Lateralization of brain activity pattern during unilateral movement in Parkinson's disease

We investigated the lateralization of brain activity pattern during performance of unilateral movement in drug‐naïve Parkinson's disease (PD) patients with only right hemiparkinsonian symptoms. Functional MRI was obtained when the subjects performed strictly unilateral right hand movement. A laterality index was calculated to examine the lateralization. Patients had decreased activity in the left putamen and left supplementary motor area, but had increased activity in the right primary motor cortex, right premotor cortex, left postcentral gyrus, and bilateral cerebellum. The laterality index was significantly decreased in PD patients compared with controls (0.41 ± 0.14 vs. 0.84 ± 0.09). The connectivity from the left putamen to cortical motor regions and cerebellum was decreased, while the interactions between the cortical motor regions, cerebellum, and right putamen were increased. Our study demonstrates that in early PD, the lateralization of brain activity during unilateral movement is significantly reduced. The dysfunction of the striatum–cortical circuit, decreased transcallosal inhibition, and compensatory efforts from cortical motor regions, cerebellum, and the less affected striatum are likely reasons contributing to the reduced motor lateralization. The disruption of the lateralized brain activity pattern might be a reason underlying some motor deficits in PD, like mirror movements or impaired bilateral motor coordination. Hum Brain Mapp 36:1878–1891, 2015. © 2015 Wiley Periodicals, Inc .     

MRI volumetric and 31P MRS metabolic correlates of caudate nucleus in antipsychotic-naïve schizophrenia

Objective: To examine the volumetric and metabolic correlates of caudate nucleus in antipsychotic‐naïve schizophrenia patients in comparison with healthy controls. Method: Twelve antipsychotic‐naïve schizophrenia patients and 13 healthy controls underwent ³¹P magnetic resonance spectroscopy of basal ganglia. Magnetic resonance imaging volume of caudate nuclei was measured using scion image software. Results: Patients had significantly smaller caudate volume than healthy controls. Phosphocreatine (PCr)/total phosphorous and PCr/total adenosine tri‐phosphate ratios of both caudate nuclei were significantly lower in patients than controls. Significant negative correlation was found between the left caudate volume and left PCr/total phosphorus ratio in the patients. Age at onset of psychosis had i) significant negative correlation with right and left caudate volumes and ii) significant positive correlation with left PCr/total phosphorus ratio. Conclusion: The metabolic and volumetric abnormalities of caudate nucleus in antipsychotic‐naïve schizophrenia patients support neurodevelopmental etiopathogenesis.     

Dopaminergic modulation of motor network compensatory mechanisms in Parkinson's disease

The dopaminergic system has a unique gating function in the initiation and execution of movements. When the interhemispheric imbalance of dopamine inherent to the healthy brain is disrupted, as in Parkinson's disease (PD), compensatory mechanisms act to stave off behavioral changes. It has been proposed that two such compensatory mechanisms may be (a) a decrease in motor lateralization, observed in drug‐naïve PD patients and (b) reduced inhibition ‐ increased facilitation. Seeking to investigate the differential effect of dopamine depletion and subsequent substitution on compensatory mechanisms in non‐drug‐naïve PD, we studied 10 PD patients and 16 healthy controls, with patients undergoing two test sessions — “ON” and “OFF” medication. Using a simple visually‐cued motor response task and fMRI, we investigated cortical motor activation — in terms of laterality, contra‐ and ipsilateral percent BOLD signal change and effective connectivity in the parametric empirical Bayes framework. We found that decreased motor lateralization persists in non‐drug‐naïve PD and is concurrent with decreased contralateral activation in the cortical motor network. Normal lateralization is not reinstated by dopamine substitution. In terms of effective connectivity, disease‐related changes primarily affect ipsilaterally‐lateralized homotopic cortical motor connections, while medication‐related changes affect contralaterally‐lateralized homotopic connections. Our findings suggest that, in non‐drug‐naïve PD, decreased lateralization is no longer an adaptive cortical mechanism, but rather the result of maladaptive changes, related to disease progression and long‐term dopamine replacement. These findings highlight the need for the development of noninvasive therapies, which would promote the adaptive mechanisms of the PD brain.     

