scholarly journals Frequency and Intensity of Premonitory Urges to tic in Tourette Syndrome is associated with SMA GABA+ levels

2021 ◽  
Author(s):  
Jason He ◽  
Mark Mikkelsen ◽  
David Huddleston ◽  
Deana Crocetti ◽  
Kim Cecil ◽  
...  

Background. Individuals with Tourette syndrome (TS) often report that they express tics as a means of alleviating the experience of unpleasant sensations. These sensations are perceived as an urge to act and are referred to as premonitory urges. Premonitory urges have been the focus of recent efforts to develop interventions to reduce tic expression in those with TS. Increasing evidence points to the role of both structural and functional alterations of prefrontal and limbic brain regions regarding the experience of premonitory urges to tic in TS. This study examined the contribution of brain GABA and glutamate levels of the right primary sensorimotor cortex (SM1), supplementary motor area (SMA), and insular cortex (insula) to tic and urge severity in children with TS.Methods. Edited magnetic resonance spectroscopy was used to assess GABA+ (GABA + macromolecules) and Glx (glutamate + glutamine) of the right SM1, SMA and insula in 68 children with TS (MAge = 10.59, SDAge = 1.33) and 41 typically developing controls (MAge = 10.26, SDAge = 2.21). We first compared GABA+ and Glx levels of these brain regions between groups. We then explored the association between regional GABA+ and Glx levels with urge and tic severity. Results. GABA+ and Glx of the right SM1, SMA and insula were comparable between the children with TS and typically developing controls. In children with TS, lower levels of SMA GABA+ was associated with more severe and more frequent premonitory urges. Neither GABA+ nor Glx levels were associated with tic severity. Conclusions. These results broadly support the role of GABAergic neurotransmission within the SMA in the experience of premonitory urges in children with TS.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jason L. He ◽  
Georg Oeltzschner ◽  
Mark Mikkelsen ◽  
Alyssa Deronda ◽  
Ashley D. Harris ◽  
...  

AbstractIndividuals on the autism spectrum are often reported as being hyper- and/or hyporeactive to sensory input. These sensory symptoms were one of the key observations that led to the development of the altered excitation-inhibition (E-I) model of autism, which posits that an increase ratio of excitatory to inhibitory signaling may explain certain phenotypical expressions of autism spectrum disorders (ASD). While there has been strong support for the altered E-I model of autism, much of the evidence has come from animal models. With regard to in-vivo human studies, evidence for altered E-I balance in ASD come from studies adopting magnetic resonance spectroscopy (MRS). Spectral-edited MRS can be used to provide measures of the levels of GABA + (GABA + macromolecules) and Glx (glutamate + glutamine) in specific brain regions as proxy markers of inhibition and excitation respectively. In the current study, we found region-specific elevations of Glx in the primary sensorimotor cortex (SM1) in ASD. There were no group differences of GABA+ in either the SM1 or thalamus. Higher levels of Glx were associated with more parent reported difficulties of sensory hyper- and hyporeactivity, as well as reduced feed-forward inhibition during tactile perception in children with ASD. Critically, the finding of elevated Glx provides strong empirical support for increased excitation in ASD. Our results also provide a clear link between Glx and the sensory symptoms of ASD at both behavioral and perceptual levels.


2017 ◽  
Vol 48 (10) ◽  
pp. 1731-1737 ◽  
Author(s):  
Beata R. Godlewska ◽  
Charles Masaki ◽  
Ann L. Sharpley ◽  
Philip J. Cowen ◽  
Uzay E. Emir

