Network connectivity abnormality profile supports a categorical‐dimensional hybrid model of ADHD

Attention‐deficit/hyperactivity disorder (ADHD) is characterized by inattention, hyperactivity, and impulsivity, but there is no consensus regarding whether ADHD exists on the extreme end of a continuum of normal behavior or represents a discrete disorder. In this study, we sought to characterize both the categorical and dimensional variations in network functional connectivity in order to identify neural connectivity mechanisms of ADHD. Functional connectivity analyses of resting‐state fMRI data from 155 children with ADHD and 145 typically developing children (TDC) defined the dorsal attention network (DA), default mode network (DM), salience processing network (SAL) and executive control network (CON). Regional alterations in connectivity associated with categorical diagnoses and dimensional symptom measures (inattention and hyperactivity/impulsivity) as well as their interaction were systematically characterized. Dimensional relationships between symptom severity measures and functional connectivity that did not differ between TDC and children with ADHD were observed for each network, supporting a dimensional characterization of ADHD. However, categorical differences in functional connectivity magnitude between TDC and children with ADHD were detected after accounting for dimensional relationships, indicating the existence of categorical mechanisms independent of dimensional effects. Additionally, differential dimensional relationships for TDC versus ADHD children demonstrated categorical differences in brain–behavior relationships. The patterns of network functional organization associated with categorical versus dimensional measures of ADHD accentuate the complexity of this disorder and support a dual characterization of ADHD etiology featuring both dimensional and categorical mechanisms. Hum Brain Mapp 35:4531–4543, 2014. © 2014 Wiley Periodicals, 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.     

Local functional connectivity suggests functional immaturity in children with attention‐deficit/hyperactivity disorder

Previous studies have associated Attention‐Deficit/Hyperactivity Disorder (ADHD) with a maturational lag of brain functional networks. Functional connectivity of the human brain changes from primarily local to more distant connectivity patterns during typical development. Under the maturational lag hypothesis, we expect children with ADHD to exhibit increased local connectivity and decreased distant connectivity compared with neurotypically developing (ND) children. We applied a graph‐theory method to compute local and distant connectivity levels and cross‐sectionally compared them in a sample of 120 children with ADHD and 120 age‐matched ND children (age range = 7–17 years). In addition, we measured if potential group differences in local and distant connectivity were stable across the age range considered. Finally, we assessed the clinical relevance of observed group differences by correlating the connectivity levels and ADHD symptoms severity separately for each group. Children with ADHD exhibited more local connectivity than age‐matched ND children in multiple brain regions, mainly overlapping with default mode, fronto‐parietal and ventral attentional functional networks (p < .05‐ threshold free‐cluster enhancement–family‐wise error). We detected an atypical developmental pattern of local connectivity in somatomotor regions, that is, decreases with age in ND children, and increases with age in children with ADHD. Furthermore, local connectivity within somatomotor areas correlated positively with clinical severity of ADHD symptoms, both in ADHD and ND children. Results suggest an immature functional state of multiple brain networks in children with ADHD. Whereas the ADHD diagnosis is associated with the integrity of the system comprising the fronto‐parietal, default mode and ventral attentional networks, the severity of clinical symptoms is related to atypical functional connectivity within somatomotor areas. Additionally, our findings are in line with the view of ADHD as a disorder of deviated maturational trajectories, mainly affecting somatomotor areas, rather than delays that normalize with age.     

Disrupted functional connectivity of cerebellar default network areas in attention‐deficit/hyperactivity disorder

