Activation patterns of the dorsal medial prefrontal cortex and frontal pole predict individual differences in decision impulsivity

Intertemporal choice refers to decisions that need to weigh different rewards at different time points in the future. Decision impulsivity manifests in the tendency of choosing smaller immediate options rather than larger later ones. Previous studies have suggested that decision impulsivity in intertemporal decision-making shares similar cognitive and neural mechanisms with risky decision-making. The present study theorizes on and examines whether the activation patterns of the dorsal medial prefrontal cortex (DMPFC) and the frontal pole (FP) during the risk-taking “cups task”, as captured in the scanner, can predict the delay discounting rate (k) based on an intertemporal decision task performed outside the scanner. To this end, we scanned with functional magnetic resonance imaging (fMRI) techniques a sample of 257 college students (N?=?257) while performing the cups task. Univariate analyses showed that activation levels of the DMPFC and the FP were inversely correlated with risk preference, but not with the delay discounting rate k. Multivariate pattern analysis, which can overcome key limitations of the univariate analyses, showed that activation patterns of these two regions predict the delay discounting rate k. These results confirmed the important roles of DMPFC and FP in decision impulsivity and the utility of using multivariate pattern analysis with fMRI data involving decision making tasks.

     

Abnormalities of voxel-based whole-brain functional connectivity patterns predict the progression of hepatic encephalopathy

Resting state functional magnetic resonance imaging (fMRI) is an important tool for understanding the functional reorganization of the brain in cirrhotic patients. Previous studies revealed that functional integration failure were observed in the whole brain. However, the whole-brain functional connectivity analysis methods used in these studies have the limitation that the result relied on a priori definition of network nodes. Moreover, the utility of resting state functional connectivity in the diagnosis and prediction of hepatic encephalopathy (HE) is not well examined. In this study, we recruited 87 subjects consisting of patients without HE, with HE, and healthy controls. We employed a voxel-based, unbiased functional connectivity analysis and the functional connectivity density (FCD) metric to precisely study abnormalities in the intrinsic functional connectivity patterns of cirrhotic patients. FCD analyses showed that hub regions in the brain were less topologically important in cirrhotic patients, whereas non-hub regions became topologically important in the disease state. This trend was more apparent with the progression of cirrhosis severity. Most FCD abnormalities were associated with deficits in psychomotor function, executive control, or visual-spatial abilities (p?<?0.05, AlphaSim corrected). FCD alterations in the left inferior parietal lobe and the right hippocampal gyrus/parahippocampal gyrus were significantly correlated with cognitive ability and blood ammonia level (p?<?0.05, AlphaSim corrected). A pattern classification analysis indicated that whole-brain FCD differences distinguished cirrhotic patients from healthy controls and predicted disease severity with high accuracies. These findings suggest that voxel-based FCD analysis may be clinically important for the diagnosis and prediction of HE.     

Long-lasting connectivity changes induced by intensive first-person shooter gaming

Action videogames have been shown to induce modifications in perceptual and cognitive systems, as well as in brain structure and function. Nevertheless, whether such changes are correlated with brain functional connectivity modifications outlasting the training period is not known. Functional magnetic resonance imaging (fMRI) was used in order to quantify acute and long-lasting connectivity changes following a sustained gaming experience on a first-person shooter (FPS) game. Thirty-five healthy participants were assigned to either a gaming or a control group prior to the acquisition of resting state fMRI data and a comprehensive cognitive assessment at baseline (T0), post-gaming (T1) and at a 3 months’ follow-up (T2). Seed-based resting-state functional connectivity (rs-FC) analysis revealed a significant greater connectivity between left thalamus and left parahippocampal gyrus in the gamer group, both at T1 and at T2. Furthermore, a positive increase in the rs-FC between the cerebellum, Heschl’s gyrus and the middle frontal gyrus paralleled improvements of in-gaming performance. In addition, baseline rs-FC of left supramarginal gyrus, left middle frontal gyrus and right cerebellum were associated with individual changes in videogame performance. Finally, enhancement of perceptual and attentional measures was observed at both T1 and T2, which correlated with a pattern of rs-FC changes in bilateral occipito-temporal regions belonging to the visual and attention fMRI networks. The present findings increase knowledge on functional connectivity changes induced by action videogames, pointing to a greater and long-lasting synchronization between brain regions associated with spatial orientation, visual discrimination and motor learning even after a relatively short multi-day gaming exposure.

