A six-metabolite panel as potential blood-based biomarkers for Parkinson’s disease

AbstractCharacterisation and diagnosis of idiopathic Parkinson’s disease (iPD) is a current challenge that hampers both clinical assessment and clinical trial development with the potential inclusion of non-PD cases. Here, we used a targeted mass spectrometry approach to quantify 38 metabolites extracted from the serum of 231 individuals. This cohort is currently one of the largest metabolomic studies including iPD patients, drug-naïve iPD, healthy controls and patients with Alzheimer’s disease as a disease-specific control group. We identified six metabolites (3-hydroxykynurenine, aspartate, beta-alanine, homoserine, ornithine (Orn) and tyrosine) that are significantly altered between iPD patients and control participants. A multivariate model to predict iPD from controls had an area under the curve (AUC) of 0.905, with an accuracy of 86.2%. This panel of metabolites may serve as a potential prognostic or diagnostic assay for clinical trial prescreening, or for aiding in diagnosing pathological disease in the clinic.

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Study of cognitive impairment and genetic polymorphism of SLC41A1 (rs11240569 allele) in Parkinson’s disease in Upper Egypt: case-control study

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-021-00341-0 ◽

2021 ◽

Vol 57 (1) ◽

Author(s):

Hamdy N. El-Tallawy ◽

Tahia H. Saleem ◽

Wafaa M. Farghaly ◽

Heba Mohamed Saad Eldien ◽

Ashraf Khodaery ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Case Control Study ◽

Case Control ◽

Control Group ◽

Motor Symptoms ◽

And Control ◽

Non Motor Symptoms ◽

Control Study

Abstract Background Parkinson’s disease is one of the neurodegenerative disorders that is caused by genetic and environmental factors or interaction between them. Solute carrier family 41 member 1 within the PARK16 locus has been reported to be associated with Parkinson’s disease. Cognitive impairment is one of the non-motor symptoms that is considered a challenge in Parkinson’s disease patients. This study aimed to investigate the association of rs11240569 polymorphism; a synonymous coding variant in SLC41A1 in Parkinson’s disease patients in addition to the assessment of cognitive impairment in those patients. Results In a case -control study, rs11240569 single nucleotide polymorphisms in SLC41A1, genes were genotyped in 48 Parkinson’s disease patients and 48 controls. Motor and non-motor performance in Parkinson's disease patients were assessed by using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The genotype and allele frequencies were compared between the two groups and revealed no significant differences between case and control groups for rs11240569 in SLC41A1 gene with P value .523 and .54, respectively. Cognition was evaluated and showed the mean ± standard deviation (SD) of WAIS score of PD patients 80.4 ± 9.13 and the range was from 61 to 105, in addition to MMSE that showed mean ± SD 21.96 ± 3.8. Conclusion Genetic testing of the present study showed that rs11240569 polymorphism of SLC41A1 gene has no significant differences in distributions of alleles and genotypes between cases and control group, in addition to cognitive impairment that is present in a large proportion of PD patients and in addition to the strong correlation between cognitive impairment and motor and non-motor symptoms progression.

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Polyomic Analyses of Dopaminergic Neurons Isolated From Human Substantia Nigra in Parkinson’s Disease: An Exploratory Study.

10.21203/rs.3.rs-182873/v1 ◽

2021 ◽

Author(s):

Affif ZACCARIA ◽

Paola Antinori Malaspina ◽

Virginie Licker ◽

Enikö Kovari ◽

Johannes A Lobrinus ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Protein Expression ◽

