Imaging functional motor connectivity in hemiparetic children with perinatal stroke

Perinatal stroke causes lifelong disability, particularly hemiparetic cerebral palsy. Arterial ischemic strokes (AIS) are large, cortical, and subcortical injuries acquired near birth due to acute occlusion of the middle cerebral artery. Periventricular venous infarctions (PVI) are smaller, subcortical strokes acquired prior to 34 weeks gestation involving injury to the periventricular white matter. Both stroke types can damage motor pathways, thus, we investigated resulting alterations in functional motor networks and probed function. We measured blood oxygen level dependent (BOLD) fluctuations at rest in 38 participants [10 arterial patients (age = 14.7 ± 4.1 years), 10 venous patients (age = 13.5 ± 3.7 years), and 18 typically developing controls (TDCs) (age = 15.3 ± 5.1 years)] and explored strength and laterality of functional connectivity in the motor network. Inclusion criteria included MRI‐confirmed, unilateral perinatal stroke, symptomatic hemiparetic cerebral palsy, and 6–19 years old at time of imaging. Seed‐based functional connectivity analyses measured temporal correlations in BOLD response over the whole brain using primary motor cortices as seeds. Laterality indices based on mean z‐scores in lesioned and nonlesioned hemispheres explored laterality. In AIS patients, significant differences in both strength and laterality of motor network connections were observed compared with TDCs. In PVI patients, motor networks largely resembled those of healthy controls, albeit slightly weaker and asymmetric, despite subcortical damage and hemiparesis. Functional connectivity strengths were not related to motor outcome scores for either stroke group. This study serves as a foundation to better understand how resting‐state fMRI can assess motor functional connectivity and potentially be applied to explore mechanisms of interventional therapies after perinatal stroke.     

Predictors of coupling between structural and functional cortical networks in normal aging

Understanding how the mammalian neocortex creates cognition largely depends on knowledge about large‐scale cortical organization. Accumulated evidence has illuminated cortical substrates of cognition across the lifespan, but how topological properties of cortical networks support structure‐function relationships in normal aging remains an open question. Here we investigate the role of connections (i.e., short/long and direct/indirect) and node properties (i.e., centrality and modularity) in predicting functional‐structural connectivity coupling in healthy elderly subjects. Connectivity networks were derived from correlations of cortical thickness and cortical glucose consumption in resting state. Local‐direct connections (i.e., nodes separated by less than 30 mm) and node modularity (i.e., a set of nodes highly interconnected within a topological community and sparsely interconnected with nodes from other modules) in the functional network were identified as the main determinants of coupling between cortical networks, suggesting that the structural network in aging is mainly constrained by functional topological properties involved in the segregation of information, likely due to aging‐related deficits in functional integration. This hypothesis is supported by an enhanced connectivity between cortical regions of different resting‐state networks involved in sensorimotor and memory functions in detrimental to associations between fronto‐parietal regions supporting executive processes. Taken collectively, these findings open new avenues to identify aging‐related failures in the anatomo‐functional organization of the neocortical mantle, and might contribute to early detection of prevalent neurodegenerative conditions occurring in the late life. Hum Brain Mapp 35:2724–2740, 2014. © 2013 Wiley Periodicals, Inc .     

Altered intra‐ and inter‐network functional coupling of resting‐state networks associated with motor dysfunction in stroke

Motor functions are supported through functional integration across the extended motor system network. Individuals following stroke often show deficits on motor performance requiring coordination of multiple brain networks; however, the assessment of connectivity patterns after stroke was still unclear. This study aimed to investigate the changes in intra‐ and inter‐network functional connectivity (FC) of multiple networks following stroke and further correlate FC with motor performance. Thirty‐three left subcortical chronic stroke patients and 34 healthy controls underwent resting‐state functional magnetic resonance imaging. Eleven resting‐state networks were identified via independent component analysis (ICA). Compared with healthy controls, the stroke group showed abnormal FC within the motor network (MN), visual network (VN), dorsal attention network (DAN), and executive control network (ECN). Additionally, the FC values of the ipsilesional inferior parietal lobule (IPL) within the ECN were negatively correlated with the Fugl‐Meyer Assessment (FMA) scores (hand + wrist). With respect to inter‐network interactions, the ipsilesional frontoparietal network (FPN) decreased FC with the MN and DAN; the contralesional FPN decreased FC with the ECN, but it increased FC with the default mode network (DMN); and the posterior DMN decreased FC with the VN. In sum, this study demonstrated the coexistence of intra‐ and inter‐network alterations associated with motor‐visual attention and high‐order cognitive control function in chronic stroke, which might provide insights into brain network plasticity following stroke.     