     

Connectivity Theory of Autism: Use of Connectivity Measures in Assessing and Treating Autistic Disorders

Background. Autism is a disorder characterized by deficits in communication, social interaction, a limited range of interests, and repetitive stereotypical behavior. Although it is believed that changes in the brain leading to Autism occur early on in prenatal and early postnatal development, there is no definitive test for a diagnosis of Autism. The diagnosis is made on the basis of behavioral signs and symptoms alone and is usually not made until age 2 or later. There have been numerous neuroanatomical abnormalities noted in Autism, some of which can be linked to neuropsychological dysfunction. Recently a new theory has become prominent which suggests the disorder may be due to aberrant neural connectivity patterns. Evidence in support of this theory has come from anatomical studies of white matter as well as functional neuroimaging studies.

Methods. Most studies have employed functional magnetic resonance imaging to investigate connectivity, or electroencephalography (EEG) coherence studies. The high temporal resolution of EEG lends itself well to the investigation of cerebral connectivity. Research suggests there may be patterns of both hyper- and hypoconnectivity between various brain regions. Seven different patterns of abnormal connectivity which can be analyzed with EEG are proposed.

Results. Patterns of hyperconnectivity may be found in frontotemporal and left hemispheric regions, whereas patterns of hypoconnectivity are often seen in frontal (orbitofrontal), right posterior (occipital/parietal-temporal), frontal-posterior, and left hemispheric regions. In addition to these patterns of hypo- and hyperconnectivity, a mu rhythm complex has been identified. Treatment goals may be based on coherence anomalies identified by quantitative EEG analysis. Increased coherence between brain regions may be downtrained, whereas decreased coherence between brain regions may be uptrained. Clinical examples of each pattern and a discussion of their neurofeedback treatment are provided.

Conclusion. A theory of autistic disorders is presented that has at its' core neural connectivity disturbances. Multivariate EEG connectivity indices are utilized to formulate a typology of connectivity anomalies or patterns that have been observed over a series of autistic patients. These represent phenotypic expressions of the underlying pathology that leads to autistic symptoms. Examples demonstrate how these connectivity metrics can be used to understand autistic disturbances and formulate neurofeedback strategies for remedying these difficulties.     

Overlapping and segregated resting‐state functional connectivity in patients with major depressive disorder with and without childhood neglect

Many studies have suggested that childhood maltreatment increase risk of adulthood major depressive disorder (MDD) and predict its unfavorable treatment outcome, yet the neural underpinnings associated with childhood maltreatment in MDD remain poorly understood. Here, we seek to investigate the whole‐brain functional connectivity patterns in MDD patients with childhood maltreatment. Resting‐state functional magnetic resonance imaging was used to explore intrinsic or spontaneous functional connectivity networks of 18 MDD patients with childhood neglect, 20 MDD patients without childhood neglect, and 20 healthy controls. Whole‐brain functional networks were constructed by measuring the temporal correlations of every pairs of brain voxels and were further analyzed by using graph‐theory approaches. Relative to the healthy control group, the two MDD patient groups showed overlapping reduced functional connectivity strength in bilateral ventral medial prefrontal cortex/ventral anterior cingulate cortex. However, compared with MDD patients without a history of childhood maltreatment, those patients with such a history displayed widespread reduction of functional connectivity strength primarily in brain regions within the prefrontal‐limbic‐thalamic‐cerebellar circuitry, and these reductions significantly correlated with measures of childhood neglect. Together, we showed that the MDD groups with and without childhood neglect exhibited overlapping and segregated functional connectivity patterns in the whole‐brain networks, providing empirical evidence for the contribution of early life stress to the pathophysiology of MDD. Hum Brain Mapp 35:1154–1166, 2014. © 2013 Wiley Periodicals, Inc.     

