scholarly journals Non-Invasive Brain Stimulation Modulates GABAergic Activity In Neurofibromatosis 1

2021 ◽  
Author(s):  
Shruti Garg ◽  
Steve Williams ◽  
JeYoung Jung ◽  
Gorana Pobric ◽  
Tulika Nandi ◽  
...  
Keyword(s):  
Working Memory ◽  
Response Times ◽  
Single Gene ◽  
Occipital Cortex ◽  
Autism Spectrum ◽  
Neurofibromatosis 1 ◽  
Control Group ◽  
Resonance Spectroscopy ◽  
Left Dlpfc ◽  
Sham Intervention

Abstract BackgroundNeurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive phenotypes common to neurodevelopmental conditions such as Autism Spectrum Disorder (ASD) & Attention Deficit Hyperactivity Disorder (ADHD). GABAergic dysregulation underlies working memory impairments seen in NF1. This mechanistic experimental study investigates how inter-individual differences in GABA relate to working memory and whether application of anodal transcranial direct current stimulation (atDCS) can modulate of GABA and working memory.Methods31 adolescents with NF1 were recruited to a single-blind, sham-controlled cross-over trial. Baseline assessments included detailed working memory tests and parent reported measures. Each participant had two study visits, one with atDCS and another with sham intervention applied to the left Dorsolateral Prefrontal Cortex (DLPFC) inside the scanner. Magnetic Resonance Spectroscopy was collected before and after aTDCS/sham intervention in the left DLPFC and occipital cortex.ResultsHigher baseline GABA was associated with faster response times (RT) on verbal and visuospatial working memory measures. No correlation was observed between baseline GABA and working memory accuracy. AtDCS was associated with significantly greater reduction in GABA, as compared to sham in the left DLPFC. There was no effect of atDCS on Glx in left DLPFC and no significant effect of atDCS on GABA or Glx in the occipital cortex. There was no effect of atDCS on behavioural measures of working memory.LimitationsLimitations of this study include use of brief behavioural outcome measures post tDCS chosen to reduce participant burden and the lack of a healthy control group. The GABA levels measured in this study will contain contributions from co-edited macromolecule signal (so-called GABA+), but the relative contribution of these macromolecular signals are thought to be constant unlikely to account for within participant/session GABA changes. ConclusionsThis first such study in adolescents with NF1, showed that atDCS modulates inhibitory activity in the DLPFC. This focussed mechanism trial presents a highly promising approach to understanding complex neural pathology in neurodevelopmental disorders. Given the strong evidence linking GABA abnormalities to cognitive deficits across neurodevelopmental conditions such as ASD, modulation of GABA using atDCS offers a promising novel therapeutic approach. ClinicalTrials.gov Identifier: NCT0499142. Registered 5th August 2021; retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04991428

scholarly journals Non-invasive Brain Stimulation Modulates GABAergic Activity in Neurofibromatosis 1

2021 ◽  
Author(s):  
Shruti Garg ◽  
Steve Williams ◽  
JeYoung Jung ◽  
Gorana Pobric ◽  
Tulika Nandi ◽  
...  
Keyword(s):  
Working Memory ◽  
Response Times ◽  
Single Gene ◽  
Occipital Cortex ◽  
Autism Spectrum ◽  
Neurofibromatosis 1 ◽  
Resonance Spectroscopy ◽  
Left Dlpfc ◽  
Promising Therapeutic Approach ◽  
Dorsolateral Prefrontal