Brain structure and organization five decades after childhood onset epilepsy

The purpose of this project was to characterize brain structure and organization in persons with active and remitted childhood onset epilepsy 50 years after diagnosis compared with healthy controls. Participants from a population‐based investigation of uncomplicated childhood onset epilepsy were followed up 5 decades later. Forty‐one participants had a history of childhood onset epilepsy (mean age of onset = 5.2 years, current chronological age = 56.0 years) and were compared with 48 population‐based controls (mean age = 55.9 years). Of the epilepsy participants, 8 had persisting active epilepsy and in 33 the epilepsy had remitted. All participants underwent 3T MRI with subsequent vertex analysis of cortical volume, thickness, surface area and gyral complexity. In addition, cortical and subcortical volumes, including regions of the frontal, parietal, temporal, and occipital lobes, and subcortical structures including amygdala, thalamus, and hippocampus, were analyzed using graph theory techniques. There were modest group differences in traditional vertex‐based analyses of cortical volume, thickness, surface area and gyral index, as well as across volumes of subcortical structures, after correction for multiple comparisons. Graph theory analyses revealed suboptimal topological structural organization with enhanced network segregation and reduced global integration in the epilepsy participants compared with controls, these patterns significantly more extreme in the active epilepsy group. Furthermore, both groups with epilepsy presented a greater number of higher Z‐score regions in betweenness centrality (BC) than lower Z‐score regions compared with controls. Also, contrary to the group with remitted epilepsy, patients with active epilepsy presented most of their high BC Z‐score regions in subcortical areas including the amygdala, thalamus, hippocampus, pallidum, and accumbens. Overall, this population‐based investigation of long term outcome (5 decades) of childhood onset epilepsy reveals persisting abnormalities, especially when examined by graph theoretical measurements, and provides new insights into the very long‐term outcomes of active and remitted epilepsy. Hum Brain Mapp 38:3289–3299, 2017. © 2017 Wiley Periodicals, Inc.     

Graph theory analysis of resting‐state functional magnetic resonance imaging in essential tremor

Essential tremor (ET) is a neurological disease with both motor and nonmotor manifestations; however, little is known about its underlying brain basis. Furthermore, the overall organization of the brain network in ET remains largely unexplored. We investigated the topological properties of brain functional network, derived from resting‐state functional magnetic resonance imaging (MRI) data, in 23 ET patients versus 23 healthy controls. Graph theory analysis was used to assess the functional network organization. At the global level, the functional network of ET patients was characterized by lower small‐worldness values than healthy controls—less clustered functionality of the brain. At the regional level, compared with the healthy controls, ET patients showed significantly higher values of global efficiency, cost and degree, and a shorter average path length in the left inferior frontal gyrus (pars opercularis), right inferior temporal gyrus (posterior division and temporo‐occipital part), right inferior lateral occipital cortex, left paracingulate, bilateral precuneus bilaterally, left lingual gyrus, right hippocampus, left amygdala, nucleus accumbens bilaterally, and left middle temporal gyrus (posterior part). In addition, ET patients showed significant higher local efficiency and clustering coefficient values in frontal medial cortex bilaterally, subcallosal cortex, posterior cingulate cortex, parahippocampal gyri bilaterally (posterior division), right lingual gyrus, right cerebellar flocculus, right postcentral gyrus, right inferior semilunar lobule of cerebellum and culmen of vermis. Finally, the right intracalcarine cortex and the left orbitofrontal cortex showed a shorter average path length in ET patients, while the left frontal operculum and the right planum polare showed a higher betweenness centrality in ET patients. In conclusion, the efficiency of the overall brain functional network in ET is disrupted. Further, our results support the concept that ET is a disorder that disrupts widespread brain regions, including those outside of the brain regions responsible for tremor.     