Dynamic brain connectivity is a better predictor of PTSD than static connectivity

Using resting‐state functional magnetic resonance imaging, we test the hypothesis that subjects with post‐traumatic stress disorder (PTSD) are characterized by reduced temporal variability of brain connectivity compared to matched healthy controls. Specifically, we test whether PTSD is characterized by elevated static connectivity, coupled with decreased temporal variability of those connections, with the latter providing greater sensitivity toward the pathology than the former. Static functional connectivity (FC; nondirectional zero‐lag correlation) and static effective connectivity (EC; directional time‐lagged relationships) were obtained over the entire brain using conventional models. Dynamic FC and dynamic EC were estimated by letting the conventional models to vary as a function of time. Statistical separation and discriminability of these metrics between the groups and their ability to accurately predict the diagnostic label of a novel subject were ascertained using separate support vector machine classifiers. Our findings support our hypothesis that PTSD subjects have stronger static connectivity, but reduced temporal variability of connectivity. Further, machine learning classification accuracy obtained with dynamic FC and dynamic EC was significantly higher than that obtained with static FC and static EC, respectively. Furthermore, results also indicate that the ease with which brain regions engage or disengage with other regions may be more sensitive to underlying pathology than the strength with which they are engaged. Future studies must examine whether this is true only in the case of PTSD or is a general organizing principle in the human brain. Hum Brain Mapp 38:4479–4496, 2017. © 2017 Wiley Periodicals, Inc.     

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.     

Functional connectivity between parietal and frontal brain regions and intelligence in young children: The Generation R study

It has been shown in adults that individual differences in intelligence are related to the integrity of the interaction between parietal and frontal brain regions. Since connectivity between distant brain regions strengthens during childhood, it is unclear when in the course of development this relationship emerges. Thus, the goal of this study was to determine whether parietal‐frontal functional connectivity is associated with intelligence in young children. We performed independent component analyses on resting‐state fMRI data of 115 children (6–8 years old) to select seed and target regions for a seed/target region correlation analysis. We found that higher nonverbal intelligence was associated with increased functional connectivity between right parietal and right frontal regions, and between right parietal and dorsal anterior cingulate regions. The association between intelligence and functional connectivity between certain brain regions was stronger in girls than boys. In conclusion, we found that connectivity between the parietal and frontal lobes is critically involved in intelligence in young children. Hum Brain Mapp 34:3299–3307, 2013. © 2012 Wiley Periodicals, Inc.     

Interferon-α acutely impairs whole-brain functional connectivity network architecture – A preliminary study

Interferon-alpha (IFN-α) is a key mediator of antiviral immune responses used to treat Hepatitis C infection. Though clinically effective, IFN-α rapidly impairs mood, motivation and cognition, effects that can appear indistinguishable from major depression and provide powerful empirical support for the inflammation theory of depression. Though inflammation has been shown to modulate activity within discrete brain regions, how it affects distributed information processing and the architecture of whole brain functional connectivity networks have not previously been investigated.Here we use a graph theoretic analysis of resting state functional magnetic resonance imaging (rfMRI) to investigate acute effects of systemic interferon-alpha (IFN-α) on whole brain functional connectivity architecture and its relationship to IFN-α-induced mood change. Twenty-two patients with Hepatitis-C infection, initiating IFN-α-based therapy were scanned at baseline and 4 h after their first IFN-α dose. The whole brain network was parcellated into 110 cortical and sub-cortical nodes based on the Oxford-Harvard Atlas and effects assessed on higher-level graph metrics, including node degree, betweenness centrality, global and local efficiency.IFN-α was associated with a significant reduction in global network connectivity (node degree) (p = 0.033) and efficiency (p = 0.013), indicating a global reduction of information transfer among the nodes forming the whole brain network. Effects were similar for highly connected (hub) and non-hub nodes, with no effect on betweenness centrality (p > 0.1). At a local level, we identified regions with reduced efficiency of information exchange and a sub-network with decreased functional connectivity after IFN-α. Changes in local and particularly global functional connectivity correlated with associated changes in mood measured on the Profile of Mood States (POMS) questionnaire.IFN-α rapidly induced a profound shift in whole brain network structure, impairing global functional connectivity and the efficiency of parallel information exchange. Correlations with multiple indices of mood change support a role for global changes in brain functional connectivity architecture in coordinated behavioral responses to IFN-α.     