BackgroundThe possible role of glutamate in the pathophysiology and treatment of depression is of intense current interest. Proton magnetic resonance spectroscopy (MRS) enables the detection of glutamate in the living human brain and meta-analyses of previous MRS studies in depressed patients have suggested that glutamate levels are decreased in anterior brain regions. Nevertheless, at conventional magnetic field strengths [1.5–3 Tesla (T)], it is difficult to separate glutamate from its metabolite and precursor, glutamine, with the two often being measured together as Glx. In contrast, MRS at 7 T allows clear spectral resolution of glutamate and glutamine.MethodWe studied 55 un-medicated depressed patients and 50 healthy controls who underwent MRS scanning at 7 T with voxels placed in anterior cingulate cortex, occipital cortex and putamen (PUT). Neurometabolites were calculated using the unsuppressed water signal as a reference.ResultsCompared with controls, depressed patients showed no significant difference in glutamate in any of the three voxels studied; however, glutamine concentrations in the patients were elevated by about 12% in the PUT (p < 0.001).ConclusionsThe increase in glutamine in PUT is of interest in view of the postulated role of the basal ganglia in the neuropsychology of depression and is consistent with elevated activity in the descending cortical glutamatergic innervation to the PUT. The basal ganglia have rarely been the subject of MRS investigations in depressed patients and further MRS studies of these structures in depression are warranted.


2017 ◽  
Vol 41 (S1) ◽  
pp. S349-S350 ◽  
Author(s):  
S. Rigucci ◽  
L. Xin ◽  
P. Klauser ◽  
P.S. Baumann ◽  
L. Alameda ◽  
...  

Recent evidences have consistently reported lower glutamate (Glu) levels in various brain regions, including the medial prefrontal cortex (mPFC), in chronic schizophrenia but findings in the early (EP) or in the prodromal phase of the disorder are equivocal. Although regular cannabis use has been associated with an increased risk of subsequent psychosis and with a perturbed Glu signalling, to date, the critical question of whether or not Glu abnormalities exist in EP and are related to cannabis use remains unanswered. Magnetic resonance spectroscopy was used to measure [GlumPFC] of 35 EP subjects (18 of whom were regular cannabis users) and 33 healthy controls (HC). For correlative analysis, neuropsychological performances were scored by a comprehensive cognitive battery. [GlumPFC] was lower in EP users comparing to both HC and EP non-users (P = 0.001 and P = 0.01, respectively), while no differences were observed between HC and EP non-users. In EP users Glu declined with age (r = −0.46; P = 0.04) but this relationship was not observed in non-users. Among neuropsychological profiles, working memory was the only domain that differentiates patients depending on their cannabis use, with users having poorer performances. In summary, our research revealed that cannabis use in EP is associated with Glu decreased levels, which are normally not seen in the early phase of the disorder. This finding is in line with previous 1H-MRS studies in cannabis users without a psychotic disorder and sheds light for the role of cannabis use in the progression of the disease.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2017 ◽  
Author(s):  
Ella Striem-Amit ◽  
Gilles Vannuscorps ◽  
Alfonso Caramazza

SummaryWhat forces direct brain organization and its plasticity? When a brain region is deprived of its input would this region reorganize based on compensation for the disability and experience, or would strong limitations of brain structure limit its plasticity? People born without hands activate their sensorimotor hand region while moving body parts used to compensate for this ability (e.g. their feet). This has been taken to suggest a neural organization based on functions, such as performing manual-like dexterous actions, rather than on body parts. Here we test the selectivity for functionally-compensatory body parts in the sensorimotor cortex of people born without hands. Despite clear compensatory foot use, the sensorimotor hand area in the dysplasic subjects showed preference for body parts whose cortical territory is close to the hand area, but which are not compensatorily used as effectors. This suggests that function-based organization, originally proposed for congenital blindness and deafness, does not apply to cases of the primary sensorimotor cortex deprivation in dysplasia. This is consistent with the idea that experience-independent functional specialization occurs at relatively high levels of representation. Indeed, increased and selective foot movement preference in the dysplasics was found in the association cortex, in the inferior parietal lobule. Furthermore, it stresses the roles of neuroanatomical constraints such as topographical proximity and connectivity in determining the functional development of brain regions. These findings reveal limitations to brain plasticity and to the role of experience in shaping the functional organization of the brain.Significance StatementWhat determines the role of brain regions, and their plasticity when typical inputs or experience is not provided? To what extent can extreme compensatory use affect brain organization? We tested the functional reorganization of the primary sensorimotor cortex hand area in people born without hands, who use their feet for every-day tasks. We found that it is preferentially activated by close-by body-parts which cannot serve as effectors, and not by the feet. In contrast, foot-selective compensatory plasticity was found in the association cortex, in an area involved in tool use. This shows limitations of compensatory plasticity and experience in modifying brain organization of early topographical cortex, as compared to association cortices where function-based organization is the driving factor.ClassificationBiological Sciences\Neuroscience


