Compensatory Network Research Articles

Reorganization of the Social Brain in Individuals with Only One Intact Cerebral Hemisphere

Social cognition and emotion are ubiquitous human processes that recruit a reliable set of brain networks in healthy individuals. These brain networks typically comprise midline (e.g., medial prefrontal cortex) as well as lateral regions of the brain including homotopic regions in both hemispheres (e.g., left and right temporo-parietal junction). Yet the necessary roles of these networks, and the broader roles of the left and right cerebral hemispheres in socioemotional functioning, remains debated. Here, we investigated these questions in four rare adults whose right (three cases) or left (one case) cerebral hemisphere had been surgically removed (to a large extent) to treat epilepsy. We studied four closely matched healthy comparison participants, and also compared the patient findings to data from a previously published larger healthy comparison sample (n = 33). Participants completed standardized socioemotional and cognitive assessments to investigate social cognition. Functional magnetic resonance imaging (fMRI) data were obtained during passive viewing of a short, animated movie that distinctively recruits two social brain networks: one engaged when thinking about other agents’ internal mental states (e.g., beliefs, desires, emotions; so-called Theory of Mind or ToM network), and the second engaged when thinking about bodily states (e.g., pain, hunger; so-called PAIN network). Behavioral assessments demonstrated remarkably intact general cognitive functioning in all individuals with hemispherectomy. Social-emotional functioning was somewhat variable in the hemispherectomy participants, but strikingly, none of these individuals had consistently impaired social-emotional processing and none of the assessment scores were consistent with a psychiatric disorder. Using inter-region correlation analyses, we also found surprisingly typical ToM and PAIN networks, as well as typical differentiation of the two networks (in the intact hemisphere of patients with either right or left hemispherectomy), based on idiosyncratic reorganization of cortical activation. The findings argue that compensatory brain networks can process social and emotional information following hemispherectomy across different age levels (from 3 months to 20 years old), and suggest that social brain networks typically distributed across midline and lateral brain regions in this domain can be reorganized, to a substantial degree.

Functional Connectivity Networks and Their Recruitment During Working Memory Tasks in Adult Survivors of Childhood Brain Tumors.

Background: Assessments of functional connectivity of default mode network (DMN) and positive task-related networks (TRNs) using independent component analysis (ICA) may help describe long-term effects of childhood brain tumors and adjuvant treatments. Methods: Aiming to identify potential neuronal markers that may aid in prognosis and inform interventions to optimize outcomes, this study used ICA to evaluate the presence of functional connectivity networks and their recruitment during a letter n-back task in 23 adult survivors of childhood posterior fossa tumors (9 low grade, 14 high grade) at least 5 years past diagnosis compared with 40 age- and sex-matched healthy peers. Results: DMN components generally demonstrated increasing disengagement as task difficulty increased, and relationships between effective DMN disengagement and improved performance were observed in healthy controls (HCs). Low-grade brain tumor survivors (LGS) demonstrated unique patterns in DMN recruitment that suggested increased involvement of the medial prefrontal cortex in LGS during tasks. TRN components generally demonstrated increasing engagement, which was related to improved task performance in HCs for one executive control network (ECN) component. High-grade brain tumor survivors (HGS) demonstrated distinct challenges recruiting an ECN component at more difficult task levels and showed a relationship between recruitment of another ECN component and task performance, indicating a potential compensatory mechanism for some HGS. Conclusions: Findings suggest the importance of cognitive intervention in both survivor groups and the necessity to track LGS despite their cognitive abilities often resembling those of their healthy peers. Impact statement Distinct functional connectivity patterns were identified between both adult survivor of childhood brain tumor groups and peers during attention and working memory tasks, reflecting different damage and recovery from treatment. Survivors of low-grade tumors demonstrated unique patterns of recruitment of default mode network components in the context of similar cognitive abilities, whereas survivors of high-grade tumors demonstrated poorer cognitive abilities and may be utilizing compensatory executive control network components in the face of challenging tasks. Long-term clinical follow-up and cognitive remediation is warranted for both groups, including low grade cerebellar tumor patients who have traditionally not been monitored as closely.

Limited inhibition of multiple nodes in a driver network blocks metastasis.