Enhanced brain responsiveness during active emotional face processing in obsessive compulsive disorder

Abstract

Objectives. The abnormal processing of emotional stimuli is common to a variety of psychiatric disorders. Specifically, patients with prominent anxiety symptoms generally overreact to emotional cues, which has been linked to increased amygdala activation. However, in OCD, enhanced responses are predominantly obtained using disease-specific stimuli and preferentially involve frontostriatal systems. Methods. We assessed 21 OCD patients and 21 healthy controls with fMRI during an emotional face-processing paradigm involving active response generation to test for alterations in both brain activation and task-induced functional connectivity of the frontal cortex, the amygdala and the fusiform face area. Results. OCD patients showed significantly greater activation of “face-processing” regions including the amygdala, fusiform gyrus and dorsolateral prefrontal cortex. The reciprocal connectivity between face-processing regions was enhanced in OCD. Importantly, we detected significant correlations between patients’ clinical symptom severity and both task-related region activation and network functional connectivity. Conclusions. The results suggest that OCD patients may show enhanced brain responsiveness during emotional face-processing when tasks involve active response generation. Our findings diverge from previously described alterations in anxiety disorders, as patients showed enhanced amygdala-prefrontal connectivity as opposed to negative reciprocal interaction. This pattern would appear to be disorder-specific and was significantly related to obsessive-compulsive symptom severity.     

Functional connectivity at rest is sensitive to individual differences in executive function: A network analysis

Graph theory provides a means to understand the nature of network characteristics and connectivity between specific brain regions. Here it was used to investigate whether the network characteristics of the brain at rest are associated with three dimensions thought to underlie individual differences in executive function (EF)—common EF, shifting‐specific EF, and updating‐specific EF (Miyake and Friedman [2012]). To do so, both an a priori analysis focused mainly on select frontoparietal regions previously linked to individual differences in EF as well as a whole‐brain analysis were performed. The findings indicated that individual differences in each of the three dimensions of EF were associated with specific patterns of resting‐state connectivity both in a priori and other brain regions. More specifically, higher common EF was associated with greater integrative (i.e., more hublike) connectivity of cuneus and supplementary motor area but less integrative function of lateral frontal nodes and left temporal lobe nodes. Higher shifting‐specific EF was associated with more hublike motor‐related nodes and cingulo‐opercular nodes. Higher updating‐specific EF was associated with less hublike lateral and medial frontoparietal nodes. In general, these results suggested that higher ability in each of these three dimensions of EF was not solely characterized by the connectivity characteristics of frontoparietal regions. The pattern was complicated in that higher EF was associated with the connectivity profile of nodes outside of the traditional frontoparietal network, as well as with less hublike or centrality characteristics of some nodes within the frontoparietal network. Hum Brain Mapp 37:2959–2975, 2016. © 2016 Wiley Periodicals, Inc.     

Precuneus degeneration in nondemented elderly individuals with APOE ɛ4: Evidence from structural and functional MRI analyses

Neurodegenerative diseases such as Alzheimer's disease (AD) have been recognized to exhibit disease‐specific brain vulnerability patterns. Apolipoprotein E (APOE ) ?4 allele imparts a high genetic risk of developing AD. Whether the APOE ?4 allele damages the brain when cognitive functions are still intact is important to understand, especially for possible early detection and intervention. This study aimed to examine the selective degeneration pattern associated with the APOE ?4 allele in the brains of cognitively normal elderly subjects. We enrolled 35 cognitively healthy ?4 carriers and 40 non‐carriers (53 to 81 years old) to evaluate group differences in cortical thickness and brain activation during a memory‐encoding task. We also assessed the functional connectivity of the brain regions with both structural and functional damages. The results from the neuropsychological tests showed that the performances of ?4 carriers and non‐carriers were comparable. Primarily, we found that the precuneus exhibited thinner cortical thickness and decreased deactivation during memory encoding. Furthermore, the connectivity analyses show that carriers exhibited damaged connectivity of the precuneus to several regions in the default mode network and the attention/executive control network. Our study reveals the degeneration pattern of the ?4 allele, which could be used as a potential biomarker for early detection for possible interventions and treatments. Hum Brain Mapp 38:271–282, 2017 . © 2016 Wiley Periodicals, Inc.     