Decreased regional homogeneity in lingual gyrus,increased regional homogeneity in cuneus and correlations with panic symptom severity of first-episode,medication-naïve and late-onset panic disorder patients

This study was designed to explore regional homogeneity (ReHo), an indicator of the synchronization of brain function, in first-episode, medication-naïve and late-onset patients with panic disorder (PD). Participants comprised 30 patients and 21 healthy controls who underwent with 3-Tesla magnetic resonance imaging (MRI) scanning and ReHo functional MRI analysis. All participants were studied with clinical rating scales to assess the severity of PD symptoms. ReHo values were obtained using the REST toolbox (resting-state functional MRI data analysis toolbox). Differences in demographic data and ReHo values between the two groups were evaluated with the independent two-sample t-test function of the Statistical Package for the Social Sciences and REST. There were significant differences in clinical ratings between the two groups. No demographic differences were noted. We found decreased ReHo in the left lingual gyrus and increased ReHo in the right cuneus cortex of patients compared with controls. ReHo values of patients were negatively correlated with PD ratings in the right cuneus. ReHo differences found in the left lingual gyrus and the right cuneus might suggest sensory and inhibitory dysfunction in first-episode, medication-naïve, late-onset patients with PD.     

Reduced recruitment of motor association areas during bimanual coordination in concert pianists

Bimanual motor coordination is essential for piano playing. The functional neuronal substrate for high‐level bimanual performance achieved by professional pianists is unclear. We compared professional pianists to musically naïve controls while carrying out in‐phase (mirror) and anti‐phase (parallel) bimanual sequential finger movements during functional magnetic resonance imaging (fMRI). This task corresponds to bimanually playing scales practiced daily by pianists from the beginning of piano playing. Musicians and controls showed significantly different functional activation patterns. When comparing performance of parallel movements to rest, musically naïve controls showed stronger activations than did pianists within a network including anterior cingulate cortex, right dorsal premotor cortex, both cerebellar hemispheres, and right basal ganglia. The direct comparison of bimanual parallel to mirror movements between both groups revealed stronger signal increases in controls within mesial premotor cortex (SMA), bilateral cerebellar hemispheres and vermis, bilateral prefrontal cortex, left ventral premotor cortex, right anterior insula, and right basal ganglia. These findings suggest increased efficiency of cortical and subcortical systems for bimanual movement control in musicians. This may be fundamental to achieve high‐level motor skills allowing the musician to focus on artistic aspects of musical performance. Hum. Brain Mapping 22:206–215, 2004. © 2004 Wiley‐Liss, Inc.     

Reduced dopamine transporter binding predates impulse control disorders in Parkinson's disease

Impulse control disorders (ICD) are relatively common in Parkinson's disease (PD) and generally are regarded as adverse effects of dopamine replacement therapy, although certain demographic and clinical risk factors are also involved. Previous single‐photon emission computed tomography (SPECT) studies showed reduced ventral striatal dopamine transporter binding in Parkinson patients with ICD compared with patients without. Nevertheless, these studies were performed in patients with preexisting impulse control impairments, which impedes clear‐cut interpretation of these findings. We retrospectively procured follow‐up data from 31 medication‐naïve PD patients who underwent dopamine transporter SPECT imaging at baseline and were subsequently treated with dopamine replacement therapy. We used questionnaires and a telephone interview to assess medication status and ICD symptom development during the follow‐up period (31.5 ± 12.0 months). Eleven patients developed ICD symptoms during the follow‐up period, eight of which were taking dopamine agonists. The PD patients with ICD symptoms at follow‐up had higher baseline depressive scores and lower baseline dopamine transporter availability in the right ventral striatum, anterior‐dorsal striatum, and posterior putamen compared with PD patients without ICD symptoms. No baseline between‐group differences in age and disease stage or duration were found. The ICD symptom severity correlated negatively with baseline dopamine transporter availability in the right ventral and anterior‐dorsal striatum. The results of this preliminary study show that reduced striatal dopamine transporter availability predates the development of ICD symptoms after dopamine replacement therapy and may constitute a neurobiological risk factor related to a lower premorbid dopamine transporter availability or a more pronounced dopamine denervation in PD patients susceptible to ICD. © 2014 International Parkinson and Movement Disorder Society     