Attention‐deficit/hyperactivity disorder (ADHD) is increasingly understood as a disorder of spontaneous brain‐network interactions. The default mode network (DMN), implicated in ADHD‐linked behaviors including mind‐wandering and attentional fluctuations, has been shown to exhibit abnormal spontaneous functional connectivity (FC) within‐network and with other networks (salience, dorsal attention and frontoparietal) in ADHD. Although the cerebellum has been implicated in the pathophysiology of ADHD, it remains unknown whether cerebellar areas of the DMN (CerDMN) exhibit altered FC with cortical networks in ADHD. Here, 23 adults with ADHD and 23 age‐, IQ‐, and sex‐matched controls underwent resting state fMRI. The mean time series of CerDMN areas was extracted, and FC with the whole brain was calculated. Whole‐brain between‐group differences in FC were assessed. Additionally, relationships between inattention and individual differences in FC were assessed for between‐group interactions. In ADHD, CerDMN areas showed positive FC (in contrast to average FC in the negative direction in controls) with widespread regions of salience, dorsal attention and sensorimotor networks. ADHD individuals also exhibited higher FC (more positive correlation) of CerDMN areas with frontoparietal and visual network regions. Within the control group, but not in ADHD, participants with higher inattention had higher FC between CerDMN and regions in the visual and dorsal attention networks. This work provides novel evidence of impaired CerDMN coupling with cortical networks in ADHD and highlights a role of cerebro‐cerebellar interactions in cognitive function. These data provide support for the potential targeting of CerDMN areas for therapeutic interventions in ADHD. Hum Brain Mapp 36:3373–3386, 2015. © 2015 Wiley Periodicals, Inc.     

Increased functional connectivity between the default mode and salience networks in unmedicated adults with obsessive‐compulsive disorder

Deficits in attention have been implicated in Obsessive‐Compulsive Disorder (OCD), yet their neurobiological bases are poorly understood. In unmedicated adults with OCD (n = 30) and healthy controls (n = 32), they used resting state functional connectivity MRI (rs‐fcMRI) to examine functional connectivity between two neural networks associated with attentional processes: the default mode network (DMN) and the salience network (SN). They then used path analyses to examine putative relationships across three variables of interest: DMN‐SN connectivity, attention, and OCD symptoms. In the OCD compared with healthy control participants, there was significantly reduced inverse connectivity between the anterior medial prefrontal cortex (amPFC) and the anterior insular cortex, regions within the DMN and SN, respectively. In OCD, reduced inverse DMN‐SN connectivity was associated with both increased OCD symptom severity and decreased sustained attention. Path analyses were consistent with a potential mechanistic explanation: OCD symptoms are associated with an imbalance in DMN‐SN networks that subserve attentional processes and this effect of OCD on DMN‐SN connectivity is associated with decreased sustained attention. This work builds upon a growing literature suggesting that reduced inverse DMN‐SN connectivity may represent a trans‐diagnostic marker of attentional processes and suggests a potential mechanistic account of the relationship between OCD and attention. Reduced inverse DMN‐SN connectivity may be an important target for treatment development to improve attention in individuals with OCD. Hum Brain Mapp 38:678–687, 2017. © 2016 Wiley Periodicals, Inc.     

White‐matter abnormalities in attention deficit hyperactivity disorder: A diffusion tensor imaging study

Current evidence suggests that attention deficit hyperactivity disorder (ADHD) involves dysfunction in wide functional networks of brain areas associated with attention and cognition. This study examines the structural integrity of white‐matter neural pathways, which underpin these functional networks, connecting fronto‐striatal and fronto‐parietal circuits, in children with ADHD. Fifteen right‐handed 8 to 18‐year‐old males with ADHD‐combined type and 15 right‐handed, age, verbal, and performance IQ‐matched, healthy males underwent diffusion tensor imaging. A recent method of tract‐based spatial statistics was used to examine fractional anisotropy (FA) and mean diffusivity within major white‐matter pathways throughout the whole‐brain. White‐matter abnormalities were found in several distinct clusters within left fronto‐temporal regions and right parietal‐occipital regions. Specifically, participants with ADHD showed greater FA in white‐matter regions underlying inferior parietal, occipito‐parietal, inferior frontal, and inferior temporal cortex. Secondly, eigenvalue analysis suggests that the difference in FA in ADHD may relate to a lesser degree of neural branching within key white‐matter pathways. Tractography methods showed these regions to generally form part of white‐matter pathways connecting prefrontal and parieto‐occipital areas with the striatum and the cerebellum. Our findings demonstrate anomalous white‐matter development in ADHD in distinct cortical regions that have previously been shown to be dysfunctional or hypoactive in fMRI studies of ADHD. These data add to an emerging picture of abnormal development within fronto‐parietal cortical networks that may underpin the cognitive and attentional disturbances associated with ADHD. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

