Pregnancy and adolescence entail similar neuroanatomical adaptations: A comparative analysis of cerebral morphometric changes.

Mapping the impact of pregnancy on the human brain is essential for understanding the neurobiology of maternal caregiving. Recently, we found that pregnancy leads to a long-lasting reduction in cerebral gray matter volume. However, the morphometric features behind the volumetric reductions remain unexplored. Furthermore, the similarity between these reductions and those occurring during adolescence, another hormonally similar transitional period of life, still needs to be investigated. Here, we used surface-based methods to analyze the longitudinal magnetic resonance imaging data of a group of 25 first-time mothers (before and after pregnancy) and compare them to those of a group of 25 female adolescents (during 2 years of pubertal development). For both first-time mothers and adolescent girls, a monthly rate of volumetric reductions of 0.09 mm3 was observed. In both cases, these reductions were accompanied by decreases in cortical thickness, surface area, local gyrification index, sulcal depth, and sulcal length, as well as increases in sulcal width. In fact, the changes associated with pregnancy did not differ from those that characterize the transition during adolescence in any of these measures. Our findings are consistent with the notion that the brain morphometric changes associated with pregnancy and adolescence reflect similar hormonally primed biological processes.

Pregnancy leads to long-lasting changes in human brain structure.

Pregnancy involves radical hormone surges and biological adaptations. However, the effects of pregnancy on the human brain are virtually unknown. Here we show, using a prospective ('pre'-'post' pregnancy) study involving first-time mothers and fathers and nulliparous control groups, that pregnancy renders substantial changes in brain structure, primarily reductions in gray matter (GM) volume in regions subserving social cognition. The changes were selective for the mothers and highly consistent, correctly classifying all women as having undergone pregnancy or not in-between sessions. Interestingly, the volume reductions showed a substantial overlap with brain regions responding to the women's babies postpartum. Furthermore, the GM volume changes of pregnancy predicted measures of postpartum maternal attachment, suggestive of an adaptive process serving the transition into motherhood. Another follow-up session showed that the GM reductions endured for at least 2 years post-pregnancy. Our data provide the first evidence that pregnancy confers long-lasting changes in a woman's brain.

Stimulant drugs trigger transient volumetric changes in the human ventral striatum.

The ventral striatum (VStr) integrates mesolimbic dopaminergic and corticolimbic glutamatergic afferents and forms an essential component of the neural circuitry regulating impulsive behaviour. This structure represents a primary target of psychostimulant medication, the first-choice treatment for attention-deficit/hyperactivity disorder (ADHD), and is biochemically modified by these drugs in animals. However, the effects of stimulants on the human VStr remain to be determined. We acquired anatomical brain MRI scans from 23 never-medicated adult patients with ADHD, 31 adult patients with a history of stimulant treatment and 32 control subjects, and VStr volumes were determined using individual rater-blinded region of interest delineation on high-resolution neuroanatomical scans. Furthermore, we also extracted VStr volumes before and after methylphenidate treatment in a subsample of the medication-naïve adult patients as well as in 20 never-medicated children with ADHD. We observed smaller VStr volumes in adult patients with a history of stimulant treatment in comparison to never-medicated patients. Moreover, our longitudinal analyses uncovered a reduction of grey matter volume in the bilateral VStr in adult patients after exposure to methylphenidate, which was followed by volumetric recovery to control level. In children, the same pattern of VStr volume changes was observed after treatment with methylphenidate. These findings suggest that the altered VStr volumes previously observed in patients with ADHD may represent a transitory effect of stimulant exposure rather than an intrinsic feature of the disorder. More generally, these data show that stimulant drugs can render plastic volume changes in human VStr neuroanatomy.

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 region's 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.

Laminar thickness alterations in the fronto-parietal cortical mantle of patients with attention-deficit/hyperactivity disorder.

Although Attention-Deficit/Hyperactivity Disorder (ADHD) was initially regarded as a disorder exclusive to childhood, nowadays its prevalence in adulthood is well established. The development of novel techniques for quantifying the thickness of the cerebral mantle allows the further exploration of the neuroanatomical profiles underlying the child and adult form of the disorder. To examine the cortical mantle in children and adults with ADHD, we applied a vertex-wise analysis of cortical thickness to anatomical brain MRI scans acquired from children with (n = 43) and without ADHD (n = 41), as well as a group of adult neurotypical individuals (n = 31), adult patients with a history of stimulant treatment (n = 31) and medication-naïve adults with ADHD (n = 24). We observed several clusters of reduced laminar cortical thickness in ADHD patients in comparison to neurotypical individuals. These differences were primarily located in the dorsal attention network, including the bilateral inferior and superior parietal cortex and a section of the frontal cortex (centered on the superior frontal and precentral gyrus bilaterally). Further laminar thickness deficits were observed in the bilateral orbitofrontal cortex and medial occipital cortex. The deficits in the cortical surface were especially pronounced in the child sample, while adult patients showed a more typical laminar thickness across the cerebral mantle. These findings show that the neuroanatomical profile of ADHD, especially the childhood form of the disorder, involves robust alterations in the cortical mantle, which are most prominent in brain regions subserving attentional processing.