Whole‐brain computational modeling reveals disruption of microscale brain dynamics in HIV infected individuals

MRI‐based neuroimaging techniques have been used to investigate brain injury associated with HIV‐infection. Whole‐brain cortical mean‐field dynamic modeling provides a way to integrate structural and functional imaging outcomes, allowing investigation of microscale brain dynamics. In this study, we adopted the relaxed mean‐field dynamic modeling to investigate structural and functional connectivity in 42 HIV‐infected subjects before and after 12‐week of combination antiretroviral therapy (cART) and compared them with 46 age‐matched healthy subjects. Microscale brain dynamics were modeled by a set of parameters including two region‐specific microscale brain properties, recurrent connection strengths, and subcortical inputs. We also analyzed the relationship between the model parameters (i.e., the recurrent connection and subcortical inputs) and functional network topological characterizations, including smallworldness, clustering coefficient, and network efficiency. The results show that untreated HIV‐infected individuals have disrupted local brain dynamics that in part correlate with network topological measurements. Notably, after 12 weeks of cART, both the microscale brain dynamics and the network topological measurements improved and were closer to those in the healthy brain. This was also associated with improved cognitive performance, suggesting that improvement in local brain dynamics translates into clinical improvement.     

Positive and negative affective processing exhibit dissociable functional hubs during the viewing of affective pictures

Recent resting‐state functional magnetic resonance imaging (fMRI) studies using graph theory metrics have revealed that the functional network of the human brain possesses small‐world characteristics and comprises several functional hub regions. However, it is unclear how the affective functional network is organized in the brain during the processing of affective information. In this study, the fMRI data were collected from 25 healthy college students as they viewed a total of 81 positive, neutral, and negative pictures. The results indicated that affective functional networks exhibit weaker small‐worldness properties with higher local efficiency, implying that local connections increase during viewing affective pictures. Moreover, positive and negative emotional processing exhibit dissociable functional hubs, emerging mainly in task‐positive regions. These functional hubs, which are the centers of information processing, have nodal betweenness centrality values that are at least 1.5 times larger than the average betweenness centrality of the network. Positive affect scores correlated with the betweenness values of the right orbital frontal cortex (OFC) and the right putamen in the positive emotional network; negative affect scores correlated with the betweenness values of the left OFC and the left amygdala in the negative emotional network. The local efficiencies in the left superior and inferior parietal lobe correlated with subsequent arousal ratings of positive and negative pictures, respectively. These observations provide important evidence for the organizational principles of the human brain functional connectome during the processing of affective information. Hum Brain Mapp, 36:415–426, 2015. © 2014 Wiley Periodicals, Inc.     

Resting‐state and task‐based centrality of dorsolateral prefrontal cortex predict resilience to 1 Hz repetitive transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) is used to investigate normal brain function in healthy participants and as a treatment for brain disorders. Various subject factors can influence individual response to rTMS, including brain network properties. A previous study by our group showed that “virtually lesioning” the left dorsolateral prefrontal cortex (dlPFC; important for cognitive flexibility) using 1 Hz rTMS reduced performance on a set‐shifting task. We aimed to determine whether this behavioural response was related to topological features of pre‐TMS resting‐state and task‐based functional networks. 1 Hz (inhibitory) rTMS was applied to the left dlPFC in 16 healthy participants, and to the vertex in 17 participants as a control condition. Participants performed a set‐shifting task during fMRI at baseline and directly after a single rTMS session 1–2 weeks later. Functional network topology measures were calculated from resting‐state and task‐based fMRI scans using graph theoretical analysis. The dlPFC‐stimulated group, but not the vertex group, showed reduced setshifting performance after rTMS, associated with lower task‐based betweenness centrality (BC) of the dlPFC at baseline (p = .030) and a smaller reduction in task‐based BC after rTMS (p = .024). Reduced repeat trial accuracy after rTMS was associated with higher baseline resting state node strength of the dlPFC (p = .017). Our results suggest that behavioural response to 1 Hz rTMS to the dlPFC is dependent on baseline functional network features. Individuals with more globally integrated stimulated regions show greater resilience to rTMS effects, while individuals with more locally well‐connected regions show greater vulnerability.     

