated with activation in several common regions across the two phobia groups (thalamus, cerebellum, occipito-temporal regions) but only correlated with activation in the dorsal anterior cingulate gyrus and the anterior insula in the SP phobics. CONCLUSIONS These results suggest partially distinct neurobiological substrates of animal and BII phobias and support their current classification as two distinct subtypes in the DSM-IV-TR. Further research is needed to better understand the precise neurobiological mechanisms in BII phobia and particularly the fainting response.

Differential abnormalities of the head and body of the caudate nucleus in attention deficit-hyperactivity disorder.

The aim of the study is to present a new method for the segmentation of the caudate nucleus and use it to compare the caudate heads and bodies of an attention deficit-hyperactivity disorder (ADHD) group with those of a control group. We used a 1.5-T system to acquire magnetic resonance brain scans from 39 children with ADHD, as defined by DSM-IV TR, and 39 age, handedness and IQ matched controls. The new method for caudate head and body segmentation was applied to obtain semi-automatic volumes and asymmetric patterns. Bilateral volumetric measures of the head, body, and head-body of the caudate nuclei were compared within groups and between ADHD and control groups. Although the group factor was not significant, there were first and second order interactions. The analysis of simple effects showed that the right body and right head+body of the ADHD group was significantly smaller than in the control group, although the ADHD right caudate head was bigger. No ADHD within-group caudate differences were found. Controls showed a significantly larger left caudate head and a significantly bigger caudate right body and right head+body. Our new method for segmenting the caudate nucleus detected differential abnormalities of the right caudate head and body in the ADHD group, explaining previous heterogeneous findings in the literature.