Differential Expression ◽

Exploratory Study ◽

Substantia Nigra Pars Compacta ◽

Control Group ◽

Gene And Protein Expression ◽

And Control

Abstract Background Dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc) selectively and progressively degenerate in Parkinson’s disease (PD). Until now, molecular analyses of DA neurons in PD have been limited to genomic and transcriptomic approaches, whereas, to the best of our knowledge, no proteomic or combined polyomic study examining the protein profile of these neurons, is currently available. Methods In this exploratory study, we used laser microdissection to extract DA neurons from 10 human SNpc samples obtained at autopsy in PD patients and control subjects. Extracted RNA and proteins were identified by RNA sequencing and nano-LC-MS/MS, respectively, and the differential expression between the PD and control group was assessed. Results Qualitative analyses confirmed that the microdissection protocol preserves the integrity of our samples and offers access to specific molecular pathways. This polyomic analysis highlighted differential expression of 52 genes and 33 proteins, including molecules of interest already known to be dysregulated in PD, such as LRP2, PNMT, CXCR4, MAOA and CBLN1 genes, or the Aldehyde dehydrogenase 1 protein. On the other hand, despite the same samples were used for both analyses, correlation between RNA and protein expression was low, as exemplified by the CST3 gene encoding for the cystatin C protein. Conclusion This is the first exploratory study analyzing both gene and protein expression of LMD-dissected DA neurons from SNpc in PD. Although correlation between RNA and protein expressions was limited, this polyomic study provides an extensive and integrated overview of molecular changes identified in the PD SNpc and may offer novel insights into specific pathological processes at work in PD degeneration.

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Feasibility of a Brazilian samba protocol for patients with Parkinson's disease: a clinical non-randomized study

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20190140 ◽

2020 ◽

Vol 78 (1) ◽

pp. 13-20 ◽

Cited By ~ 1

Author(s):

Ana Cristina TILLMANN ◽

Alessandra SWAROWSKY ◽

Clynton Lourenço CORRÊA ◽

Alexandro ANDRADE ◽

Jéssica MORATELLI ◽

...

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Randomized Study ◽

General Information ◽

Control Group ◽

Action Strategies ◽

And Control ◽

Experimental Group

Abstract Background: New protocols applied in the rehabilitation of Parkinson's disease enable different action strategies for health professionals, as well as a new range of activities for these individuals. However, no valid samba protocol with activity prescription for this population was found in the literature. Objective: To investigate the feasibility of a Brazilian samba protocol in individuals with Parkinson's disease. Methods: Twenty participants, mean age of 66.4±10.7 years, diagnosed with idiopathic Parkinson 's disease, divided into: experimental group that received the intervention of Brazilian samba dance classes (10 individuals); and control group that maintained their routine activities (10 individuals). For data collection, a divided questionnaire was used: General Information; Disability stages scale; Balance and Quality of Life. Results: During class implementation, there were no falls, as all dance activities adhered to the details of the protocol steps without any changes. On average, patients completed 82.7% of activities. After 12 weeks, the experimental group had improvements in the UPDRS global score, in daily activities, and on motor examination. There was also improvement in balance scores and in the mobility domain of the quality of life in the experimental group. Conclusion: The samba protocol seems to be feasible and safe for patients with PD. Moreover, it has pleasant characteristics and offers sufficient physical benefits for combination with drug treatment. There were also benefits in social relationships and as a possible rehabilitation tool in individuals with Parkinson's disease.

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Predictors of Loss of Functional Independence in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up and Comparison with a Control Group

Diagnostics ◽

10.3390/diagnostics11101801 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1801

Author(s):

Diego Santos García ◽

Teresa de Deus Fonticoba ◽

Carlos Cores Bartolomé ◽

Lucía Naya Ríos ◽

Lucía García Roca ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Activities Of Daily Living ◽