Altered small-world brain functional networks in children with attention-deficit/hyperactivity disorder

In this study, we investigated the changes in topological architectures of brain functional networks in attention-deficit/hyperactivity disorder (ADHD). Functional magnetic resonance images (fMRI) were obtained from 19 children with ADHD and 20 healthy controls during resting state. Brain functional networks were constructed by thresholding the correlation matrix between 90 cortical and subcortical regions and further analyzed by applying graph theoretical approaches. Experimental results showed that, although brain networks of both groups exhibited economical small-world topology, altered functional networks were demonstrated in the brain of ADHD when compared with the normal controls. In particular, increased local efficiencies combined with a decreasing tendency in global efficiencies found in ADHD suggested a disorder-related shift of the topology toward regular networks. Additionally, significant alterations in nodal efficiency were also found in ADHD, involving prefrontal, temporal, and occipital cortex regions, which were compatible with previous ADHD studies. The present study provided the first evidence for brain dysfunction in ADHD from the viewpoint of global organization of brain functional networks by using resting-state fMRI.     

Degeneration of corpus callosum and recovery of motor function after stroke: A multimodal magnetic resonance imaging study

Animal models of stroke demonstrated that white matter ischemia may cause both axonal damage and myelin degradation distant from the core lesion, thereby impacting on behavior and functional outcome after stroke. We here used parameters derived from diffusion magnetic resonance imaging (MRI) to investigate the effect of focal white matter ischemia on functional reorganization within the motor system. Patients (n = 18) suffering from hand motor deficits in the subacute or chronic stage after subcortical stroke and healthy controls (n = 12) were scanned with both diffusion MRI and functional MRI while performing a motor task with the left or right hand. A laterality index was employed on activated voxels to assess functional reorganization across hemispheres. Regression analyses revealed that diffusion MRI parameters of both the ipsilesional corticospinal tract (CST) and corpus callosum (CC) predicted increased activation of the unaffected hemisphere during movements of the stroke‐affected hand. Changes in diffusion MRI parameters possibly reflecting axonal damage and/or destruction of myelin sheath correlated with a stronger bilateral recruitment of motor areas and poorer motor performance. Probabilistic fiber tracking analyses revealed that the region in the CC correlating with the fMRI laterality index and motor deficits connected to sensorimotor cortex, supplementary motor area, ventral premotor cortex, superior parietal lobule, and temporoparietal junction. The results suggest that degeneration of transcallosal fibers connecting higher order sensorimotor regions constitute a relevant factor influencing cortical reorganization and motor outcome after subcortical stroke. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

The retrosplenial cortex: A memory gateway between the cortical default mode network and the medial temporal lobe

The default mode network (DMN) involves interacting cortical areas, including the posterior cingulate cortex (PCC) and the retrosplenial cortex (RSC), and subcortical areas, including the medial temporal lobe (MTL). The degree of functional connectivity (FC) within the DMN, particularly between MTL and medial‐parietal subsystems, relates to episodic memory (EM) processes. However, past resting‐state studies investigating the link between posterior DMN‐MTL FC and EM performance yielded inconsistent results, possibly reflecting heterogeneity in the degree of connectivity between MTL and specific cortical DMN regions. Animal work suggests that RSC has structural connections to both cortical DMN regions and MTL, and may thus serve as an intermediate layer that facilitates information transfer between cortical and subcortical DMNs. We studied 180 healthy old adults (aged 64–68 years), who underwent comprehensive assessment of EM, along with resting‐state fMRI. We found greater FC between MTL and RSC than between MTL and the other cortical DMN regions (e.g., PCC), with the only significant association with EM observed for MTL‐RSC FC. Mediational analysis showed that MTL‐cortical DMN connectivity increased with RSC as a mediator. Further analysis using a graph‐theoretical approach on DMN nodes revealed the highest betweenness centrality for RSC, confirming that a high proportion of short paths among DMN regions pass through RSC. Importantly, the degree of RSC mediation was associated with EM performance, suggesting that individuals with greater mediation have an EM advantage. These findings suggest that RSC forms a critical gateway between MTL and cortical DMN to support EM in older adults.     

