scholarly journals The within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in Nrxn2 deletion mice

2018 ◽  
Author(s):  
Eleftheria Pervolaraki ◽  
Adam L. Tyson ◽  
Francesca Pibiri ◽  
Steven L. Poulter ◽  
Amy C. Reichelt ◽  
...  

AbstractBackgroundOf the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role for NRXN2 in generating altered social behaviours. Autism has been conceptualised as a disorder of atypical connectivity, yet how single-gene mutations affect such connectivity remains under-explored. To attempt to address this, we have developed a quantitative analysis of microstructure and structural connectivity leveraging diffusion tensor MRI (DTI) with high-resolution 3D imaging in optically cleared (CLARITY) brain tissue in the same mouse, applied here to the Nrxn2α knockout (KO) model.MethodsFixed brains of Nrxn2α KO mice underwent DTI using 9.4T MRI, and diffusion properties of socially-relevant brain regions were quantified. The same tissue was then subjected to CLARITY to immunolabel axons and cell bodies, which were also quantified.ResultsDTI revealed decreases in fractional anisotropy and increases in apparent diffusion coefficient in the amygdala (including the basolateral nuclei), the anterior cingulate cortex, the orbitofrontal cortex and the hippocampus. Radial diffusivity of the anterior cingulate cortex and orbitofrontal cortex was significantly increased in Nrxn2α KO mice, as were tracts between the amygdala and the orbitofrontal cortex. Using CLARITY, we find significantly altered axonal orientation in the amygdala, orbitofrontal cortex and the anterior cingulate cortex, which was unrelated to cell density.ConclusionsOur findings demonstrate that deleting a single neurexin gene (Nrxn2α) induces atypical structural connectivity within socially-relevant brain regions. More generally, our combined within-subject DTI and CLARITY approach presents a new, more sensitive method of revealing hitherto undetectable differences in the autistic brain.

2021 ◽  
Vol 11 (8) ◽  
pp. 1096
Author(s):  
Yixuan Chen

Decision making is crucial for animal survival because the choices they make based on their current situation could influence their future rewards and could have potential costs. This review summarises recent developments in decision making, discusses how rewards and costs could be encoded in the brain, and how different options are compared such that the most optimal one is chosen. The reward and cost are mainly encoded by the forebrain structures (e.g., anterior cingulate cortex, orbitofrontal cortex), and their value is updated through learning. The recent development on dopamine and the lateral habenula’s role in reporting prediction errors and instructing learning will be emphasised. The importance of dopamine in powering the choice and accounting for the internal state will also be discussed. While the orbitofrontal cortex is the place where the state values are stored, the anterior cingulate cortex is more important when the environment is volatile. All of these structures compare different attributes of the task simultaneously, and the local competition of different neuronal networks allows for the selection of the most appropriate one. Therefore, the total value of the task is not encoded as a scalar quantity in the brain but, instead, as an emergent phenomenon, arising from the computation at different brain regions.


2019 ◽  
Vol 29 ◽  
pp. S141-S142
Author(s):  
L. Herrmann ◽  
V. Kasties ◽  
Y. Fan ◽  
L. Danyeli ◽  
T. Tar ◽  
...  

2021 ◽  
Author(s):  
Ting-Peng Liang ◽  
Yuwen Li ◽  
Nai-Shing Yen ◽  
Ofir Turel ◽  
Sen-Mou Hsu