Abstract Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive phenotypes common to neurodevelopmental conditions such as Autism Spectrum Disorder (ASD) & Attention Deficit Hyperactivity Disorder (ADHD). GABAergic dysregulation underlies working memory impairments seen in NF1. This mechanistic experimental study investigates whether application of anodal transcranial direct current stimulation (atDCS) can modulate GABA and working memory in NF1. 31 adolescents with NF1 were recruited to this single-blind sham-controlled cross-over randomized trial. Active or sham tDCS was applied to the left Dorsolateral Prefrontal Cortex (DLPFC) and Magnetic Resonance Spectroscopy was collected before and after intervention in the left DLPFC and occipital cortex. Higher baseline GABA in the left DLPFC was associated with faster response times (RT) on baseline working memory measures. AtDCS was seen to significantly reduced GABA as compared to sham stimulation in the left DLPFC. There was no effect of atDCS on Glutamate/glutamine (Glx) in the left DLPFC or on GABA/Glx in the occipital cortex. This first such study in adolescents with NF1, showed that atDCS modulates inhibitory activity in the DLPFC. Given the strong evidence linking GABA abnormalities to cognitive deficits across neurodevelopmental conditions such as ASD, modulation of GABA using atDCS offers a promising therapeutic approach.ClinicalTrials.gov Identifier: NCT0499142. Registered 05/08/2021; retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04991428

A Proton Magnetic Resonance Spectroscopic Study in Autism Spectrum Disorder Using a 3-Tesla Clinical Magnetic Resonance Imaging (MRI) System: The Anterior Cingulate Cortex and the Left Cerebellum

2017 ◽  
Vol 32 (8) ◽  
pp. 731-739 ◽  
Author(s):  
Hiromichi Ito ◽  
Kenji Mori ◽  
Masafumi Harada ◽  
Sonoka Hisaoka ◽  
Yoshihiro Toda ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Magnetic Resonance ◽  
Anterior Cingulate Cortex ◽  
Proton Magnetic Resonance ◽  
Cingulate Cortex ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Anterior Cingulate ◽  
Control Group ◽  
Resonance Spectroscopy

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.

Executive Function Deficits in Patients after Cerebellar Neurosurgery

2015 ◽  
Vol 22 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Monika Mak ◽  
Ernest Tyburski ◽  
Łukasz Madany ◽  
Andrzej Sokołowski ◽  
Agnieszka Samochowiec
Keyword(s):  
Working Memory ◽  
Executive Functions ◽  
Response Times ◽  
Digit Span ◽  
Wisconsin Card Sorting Test ◽  
Control Group ◽  
Card Sorting ◽  
Mediating Role ◽  
Regulatory Processes ◽  
Perseverative Errors

AbstractThe cerebellum has long been perceived as a structure responsible for the human motor function. According to the contemporary approach, however, it plays a significant role in complex behavior regulatory processes. The aim of this study was to describe executive functions in patients after cerebellar surgery. The study involved 30 patients with cerebellar pathology. The control group comprised 30 neurologically and mentally healthy individuals, matched for sex, age, and number of years of education. Executive functions were measured by the Wisconsin Card Sorting Test (WCST), Stroop Color Word Test (SCWT), Trail Making Test (TMT), and working memory by the Digit Span. Compared to healthy controls, patients made more Errors and Perseverative errors in the WCST, gave more Perseverative responses, and had a lower Number of categories completed. The patients exhibited higher response times in all three parts of the SCWT and TMT A and B. No significant differences between the two groups were reported in their performance of the SCWT and TMT with regard to the measures of absolute or relative interference. The patients had lower score on the backward Digit Span. Patients with cerebellar pathology may exhibit some impairment within problem solving and working memory. Their worse performance on the SCWT and TMT could, in turn, stem from their poor motor–somatosensory control, and not necessarily executive deficits. Our results thus support the hypothesis of the cerebellum’s mediating role in the regulation of the activity of the superordinate cognitive control network in the brain. (JINS, 2016, 22, 47–57)

scholarly journals GABA alterations in pediatric sport concussion

Neurology ◽  
2017 ◽  
Vol 89 (21) ◽  
pp. 2151-2156 ◽  
Author(s):  
Seth D. Friedman ◽  
Andrew V. Poliakov ◽  
Christopher Budech ◽  
Dennis W.W. Shaw ◽  
David Breiger ◽  
...  
Keyword(s):  
Working Memory ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Frontal Lobe ◽  
Memory Task ◽  
Patient Specific ◽  
Control Group ◽  
Resonance Spectroscopy ◽  
Sport Concussion ◽  
Task Activation