2009 ◽  
Vol 450 (2) ◽  
pp. 75-79 ◽  
Author(s):  
Yasunori Kotani ◽  
Yoshimi Ohgami ◽  
Yumiko Kuramoto ◽  
Tetsuji Tsukamoto ◽  
Yusuke Inoue ◽  
...  

2014 ◽  
Vol 26 (2) ◽  
pp. 380-394 ◽  
Author(s):  
Aiden E. G. F. Arnold ◽  
Andrea B. Protzner ◽  
Signe Bray ◽  
Richard M. Levy ◽  
Giuseppe Iaria

Spatial orientation is a complex cognitive process requiring the integration of information processed in a distributed system of brain regions. Current models on the neural basis of spatial orientation are based primarily on the functional role of single brain regions, with limited understanding of how interaction among these brain regions relates to behavior. In this study, we investigated two sources of variability in the neural networks that support spatial orientation—network configuration and efficiency—and assessed whether variability in these topological properties relates to individual differences in orientation accuracy. Participants with higher accuracy were shown to express greater activity in the right supramarginal gyrus, the right precentral cortex, and the left hippocampus, over and above a core network engaged by the whole group. Additionally, high-performing individuals had increased levels of global efficiency within a resting-state network composed of brain regions engaged during orientation and increased levels of node centrality in the right supramarginal gyrus, the right primary motor cortex, and the left hippocampus. These results indicate that individual differences in the configuration of task-related networks and their efficiency measured at rest relate to the ability to spatially orient. Our findings advance systems neuroscience models of orientation and navigation by providing insight into the role of functional integration in shaping orientation behavior.


2021 ◽  
Author(s):  
Radek Ptak ◽  
Elena Pedrazzini

Abstract The right temporoparietal junction (rTPJ) and insula both play a key role for the processing of relevant stimuli. However, while both have been conceived as neural “switches” that detect salient events and redirect the focus of attention, it remains unclear how these brain regions interact to achieve this behavioral goal. Here, we tested human participants with focal left-hemispheric or right-hemispheric lesions in a spatial cuing task that requires participants to react to lateralized stimuli preceded by a distracter that shares or does not share a relevant feature with the target. Using machine learning to identify significant lesion–behavior relationships, we found that rTPJ damage produces distinctive, pathologically increased attentional capture, but only by relevant distracters. Functional connectivity analyses revealed that the degree of capture is positively associated with a functional connection between insula and rTPJ, together with functional isolation of the rTPJ from right dorsal prefrontal cortex (dPFC). These findings suggest a mechanistic model where the insula–rTPJ connection constitutes a crucial functional unit that breaks attentional focus upon detection of behaviorally relevant events, while the dPFC appears to attune this activity.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ian Krajbich ◽  
Andres Mitsumasu ◽  
Rafael Polania ◽  
Christian C Ruff ◽  
Ernst Fehr

Recent studies have suggested close functional links between overt visual attention and decision making. This suggests that the corresponding mechanisms may interface in brain regions known to be crucial for guiding visual attention – such as the frontal eye field (FEF). Here, we combined brain stimulation, eye tracking, and computational approaches to explore this possibility. We show that inhibitory transcranial magnetic stimulation (TMS) over the right FEF has a causal impact on decision making, reducing the effect of gaze dwell time on choice while also increasing reaction times. We computationally characterize this putative mechanism by using the attentional drift diffusion model (aDDM), which reveals that FEF inhibition reduces the relative discounting of the non-fixated option in the comparison process. Our findings establish an important causal role of the right FEF in choice, elucidate the underlying mechanism, and provide support for one of the key causal hypotheses associated with the aDDM.


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