Modulation of task‐related cortical connectivity in the acute and subacute phase after stroke

The functional relevance of cortical reorganization post‐stroke is still not well understood. In this study, we investigated task‐specific modulation of cortical connectivity between neural oscillations in key motor regions during the early phase after stroke. EEG and EMG recordings were examined from 15 patients and 18 controls during a precision grip task using the affected hand. Each patient attended two sessions in the acute and subacute phase (median of 3 and 34 days) post‐stroke. Dynamic causal modelling (DCM) for induced responses was used to investigate task‐specific modulations of oscillatory couplings in a bilateral network comprising supplementary motor area (SMA), dorsal premotor cortex (PMd) and primary motor cortex (M1). Fourteen models were constructed for each subject, and the input induced by the experimental manipulation (task) was set to inferior parietal lobule (IPL). Bayesian model selection favoured a fully connected model. A reduced coupling from SMA and intact M1 in the γ‐band (31–48 Hz) to lesioned M1 in the β‐band (15–30 Hz) was observed in patients in the acute phase compared to controls. Behavioural performance improved significantly in the subacute phase, while an increased positive coupling from intact PMd to lesioned M1 and a less negative modulation from lesioned M1 to intact M1 were observed for patients compared to controls both from the γ‐band to the β‐band. We infer that the observed differences in cross‐frequency cortical interactions are important for functional recovery.     

Spectral signatures of mirror movements in the sensori‐motor connectivity in kallmann syndrome

Mirror movements (MM) might be observed in congenital and acquired neurodegenerative conditions but their anatomic‐functional underpinnings are still largely elusive. This study investigated the spectral changes of resting‐state functional connectivity in Kallmann Syndrome (hypogonadotropic hypogonadism with hypo/anosmia with or without congenital MM) searching for insights into the phenomenon of MM. Forty‐four Kallmann syndrome patients (21 with MM) and 24 healthy control subjects underwent task (finger tapping) and resting‐state functional MRI. The spatial pattern of task‐related activations was used to mask regions and select putative motor networks in a spatially independent component analysis of resting‐state signals. For each resting‐state independent component time‐course power spectrum, we extracted the relative contribution of four separate bands: slow‐5 (0.01–0.027 Hz), slow‐4 (0.027–0.073 Hz), slow‐3 (0.073–0.198 Hz), slow‐2 (0.198–0.25 Hz), and analyzed the variance between groups. For the sensorimotor network, the analysis revealed a significant group by frequency interaction (P = 0.002) pointing to a frequency shift in the spectral content among subgroups with lower slow‐5 band and higher slow‐3 band contribution in Kallmann patients with MM versus controls (P = 0.028) and with lower slow‐5 band contribution between patients with and without MM (P = 0.057). In specific regions, as obtained from hand motor activation task analysis, spectral analyses demonstrated a lower slow‐5 band contribution in Kallmann patients with MM versus both controls and patients without MM (P < 0.05). In Kallmann syndrome, the peculiar phenomenon of bimanual synkinesis is associated at rest with regionally and spectrally selective functional connectivity changes pointing to a distinctive cortical and subcortical functional reorganization. Hum Brain Mapp 39:42–53, 2018. © 2017 Wiley Periodicals, Inc.     