Metastasis suppression by high-dose, multi-drug targeting is unsuccessful due to network heterogeneity and compensatory network activation. Here, we show that targeting driver network signaling capacity by limited inhibition of core pathways is a more effective anti-metastatic strategy. This principle underlies the action of a physiological metastasis suppressor, Raf Kinase Inhibitory Protein (RKIP), that moderately decreases stress-regulated MAP kinase network activity, reducing output to transcription factors such as pro-metastastic BACH1 and motility-related target genes. We developed a low-dose four-drug mimic that blocks metastatic colonization in mouse breast cancer models and increases survival. Experiments and network flow modeling show limited inhibition of multiple pathways is required to overcome variation in MAPK network topology and suppress signaling output across heterogeneous tumor cells. Restricting inhibition of individual kinases dissipates surplus signal, preventing threshold activation of compensatory kinase networks. This low-dose multi-drug approach to decrease signaling capacity of driver networks represents a transformative, clinically relevant strategy for anti-metastatic treatment.

The Role of Institutional and Structural Differences for City-Specific Arrangements of Urban Migration Regimes

In recent years, an increasing influx of migrants to Europe has led to a heated public discourse about integration capacities within receiving countries such as Germany. During this period, German society, with its changeful immigration history, is again challenged to provide policy responses and foster migrant integration, especially in urban areas. The efforts of cities along that path, however, vary greatly. Complementing locality approaches on immigration and integration policies, which are focused on metropolises and the U.S.-American context, this article is an empirical application for understanding institutional and structural conditions for local variations in integration strategies in Germany by presenting a comparative analysis of four mid-sized cities. The particular research interest lies on discourses from interviews with local authorities and civil society actors. Our analysis reveals city-specific streamlines: For instance, discourses at a center of the ‘knowledge society’ focused on a strong municipal power structure that allowed communally-financed, sustainable projects to evolve from a historically-grounded commitment to welcome migrants and from high financial capacities at its disposal. In another case, discourses revolved around a city’s financially constraints, which were equalized by compensatory civil society networks. In other cities, progress was associated with spontaneous local happenings or individual innovative leadership. These street-level patterns create a degree of locality within the global migration discourse, since they emerge from the interplay of financial, economic, and demographic features; historical concepts; or local events. We therefore contend that urban planning initiatives would profit from considering place-specific institutions that influence integration stakeholders, which are regime-makers and foster institutional, migration-led changes.

Resting State Connectivity Is Modulated by Motor Learning in Individuals After Stroke

Objective Activity patterns across brain regions that can be characterized at rest (ie, resting-state functional connectivity [rsFC]) are disrupted after stroke and linked to impairments in motor function. While changes in rsFC are associated with motor recovery, it is not clear how rsFC is modulated by skilled motor practice used to promote recovery. The current study examined how rsFC is modulated by skilled motor practice after stroke and how changes in rsFC are linked to motor learning. Methods Two groups of participants (individuals with stroke and age-matched controls) engaged in 4 weeks of skilled motor practice of a complex, gamified reaching task. Clinical assessments of motor function and impairment, and brain activity (via functional magnetic resonance imaging) were obtained before and after training. Results While no differences in rsFC were observed in the control group, increased connectivity was observed in the sensorimotor network, linked to learning in the stroke group. Relative to healthy controls, a decrease in network efficiency was observed in the stroke group following training. Conclusions Findings indicate that rsFC patterns related to learning observed after stroke reflect a shift toward a compensatory network configuration characterized by decreased network efficiency.

Domain compensatory adversarial networks for partial domain adaptation

Domain compensatory adversarial networks for partial domain adaptation

In‐out‐test and inverse translational medicine: When a new clinical paradigm is needed to find new biomarker perspectives