Dopaminergic modulation of resting‐state functional connectivity in de novo patients with Parkinson's disease

Parkinson's disease (PD) is characterized by degenerative changes of nigral dopamine neurons, resulting in the dopaminergic denervation of the striatum. Resting state networks studies have demonstrated that dopamine modulates distinct network connectivity patterns in both a linear and a nonlinear fashion, but quantitative analyses of dopamine‐dependent functional connectivity secondary to PD pathology were less informative. In the present study, we performed a correlation analysis between striatal dopamine levels assessed quantitatively by FP‐CIT positron emission tomography imaging and resting‐state functional connectivity in 23 drug naïve de novo patients with PD to elucidate dopamine‐dependent functional networks. The major finding is that the patterns of dopamine‐dependent positive functional connectivity varied depending on the location of striatal seeds. Dopamine‐dependent functional connectivity with the caudate predominantly overlay pericentral cortical areas, whereas dopamine‐dependent structures functionally connected with the posterior putamen predominantly involved cerebellar areas. The dorsolateral frontal area overlapped as a dopamine‐dependent cortical region that was positively connected with the anterior and posterior putamen. On the other hand, cortical areas where functional connectivity from the posterior cingulate was negatively correlated with dopaminergic status in the posterior putamen were localized in the left anterior prefrontal area and the parietal area. Additionally, functional connectivity between the anterior putamen and mesiofrontal areas was negatively coupled with striatal dopamine levels. The present study demonstrated that dopamine‐dependent functional network connectivity secondary to PD pathology mainly exhibits a consistent pattern, albeit with some variation. These patterns may reflect the diverse effects of dopaminergic medication on parkinsonian‐related motor and cognitive performance. Hum Brain Mapp 35:5431–5441, 2014. © 2014 Wiley Periodicals, Inc .     

Alterations in amplitude of low frequency fluctuation in treatment‐naïve major depressive disorder measured with resting‐state fMRI

There are limited resting‐state functional magnetic resonance imaging (fMRI) studies in major depressive disorder (MDD). Of these studies, functional connectivity analyses are mostly used. However, a new method based on the magnitude of low frequency fluctuation (LFF) during resting‐state fMRI may provide important insight into MDD. In this study, we examined the amplitude of LFF (ALFF) within the whole brain during resting‐state fMRI in 30 treatment‐naïve MDD subjects and 30 healthy control (HC) subjects. When compared with HC, MDD subjects showed increased ALFF in the frontal cortex (including the bilateral ventral/dorsal anterior cingulate cortex, orbitofrontal cortex, premotor cortex, ventral prefrontal cortex, left dorsal lateral frontal cortex, left superior frontal cortex), basal ganglia (including the right putamen and left caudate nucleus), left insular cortex, right anterior entorhinal cortex and left inferior parietal cortex, together with decreased ALFF in the bilateral occipital cortex, cerebellum hemisphere, and right superior temporal cortex. These findings may relate to characteristics of MDD, such as excessive self‐referential processing and deficits in cognitive control of emotional processing, which may contribute to the persistent and recurrent nature of the disorder. Hum Brain Mapp 35:4979–4988, 2014. © 2014 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Aberrant regional homogeneity in Parkinson’s disease: A voxel-wise meta-analysis of resting-state functional magnetic resonance imaging studies

