scholarly journals Loss of function in the autism and learning disabilities associated gene Nf1 disrupts corticocortical and corticostriatal functional connectivity in human and mouse

2019 ◽  
Author(s):  
Ben Shofty ◽  
Eyal Bergmann ◽  
Gil Zur ◽  
Jad Asleh ◽  
Noam Bosak ◽  
...  

ABSTRACTChildren with the autosomal dominant single gene disorder, neurofibromatosis type 1 (NF1), display multiple structural and functional changes in the central nervous system, resulting in neuropsychological cognitive abnormalities. Here we assessed the pathological functional organization that may underlie the behavioral impairments in NF1 using resting-state functional connectivity MRI. Coherent spontaneous fluctuations in the fMRI signal across the entire brain were used to interrogate the pattern of functional organization of corticocortical and corticostriatal networks in both NF1 pediatric patients and mice with a heterozygous mutation in the Nf1 gene (Nf1+/-). Children with NF1 demonstrated abnormal organization of cortical association networks and altered posterior-anterior functional connectivity in the default network. Examining the contribution of the striatum revealed that corticostriatal functional connectivity was altered. NF1 children demonstrated reduced functional connectivity between striatum and the frontoparietal network and increased striatal functional connectivity with the limbic network. Awake passive mouse functional connectivity MRI in Nf1+/- mice similarly revealed reduced posterior-anterior connectivity along the cingulate cortex as well as disrupted corticostriatal connectivity. The striatum of Nf1+/- mice showed increased functional connectivity to somatomotor and frontal cortices and decreased functional connectivity to the auditory cortex. Collectively, these results demonstrate similar alterations across species, suggesting that NF1 pathogenesis is linked to striatal dysfunction and disrupted corticocortical connectivity in the default network.

2018 ◽  
Vol 30 (5) ◽  
pp. 722-736 ◽  
Author(s):  
Eun Young Choi ◽  
Garrett K. Drayna ◽  
David Badre

Patient lesion and neuroimaging studies have identified a rostral-to-caudal functional gradient in the lateral frontal cortex (LFC) corresponding to higher-order (complex or abstract) to lower-order (simple or concrete) cognitive control. At the same time, monkey anatomical and human functional connectivity studies show that frontal regions are reciprocally connected with parietal and temporal regions, forming parallel and distributed association networks. Here, we investigated the link between the functional gradient of LFC regions observed during control tasks and the parallel, distributed organization of association networks. Whole-brain fMRI task activity corresponding to four orders of hierarchical control [Badre, D., & D'Esposito, M. Functional magnetic resonance imaging evidence for a hierarchical organization of the prefrontal cortex. Journal of Cognitive Neuroscience, 19, 2082–2099, 2007] was compared with a resting-state functional connectivity MRI estimate of cortical networks [Yeo, B. T., Krienen, F. M., Sepulcre, J., Sabuncu, M. R., Lashkari, D., Hollinshead, M., et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of Neurophysiology, 106, 1125–1165, 2011]. Critically, at each order of control, activity in the LFC and parietal cortex overlapped onto a common association network that differed between orders. These results are consistent with a functional organization based on separable association networks that are recruited during hierarchical control. Furthermore, corticostriatal functional connectivity MRI showed that, consistent with their participation in functional networks, rostral-to-caudal LFC and caudal-to-rostral parietal regions had similar, order-specific corticostriatal connectivity that agreed with a striatal gating model of hierarchical rule use. Our results indicate that hierarchical cognitive control is subserved by parallel and distributed association networks, together forming multiple localized functional gradients in different parts of association cortex. As such, association networks, while connectionally organized in parallel, may be functionally organized in a hierarchy via dynamic interaction with the striatum.


Cephalalgia ◽  
2021 ◽  
pp. 033310242110466
Author(s):  
Roberta Messina ◽  
Maria A Rocca ◽  
Paola Valsasina ◽  
Paolo Misci ◽  
Massimo Filippi

Objective To elucidate the hypothalamic involvement in episodic migraine and investigate the association between hypothalamic resting state functional connectivity changes and migraine patients’ clinical characteristics and disease progression over the years. Methods Ninety-one patients with episodic migraine and 73 controls underwent interictal resting state functional magnetic resonance imaging. Twenty-three patients and controls were re-examined after a median of 4.5 years. Hypothalamic resting state functional connectivity changes were investigated using a seed-based correlation approach. Results At baseline, a decreased functional interaction between the hypothalamus and the parahippocampus, cerebellum, temporal, lingual and orbitofrontal gyrus was found in migraine patients versus controls. Increased resting state functional connectivity between the hypothalamus and bilateral orbitofrontal gyrus was demonstrated in migraine patients at follow-up versus baseline. Migraine patients also experienced decreased right hypothalamic resting state functional connectivity with ipsilateral lingual gyrus. A higher migraine attack frequency was associated with decreased hypothalamic-lingual gyrus resting state functional connectivity at baseline, while greater headache impact at follow-up correlated with decreased hypothalamic-orbitofrontal gyrus resting state functional connectivity at baseline. At follow-up, a lower frequency of migraine attacks was associated with higher hypothalamic-orbitofrontal gyrus resting state functional connectivity. Conclusions During the interictal phase, the hypothalamus modulates the activity of pain and visual processing areas in episodic migraine patients. The hypothalamic-cortical interplay changes dynamically over time according to patients’ clinical features.


2017 ◽  
Vol 11 ◽  
Author(s):  
Hiroki Togo ◽  
Jaroslav Rokicki ◽  
Kenji Yoshinaga ◽  
Tatsuhiro Hisatsune ◽  
Hiroshi Matsuda ◽  
...  