AbstractBackgroundPROA project is based in the Neurology Service and the Investigation Unit at the Hospital Dr. Negrin (Canary Islands, Spain). PROA aims to find new ways to a better understanding of cognitive and biological mechanisms of normal aging and Alzheimer's disease (AD). This study shows previous, preliminary and ongoing PROA project data about the relationship between clinical assessment and biomarkers in Alzheimer’s disease research. It is considered the contribution of In‐out test, a paradigm hypothesized to avoid reliance on executive function, which may compensate damaged memory networks. Unlike other tests using the hippocampal amnesia paradigm, that assess memory after effective encoding of information, the In‐out‐test provokes an interference during encoding by means of a simultaneous executive task. According to this model the memory deficit in prodromal AD can be unmasked when those compensatory networks are saturated by an executive activity without being able to compensate the already damaged mnemonic activity.MethodNeuropsychological assessment: Neuropsychological battery: episodic (Free and cued Selective Reminding Test‐ FCSRT), shot‐term, visual memory, visuospacial and constructive praxis; executive functions; Daily living and instrumental activities. In‐out‐test: Assesses episodic memory after the patient performs a categorization task and memorizes 6 words simultaneously. The time taken to complete this test was 5 to 12 minutes.ResultCross‐sectional study: ICC (Intraclass correlation) between the In‐out‐test and FCSRT r= 0.87 (p=0.001). ICC between the In‐out‐test and Aβ42 and P‐tau/Aβ42 for controls: 0.73 and 0.75 respectively; P‐tau for MCI: 0.77 and total sample: 0.70; Aβ42 for dementia: 0.71. All ICC measures between FCSRT and biomarkers were ≤ 0.264. Sensitivity: 0.93; specificity: 0.77. Predictive value for In‐out‐tet, Positive:0.89; negative: 0.83. Conversion study: Agreement (Kappa): In‐out‐test: 0.67/0.61 (memory/learning); FCSRT: 0.57; P‐tau/Aβ42: 0.126. P‐tau(50ng/ml): 0.40. Aβ42 (500 ng/ml): 0.07ConclusionCompensatory mechanisms in prodromal AD might be a confounding factor in the early detection by classical hippocampal amnesia paradigm and even by csf biomarkers. In‐out‐test may play a roll unmasking the memory deficit in the early stages of AD. In orfer to find new reliable biomarkers for aging and AD, PROA project will focused on new targets such as oxidative stress, phosphorilation, microbiota and telomers.

Abstract 5038: Limited inhibition of multiple nodes in a driver network blocks metastasis

Abstract High-dose, single-drug treatment is unsuccessful at suppressing metastasis due to cellular heterogeneity and feedback activation. Here we demonstrate that targeting driver network signaling capacity by limited inhibition at multiple nodes is a more effective anti-metastatic strategy. A physiological metastasis suppressor, Raf Kinase Inhibitory Protein, decreases the activity of multiple kinases in the stress-regulated MAP kinase (MAPK) network and reduces the output to metastatic transcription factor BACH1 that upregulates motility-related genes. This effect is mimicked by a low-dose four-drug cocktail (4D-MAPKi) that blocks metastatic colonization in mouse breast cancer models and increases survival. Drug treatment and network modeling show that 1) multi-kinase inhibition is required to suppress signaling output across cells with different MAPK network topologies, and 2) restricting inhibition of individual kinases prevents threshold activation of other compensatory kinase networks. This low-dose multi-drug approach to decrease signaling capacity of a driver network represents a transformative, clinically-relevant strategy for anti-metastatic treatment. Citation Format: Ali Ekrem Yesilkanal, Dongbo Yang, Payal Tiwari, Alan U. Sabino, Jiyoung Lee, Xiao-He Xie, Siqi Sun, Christopher Dann, Ethan Steinberg, Timothy Stuhlmiller, Casey Frankenberger, Elizabeth Goldsmith, Gary L. Johnson, Alexandre F. Ramos, Marsha Rosner. Limited inhibition of multiple nodes in a driver network blocks metastasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5038.

Sensory Inhibition Is Related to Variable Speech Perception in Noise in Adults With Normal Hearing.