Studies of abnormal regional homogeneity (ReHo) in Parkinson’s disease (PD) have reported inconsistent results. Therefore, we conducted a meta-analysis using the Seed-based d Mapping software package to identify the most consistent and replicable findings. A systematic literature search was performed to identify eligible whole-brain resting-state functional magnetic resonance imaging studies that had measured differences in ReHo between patients with PD and healthy controls between January 2000 and June 4, 2016. A total of ten studies reporting 11 comparisons (212 patients; 182 controls) were included. Increased ReHo was consistently identified in the bilateral inferior parietal lobules, bilateral medial prefrontal cortices, and left cerebellum of patients with PD when compared to healthy controls, while decreased ReHo was observed in the right putamen, right precentral gyrus, and left lingual gyrus. The results of the current meta-analysis demonstrate a consistent and coexistent pattern of impairment and compensation of intrinsic brain activity that predominantly involves the default mode and motor networks, which may advance our understanding of the pathophysiological mechanisms underlying PD.     

White matter abnormalities in drug-naïve patients with obsessive-compulsive disorder: a diffusion tensor study before and after citalopram treatment

Objective: The aim was to investigate the white matter abnormalities of drug‐naïve patients with obsessive–compulsive disorder (OCD) using diffusion tensor‐imaging and the white matter changes in the patients after pharmacotherapy. Method: Thirteen drug‐naïve OCD patients and 13 age‐ and sex‐matched healthy comparison subjects were examined using diffusion tensor‐imaging and structural magnetic resonance imaging. Measurements were made in OCD patients before and after 12 weeks of citalopram treatment. Results: Compared with controls, the drug‐naïve OCD patients showed significant increases in fractional anisotropy (FA) in the corpus callosum, the internal capsule and white matter in the area superolateral to the right caudate. The increases in FA were mostly no longer observed in patients after 12 weeks of treatment compared with controls. Conclusion: Our findings suggest that white matter alterations are associated with the pathophysiology of OCD, and the abnormalities may be partly reversible with pharmacotherapy.     

Functional networks in motor sequence learning: abnormal topographies in Parkinson's disease

We examined the neural circuitry underlying the explicit learning of motor sequences in normal subjects and patients with early stage Parkinson's disease (PD) using 15O-water (H2 15O) positron emission tomography (PET) and network analysis. All subjects were scanned while learning motor sequences in a task emphasizing explicit learning, and during a kinematically controlled motor execution reference task. Because different brain networks are thought to subserve target acquisition and retrieval during motor sequence learning, we used separate behavioral indices to quantify these aspects of learning during the PET experiments. In the normal cohort, network analysis of the PET data revealed a significant covariance pattern associated with acquisition performance. This topography was characterized by activations in the left dorsolateral prefrontal cortex (PFdl), rostral supplementary motor area (preSMA), anterior cingulate cortex, and in the left caudate/putamen. A second independent covariance pattern was associated with retrieval performance. This topography was characterized by bilateral activations in the premotor cortex (PMC), and in the right precuneus and posterior parietal cortex. The normal learning-related topographies failed to predict acquisition performance in PD patients and predicted retrieval performance less accurately in the controls. A separate network analysis was performed to identify discrete learning-related topographies in the PD cohort. In PD patients, acquisition performance was associated with a covariance pattern characterized by activations in the left PFdl, ventral prefrontal, and rostral premotor regions, but not in the striatum. Retrieval performance in PD patients was associated with a covariance pattern characterized by activations in the right PFdl, and bilaterally in the PMC, posterior parietal cortex, and precuneus. These results suggest that in early stage PD sequence learning networks are associated with additional cortical activation compensating for abnormalities in basal ganglia function.     