Intrinsic functional connectivity variance and state‐specific under‐connectivity in autism

Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with altered brain connectivity. Previous neuroimaging research demonstrates inconsistent results, particularly in studies of functional connectivity in ASD. Typically, these inconsistent findings are results of studies using static measures of resting‐state functional connectivity. Recent work has demonstrated that functional brain connections are dynamic, suggesting that static connectivity metrics fail to capture nuanced time‐varying properties of functional connections in the brain. Here we used a dynamic functional connectivity approach to examine the differences in the strength and variance of dynamic functional connections between individuals with ASD and healthy controls (HCs). The variance of dynamic functional connections was defined as the respective standard deviations of the dynamic functional connectivity strength across time. We utilized a large multicenter dataset of 507 male subjects (209 with ASD and 298 HC, from 6 to 36 years old) from the Autism Brain Imaging Data Exchange (ABIDE) to identify six distinct whole‐brain dynamic functional connectivity states. Analyses demonstrated greater variance of widespread long‐range dynamic functional connections in ASD (P < 0.05, NBS method) and weaker dynamic functional connections in ASD (P < 0.05, NBS method) within specific whole‐brain connectivity states. Hypervariant dynamic connections were also characterized by weaker connectivity strength in ASD compared with HC. Increased variance of dynamic functional connections was also related to ASD symptom severity (ADOS total score) (P < 0.05), and was most prominent in connections related to the medial superior frontal gyrus and temporal pole. These results demonstrate that greater intraindividual dynamic variance is a potential biomarker of ASD. Hum Brain Mapp 38:5740–5755, 2017. © 2017 Wiley Periodicals, Inc.     

The cerebellum after trauma: Resting‐state functional connectivity of the cerebellum in posttraumatic stress disorder and its dissociative subtype

The cerebellum plays a key role not only in motor function but also in affect and cognition. Although several psychopathological disorders have been associated with overall cerebellar dysfunction, it remains unclear whether different regions of the cerebellum contribute uniquely to psychopathology. Accordingly, we compared seed‐based resting‐state functional connectivity of the anterior cerebellum (lobule IV–V), of the posterior cerebellum (Crus I), and of the anterior vermis across posttraumatic stress disorder (PTSD; n = 65), its dissociative subtype (PTSD + DS; n = 37), and non‐trauma‐exposed healthy controls (HC; n = 47). Here, we observed decreased functional connectivity of the anterior cerebellum and anterior vermis with brain regions involved in somatosensory processing, multisensory integration, and bodily self‐consciousness (temporo‐parietal junction, postcentral gyrus, and superior parietal lobule) in PTSD + DS as compared to PTSD and HC. Moreover, the PTSD + DS group showed increased functional connectivity of the posterior cerebellum with cortical areas related to emotion regulation (ventromedial prefrontal and orbito‐frontal cortex, subgenual anterior cingulum) as compared to PTSD. By contrast, PTSD showed increased functional connectivity of the anterior cerebellum with cortical areas associated with visual processing (fusiform gyrus), interoceptive awareness (posterior insula), memory retrieval, and contextual processing (hippocampus) as compared to HC. Finally, we observed decreased functional connectivity between the posterior cerebellum and prefrontal regions involved in emotion regulation, in PTSD as compared to HC. These findings not only highlight the crucial role of each cerebellar region examined in the psychopathology of PTSD but also reveal unique alterations in functional connectivity distinguishing the dissociative subtype of PTSD versus PTSD.     