Purpose Speech perception in noise (SPiN) varies widely in individuals with normal hearing, which may be attributed to factors that are not reflected in the audiogram, such as inhibition. However, inhibition is involved at both sensory and cognitive stages of auditory perception, and while inhibition at the cognitive level has been shown to be a significant factor in SPiN processes, it is unknown whether sensory inhibition may also contribute to SPiN variability. Therefore, the goal of this study was to evaluate sensory inhibition in adults with normal hearing and mild SPiN impairment. Method Cortical auditory evoked potentials (CAEPs) were recorded in 49 adults via high-density electroencephalography using an auditory gating paradigm. Participants were categorized according to a median signal-to-noise ratio (SNR) loss of 1.5 dB: typical SNR loss ≤ 1.5 dB (n = 32), mild SNR loss > 1.5 dB (n = 17). CAEP gating responses were compared and correlated with SNR loss and extended high-frequency thresholds. Current density reconstructions were performed to qualitatively observe underlying cortical inhibitory networks in each group. Results In comparison to adults with typical SPiN ability, adults with mild SPiN impairment showed an absence of the gating response. A CAEP gating component (P2) reflected decreased sensory inhibition and correlated with increased SNR loss. Extended high-frequency thresholds were also found to correlate with SNR loss, but not gating function. An atypical cortical inhibitory network was observed in the mild SNR loss group, with reduced frontal and absent prefrontal activation. Conclusion Sensory inhibition appears to be atypical and related to SPiN deficits in adults with mild impairment. In addition, cortical inhibitory networks appear to be incomplete, with a possible compensatory parietal network. Further research is needed to delineate between types or levels of central inhibitory mechanisms and their contribution to SPiN processes.

Auditory Gating in Hearing Loss

Sensory gating is a measure used to evaluate inhibitory deficits underlying neurological disorders. However, the effects of hearing loss (HL), thought to decrease inhibition, remain unknown on gating function. The goal of this study was to investigate gating performance in HL. This was a prospective, cross-sectional study with independent group comparison and correlational design. Eleven adults (mean age/standard deviation = 47.546 ± 7.967 years) with normal hearing (NH) and 11 adults (mean age/standard deviation = 56.273 ± 13.871 years) with mild-moderate high-frequency HL. Cortical auditory evoked potentials (CAEPs) were recorded in response to tonal pairs via high-density electroencephalography. The CAEP response to the second tone in the pair (S2) was compared with the response to the first tone in the pair (S1) within groups. Amplitude gating indices were compared between groups and correlated with auditory behavioral measures. Current density reconstructions were performed to estimate cortical gating generators. Amplitude gating indices were decreased and correlated with elevated auditory thresholds. Gating generators in temporal, frontal, and prefrontal regions were localized in the NH group, while HL gating was localized in mainly temporal and parietal areas. Reduced inhibition may be associated with compensatory cortical gating networks in HL and should be considered when utilizing gating in clinical populations.

Osteoclast-mediated bone resorption is controlled by a compensatory network of secreted and membrane-tethered metalloproteinases.

Osteoclasts actively remodel both the mineral and proteinaceous components of bone during normal growth and development as well as pathologic states ranging from osteoporosis to bone metastasis. The cysteine proteinase cathepsin K confers osteoclasts with potent type I collagenolytic activity; however, cathepsin K-null mice, as well as cathepsin K-mutant humans, continue to remodel bone and degrade collagen by as-yet-undefined effectors. Here, we identify a cathepsin K-independent collagenolytic system in osteoclasts that is composed of a functionally redundant network of the secreted matrix metalloproteinase MMP9 and the membrane-anchored matrix metalloproteinase MMP14. Unexpectedly, whereas deleting either of the proteinases individually leaves bone resorption intact, dual targeting of Mmp9 and Mmp14 inhibited the resorptive activity of mouse osteoclasts in vitro and in vivo and human osteoclasts in vitro. In vivo, Mmp9/Mmp14 conditional double-knockout mice exhibited marked increases in bone density and displayed a highly protected status against either parathyroid hormone- or ovariectomy-induced pathologic bone loss. Together, these studies characterize a collagenolytic system operative in mouse and human osteoclasts and identify the MMP9/MMP14 axis as a potential target for therapeutic interventions for bone-wasting disease states.