Objective:To evaluate whether frontal-lobe magnetic resonance spectroscopy measures of γ-aminobutyric acid (GABA) would be altered in a sample of adolescents scanned after sport concussion because mild traumatic brain injury is often associated with working memory problems.Methods:Eleven adolescents (age 14–17 years) who had sustained a first-time sport concussion were studied with MRI/magnetic resonance spectroscopy within 23 to 44 days after injury (mean 30.4 ± 6.1 days). Age- and sex-matched healthy controls, being seen for sports-related injuries not involving the head and with no history of concussion, were also examined. GABA/creatine + phosphocreatine (Cre) was measured in left-sided frontal lobe and central posterior cingulate regions. The frontal voxel was positioned to overlap with patient-specific activation on a 1-back working memory task.Results:Increased GABA/Cre was shown in the frontal lobe for the concussed group. A decreased relationship was observed in the parietal region. High correlations between GABA/Cre and task activation were observed for the control group in the frontal lobe, a relationship not shown in the concussed participants.Conclusions:GABA/Cre appears increased in a region colocalized with working memory task activation after sport concussion. Further work extending these results in larger samples and at time points across the injury episode will aid in refining the clinical significance of these observations.

scholarly journals Working Memory Depletion Affects Intertemporal Choice Among Internet Addicts and Healthy Controls

2021 ◽  
Vol 12 ◽  
Author(s):  
Hongxia Li
Keyword(s):  
Working Memory ◽  
Delay Discounting ◽  
Intertemporal Choice ◽  
Response Times ◽  
Memory Task ◽  
Reaction Times ◽  
Self Report ◽  
The Internet ◽  
Control Group ◽  
Healthy Controls

Addiction to the Internet has emerged as a new kind of addictive behavior. Although previous studies have revealed that impairments in working memory led to suboptimal decision making (e.g., a greater willingness to choose smaller, more immediate rewards), little is known about how working memory affects intertemporal choice in Internet addicts and normal users. Thus, this study’s aim was to investigate the effect of working memory task on intertemporal choice in 33 participants addicted to internet and 25 healthy controls. Participants were administered (a) a test for Internet Addiction, (b) a single delay discounting self-report questionnaire (c) a working memory task. Differences between the Internet addicts and the control group were observed in terms of delay discounting rates, reaction times, and in memory accuracy rates. We observed significantly higher delay discounting rates among individuals addicted to the Internet. Moreover, it was documented that reaction times follow the 4-level working memory condition were significantly longer than follow the 2-level condition, in both the Internet addicts and the control group. The current findings suggest that Internet addicts are more likely to make short-sighted decisions than normal Internet users. The higher the level of working memory, the more likely an individual is to choose the present smaller reward, thus making short-sighted decisions, and have longer response times.

scholarly journals Cognitive and Electrophysiological Correlates of Working Memory Impairments in Neurofibromatosis Type 1

2021 ◽  
Author(s):  
Gorana Pobric ◽  
Jason R. Taylor ◽  
Hemavathy M. Ramalingam ◽  
Emily Pye ◽  
Louise Robinson ◽  
...  
Keyword(s):  
Working Memory ◽  
Single Gene ◽  
Neurofibromatosis Type ◽  
Event Related Potential ◽  
P300 Amplitude ◽  
Group Differences ◽  
Control Group ◽  
P300 Latency ◽  
Memory Impairments