Behavioral and structural effects of unilateral intrastriatal injections of botulinum neurotoxin a in the rat model of Parkinson's disease

Botulinum neurotoxin (BoNT) inhibits the release of acetylcholine from presynaptic vesicles through its proteinase activity cleaving the SNARE complex. Parkinson's disease (PD) is associated with locally increased cholinergic activity in the striatum. Therefore, the present study investigates the effect of unilateral intrastriatal BoNT‐A injection in naïve rats on striatal morphology; i.e., the total number of Nissl‐stained neurons and the volume of caudate‐putamen (CPu) were estimated. Furthermore, stainings for markers of gliosis (glial fibrillary acidic protein) and microglia (Iba1) were performed. In addition, the potential beneficial effects of a unilateral intrastriatal injection of BoNT‐A on motor activity in the rat model of hemi‐PD were evaluated. Hemi‐PD was induced by unilateral injection of 6‐hydroxydopamine (6‐OHDA) into the right medial forebrain bundle. Six weeks later, rats received an ipsilateral intrastriatal injection of BoNT‐A. Behaviorally, motor performance was tested. The total number of CPu neurons and the striatal volume were not significantly different between the BoNT‐A‐injected right and the intact left hemispheres of naïve rats. In hemi‐PD rats, intrastriatal BoNT‐A abolished apomorphine‐induced rotations, increased amphetamine‐induced rotations, and tended to improve left forelimb usage. Forced motor function in the accelerod test was not significantly changed by BoNT‐A, and open field activity was also unaltered compared with sham treatment. Thus, intrastriatal BoNT‐A affects spontaneous motor activity of hemi‐PD rats to a minor degree compared with drug‐induced motor function. In the future, tests assessing the cognitive and emotional performance should be performed to ascertain finally the potential therapeutic usefulness of intrastriatal BoNT‐A for PD. © 2013 Wiley Periodicals, Inc.     

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. Hum Brain Mapp 35:1261–1272, 2014. © 2013 Wiley Periodicals, Inc.     

Basal ganglia hypoactivity during grip force in drug naïve Parkinson's disease

The basal ganglia (BG) are impaired in Parkinson's disease (PD), but it remains unclear which nuclei are impaired during the performance of motor tasks in early‐stage PD. Therefore, this study was conducted to determine which nuclei function abnormally, and whether cortical structures are also affected by early‐stage PD. The study also determined if cerebellar hyperactivity is found early in the course of PD. Blood oxygenation level dependent activation was compared between 14 early‐stage drug‐naïve PD patients and 14 controls performing two precision grip force tasks using functional magnetic resonance imaging at 3 T. The grip tasks used in this study were chosen because both tasks are known to provide robust activation in BG nuclei, and the two tasks were similar except that the 2‐s task required more switching between contraction and relaxation than the 4‐s task. The 4‐s task revealed that PD patients were hypoactive relative to controls only in putamen and external globus pallidus, and thalamus. In the 2‐s task, PD patients were hypoactive throughout all BG nuclei, thalamus, M1, and supplementary motor area. There were no differences in cerebellar activation between groups during either task. Regions of interest analysis revealed that the hypoactivity observed in PD patients during the 2‐s task became more pronounced over time as patients performed the task. This suggests that a motor task that requires switching can accentuate abnormal activity throughout all BG nuclei of early‐stage, drug‐naive PD, and that the abnormal activity becomes more pronounced with repeated task performance in these patients. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Stepwise functional connectivity reveals altered sensory‐multimodal integration in medication‐naïve adults with attention deficit hyperactivity disorder