Daily Living ◽

Functional Independence ◽

Control Group ◽

Lemeshow Test ◽

Group A ◽

And Control

Background and objective: The aim of this study was to compare the progression of independence in activities of daily living (ADL) in Parkinson’s disease (PD) patients versus a control group, as well as to identify predictors of disability progression and functional dependency (FD). Patients and Methods: PD patients and control subjects, who were recruited from 35 centers of Spain from the COPPADIS cohort between January 2016 and November 2017 (V0), were included. Patients and subjects were then evaluated again at the 2-year follow-up (V2). Disability was assessed with the Schwab & England Activities of Daily Living Scale (S&E-ADLS) at V0 and V2. FD was defined as an S&E-ADLS score less than 80%. Results: In the PD group, a significant decrease in the S&E-ADLS score from V0 to V2 (N = 507; from 88.58 ± 10.19 to 84.26 ± 13.38; p < 0.0001; Cohen’s effect size = −0.519) was observed but not in controls (N = 124; from 98.87 ± 6.52 to 99.52 ± 2.15; p = 0.238). When only patients considered functional independent at baseline were included, 55 out of 463 (11.9%) converted to functional dependent at V2. To be a female (OR = 2.908; p = 0.009), have longer disease duration (OR = 1.152; p = 0.002), have a non-tremoric motor phenotype at baseline (OR = 3.574; p = 0.004), have a higher score at baseline in FOGQ (OR = 1.244; p < 0.0001) and BDI-II (OR = 1.080; p = 0.008), have a lower score at baseline in PD-CRS (OR = 0.963; p = 0.008), and have a greater increase in the score from V0 to V2 in UPDRS-IV (OR = 1.168; p = 0.0.29), FOGQ (OR = 1.348; p < 0.0001) and VAFS-Mental (OR = 1.177; p = 0.013) (adjusted R-squared 0.52; Hosmer and Lemeshow test = 0.94) were all found to be independent predictors of FD at V2. Conclusions: In conclusion, autonomy for ADL worsens in PD patients compared to controls. Cognitive impairment, gait problems, fatigue, depressive symptoms, more advanced disease, and a non-tremor phenotype are independent predictors of FD in the short-term.

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Urinary symptoms in Parkinson's disease: prevalence and associated factors

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2003000300007 ◽

2003 ◽

Vol 61 (2B) ◽

pp. 359-363 ◽

Cited By ~ 84

Author(s):

Raimundo Nonato Campos-Sousa ◽

Elizabeth Quagliato ◽

Benedito Borges da Silva ◽

Reynaldo Mendes de Carvalho Jr. ◽

Suilane Coelho Ribeiro ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Brain Magnetic Resonance Imaging ◽

Cross Sectional Study ◽

Urinary Dysfunction ◽

Urinary Symptoms ◽

Control Group ◽

Cross Sectional ◽

Urinary Tract Symptoms ◽

And Control

The authors present a cross-sectional study involving 61 patients with idiopathic Parkinson's disease (PD) who were consecutively examined and compared to a control group with 74 subjects. Only patients who fulfilled the standard diagnostic criteria for PD and whose brain magnetic resonance imaging was normal were included. The objective of the study was to evaluate the prevalence of inferior urinary tract symptoms in PD and to study the possible association between clinical factors to urinary dysfunction. ln the patient group, 39.3% presented urinary symptoms when compared to 10.8% in the control group. All symptomatic patients presented irritative symptoms. The most common irritative symptom PD was nocturia, followed by frequency and urinary incontinence. Around 25% of the patients presented functional obstructive symptoms determined by the disease. The most frequent obstructive symptom was incomplete emptying of the bladder. Only the age of the patients and control group were correlated with urinary dysfunction.

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Effects of Health Qigong Exercises on Relieving Symptoms of Parkinson’s Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/5935782 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 11

Author(s):

Xiao Lei Liu ◽

Shihui Chen ◽

Yongtai Wang

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Repeated Measures ◽

The Body ◽

Control Group ◽

Control Groups ◽

Timed Up And Go ◽

Muscle Hardness ◽

Hand Eye Coordination ◽

And Control

The purpose of this study was to investigate the effects of Health Qigong on the treatment and releasing symptoms of Parkinson’s disease (PD). Fifty-four moderate PD patients (N=54) were randomly divided into experimental and control groups. Twenty-eight PD patients were placed in the experimental group in which the prescribed medication plus Health Qigong exercise will be used as intervention. The other 26 PD patients as the control group were treated only with regular medication. Ten-week intervention had been conducted for the study, and participants completed the scheduled exercises 5 times per week for 60 minutes each time (10 minutes for warm-up, 40 minutes for the exercise, and 10 minutes for cooldown). Data which included the muscle hardness, one-legged blind balance, physical coordination, and stability was collected before, during, and after the intervention. Comparisons were made between the experimental and control groups through the Repeated Measures ANOVA. The results showed that PD patients demonstrate a significant improvement in muscle hardness, the timed “up and go,” balance, and hand-eye coordination (the turn-over-jars test). There were no significant differences between the two groups in gender, age, and course of differences (P<0.05). The study concluded that Health Qigong exercises could reduce the symptoms of Parkinson’s disease and improve the body functions of PD patients in both the mild and moderate stages. It can be added as an effective treatment of rehabilitation therapy for PD.