Abstract 53: Missense Pathogenic Variants in ANO1 Predispose to Moyamoya Disease

Introduction: Moyamoya disease (MMD) is a cerebrovascular disease often causing pediatric onset strokes and characterized by progressive bilateral occlusion of the distal internal carotid arteries and formation of a compensatory network of collateral vessels. Several genes harbor variants that increase the risk for MMD, but the majority of cases of European descent does not have an identified genetic cause. Hypothesis: MMD is associated with significant genetic heterogeneity, i.e., many genes in the human genome can be altered to predispose to this condition. Methods: To identify novel genes for MMD, exome sequencing was performed on DNA from 145 individuals from 80 families with one or more affected members. Bioinformatics filtering included a CADD (GRCh37-v1.4) score > 20 and a minor allele frequency < 0.0001 in gnomAD (v2.1.1 controls). For a subset of ANO1 mutant alleles, we characterized the channel activities via patch recording and assessed protein localization in heterologous cell cultures. Results: We identified 6 rare variants in ANO1 ( TMEM16A ), which encodes an evolutionarily conserved calcium-activated chloride channel. One rare heterozygous variant, p.Met658Val (CADD: 22.9, absent in gnomAD), was found in two very distantly related MMD families and segregated with disease in multiple affected members; p.Glu459Lys and p.Arg890Gln were identified in two unrelated affected probands. Through Matchmaker Exchange (MyGene2) collaboration, we identified 3 additional rare variants: homozygous p.Glu170Lys in a consanguineous MMD family, heterozygous p.Thr740Ile in a MMD case and p.Ala333Ser in a case with ischemic stroke. Functional analyses determined that p.Glu170Lys affects channel gating and calcium sensitivity, producing much smaller chloride current, but the channel itself is more sensitive to calcium, which means it is more likely to open. Ano1 knock out (KO) in mice is lethal by 1 week of age with pathology in multiple organ systems. Smooth muscle cells-specific KO is not lethal, and phenotyping of these mice is ongoing. Conclusions: ANO1 is a novel gene predisposing to MMD and future studies will focus on defining the role of ANO1 protein to connect the altered gene to the occlusive lesions observed in MMD patients.

Co-delivery of 2-Deoxyglucose and a glutamine metabolism inhibitor V9302 via a prodrug micellar formulation for synergistic targeting of metabolism in cancer

The unique metabolic demand of cancer cells suggests a new therapeutic strategy targeting the metabolism in cancers. V9302 is a recently reported inhibitor of ASCT2 amino acid transporter which shows promising antitumor activity by blocking glutamine uptake. However, its poor solubility in aqueous solutions and tumor cells’ compensatory metabolic shift to glucose metabolism may limit the antitumor efficacy of V9302. 2-Deoxyglucose (2-DG), a derivative of glucose, has been developed as a potential antitumor agent through inhibiting glycolysis in tumor cells. In order to achieve enhanced antitumor effect by inhibiting both metabolic pathways, a 2-DG prodrug-based micellar carrier poly-(oligo ethylene glycol)-co-poly(4-((4-oxo-4-((4-vinylbenzyl)oxy)butyl)disulfaneyl)butanoic acid)-(2-deoxyglucose) (POEG-p-2DG) was developed. POEG-p-2DG well retained the pharmacological activity of 2-DG in vitro and in vivo, More importantly, POEG-p-2DG could self-assemble to form micelles that were capable of loading V9302 to achieve co-delivery of 2-DG and V9302. V9302-loaded POEG-p2DG micelles were small in sizes (~10 nm), showed a slow kinetics of drug release and demonstrated targeted delivery to tumor. In addition, V9302 loaded POEG-p-2DG micelles exhibited improved anti-tumor efficacy both in vitro and in vivo. Interestingly, 2-DG treatment further decreased the glutamine uptake when combined with V9302, likely due to inhibition of ASCT2 glycosylation. These results suggest that POEG-p2DG prodrug micelles may serve as a dual functional carrier for V9302 to achieve synergistic targeting of metabolism in cancers. Statement of significanceUnique cancer cell's metabolism profile denotes a new therapeutic strategy. V9302 is a recently reported glutamine metabolism inhibitor that shows promising antitumor activity. However, its poor waster solubility and tumor cell's compensatory metabolic network may limit its potential clinical application. 2-Deoxyglucose(2-DG) is a widely used glycolysis inhibitor. However, its clinical application is hindered by low efficacy as monotherapy. Thus, in this study, we developed a redox-sensitive, 2-DG-based prodrug polymer, as a dual-functional carrier for co-delivery of V9302 and 2-DG as a combination strategy. V9302 loaded POEG-p-2DG micelle showed significantly improved antitumor activity through synergistic targeting of both glutamine and glycolysis metabolism pathway. More interestingly, POEG-p-2DG itself further facilitates inhibition of glutamine metabolism, likely through inhibition of ASCT2 glycosylation.

Deep sequence analysis of HIV adaptation following vertical transmission reveals the impact of immune pressure on the evolution of HIV.