Abstract Background: Escalation of commitment is a common bias in human decision making. The present study examined (1) differences in neural recruitment for escalation and de-escalation decisions of prior investments, and (2) how the activations of these brain networks are modulated by two factors that are often argued to modulate the behavior: (i) self-responsibility, and (ii) framing of the success probabilities. Results: Imaging data were obtained from functional magnetic resonance imaging (fMRI) applied to 29 participants. A whole-brain analysis was conducted to compare brain activations between conditions. ROI analysis, then, was used to examine if these significant activations were modulated by two contextual factors. Finally, mediation analysis was applied to explore how the contextual factors affect escalation decisions through brain activations. The findings showed that (1) escalation decisions are faster than de-escalation decisions, (2) the corresponding network of brain regions recruited for escalation (anterior cingulate cortex, insula and precuneus) decisions differs from this recruited for de-escalation decisions (inferior and superior frontal gyri), (3) the switch from escalation to de-escalation is primarily frontal gyri dependent, and (4) activation in the anterior cingulate cortex, insula and precuneus were further increased in escalation decisions, when the outcome probabilities of the follow-up investment were positively framed; and activation in the inferior and superior frontal gyri in de-escalation decisions were increased when the outcome probabilities were negatively framed. Conclusions: Escalation and de-escalation decisions recruit different brain regions. Framing of possible outcomes as negative leads to escalation decisions through recruitment of the inferior frontal gyrus. Responsibility for decisions affects escalation decisions through recruitment of the superior (inferior) gyrus, when the decision is framed positively (negatively).


2021 ◽  
Vol 30 ◽  
Author(s):  
G. Schiena ◽  
G. Franco ◽  
A. Boscutti ◽  
G. Delvecchio ◽  
E. Maggioni ◽  
...  

Abstract Aims In the search for effective therapeutic strategies for depression, repetitive transcranial magnetic stimulation (rTMS) emerged as a non-invasive, promising treatment. This is because the antidepressant effect of rTMS might be related to neuronal plasticity mechanisms possibly reverting connectivity alterations often observed in depression. Therefore, in this review, we aimed at providing an overview of the findings reported by studies investigating functional and structural connectivity changes after rTMS in depression. Methods A bibliographic search was conducted on PubMed, including studies that used unilateral, excitatory (⩾10 Hz) rTMS treatment targeted on the left dorsolateral prefrontal cortex (DLPFC) in unipolar depressed patients. Results The majority of the results showed significant TMS-induced changes in functional connectivity (FC) between areas important for emotion regulation, including the DLPFC and the subgenual anterior cingulate cortex, and among regions that are part of the major resting-state networks, such as the Default Mode Network, the Salience Networks and the Central Executive Network. Finally, in diffusion tensor imaging studies, it has been reported that rTMS appeared to increase fractional anisotropy in the frontal lobe. Limitations The small sample size, the heterogeneity of the rTMS stimulation parameters, the concomitant use of psychotropic drugs might have limited the generalisability of the results. Conclusions Overall, rTMS treatment induces structural and FC changes in brain regions and networks implicated in the pathogenesis of unipolar depression. However, whether these changes underlie the antidepressant effect of rTMS still needs to be clarified.


2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Zitong Xu ◽  
JunFan Fang ◽  
Xuaner Xiang ◽  
HaiJu Sun ◽  
SiSi Wang ◽  
...  

Objective. Electroacupuncture (EA) is reported effective in alleviating pain-related emotion; however, the underlying mechanism of its effects still needs to be elucidated. The NPS-NPSR system has been validated for the involvement in the modulation of analgesia and emotional behavior. Here, we aimed to investigate the role of the NPS-NPSR system in the anterior cingulate cortex (ACC), hypothalamus, and central amygdala (CeA) in the use of EA to relieve affective pain modeled by complete Freund’s adjuvant- (CFA-) evoked conditioned place aversion (C-CPA). Materials and Methods. CFA injection combined with a CPA paradigm was introduced to establish the C-CPA model, and the elevated O-maze (EOM) was used to test the behavioral changes after model establishment. We further explored the expression of NPS and NPSR at the protein and gene levels in the brain regions of interest by immunofluorescence staining and quantitative real-time PCR. Results. We observed that EA stimulation delivered to the bilateral Zusanli (ST36) and Kunlun (BL60) acupoints remarkably inhibited sensory pain, pain-evoked place aversion, and anxiety-like behavior. The current study showed that EA significantly enhanced the protein expression of this peptide system in the ACC and hypothalamus, while the elevated expression of NPSR protein alone was just confined to the affected side in the CeA. Moreover, EA remarkably upregulated the mRNA expression of NPS in CeA, ACC, and hypothalamus and NPSR mRNA in the hypothalamus and CeA. Conclusions. These data suggest the effectiveness of EA in alleviating affective pain, and these benefits may at least partially be attributable to the upregulation of the NPS-NPSR system in the ACC and hypothalamus.