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.

Training-induced neuroanatomical plasticity in ADHD: a tensor-based morphometric study.

Experience-based neuroplasticity has typically been associated with functional changes, but growing evidence indicates that training can also render dynamic structural alterations in the brain. Although research on training-induced morphological plasticity has consistently demonstrated rapid increases of gray matter volume in task-related regions, no studies have examined if local volumetric reductions in gray matter associated with certain psychiatric disorders may be reversible by adequate training. We aimed to assess whether a training program applied to ADHD patients can contravene some of the associated neuroanatomical alterations. High-resolution anatomical scans were acquired before and after the training period, and a whole-brain tensor-based morphometric approach was applied to extract a voxel-wise estimation of longitudinal changes in regional gray matter volume. Our results show focal volumetric gray matter increases in bilateral middle frontal cortex and right inferior-posterior cerebellum after cognitive training compared with the ADHD control group. The extent of gray matter volume increase in the inferior-posterior cerebellum was associated with attentional performance. These findings illustrate the capacity of the nervous system for rapid morphological adjustments in response to environmental triggers. Moreover, the dorsolateral prefrontal cortex and cerebellum are commonly considered sites of volumetric reduction in ADHD, and the inferior-posterior lobule of the cerebellum is associated with progressive symptom-related volume loss. Hence, the clusters of volumetric change observed in our study were confined to structures typically characterized by volume reduction in ADHD patients, providing preliminary indications that cognitive training may contravene some of the neuroanatomical deficits associated with the disorder.

Neuroimaging in the diagnosis of ADHD: where we are and where we are going.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent childhood psychiatric disorder. ADHD manifests with symptoms of inattention, hyperactivity and/or impulsivity that pervade in the familiar, academic and social spheres. There are serious concerns about the widespread misdiagnosis of ADHD that, together with the fast growing use of neuroimaging techniques in ADHD research, have prompted an inquiry into the feasibility of an imaging test for the diagnosis of ADHD that could aid in clinical practice. AREAS COVERED: This article consists of a brief review of the main neuroimaging research findings in ADHD and its contributions to the current understanding of the ADHD neurobiology, highlighting aspects that could eventually be utilized as a basis for diagnostic tests. The paper then outlines and applies a multiphase approach for developing diagnostic imaging tests in psychiatry to evaluate their prospects for the diagnosis of ADHD as well as evaluating a recently proposed diagnostic imaging test. EXPERT OPINION: It appears obvious that a diagnostic imaging test for ADHD should be based on the state-of-the-art neuroimaging techniques now available from ADHD neurobiology research. However, the deriviation of an imaging diagnostic tool from neuroimaging research is not as straightforward as it may seem, with several prerequisites that must be met in advance. The author suggests that a consistent decreased volume of right caudate nucleus in ADHD samples could provide a good basis for any future diagnostic imaging test.

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.

Cerebellar neurometabolite abnormalities in pediatric attention/deficit hyperactivity disorder: a proton MR spectroscopic study.

We designed a case-control proton magnetic resonance spectroscopic study comparing the cerebellar and prefrontal regions of a group of 17 ADHD (attention deficit/hyperactivity disorder) medicated children and a group of 17 control children matched for laterality, gender and age. As we had found decreased gray matter volume in the right prefrontal region and the left cerebellar hemisphere in a previous voxel-based morphometry study conducted on an independent ADHD sample, we tested the hypothesis that these regions should show neurometabolite abnormalities. MRI (magnetic resonance imaging) was performed with a 1.5 T system; spectral acquisition was performed with a single-voxel technique and a PRESS sequence. Two volumes of interest were selected in the right prefrontal region and the left cerebellar hemisphere. NAA (N-acetylaspartate), Cre (creatine), Cho (choline), MI (myo-inositol) and Glx (glutamate-glutamine) resonance intensities were absolutely quantified. In the left cerebellar hemisphere, ADHD children showed significant decreased MI and NAA absolute concentrations with high effect sizes (p=0.004, ES=1.184; p=0.001, ES=1.083). The diminished absolute concentration of the NAA could be related to a gray matter volume decrease in the same cerebellar region found in the previous voxel-based morphometry MRI study, while the reduced MI absolute concentration could express a decreased glial density. This is the first proton MR spectroscopic study examining the cerebellum and it provides additional support for the role of cerebellum in the ADHD neurobiology.

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.