Predicting effective connectivity from resting‐state networks in healthy elderly and patients with prodromal Alzheimer's disease

Using functional neuroimaging techniques two aspects of functional integration in the human brain have been investigated, functional connectivity and effective connectivity. In this study we examined both connectivity types in parallel within an executive attention network during rest and while performing an attention task. We analyzed the predictive value of resting‐state functional connectivity on task‐induced effective connectivity in patients with prodromal Alzheimer's disease (AD) and healthy elderly. We found that in healthy elderly, functional connectivity was a significant predictor for effective connectivity, however, it was frequency‐specific. Effective top‐down connectivity emerging from prefrontal areas was related with higher frequencies of functional connectivity (e.g., 0.08–0.15 Hz), in contrast to effective bottom‐up connectivity going to prefrontal areas, which was related to lower frequencies of functional connectivity (e.g., 0.001–0.03 Hz). In patients, the prediction of effective connectivity by functional connectivity was disturbed. We conclude that functional connectivity and effective connectivity are interrelated in healthy brains but this relationship is aberrant in very early AD. Hum Brain Mapp 35:954–963, 2014. © 2013 Wiley Periodicals, Inc.     

The effects of methylphenidate on whole brain intrinsic functional connectivity

Methylphenidate (MPH) is an indirect dopaminergic and noradrenergic agonist that is used to treat attention deficit hyperactivity disorder and that has shown therapeutic potential in neuropsychiatric diseases such as depression, dementia, and Parkinson's disease. While effects of MPH on task‐induced brain activation have been investigated, little is known about how MPH influences the resting brain. To investigate the effects of 40 mg of oral MPH on intrinsic functional connectivity, we used resting state fMRI in 54 healthy male subjects in a double‐blind, randomized, placebo‐controlled study. Functional connectivity analysis employing ICA revealed seven resting state networks (RSN) of interest. Connectivity strength between the dorsal attention network and the thalamus was increased after MPH intake. Other RSN located in association cortex areas, such as the left and right frontoparietal networks and the executive control network, showed MPH‐induced connectivity increase to sensory‐motor and visual cortex regions and connectivity decrease to cortical and subcortical components of cortico‐striato‐thalamo‐cortical circuits (CST). RSN located in sensory‐motor cortex areas showed the opposite pattern with MPH‐induced connectivity increase to CST components and connectivity decrease to sensory‐motor and visual cortex regions. Our results provide evidence that MPH does not only alter intrinsic connectivity between brain areas involved in sustained attention, but that it also induces significant changes in the cortico‐cortical and cortico‐subcortical connectivity of many other cognitive and sensory‐motor RSN. Hum Brain Mapp 35:5379–5388, 2014. © 2014 Wiley Periodicals, Inc.     

Structural and functional connectivity of the human brain in autism spectrum disorders and attention‐deficit/hyperactivity disorder: A rich club‐organization study

Attention‐deficit/hyperactive disorder (ADHD) and autism spectrum disorders (ASD) are two of the most common and vexing neurodevelopmental disorders among children. Although the two disorders share many behavioral and neuropsychological characteristics, most MRI studies examine only one of the disorders at a time. Using graph theory combined with structural and functional connectivity, we examined the large‐scale network organization among three groups of children: a group with ADHD (8–12 years, n = 20), a group with ASD (7–13 years, n = 16), and typically developing controls (TD) (8–12 years, n = 20). We apply the concept of the rich‐club organization, whereby central, highly connected hub regions are also highly connected to themselves. We examine the brain into two different network domains: (1) inside a rich‐club network phenomena and (2) outside a rich‐club network phenomena. The ASD and ADHD groups had markedly different patterns of rich club and non rich‐club connections in both functional and structural data. The ASD group exhibited higher connectivity in structural and functional networks but only inside the rich‐club networks. These findings were replicated using the autism brain imaging data exchange dataset with ASD (n = 85) and TD (n = 101). The ADHD group exhibited a lower generalized fractional anisotropy and functional connectivity inside the rich‐club networks, but a higher number of axonal fibers and correlation coefficient values outside the rich club. Despite some shared biological features and frequent comorbity, these data suggest ADHD and ASD exhibit distinct large‐scale connectivity patterns in middle childhood. Hum Brain Mapp 35:6032–6048, 2014. © 2014 Wiley Periodicals, Inc.     