2003 ◽  
Vol 90 (3) ◽  
pp. 1865-1876 ◽  
Author(s):  
Ivan E.T. de Araujo ◽  
Morten L. Kringelbach ◽  
Edmund T. Rolls ◽  
Francis McGlone

In an event-related functional magnetic resonance imaging (fMRI) study in humans it was shown, first, that water produces activations in cortical taste areas (in particular the frontal operculum/anterior insula which is the primate primary taste cortex, and the caudal orbitofrontal/secondary taste cortex) comparable to those produced by the prototypical tastants salt and glucose. Second, the activations in the frontal operculum/anterior insula produced by water when thirsty were still as large after the subjects had consumed water to satiety. Third, in contrast, the responses to water in the caudal orbitofrontal cortex were modulated by the physiological state of the body, in that responses to the oral delivery of water in this region were not found after the subjects had drunk water to satiety. Fourth, further evidence that the reward value or pleasantness of water is represented in the orbitofrontal cortex was that a positive correlation with the subjective ratings of the pleasantness of the water was found with activations in the caudal and anterior orbitofrontal cortex, and also in the anterior cingulate cortex. Fifth, it was found that a region of the middle part of the insula was also activated by water in the mouth, and further, that this activation only occurred when thirsty. Sixth, analyses comparing pre- and postsatiety periods (i.e., when thirsty and when not thirsty) independently of stimulus delivery revealed higher activity levels in the rostral anterior cingulate cortex. The activity of the rostral anterior cingulate cortex thus appears to reflect the thirst level or motivational state of the subjects.


2017 ◽  
Vol 32 (8) ◽  
pp. 731-739 ◽  
Author(s):  
Hiromichi Ito ◽  
Kenji Mori ◽  
Masafumi Harada ◽  
Sonoka Hisaoka ◽  
Yoshihiro Toda ◽  
...  

The pathophysiology of autism spectrum disorder (ASD) is not fully understood. We used proton magnetic resonance spectroscopy to investigate metabolite concentration ratios in the anterior cingulate cortex and left cerebellum in ASD. In the ACC and left cerebellum studies, the ASD group and intelligence quotient- and age-matched control group consisted of 112 and 114 subjects and 65 and 45 subjects, respectively. In the ASD group, γ-aminobutyric acid (GABA)+/ creatine/phosphocreatine (Cr) was significantly decreased in the anterior cingulate cortex, and glutamate (Glu)/Cr was significantly increased and GABA+/Cr was significantly decreased in the left cerebellum compared to those in the control group. In addition, both groups showed negative correlations between Glu/Cr and GABA+/Cr in the left cerebellum, and positive correlations between GABA+/Cr in the anterior cingulate cortex and left cerebellum. ASD subjects have hypoGABAergic alterations in the anterior cingulate cortex and hyperglutamatergic/hypoGABAergic alterations in the left cerebellum.


2014 ◽  
Vol 111 (9) ◽  
pp. 1717-1720 ◽  
Author(s):  
Abbas Khani

Recently, the functional specialization of prefrontal areas of the brain, and, specifically, the functional dissociation of the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC), during decision making have become a particular focus of research. A number of neuropsychological and lesion studies have shown that the OFC and ACC have dissociable functions in various dimensions of decision making, which are supported by their different anatomical connections. A recent single-neuron study, however, described a more complex picture of the functional dissociation between these two frontal regions during decision making. Here, I discuss the results of that study and consider alternative interpretations in connection with other findings.


Sign in / Sign up

Export Citation Format

Share Document