Levodopa affects functional brain networks in parkinsonian resting tremor

Resting tremor in idiopathic Parkinson's disease (PD) is associated with an oscillatory network comprising cortical as well as subcortical brain areas. To shed light on the effect of levodopa on these network interactions, we investigated 10 patients with tremor‐dominant PD and reanalyzed data in 11 healthy volunteers mimicking PD resting tremor. To this end, we recorded surface electromyograms of forearm muscles and neuromagnetic activity using a 122‐channel whole‐head magnetometer (MEG). Measurements were performed after overnight withdrawal of levodopa (OFF) and 30 min after oral application of fast‐acting levodopa (ON). During OFF, patients showed the typical antagonistic resting tremor. Using the analysis tool Dynamic Imaging of Coherent Sources, we identified the oscillatory network associated with tremor comprising contralateral primary sensorimotor cortex (S1/M1), supplementary motor area (SMA), contralateral premotor cortex (PMC), thalamus, secondary somatosensory cortex (S2), posterior parietal cortex (PPC), and ipsilateral cerebellum oscillating at 8 to 10 Hz. After intake of levodopa, we found a significant decrease of cerebro‐cerebral coupling between thalamus and motor cortical areas. Similarly, in healthy controls mimicking resting tremor, we found a significant decrease of functional interaction within a thalamus–premotor–motor network during rest. However, in patients with PD, decrease of functional interaction between thalamus and PMC was significantly stronger when compared with healthy controls. These data support the hypothesis that (1) in patients with PD the basal ganglia and motor cortical structures become more closely entrained and (2) levodopa is associated with normalization of the functional interaction between thalamus and motor cortical areas. © 2008 Movement Disorder Society     

Altered Resting-State Signals in Patients with Acute Stroke In or Under the Thalamus

Previous studies have suggested that cortical functional reorganization is associated with motor recovery after stroke and that normal afferent sensory information is very important in that process. In this study, we selected patients who had a stroke in or under the thalamus, with potentially impaired afferent sensory information and analyzed the differences between these patients and healthy controls at three levels: brain regions, the functional connectivity between brain areas, and the whole-brain functional network. Compared with healthy controls, regional homogeneities in the left middle temporal gyrus decreased and functional connectivity between the left middle temporal gyrus and the stroke area increased in the patients. However, there was no significant change in the whole-brain functional network. By focusing on stroke located in or under the thalamus, our study contributes to wider inquiries into understanding and treating stroke.     

Network dynamics engaged in the modulation of motor behavior in stroke patients

Stroke patients with motor deficits typically feature enhanced neural activity in several cortical areas when moving their affected hand. However, also healthy subjects may show higher levels of neural activity in tasks with higher motor demands. Therefore, the question arises to what extent stroke‐related overactivity reflects performance‐level‐associated recruitment of neural resources rather than stroke‐induced neural reorganization. We here investigated which areas in the lesioned brain enable the flexible adaption to varying motor demands compared to healthy subjects. Accordingly, eleven well‐recovered left‐hemispheric chronic stroke patients were scanned using functional magnetic resonance imaging. Motor system activity was assessed for fist closures at increasing movement frequencies performed with the affected/right or unaffected/left hand. In patients, an increasing movement rate of the affected hand was associated with stronger neural activity in ipsilesional/left primary motor cortex (M1) but unlike in healthy controls also in contralesional/right dorsolateral premotor cortex (PMd) and contralesional/right superior parietal lobule (SPL). Connectivity analyses using dynamic causal modeling revealed stronger coupling of right SPL onto affected/left M1 in patients but not in controls when moving the affected/right hand independent of the movement speed. Furthermore, coupling of right SPL was positively coupled with the “active” ipsilesional/left M1 when stroke patients moved their affected/right hand with increasing movement frequency. In summary, these findings are compatible with a supportive role of right SPL with respect to motor function of the paretic hand in the reorganized brain.     