Network‐selectivity and stimulus‐discrimination in the primary visual cortex: cell‐assembly dynamics

Visual neurons coordinate their responses in relation to the stimulus; however, the complex interplay between a stimulus and the functional dynamics of an assembly still eludes neuroscientists. To this aim, we recorded cell assemblies from multi‐electrodes in the primary visual cortex of anaesthetized cats in response to randomly presented sine‐wave drifting gratings whose orientation tilted in 22.5° steps. Cross‐correlograms revealed the functional connections at all the tested orientations. We show that a cell‐assembly discriminates between orientations by recruiting a ‘salient’ functional network at every presented orientation, wherein the connections and their strengths (peak‐probabilities in the cross‐correlogram) change from one orientation to another. Within these assemblies, closely tuned neurons exhibited increased connectivity and connection‐strengths compared with differently tuned neurons. Minimal connectivity between untuned neurons suggests the significance of neuronal selectivity in assemblies. This study reflects upon the dynamics of functional connectivity, and brings to the fore the importance of a ‘signature’ functional network in an assembly that is strictly related to a specific stimulus. It appears that an assembly is the major ‘functional unit’ of information processing in cortical circuits, rather than the individual neurons.     

Resting‐state fMRI detects the effects of learning in short term: A visual search training study

Can resting‐state functional connectivity (rs‐FC) detect the impact of learning on the brain in the short term? To test this possibility, we have combined task‐FC and rs‐FC tested before and after a 30‐min visual search training. Forty‐two healthy adults (20 men) divided into no‐contact control and trained groups completed the study. We studied the connectivity between four different regions of the brain involved in visual search: the primary visual area, the right posterior parietal cortex (rPPC), the right dorsolateral prefrontal cortex (rDLPFC), and the dorsal anterior cingulate cortex (dACC). Task‐FC showed increased connectivity between the rPPC and rDLPFC and between the dACC and rDLPFC from pretraining to posttraining for both the control group and the trained group, suggesting that connectivity between these areas increased with task repetition. In rs‐FC, we found enhanced connectivity between these regions in the trained group after training, especially in those with better learning. Whole brain independent component analyses did not reveal any change in main networks after training. These results imply that rs‐FC may not only predict individual differences in task performance, but rs‐FC might also serve to monitor the impact of learning on the brain after short periods of cognitive training, localizing them in brain areas specifically involved in training.     

Dysfunctional attentional networks in children with attention deficit/hyperactivity disorder: evidence from an event-related functional magnetic resonance imaging study.

BACKGROUND: Although there is evidence for attentional dysfunction in children with attention deficit/hyperactivity disorder (ADHD), the neural basis of these deficits remains poorly understood. METHODS: We used event-related functional magnetic resonance imaging (fMRI) to investigate brain activations related to three particular aspects of attention: alerting, reorienting, and executive control. Sixteen medication-naive boys with ADHD and 16 healthy boys, aged 8 to 12 years, were studied. RESULTS: Behaviorally, children with ADHD showed a significant impairment only in their executive control system compared to healthy subjects. Neurally, children with ADHD (relative to controls) recruited deviant brain regions for all three attentional networks: less right-sided activation in the anterior cingulate gyrus during alerting, more fronto-striatal-insular activation during reorienting, and less fronto-striatal activation for executive control. ADHD symptom severity was associated with dysregulation of the blood oxygen level dependent (BOLD) signal within the putamen during reorienting and executive control. CONCLUSIONS: Our results demonstrated altered brain mechanism in ADHD associated with all three attentional networks investigated. For alerting and executive attention, our data indicate a deviant mechanism of cortical control, while ADHD children may have adopted altered strategies for reorienting of attention. Our results also stress the etiological role of functional abnormalities in the putamen in medication-naive ADHD.     