AbstractNeurofibromatosis 1 (NF1) is a single gene disorder associated with working Memory (WM) impairments. The aim of this study was to investigate P300 event-related potential (ERP) associated with WM in NF1. Sixteen adolescents with NF1 were compared with controls on measures of WM and EEG was recorded during a WM nback task. The NF1 group showed poorer performance on measures of WM as compared to the control group. No group differences were observed in P300 amplitude at Pz, but P300 latency was shorter in the NF1 group. Topographic analyses of P300 amplitude showed group differences indicating neural processing differences in the NF1 group relative to controls, which possibly contribute to the cognitive deficits seen in this population.

scholarly journals Prediction learning in adults with autism and its molecular correlates

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Laurie-Anne Sapey-Triomphe ◽  
Joke Temmerman ◽  
Nicolaas A. J. Puts ◽  
Johan Wagemans
Keyword(s):  
Inferior Frontal Gyrus ◽  
Occipital Cortex ◽  
Learning Task ◽  
Autism Spectrum ◽  
Resonance Spectroscopy ◽  
Sensory Sensitivity ◽  
Adults With Autism ◽  
Rotation Direction ◽  
Autistic Adults ◽  
The Right

Abstract Background According to Bayesian hypotheses, individuals with Autism Spectrum Disorder (ASD) have difficulties making accurate predictions about their environment. In particular, the mechanisms by which they assign precision to predictions or sensory inputs would be suboptimal in ASD. These mechanisms are thought to be mostly mediated by glutamate and GABA. Here, we aimed to shed light on prediction learning in ASD and on its neurobiological correlates. Methods Twenty-six neurotypical and 26 autistic adults participated in an associative learning task where they had to learn a probabilistic association between a tone and the rotation direction of two dots, in a volatile context. They also took part in magnetic resonance spectroscopy (MRS) measurements to quantify Glx (glutamate and glutamine), GABA + and glutathione in a low-level perceptual region (occipital cortex) and in a higher-level region involved in prediction learning (inferior frontal gyrus). Results Neurotypical and autistic adults had their percepts biased by their expectations, and this bias was smaller for individuals with a more atypical sensory sensitivity. Both groups were able to learn the association and to update their beliefs after a change in contingency. Interestingly, the percentage of correct predictions was correlated with the Glx/GABA + ratio in the occipital cortex (positive correlation) and in the right inferior frontal gyrus (negative correlation). In this region, MRS results also showed an increased concentration of Glx in the ASD group compared to the neurotypical group. Limitations We used a quite restrictive approach to select the MR spectra showing a good fit, which led to the exclusion of some MRS datasets and therefore to the reduction of the sample size for certain metabolites/regions. Conclusions Autistic adults appeared to have intact abilities to make predictions in this task, in contrast with the Bayesian hypotheses of ASD. Yet, higher ratios of Glx/GABA + in a frontal region were associated with decreased predictive abilities, and ASD individuals tended to have more Glx in this region. This neurobiological difference might contribute to suboptimal predictive mechanisms in ASD in certain contexts.

scholarly journals Developmental trends of hot and cool executive function in school-aged children with and without autism spectrum disorder: Links with theory of mind

2018 ◽  
Vol 31 (02) ◽  
pp. 541-556 ◽  
Author(s):  
Evangelia-Chrysanthi Kouklari ◽  
Stella Tsermentseli ◽  
Claire P. Monks
Keyword(s):  
Autism Spectrum Disorder ◽  
Working Memory ◽  
Executive Function ◽  
Theory Of Mind ◽  
Longitudinal Design ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Control Group ◽  
Children With Asd ◽  
The Impact

AbstractThe development of executive function (EF) in autism spectrum disorder (ASD) has been investigated using only “cool”-cognitive EF tasks while there is limited knowledge regarding the development of “hot”-affective EF. Although cool EF development and its links to theory of mind (ToM) have been widely examined, understanding of the influence of hot EF to ToM mechanisms is minimal. The present study introduced a longitudinal design to examine the developmental changes in cool and hot EF of children with ASD (n = 45) and matched (to age and IQ) controls (n = 37) as well as the impact of EF on ToM development over a school year. For children with ASD, although selective cool (working memory and inhibition) and hot (affective decision making) EF domains presented age-related improvements, they never reached the performance level of the control group. Early cool working memory predicted later ToM in both groups but early hot delay discounting predicted later ToM only in the ASD group. No evidence was found for the reverse pattern (early ToM predicting later EF). These findings suggest that improvements in some EF aspects are evident in school age in ASD and highlight the crucial role that both cool and hot EF play in ToM development.