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     

Differences between child and adult large‐scale functional brain networks for reading tasks

Reading is an important high‐level cognitive function of the human brain, requiring interaction among multiple brain regions. Revealing differences between children's large‐scale functional brain networks for reading tasks and those of adults helps us to understand how the functional network changes over reading development. Here we used functional magnetic resonance imaging data of 17 adults (19–28 years old) and 16 children (11–13 years old), and graph theoretical analyses to investigate age‐related changes in large‐scale functional networks during rhyming and meaning judgment tasks on pairs of visually presented Chinese characters. We found that: (1) adults had stronger inter‐regional connectivity and nodal degree in occipital regions, while children had stronger inter‐regional connectivity in temporal regions, suggesting that adults rely more on visual orthographic processing whereas children rely more on auditory phonological processing during reading. (2) Only adults showed between‐task differences in inter‐regional connectivity and nodal degree, whereas children showed no task differences, suggesting the topological organization of adults’ reading network is more specialized. (3) Children showed greater inter‐regional connectivity and nodal degree than adults in multiple subcortical regions; the hubs in children were more distributed in subcortical regions while the hubs in adults were more distributed in cortical regions. These findings suggest that reading development is manifested by a shift from reliance on subcortical to cortical regions. Taken together, our study suggests that Chinese reading development is supported by developmental changes in brain connectivity properties, and some of these changes may be domain‐general while others may be specific to the reading domain.     

Altered cortical thickness and structural covariance networks in upper limb amputees: A graph theoretical analysis

Background

The extensive functional and structural remodeling that occurs in the brain after amputation often results in phantom limb pain (PLP). These closely related phenomena are still not fully understood.

Methods

Using magnetic resonance imaging (MRI) and graph theoretical analysis (GTA), we explored how alterations in brain cortical thickness (CTh) and structural covariance networks (SCNs) in upper limb amputees (ULAs) relate to PLP. In all, 45 ULAs and 45 healthy controls (HCs) underwent structural MRI. Regional network properties, including nodal degree, betweenness centrality (BC), and node efficiency, were analyzed with GTA. Similarly, global network properties, including global efficiency (Eglob), local efficiency (Eloc), clustering coefficient (Cp), characteristic path length (Lp), and the small-worldness index, were evaluated.

Results

Compared with HCs, ULAs had reduced CThs in the postcentral and precentral gyri contralateral to the amputated limb; this decrease in CTh was negatively correlated with PLP intensity in ULAs. ULAs showed varying degrees of change in node efficiency in regional network properties compared to HCs (p < 0.005). There were no group differences in Eglob, Eloc, Cp, and Lp properties (all p > 0.05). The real-worldness SCN of ULAs showed a small-world topology ranging from 2% to 34%, and the area under the curve of the small-worldness index in ULAs was significantly different compared to HCs (p < 0.001).

Conclusion

These results suggest that the topological organization of human CNS functional networks is altered after amputation of the upper limb, providing further support for the cortical remapping theory of PLP.     

Genetic load determines atrophy in hand cortico‐striatal pathways in presymptomatic Huntington's disease

Huntington's disease (HD) is an inherited neurodegenerative disorder that causes progressive breakdown of striatal neurons. Standard white matter integrity measures like fractional anisotropy and mean diffusivity derived from diffusion tensor imaging were analyzed in prodromal‐HD subjects; however, they studied either a whole brain or specific subcortical white matter structures with connections to cortical motor areas. In this work, we propose a novel analysis of a longitudinal cohort of 243 prodromal‐HD individuals and 88 healthy controls who underwent two or more diffusion MRI scans as part of the PREDICT‐HD study. We separately trace specific white matter fiber tracts connecting the striatum (caudate and putamen) with four cortical regions corresponding to the hand, face, trunk, and leg motor areas. A multi‐tensor tractography algorithm with an isotropic volume fraction compartment allows estimating diffusion of fast‐moving extra‐cellular water in regions containing crossing fibers and provides quantification of a microstructural property related to tissue atrophy. The tissue atrophy rate is separately analyzed in eight cortico‐striatal pathways as a function of CAG‐repeats (genetic load) by statistically regressing out age effect from our cohort. The results demonstrate a statistically significant increase in isotropic volume fraction (atrophy) bilaterally in hand fiber connections to the putamen with increasing CAG‐repeats, which connects the genetic abnormality (CAG‐repeats) to an imaging‐based microstructural marker of tissue integrity in specific white matter pathways in HD. Isotropic volume fraction measures in eight cortico‐striatal pathways are also correlated significantly with total motor scores and diagnostic confidence levels, providing evidence of their relevance to HD clinical presentation.