A surface‐based technique for mapping homotopic interhemispheric connectivity: Development,characterization, and clinical application

The functional organization of the human brain consists of a high degree of connectivity between interhemispheric homologous regions. The degree of homotopic organization is known to vary across the cortex and homotopic connectivity is high in regions that share cross‐hemisphere structural connections or are activated by common input streams (e.g., the visual system). Damage to one or both regions, as well as damage to the connections between homotopic regions, could disrupt this functional organization. Here were introduce and test a computationally efficient technique, surface‐based homotopic interhermispheric connectivity (sHIC), that leverages surface‐based registration and processing techniques in an attempt to improve the spatial specificity and accuracy of cortical interhemispheric connectivity estimated with resting state functional connectivity. This technique is shown to be reliable both within and across subjects. sHIC is also characterized in a dataset of nearly 1000 subjects. We confirm previous results showing increased interhemispheric connectivity in primary sensory regions, and reveal a novel rostro‐caudal functionally defined network level pattern of sHIC across the brain. In addition, we demonstrate a structural–functional relationship between sHIC and atrophy of the corpus callosum in multiple sclerosis (r = 0.2979, p = 0.0461). sHIC presents as a sensitive and reliable measure of cortical homotopy that may prove useful as a biomarker in neurologic disease. Hum Brain Mapp 37:2849–2868, 2016. © 2016 Wiley Periodicals, Inc.     

Addressing challenges of high spatial resolution UHF fMRI for group analysis of higher‐order cognitive tasks: An inter‐sensory task directing attention between visual and somatosensory domains

Functional MRI at ultra‐high field (UHF, ≥7 T) provides significant increases in BOLD contrast‐to‐noise ratio (CNR) compared with conventional field strength (3 T), and has been exploited for reduced field‐of‐view, high spatial resolution mapping of primary sensory areas. Applying these high spatial resolution methods to investigate whole brain functional responses to higher‐order cognitive tasks leads to a number of challenges, in particular how to perform robust group‐level statistical analyses. This study addresses these challenges using an inter‐sensory cognitive task which modulates top‐down attention at graded levels between the visual and somatosensory domains. At the individual level, highly focal functional activation to the task and task difficulty (modulated by attention levels) were detectable due to the high CNR at UHF. However, to assess group level effects, both anatomical and functional variability must be considered during analysis. We demonstrate the importance of surface over volume normalisation and the requirement of no spatial smoothing when assessing highly focal activity. Using novel group analysis on anatomically parcellated brain regions, we show that in higher cognitive areas (parietal and dorsal‐lateral‐prefrontal cortex) fMRI responses to graded attention levels were modulated quadratically, whilst in visual cortex and VIP, responses were modulated linearly. These group fMRI responses were not seen clearly using conventional second‐level GLM analyses, illustrating the limitations of a conventional approach when investigating such focal responses in higher cognitive regions which are more anatomically variable. The approaches demonstrated here complement other advanced analysis methods such as multivariate pattern analysis, allowing UHF to be fully exploited in cognitive neuroscience.     

Resting‐state frontostriatal functional connectivity in Parkinson's disease–related apathy

One of the most common neuropsychiatric symptoms in Parkinson's disease (PD) is apathy, affecting between 23% and 70% of patients and thought to be related to frontostriatal dopamine deficits. In the current study, we assessed functional resting‐state frontostriatal connectivity and structural changes associated with the presence of apathy in a large sample of PD subjects and healthy controls, while controlling for the presence of comorbid depression and cognitive decline. Thirty‐one healthy controls (HC) and 62 age‐, sex‐, and education‐matched PD patients underwent resting‐state functional magnetic resonance imaging (MRI). Apathy symptoms were evaluated with the Apathy Scale (AS). The 11 Beck Depression Inventory‐II items that measure dysphoric mood symptoms as well as relevant neuropsychological scores were used as nuisance factors in connectivity analyses. Voxel‐wise analyses of functional connectivity between frontal lobes (limbic, executive, rostral motor, and caudal motor regions), striata (limbic, executive, sensorimotor regions), and thalami were performed. Subcortical volumetry/shape analysis and fronto‐subcortical voxel‐based morphometry were performed to assess associated structural changes. Twenty‐five PD patients were classified as apathetic (AS > 13). Apathetic PD patients showed functional connectivity reductions compared with HC and with non‐apathetic patients, mainly in left‐sided circuits, and predominantly involving limbic striatal and frontal territories. Similarly, severity of apathy negatively correlated with connectivity in these circuits. No significant effects were found in structural analyses. Our results indicate that the presence of apathy in PD is associated with functional connectivity reductions in frontostriatal circuits, predominating in the left hemisphere and mainly involving its limbic components. © 2015 International Parkinson and Movement Disorder Society     