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Multiomic Analyses of Dopaminergic Neurons Isolated from Human Substantia Nigra in Parkinson’s Disease: A Descriptive and Exploratory Study

Cellular and Molecular Neurobiology ◽

10.1007/s10571-021-01146-8 ◽

2021 ◽

Author(s):

Affif Zaccaria ◽

Paola Antinori ◽

Virginie Licker ◽

Enikö Kövari ◽

Johannes A. Lobrinus ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Protein Expression ◽

Differential Expression ◽

Dopaminergic Neurons ◽

Exploratory Study ◽

Control Group ◽

Gene And Protein Expression ◽

And Control

AbstractDopaminergic neurons (DA) of the substantia nigra pars compacta (SNpc) selectively and progressively degenerate in Parkinson’s disease (PD). Until now, molecular analyses of DA in PD have been limited to genomic or transcriptomic approaches, whereas, to the best of our knowledge, no proteomic or combined multiomic study examining the protein profile of these neurons is currently available. In this exploratory study, we used laser capture microdissection to extract regions from DA in 10 human SNpc obtained at autopsy in PD patients and control subjects. Extracted RNA and proteins were identified by RNA sequencing and nanoliquid chromatography–mass spectrometry, respectively, and the differential expression between PD and control group was assessed. Qualitative analyses confirmed that the microdissection protocol preserves the integrity of our samples and offers access to specific molecular pathways. This multiomic analysis highlighted differential expression of 52 genes and 33 proteins, including molecules of interest already known to be dysregulated in PD, such as LRP2, PNMT, CXCR4, MAOA and CBLN1 genes, or the Aldehyde dehydrogenase 1 protein. On the other hand, despite the same samples were used for both analyses, correlation between RNA and protein expression was low, as exemplified by the CST3 gene encoding for the cystatin C protein. This is the first exploratory study analyzing both gene and protein expression of laser-dissected neuronal parts from SNpc in PD. Data are available via ProteomeXchange with identifier PXD024748 and via GEO with identifier GSE 169755.

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Adapted functional training versus Mat Pilates in motor and non-motor symptoms of individuals with Parkinson's disease: study protocol for a randomized controlled clinical trial Functional training versus Mat Pilates in Parkinson's disease

10.21203/rs.3.rs-62891/v1 ◽

2021 ◽

Author(s):

Jéssica Moratelli ◽

Kettlyn Hames Alexandre ◽

Leonessa Boing ◽

Melissa de Carvalho Souza Vieira ◽

Adriana Coutinho de Azevedo Guimarães

Keyword(s):

Parkinson’S Disease ◽

Clinical Trial ◽

Parkinson's Disease ◽

Cardiorespiratory Fitness ◽

Control Group ◽

Controlled Clinical Trial ◽

Motor Symptoms ◽

Functional Training ◽

Randomized Controlled ◽

Non Motor Symptoms

Abstract Background: Motor and non-motor symptoms affect the life of those living with Parkinson's disease, and it is clear that exercise offers benefits in these aspects. However, the effects of adapted functional training interventions and the Mat Pilates as a form of rehabilitation for the disease in question have not yet been established. Thus, this study aims to propose an adapted functional training protocol and Mat Pilates for individuals with Parkinson's disease and to evaluate the effects on motor symptoms (balance, cardiorespiratory fitness, lower and upper limb strength, flexibility and agility), as well as , in non-motor symptoms (cognition, depressive symptoms, mood state, anxiety and finitude) by means of a randomized controlled trial. Methods: Protocol for a randomized clinical trial in which 45 individuals with Parkinson's disease will be recruited and randomly allocated to one of three groups: (1) functional training; (2) Mat Pilates; (3) control group. Both intervention groups will have 60-minute classes twice a week for 12 weeks. The primary outcome will be analyzed by balancing with the Mini-BESTest test. Secondary outcomes will include cognition, aging perspective, mood, anxiety, depression, mobility, muscle strength, handgrip strength, flexibility, range of motion, and cardiorespiratory fitness. The evaluations will be performed in the pre-intervention period (baseline), after 12 weeks of intervention, after 3 months, 6 months and 1 year of intervention. Discussion: This will be the first randomized trial to compare the effects of functional training and Mat Pilates in a population with Parkinson's disease. It is hypothesized that improvements in motor and non-motor symptoms will be greater and more lasting after functional training and Mat Pilates interventions than those that maintain their routine activities, given the benefits of exercise and the unprecedented protocols in this disease.Trial registrationRegistry name: Registro Brasileiro de Ensaios Clínicos (ReBEC)Registration number: RBR-6ckggnDate of registration: September 29, 2020. Trial was prospectively registered