scholarly journals Changes in Human Brain Glutamate Concentration during Hypoglycemia: Insights into Cerebral Adaptations in Hypoglycemia-Associated Autonomic Failure in Type 1 Diabetes

2014 ◽  
Vol 34 (5) ◽  
pp. 876-882 ◽  
Author(s):  
Melissa Terpstra ◽  
Amir Moheet ◽  
Anjali Kumar ◽  
Lynn E Eberly ◽  
Elizabeth Seaquist ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Human Brain ◽  
Autonomic Failure ◽  
Occipital Cortex ◽  
Metabolic Adaptation ◽  
Control Group ◽  
Resonance Spectroscopy ◽  
Control Groups ◽  
Glutamate Concentration

Hypoglycemia-associated autonomic failure (HAAF) is a condition in which patients with type 1 diabetes (T1D) who experience frequent hypoglycemia develop defective glucose counter-regulation and become unable to sense hypoglycemia. Brain glutamate may be involved in the mechanism of HAAF. The goal of this study was to follow the human brain glutamate concentration during experimentally induced hypoglycemia in subjects with and without HAAF. 1H magnetic resonance spectroscopy was used to track the occipital cortex glutamate concentration throughout a euglycemic clamp followed immediately by a hypoglycemic clamp. T1D patients with HAAF were studied in comparison to two control groups, i.e., T1D patients without HAAF and healthy controls ( n = 5 per group). Human brain glutamate concentration decreased ( P≥0.01) after the initiation of hypoglycemia in the two control groups, but a smaller trend toward a decrease in patients with HAAF did not reach significance ( P>0.05). These findings are consistent with a metabolic adaptation in HAAF to provide higher glucose and/or alternative fuel to the brain, eliminating the need to oxidize glutamate. In an exploratory analysis, we detected additional metabolite changes in response to hypoglycemia in the T1D patient without HAAF control group, namely, increased aspartate and decreased lactate.

scholarly journals An exploratory study on the role of foreign language aptitudes in instructed pragmatics learning in L2 Chinese

2017 ◽  
Vol 6 (1) ◽  
pp. 103-128
Author(s):  
Shuai Li
Keyword(s):  
Working Memory ◽  
Treatment Group ◽  
Foreign Language ◽  
Response Times ◽  
Control Group ◽  
Production Test ◽  
Aptitude Tests ◽  
L2 Chinese ◽  
Grammatical Sensitivity ◽  
Rote Memory

AbstractThis study investigated whether and how foreign language (FL) aptitudes interacted with different instructional conditions to affect pragmatic gains in L2 Chinese. Fifty American learners of Chinese were randomly assigned to an (explicit) input-based treatment group, an (explicit) output-based treatment group, and a control group. Following a metapragmatic session, the two treatment groups practiced target request-making forms through their respective computer programs, while the control group did not practice. Gains in pragmatic performance were measured by a listening judgment test and an oral production test at immediate and delayed posttests. The participants also completed three foreign language (FL) aptitude tests assessing rote memory, grammatical sensitivity, and working memory. The results revealed different patterns of correlation between FL aptitudes and pragmatic gains. The input group showed positive correlations between working memory and reductions in judgment response times at both immediate and delayed posttests. The output group showed a positive correlation between grammatical sensitivity and gains in production speech rates at immediate posttest; a negative correlation was also found between rote memory and reductions in production planning times made at immediate posttest.

Sign in / Sign up

Export Citation Format

Share Document