Human immunodeficiency virus (HIV) can adapt to an individual’s T cell immune response via genomic mutations that affect antigen recognition and impact disease outcome. These viral adaptations are specific to the host’s human leucocyte antigen (HLA) alleles, as these molecules determine which peptides are presented to T cells. As HLA molecules are highly polymorphic at the population level, horizontal transmission events are most commonly between HLA-mismatched donor/recipient pairs, representing new immune selection environments for the transmitted virus. In this study, we utilised a deep sequencing approach to determine the HIV quasispecies in 26 mother-to-child transmission pairs where the potential for founder viruses to be pre-adapted is high due to the pairs being haplo-identical at HLA loci. This scenario allowed the assessment of specific HIV adaptations following transmission in either a non-selective immune environment, due to recipient HLA mismatched to original selecting HLA, or a selective immune environment, mediated by matched donor/recipient HLA. We show that the pattern of reversion or fixation of HIV adaptations following transmission provides insight into the replicative cost, and likely compensatory networks, associated with specific adaptations in vivo. Furthermore, although transmitted viruses were commonly heavily pre-adapted to the child’s HLA genotype, we found evidence of de novo post-transmission adaptation, representing new epitopes targeted by the child’s T cell response. High-resolution analysis of HIV adaptation is relevant when considering vaccine and cure strategies for individuals exposed to adapted viruses via transmission or reactivated from reservoirs.

Update on intensive motor training in spinocerebellar ataxia: time to move a step forward?

Some evidence suggests that high-intensity motor training slows down the severity of spinocerebellar ataxia. However, whether all patients might benefit from these activities, and by which activity, and the underlying mechanisms remain unclear. We provide an update on the effect and limitations of different training programmes in patients with spinocerebellar ataxias. Overall, data converge of the finding that intensive training is still based either on conventional rehabilitation protocols or whole-body controlled videogames (“exergames”). Notwithstanding the limitations, short-term improvement is observed, which tends to be lost once the training is stopped. Exergames and virtual reality can ameliorate balance, coordination, and walking abilities, whereas the efficacy of adapted physical activity, gym, and postural exercises depends on the disease duration and severity. In conclusion, although a disease-modifying effect has not been demonstrated, constant, individually tailored, high-intensity motor training might be effective in patients with degenerative ataxia, even in those with severe disease. These approaches may enhance the remaining cerebellar circuitries or plastically induce compensatory networks. Further research is required to identify predictors of training success, such as the type and severity of ataxia and the level of residual functioning.

Intelligent PV Power System With Unbalanced Current Compensation Using CFNN-AMF

A novel method is proposed to compensate the three-phase unbalanced currents of power grid under three-phase unbalanced load for a two-stage photovoltaic (PV) power system without the augmentation of active power filter. The PV power system is composed of an interleaved dc/dc converter and a three-level neutral-point clamped inverter. Moreover, the PV power system possesses the smart inverter function, in which the output active and reactive powers of the PV inverter are predetermined by a power factor according to grid codes of the utilities. In the proposed method, $dq0$ -axis compensation currents are obtained through low-pass filters to compensate the three-phase unbalanced currents of power grid. Furthermore, in order to improve the control performance of the dc bus voltage of the PV power system under unbalanced load variation condition, an online-trained compensatory neural fuzzy network with an asymmetric membership function (CFNN-AMF) is proposed to replace the traditional proportional-integral controller for the dc bus voltage control. In the proposed CFNN-AMF, the compensatory parameter to integrate pessimistic and optimistic operations of fuzzy systems is embedded in the CFNN. In addition, the dimensions of the Gaussian membership functions are directly extended to AMFs. Additionally, the proposed controllers of the PV power system are implemented by two control platforms using floating-point digital signal processor. Finally, excellent compensation performance for the three-phase currents of power grid under three-phase unbalanced load can be achieved from the experimental results.

Age-Related Atrophy and Compensatory Neural Networks in Reading Comprehension.