Neuroimaging studies indicate that children with attention‐deficit/hyperactivity disorder (ADHD) present alterations in several functional networks of the sensation‐to‐cognition spectrum. These alterations include functional overconnectivity within sensory regions and underconnectivity between sensory regions and neural hubs supporting higher order cognitive functions. Today, it is unknown whether this same pattern of alterations persists in adult patients with ADHD who had never been medicated for their condition. The aim of the present study was to assess whether medication‐naïve adults with ADHD presented alterations in functional networks of the sensation‐to‐cognition spectrum. Thirty‐one medication‐naïve adults with ADHD and twenty‐two healthy adults underwent resting‐state functional magnetic resonance imaging (rs‐fMRI). Stepwise functional connectivity (SFC) was used to characterize the pattern of functional connectivity between sensory seed regions and the rest of the brain at direct, short, intermediate, and long functional connectivity distances, thus covering the continuum from the sensory input to the neural hubs supporting higher order cognitive functions. As compared to controls, adults with ADHD presented increased SFC degree within primary sensory regions and decreased SFC degree between sensory seeds and higher order integration nodes. In addition, they exhibited decreased connectivity degree between sensory seeds and regions of the default‐mode network. Consistently, the higher the score in clinical severity scales the lower connectivity degree between seed regions and the default mode network.     

Regional and network properties of white matter function in Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder with dysfunction in cortices as well as white matter (WM) tracts. While the changes to WM structure have been extensively investigated in PD, the nature of the functional changes to WM remains unknown. In this study, the regional activity and functional connectivity of WM were compared between PD patients (n = 57) and matched healthy controls (n = 52), based on multimodel magnetic resonance imaging data sets. By tract‐based spatial statistical analyses of regional activity, patients showed decreased structural‐functional coupling in the left corticospinal tract compared to controls. This tract also displayed abnormally increased functional connectivity within the left post‐central gyrus and left putamen in PD patients. At the network level, the WM functional network showed small‐worldness in both controls and PD patients, yet it was abnormally increased in the latter group. Based on the features of the WM functional connectome, previously un‐evaluated individuals could be classified with fair accuracy (73%) and area under the curve of the receiver operating characteristics (75%). These neuroimaging findings provide direct evidence for WM functional changes in PD, which is crucial to understand the functional role of fiber tracts in the pathology of neural circuits.     

No associations between medial temporal lobe volumes and verbal learning/memory in emerging psychosis

Grey matter (GM) volume alterations have been repeatedly demonstrated in patients with first episode psychosis (FEP). Some of these neuroanatomical abnormalities are already evident in the at‐risk mental state (ARMS) for psychosis. Not only GM alterations but also neurocognitive impairments predate the onset of frank psychosis with verbal learning and memory (VLM) being among the most impaired domains. Yet, their interconnection with alterations in GM volumes remains ambiguous. Thus, we evaluated associations of different subcortical GM volumes in the medial temporal lobe with VLM performance in antipsychotic‐naïve ARMS and FEP patients. Data from 59 ARMS and 31 FEP patients, collected within the prospective Früherkennung von Psychosen study, were analysed. Structural T1‐weighted images were acquired using a 3 Tesla magnetic resonance imaging scanner. VLM was assessed using the California Verbal Learning Test and its factors Attention Span, Learning Efficiency, Delayed Memory and Inaccurate Memory. FEP patients showed significantly enlarged volumes of hippocampus, pallidum, putamen and thalamus compared to ARMS patients. A significant negative association between amygdala and pallidum volume and Attention Span was found in ARMS and FEP patients combined, which however did not withstand correction for multiple testing. Although we found significant between‐group differences in subcortical volumes and VLM is among the most impaired cognitive domains in emerging psychosis, we could not demonstrate an association between low performance and subcortical GM volumes alterations in antipsychotic‐naïve patients. Hence, deficits in this domain do not appear to stem from alterations in subcortical structures.     

Cognitive executive impairment and dopaminergic deficits in de novo Parkinson's disease