Functional connectivity with anterior cingulate and orbitofrontal cortices during decision-making

Recent neuroscience research is beginning to discover the brain regions involved in decision-making under uncertainty, but little is known about whether or how these regions functionally interact with each other. Here, we used event-related functional magnetic resonance imaging to examine both changes in overall activity and changes in functional connectivity during risk-taking. Results showed that choosing high-risk over low-risk decisions was associated with increased activity in both anterior cingulate and orbitofrontal cortices. Connectivity analyses revealed that largely distinct, but somewhat overlapping, cortical and subcortical regions exhibited significant functional connectivity with anterior cingulate and orbitofrontal cortices. Additionally, connectivity with the anterior cingulate in some regions, including the orbitofrontal cortex and nucleus accumbens, was modulated by the decision participants chose. These findings (1) elucidate large networks of brain regions that are functionally connected with both anterior cingulate and orbitofrontal cortices during decision-making and (2) demonstrate that the roles of orbitofrontal and anterior cingulate cortices can be functionally differentiated by examining patterns of connectivity.     

Efficiency of weak brain connections support general cognitive functioning

Brain network topology provides valuable information on healthy and pathological brain functioning. Novel approaches for brain network analysis have shown an association between topological properties and cognitive functioning. Under the assumption that “stronger is better”, the exploration of brain properties has generally focused on the connectivity patterns of the most strongly correlated regions, whereas the role of weaker brain connections has remained obscure for years. Here, we assessed whether the different strength of connections between brain regions may explain individual differences in intelligence. We analyzed‐functional connectivity at rest in ninety‐eight healthy individuals of different age, and correlated several connectivity measures with full scale, verbal, and performance Intelligent Quotients (IQs). Our results showed that the variance in IQ levels was mostly explained by the distributed communication efficiency of brain networks built using moderately weak, long‐distance connections, with only a smaller contribution of stronger connections. The variability in individual IQs was associated with the global efficiency of a pool of regions in the prefrontal lobes, hippocampus, temporal pole, and postcentral gyrus. These findings challenge the traditional view of a prominent role of strong functional brain connections in brain topology, and highlight the importance of both strong and weak connections in determining the functional architecture responsible for human intelligence variability. Hum Brain Mapp 35:4566–4582, 2014. © 2014 Wiley Periodicals, Inc .     

Spatio‐temporal dynamics of resting‐state brain networks improve single‐subject prediction of schizophrenia diagnosis

Correlation in functional MRI activity between spatially separated brain regions can fluctuate dynamically when an individual is at rest. These dynamics are typically characterized temporally by measuring fluctuations in functional connectivity between brain regions that remain fixed in space over time. Here, dynamics in functional connectivity were characterized in both time and space. Temporal dynamics were mapped with sliding‐window correlation, while spatial dynamics were characterized by enabling network regions to vary in size (shrink/grow) over time according to the functional connectivity profile of their constituent voxels. These temporal and spatial dynamics were evaluated as biomarkers to distinguish schizophrenia patients from controls, and compared to current biomarkers based on static measures of resting‐state functional connectivity. Support vector machine classifiers were trained using: (a) static, (b) dynamic in time, (c) dynamic in space, and (d) dynamic in time and space characterizations of functional connectivity within canonical resting‐state brain networks. Classifiers trained on functional connectivity dynamics mapped over both space and time predicted diagnostic status with accuracy exceeding 91%, whereas utilizing only spatial or temporal dynamics alone yielded lower classification accuracies. Static measures of functional connectivity yielded the lowest accuracy (79.5%). Compared to healthy comparison individuals, schizophrenia patients generally exhibited functional connectivity that was reduced in strength and more variable. Robustness was established with replication in an independent dataset. The utility of biomarkers based on temporal and spatial functional connectivity dynamics suggests that resting‐state dynamics are not trivially attributable to sampling variability and head motion.     