Neuroanatomical correlates of attention‐deficit–hyperactivity disorder accounting for comorbid oppositional defiant disorder and conduct disorder

Aim: An increasing number of neuroimaging studies have been conducted to uncover the pathophysiology of attention‐deficit–hyperactivity disorder (ADHD). The findings are inconsistent, however, at least partially due to methodological differences. In the present study voxel‐based morphometry (VBM) was used to evaluate brain morphology in ADHD subjects after taking into account the confounding effect of oppositional defiant disorder (ODD) and conduct disorder (CD) comorbidity. Methods: Eighteen children with ADHD and 17 age‐ and gender‐matched typically developing subjects underwent high‐spatial resolution magnetic resonance imaging. The regional gray matter volume differences between the children with ADHD and controls were examined with and without accounting for comorbid ODD and CD in a voxel‐by‐voxel manner throughout the entire brain. Results: The VBM indicated significantly smaller regional gray matter volume in regions including the bilateral temporal polar and occipital cortices and the left amygdala in subjects with ADHD compared with controls. Significantly smaller regional gray matter volumes were demonstrated in more extensive regions including the bilateral temporal polar cortices, bilateral amygdala, right occipital cortex, right superior temporal sulcus, and left middle frontal gyrus after controlling for the confounding effect of comorbid ODD and CD. Conclusion: Morphological abnormalities in ADHD were seen not only in the regions associated with executive functioning but also in the regions associated with social cognition. When the effect of comorbid CD and ODD was taken into account, there were more extensive regions with significantly smaller volume in ADHD compared to controls.     

Aberrant functional network connectivity in psychopathy from a large (N = 985) forensic sample

Psychopathy is a personality disorder characterized by antisocial behavior, lack of remorse and empathy, and impaired decision making. The disproportionate amount of crime committed by psychopaths has severe emotional and economic impacts on society. Here we examine the neural correlates associated with psychopathy to improve early assessment and perhaps inform treatments for this condition. Previous resting‐state functional magnetic resonance imaging (fMRI) studies in psychopathy have primarily focused on regions of interest. This study examines whole‐brain functional connectivity and its association to psychopathic traits. Psychopathy was hypothesized to be characterized by aberrant functional network connectivity (FNC) in several limbic/paralimbic networks. Group‐independent component and regression analyses were applied to a data set of resting‐state fMRI from 985 incarcerated adult males. We identified resting‐state networks (RSNs), estimated FNC between RSNs, and tested their association to psychopathy factors and total summary scores (Factor 1, interpersonal/affective; Factor 2, lifestyle/antisocial). Factor 1 scores showed both increased and reduced functional connectivity between RSNs from seven brain domains (sensorimotor, cerebellar, visual, salience, default mode, executive control, and attentional). Consistent with hypotheses, RSNs from the paralimbic system—insula, anterior and posterior cingulate cortex, amygdala, orbital frontal cortex, and superior temporal gyrus—were related to Factor 1 scores. No significant FNC associations were found with Factor 2 and total PCL‐R scores. In summary, results suggest that the affective and interpersonal symptoms of psychopathy (Factor 1) are associated with aberrant connectivity in multiple brain networks, including paralimbic regions.     