Cognitive impairment in Parkinson's disease (PD) is common and does directly impact patients' everyday functioning. However, the underlying mechanisms of early cognitive decline are not known. This study explored the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug‐naïve PD patients and tested the hypothesis that executive dysfunction in PD is associated with striatal dopaminergic depletion. A cross‐sectional multicenter cohort of 339 PD patients and 158 healthy controls from the Parkinson's Progression Markers Initiative study was analyzed. Each individual underwent cerebral single‐photon emission CT (SPECT) and a standardized neuropsychological assessment with tests of memory as well as visuospatial and executive function. SPECT imaging was performed with [¹²³I]FP‐CIT, and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios, cognitive domain scores, and age was analyzed using Pearson's correlations, partial correlation, and conditional process analysis. A small, but significant, positive association between total striatal dopamine transporter binding and the attention/executive domain was found (r = 0.141; P = 0.009) in PD, but this was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with PD were mediated by an age‐moderated striatal dopaminergic deficit. Our findings support the hypothesis that nigrostriatal dopaminergic deficit is associated with executive impairment, but not to memory or visuospatial impairment, in early PD. © 2014 International Parkinson and Movement Disorder Society     

Disorder‐specific inferior prefrontal hypofunction in boys with pure attention‐deficit/hyperactivity disorder compared to boys with pure conduct disorder during cognitive flexibility

Background. Problems with cognitive flexibility have been observed in patients with attention deficit hyperactivity disorder (ADHD) and in patients with conduct disorder (CD), characterized by the violation of societal rules and the rights of others. Functional magnetic resonance imaging (fMRI) of cognitive switching, however, has only been investigated in patients with ADHD, including comorbidity with CD, finding frontostriatal and temporoparietal underactivation. This study investigates disorder‐specific functional abnormalities during cognitive flexibility between medication‐naïve children and adolescents with noncomorbid CD and those with noncomorbid ADHD compared to healthy controls. Methods. Event‐related fMRI was used to compare brain activation of 14 boys with noncomorbid, childhood‐onset CD, 14 boys with noncomorbid ADHD, and 20 healthy comparison boys during a visual–spatial Switch task. Results. Behaviorally, children with ADHD compared to children with CD had significantly slower reaction times to switch compared to repeat trials. The fMRI comparison showed that the patients with ADHD compared to both controls and patients with CD showed underactivation in right and left inferior prefrontal cortex. No disorder‐specific brain underactivation was observed in patients with CD. Only when compared with controls alone, the disruptive behavior group showed reduced activation in bilateral temporoparietal and occipital brain regions. Conclusions. The findings extend previous evidence for disorder‐specific underactivation in patients with ADHD compared to patients with CD in inferior prefrontal cortex during tasks of inhibitory control to the domain of cognitive flexibility. Inferior prefrontal underactivation thus appears to be a disorder‐specific neurofunctional biomarker for ADHD when compared with patients with CD. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Disrupted brain functional networks in drug‐naïve children with attention deficit hyperactivity disorder assessed using graph theory analysis

Neuroimaging studies have revealed functional brain network abnormalities in attention deficit hyperactivity disorder (ADHD), but the results have been inconsistent, potentially related to confounding medication effects. Furthermore, specific topological alterations in functional networks and their role in behavioral inhibition dysfunction remain to be established. Resting‐state functional magnetic resonance imaging was performed on 51 drug‐naïve children with ADHD and 55 age‐matched healthy controls. Brain functional networks were constructed by thresholding the partial correlation matrices of 90 brain regions, and graph theory was used to analyze network topological properties. The Stroop test was used to assess cognitive inhibitory abilities. Nonparametric permutation tests were used to compare the topological architectures in the two groups. Compared with healthy subjects, brain networks in ADHD patients demonstrated altered topological characteristics, including lower global (FDR q = 0.01) and local efficiency (p = 0.032, uncorrected) and a longer path length (FDR q = 0.01). Lower nodal efficiencies were found in the left inferior frontal gyrus and anterior cingulate cortex in the ADHD group (FDR both q < 0.05). Altered global and nodal topological efficiencies were associated with the severity of inhibitory cognitive control deficits and hyperactivity symptoms in ADHD (p <0 .05). Alterations in network topologies in drug‐naïve ADHD patients indicate weaker small‐worldization with decreased segregation and integration of functional brain networks. Deficits in the cingulo‐fronto‐parietal attention network were associated with inhibitory control deficits.