Intelligence‐related differences in the asymmetry of spontaneous cerebral activity

Recent evidence suggests the spontaneous BOLD signal synchronization of corresponding interhemispheric, homotopic regions as a stable trait of human brain physiology, with emerging differences in such organization being also related to some pathological conditions. To understand whether such brain functional symmetries play a role into higher‐order cognitive functioning, here we correlated the functional homotopy profiles of 119 healthy subjects with their intelligence level. Counterintuitively, reduced homotopic connectivity in above average‐IQ versus average‐IQ subjects was observed, with significant reductions in visual and somatosensory cortices, supplementary motor area, rolandic operculum, and middle temporal gyrus, possibly suggesting that a downgrading of interhemispheric talk at rest could be associated with higher cognitive functioning. These regions also showed an increased spontaneous synchrony with medial structures located in ipsi‐ and contralateral hemispheres, with such pattern being mostly detectable for regions placed in the left hemisphere. The interactions with age and gender have been also tested, with different patterns for subjects above and below 25 years old and less homotopic connectivity in the prefrontal cortex and posterior midline regions in female participants with higher IQ scores. These findings support prior evidence suggesting a functional role for homotopic connectivity in human cognitive expression, promoting the reduction of synchrony between primary sensory regions as a predictor of higher intelligence levels. Hum Brain Mapp 36:3586–3602, 2015. © 2015 Wiley Periodicals, Inc .     

Postoperative axonal changes in the contralateral hemisphere in children with medically refractory epilepsy: A longitudinal diffusion tensor imaging connectome analysis

To determine brain plasticity changes due to resective epilepsy surgery in children, we performed a longitudinal connectome analysis on the pattern of axonal connectivity in the contralateral hemisphere. Pre‐ and postoperative diffusion tensor imaging (DTI) data were acquired from 35 children with intractable focal epilepsy. A total of 54 brain regions of interest (ROIs) were generated in the hemisphere contralateral to the resection. Within a 54 × 54 connectivity matrix, a pairwise connectivity score was calculated for each connection between two ROIs, based on the DTI fiber streamline number in each connection. A permuted Spearman's ρ‐rank analysis was used to identify specific inter‐regional connections showing a significant association between the postoperative change of connectivity score and clinical variables. Nineteen connections in the contralateral hemisphere showed postoperative increases in the strength of connectivity. Postoperative increase in connectivity between insular–inferior frontal operculum regions as well as that between superior frontal orbital and mid frontal orbital regions were both significantly associated with a larger surgical resection volume (ρ > +0.40) and a younger patient age (ρ > ?0.34). These increases were more robust in patients with frontal resection and in those achieving seizure freedom. Neuropsychological evaluation on subsets of patients revealed that such increases in connectivity were associated with preserved or improved cognitive functions such as visual memory and planning. Resective epilepsy surgery may lead to increased contralateral axonal connectivity in children with focal epilepsy. Our data lead to a hypothesis that such increased connectivity may be an imaging marker of postoperative brain plasticity to compensate for cognitive function. Hum Brain Mapp 37:3946–3956, 2016. © 2016 Wiley Periodicals, Inc.     

Functional brain network abnormalities during verbal working memory performance in adolescents and young adults with dyslexia

Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional neuroanatomy underlying cognitive dysfunction in dyslexia. In this study, functional magnetic resonance imaging and multivariate analytic techniques were used to investigate patterns of functional connectivity during a verbal WM task in individuals with dyslexia (n = 12) and control subjects (n = 13). Dyslexics were not significantly slower than controls; however, they were less accurate with increasing WM demand. Independent component analysis identified 18 independent components (ICs) among which two ICs were selected for further analyses. These ICs included functional networks which were positively correlated with the delay period of the activation task in both healthy controls and dyslexics. Connectivity abnormalities in dyslexics were detected within both networks of interest: within a “phonological” left-lateralized prefrontal network, increased functional connectivity was found in left prefrontal and inferior parietal regions. Within an “executive” bilateral frontoparietal network, dyslexics showed a decreased connectivity pattern comprising bilateral dorsolateral prefrontal and posterior parietal regions, while increased connectivity was found in the left angular gyrus, the left hippocampal cortex and the right thalamus. The functional connectivity strength in the latter regions was associated with WM task accuracy and with the numbers of errors during a spelling test. These data suggest functional connectivity abnormalities in two spatiotemporally dissociable brain networks underlying WM dysfunction in individuals with dyslexia.