Reward breaks through center‐surround inhibition via anterior insula

Focusing attention on a target creates a center‐surround inhibition such that distractors located close to the target do not capture attention. Recent research showed that a distractor can break through this surround inhibition when associated with reward. However, the brain basis for this reward‐based attention is unclear. In this fMRI study, we presented a distractor associated with high or low reward at different distances from the target. Behaviorally the low‐reward distractor did not capture attention and thus did not cause interference, whereas the high‐reward distractor captured attention only when located near the target. Neural activity in extrastriate cortex mirrored the behavioral pattern. A comparison between the high‐reward and the low‐reward distractors presented near the target (i.e., reward‐based attention) and a comparison between the high‐reward distractors located near and far from the target (i.e., spatial attention) revealed a common frontoparietal network, including inferior frontal gyrus and inferior parietal sulcus as well as the visual cortex. Reward‐based attention specifically activated the anterior insula (AI). Dynamic causal modelling showed that reward modulated the connectivity from AI to the frontoparietal network but not the connectivity from the frontoparietal network to the visual cortex. Across participants, the reward‐based attentional effect could be predicted both by the activity in AI and by the changes of spontaneous functional connectivity between AI and ventral striatum before and after reward association. These results suggest that AI encodes reward‐based salience and projects it to the stimulus‐driven attentional network, which enables the reward‐associated distractor to break through the surround inhibition in the visual cortex. Hum Brain Mapp 36:5233–5251, 2015. © 2015 Wiley Periodicals, Inc.     

Functional connectivity for an “Island of sparing” in autism spectrum disorder: An fMRI study of visual search

Although autism is usually characterized with respect to sociocommunicative impairments, visual search is known as a domain of relative performance strength in this disorder. This study used functional MRI during visual search in children with autism spectrum disorder (n = 19; mean age = 13;10) and matched typically developing children (n = 19; mean age = 14;0). We selected regions of interest within two attentional networks known to play a crucial role in visual search processes, such as goal‐directed selective attention, filtering of irrelevant distractors, and detection of behaviorally‐relevant information, and examined activation and connectivity within and between these attentional networks. Additionally, based on prior research suggesting links between visual search abilities and autism symptomatology, we tested for correlations between sociocommunicative impairments and behavioral and neural indices of search. Contrary to many previous functional connectivity magnetic resonance imaging studies of autism that reported functional underconnectivity for task domains of weakness, we found atypically increased connectivity within and between attentional networks in autism. Additionally, we found increased functional connectivity for occipital regions, both locally and for long‐distance connections with frontal regions. Both behavioral and neural indices of search were correlated with sociocommunicative impairment in children with autism. This association suggests that strengths in nonsocial visuospatial processing may be related to the development of core autistic sociocommunicative impairments. Hum Brain Mapp 34:2524–2537, 2013. © 2012 Wiley Periodicals, Inc.     

A three‐wave longitudinal study of subcortical–cortical resting‐state connectivity in adolescence: Testing age‐ and puberty‐related changes

Adolescence is the transitional period between childhood and adulthood, characterized by substantial changes in reward‐driven behavior. Although reward‐driven behavior is supported by subcortical‐medial prefrontal cortex (PFC) connectivity, the development of these circuits is not well understood. Particularly, while puberty has been hypothesized to accelerate organization and activation of functional neural circuits, the relationship between age, sex, pubertal change, and functional connectivity has hardly been studied. Here, we present an analysis of resting‐state functional connectivity between subcortical structures and the medial PFC, in 661 scans of 273 participants between 8 and 29 years, using a three‐wave longitudinal design. Generalized additive mixed model procedures were used to assess the effects of age, sex, and self‐reported pubertal status on connectivity between subcortical structures (nucleus accumbens, caudate, putamen, hippocampus, and amygdala) and cortical medial structures (dorsal anterior cingulate, ventral anterior cingulate, subcallosal cortex, frontal medial cortex). We observed an age‐related strengthening of subcortico‐subcortical and cortico‐cortical connectivity. Subcortical–cortical connectivity, such as, between the nucleus accumbens—frontal medial cortex, and the caudate—dorsal anterior cingulate cortex, however, weakened across age. Model‐based comparisons revealed that for specific connections pubertal development described developmental change better than chronological age. This was particularly the case for changes in subcortical–cortical connectivity and distinctively for boys and girls. Together, these findings indicate changes in functional network strengthening with pubertal development. These changes in functional connectivity may maximize the neural efficiency of interregional communication and set the stage for further inquiry of biological factors driving adolescent functional connectivity changes.