NeuroImage ◽  
2014 ◽  
Vol 90 ◽  
pp. 235-245 ◽  
Author(s):  
Kevin C. Chan ◽  
Shu-Juan Fan ◽  
Russell W. Chan ◽  
Joe S. Cheng ◽  
Iris Y. Zhou ◽  
...  

2019 ◽  
Vol 116 (8) ◽  
pp. 3316-3321 ◽  
Author(s):  
Claire O’Callaghan ◽  
James M. Shine ◽  
John R. Hodges ◽  
Jessica R. Andrews-Hanna ◽  
Muireann Irish

Mind wandering represents the human capacity for internally focused thought and relies upon the brain’s default network and its interactions with attentional networks. Studies have characterized mind wandering in healthy people, yet there is limited understanding of how this capacity is affected in clinical populations. This paper used a validated thought-sampling task to probe mind wandering capacity in two neurodegenerative disorders: behavioral variant frontotemporal dementia [(bvFTD); n = 35] and Alzheimer’s disease [(AD); n = 24], compared with older controls (n = 37). These patient groups were selected due to canonical structural and functional changes across sites of the default and frontoparietal networks and well-defined impairments in cognitive processes that support mind wandering. Relative to the controls, bvFTD patients displayed significantly reduced mind wandering capacity, offset by a significant increase in stimulus-bound thought. In contrast, AD patients demonstrated comparable levels of mind wandering to controls, in the context of a relatively subtle shift toward stimulus-/task-related forms of thought. In the patient groups, mind wandering was associated with gray matter integrity in the hippocampus/parahippocampus, striatum, insula, and orbitofrontal cortex. Resting-state functional connectivity revealed associations between mind wandering capacity and connectivity within and between regions of the frontoparietal and default networks with distinct patterns evident in patients vs. controls. These findings support a relationship between altered mind wandering capacity in neurodegenerative disorders and structural and functional integrity of the default and frontoparietal networks. This paper highlights a dimension of cognitive dysfunction not well documented in neurodegenerative disorders and validates current models of mind wandering in a clinical population.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Charles J. Lynch ◽  
Benjamin M. Silver ◽  
Marc J. Dubin ◽  
Alex Martin ◽  
Henning U. Voss ◽  
...  

Abstract Resting state functional connectivity magnetic resonance imaging (fMRI) is a tool for investigating human brain organization. Here we identify, visually and algorithmically, two prevalent influences on fMRI signals during 440 h of resting state scans in 440 healthy young adults, both caused by deviations from normal breathing which we term deep breaths and bursts. The two respiratory patterns have distinct influences on fMRI signals and signal covariance, distinct timescales, distinct cardiovascular correlates, and distinct tendencies to manifest by sex. Deep breaths are not sex-biased. Bursts, which are serial taperings of respiratory depth typically spanning minutes at a time, are more common in males. Bursts share features of chemoreflex-driven clinical breathing patterns that also occur primarily in males, with notable neurological, psychiatric, medical, and lifespan associations. These results identify common breathing patterns in healthy young adults with distinct influences on functional connectivity and an ability to differentially influence resting state fMRI studies.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S4-S4
Author(s):  
Jose Maximo ◽  
Frederic Briend ◽  
William Armstrong ◽  
Nina Kraguljac ◽  
Adrienne Lahti

Abstract Background Schizophrenia is thought to be a disorder of brain dysconnectivity. An imbalance between cortical excitation/inhibition is also implicated, but the link between these abnormalities remains unclear. The present study used resting state functional connectivity MRI (rs-fcMRI) and magnetic resonance spectroscopy (MRS) to investigate how measurements of glutamate + glutamine (Glx) in the anterior cingulate cortex (ACC) relate to rs-fcMRI in medication-naïve first episode psychosis (FEP) subjects compared to healthy controls (HC). Based on our previous findings, we hypothesized that in HC would show correlations between Glx and rs-fMRI in the salience and default mode network, but these relationships would be altered in FEP. Methods Data from 53 HC (age = 24.70 ±6.23, 34M/19F) and 60 FEP (age = 24.08 ±6.29, 38M/22F) were analyzed. To obtain MRS data, a voxel was placed in the ACC (PRESS, TR/TE = 2000/80ms). Metabolite concentrations were quantified with respect to internal water using the AMARES algorithm in jMRUI. rs-fMRI data were processed using a standard preprocessing pipeline in the CONN toolbox. BOLD signal from a priori brain regions of interest from posterior cingulate cortex (default mode network, DMN), anterior cingulate cortex (salience network, SN), and right posterior parietal cortex (central executive network, CEN) were extracted and correlated with the rest of the brain to measure functional connectivity (FC). Group analyses were performed on Glx, FC, and Glx-FC interactions while controlling for age, gender, and motion when applicable. FC and Glx-FC analyses were performed using small volume correction [(p < 0.01, threshold-free cluster enhancement corrected (TFCE)]. Results No significant between-group differences were found in Glx concentration in the ACC [F(1, 108) = 0.34, p = 0.56], but reduced FC was found on each network in FEP compared to HC (pTFCE corrected). Group Glx-FC interactions were found in the form of positive correlations between Glx and FC in DMN and SN in the HC group, but not in FEP; and negative correlations in CEN in HC, but not in FEP. Discussion While we did not find significant group differences in ACC Glx measurements, ACC Glx modulated FC differentially in FEP and HC. Positive correlations between Glx and FC were found in the SN and DMN, suggesting long range modulation of the two networks in HC, but not in FEP. Additionally, negative correlations between Glx and FC were found in CEN in HC, but not in FEP. Overall, these results suggest that even in the absence of group differences in Glx concentration, the long-range modulation of these 3 networks by ACC Glx is altered in FEP.


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