Despite changes to brain integrity with aging, some functions like basic language processes remain remarkably preserved. One theory for the maintenance of function in light of age-related brain atrophy is the engagement of compensatory brain networks. This study examined age-related changes in the neural networks recruited for simple language comprehension. Sixty-five adults (native English-speaking, right-handed, and cognitively normal) aged 17-85 years underwent a functional magnetic resonance imaging (fMRI) reading paradigm and structural scanning. The fMRI data were analyzed using independent component analysis to derive brain networks associated with reading comprehension. Two typical frontotemporal language networks were identified, and these networks remained relatively stable across the wide age range. In contrast, three attention-related networks showed increased activation with increasing age. Furthermore, the increased recruitment of a dorsal attention network was negatively correlated to gray matter thickness in temporal regions, whereas an anterior frontoparietal network was positively correlated to gray matter thickness in insular regions. We found evidence that older adults can exert increased effort and recruit additional attentional resources to maintain their reading abilities in light of increased cortical atrophy.

The influence of age and ASD on verbal fluency networks

BackgroundThe integrity and connectivity of the frontal lobe, which subserves fluency, may be compromised by both ASD and aging. Alternate networks often integrate to help compensate for compromised functions during aging. We used network analyses to study how compensation may overcome age-related compromised in individuals with ASD. MethodParticipants consisted of middle-aged (40–60; n = 24) or young (18–25; n = 18) right-handed males who have a diagnosis of ASD, and age- and IQ-matched control participants (n = 20, 14, respectively). All performed tests of language and executive functioning and a fluency functional MRI task. We first used group individual component analysis (ICA) for each of the 4 groups to determine whether different networks were engaged. An SPM analysis was used to compare activity detected in the network nodes from the ICA analyses. ResultsThe individuals with ASD performed more slowly on two cognitive tasks (Stroop word reading and Trailmaking Part A). The 4 groups engaged different networks during the fluency fMRI task despite equivalent performance. Comparisons of specific regions within these networks indicated younger individuals had greater engagement of the thalamus and supplementary speech area, while older adults engaged the superior temporal gyrus. Individuals with ASD did not disengage from the Default Mode Network during word generation. ConclusionInteractions between diagnosis and aging were not found in this study of young and middle-aged men, but evidence for differential engagement of compensatory networks was observed.

Posterior circulation involvement and collateral flow pattern in moyamoya disease with the RNF213 polymorphism.

Moyamoya disease is a chronic cerebrovascular disorder characterized by progressive stenosis of the circle of Willis with a compensatory collateral vessel network. Recent studies have identified the ring finger protein 213 gene (RNF213) as the unique susceptibility gene for moyamoya disease. The purpose of this study was to compare clinical features of moyamoya disease, especially angiographic findings, between patients with and without the RNF213 mutation. Blood samples from 35 patients with moyamoya disease were obtained between May 2016 and May 2017. Information on age at the time of diagnosis, sex, and initial symptom were obtained via retrospective chart review. Angiographic records were evaluated. RNF213 variants were detected in the 28 of 35 patients (80%), including all pediatric patients (100%) and 18 of 25 adult patients (72%) in our cohort. Leptomeningeal collateral flow from posterior to anterior circulation was more frequent in the RNF213-negative group than in the RNF213-positive group (100% versus 38.9%; p = 0.020). Posterior cerebral arterial territorial involvement was more frequently observed in RNF213-positive patients than in RNF213-negative patients (50% versus 0%; p = 0.027). RNF213 may play a significant role in the development of collateral anastomoses.

Neural correlates of phonological processing: Disrupted in children with dyslexia and enhanced in musically trained children

Phonological processing has been postulated as a core area of deficit among children with dyslexia. Reduced brain activation during phonological processing in children with dyslexia has been observed in left-hemispheric temporoparietal regions. Musical training has shown positive associations with phonological processing abilities, but the neural mechanisms underlying this relationship remain unspecified. The present research aims to distinguish neural correlates of phonological processing in school-age typically developing musically trained children, musically untrained children, and musically untrained children with dyslexia utilizing fMRI. A whole-brain ANCOVA, accounting for gender and nonverbal cognitive abilities, identified a main effect of group in bilateral temporoparietal regions. Subsequent region-of-interest analyses replicated temporoparietal hypoactivation in children with dyslexia relative to typically developing children. By contrast, musically trained children showed greater bilateral activation in temporoparietal regions when compared to each musically untrained group. Therefore, musical training shows associations with enhanced bilateral activation of left-hemispheric regions known to be important for reading. Findings suggest that engagement of these regions through musical training may underlie the putative positive effects of music on reading development. This supports the hypothesis that musical training may facilitate the development of a bilateral compensatory neural network, which aids children with atypical function in left-hemispheric temporoparietal regions.