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Kinematic variables of gait and quality of life in Parkinsonians after different treadmill trainings: a randomized control trial

Motricidade ◽

10.6063/motricidade.10809 ◽

2018 ◽

Vol 14 (1) ◽

pp. 29

Author(s):

Maira Peloggia Cursino ◽

Doralice Fernanda Raquel ◽

Camilla Zamfolini Hallal ◽

Flávia Roberta Faganello Navega

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Step Length ◽

Gait Training ◽

Control Group ◽

Weight Support ◽

Partial Body ◽

And Control

The aim of this study was to analyse and compare the effects of gait training on a treadmill associated with partial body weight support (PBWS) or auditory stimulus (AS) and the kinematic variables of gait and quality of life (QOL) in patients with Parkinson's disease (PD). Twenty-one volunteers with PD participated and were divided into: group with PBWS (GPBWS) with AS (GAS), and control group (CG). Soil step length (SL), SL variability (SLV), step width (SW), SW variability (SWV), gait speed (GS), and QOL were evaluated by the Parkinson’s Disease Questionnaire-39 (PDQ-39). The training was performed for six weeks, with three weekly sessions of 30 minutes. The results showed homogeneity of groups (p> 0.05). There was an increase of SW in the GPBWS (p= 0.006) and GS in the GAS (p= 0.048) and decreased PDQ-39 in the CG (p= 0.005) and GAS (p= 0.006). For groups, regardless of evaluation, there were differences in SWV between the GPBWS and GAS (p= 0.030); for evaluations, independently of groups, there were differences in GS (p= 0.048) and PDQ-39 (p= 0.002). It was concluded that, among the studied conditions, there was a significant improvement for the groups: AS in GS and QOL, CG in QOL and GPBWS did not improve. Thus, considering the clinical effect, treadmill training, independently of the stimuli, is clinically advantageous for gait improvements and QOL. The aim of this study was to analyse and compare the effects of gait training on a treadmill associated with partial body weight support (PBWS) or auditory stimulus (AS) and the kinematic variables of gait and quality of life (QOL) in patients with Parkinson's disease (PD). Twenty-one volunteers with PD participated and were divided into: group with PBWS (GPBWS) with AS (GAS), and control group (CG). Soil step length (SL), SL variability (SLV), step width (SW), SW variability (SWV), gait speed (GS), and QOL were evaluated by the Parkinson’s Disease Questionnaire-39 (PDQ-39). The training was performed for six weeks, with three weekly sessions of 30 minutes. The results showed homogeneity of groups (p> 0.05). There was an increase of SW in the GPBWS (p= 0.006) and GS in the GAS (p= 0.048) and decreased PDQ-39 in the CG (p= 0.005) and GAS (p= 0.006). For groups, regardless of evaluation, there were differences in SWV between the GPBWS and GAS (p= 0.030); for evaluations, independently of groups, there were differences in GS (p= 0.048) and PDQ-39 (p= 0.002). It was concluded that, among the studied conditions, there was a significant improvement for the groups: AS in GS and QOL, CG in QOL and GPBWS did not improve. Thus, considering the clinical effect, treadmill training, independently of the stimuli, is clinically advantageous for gait improvements and QOL.

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2334 Neural correlates of externally Versus internally guided dance-based therapies for people with Parkinson’s disease

Journal of Clinical and Translational Science ◽

10.1017/cts.2018.99 ◽

2018 ◽

Vol 2 (S1) ◽

pp. 21-21

Author(s):

Amrit Kashyap ◽

Madeleine Hackney ◽

Venkatagiri Krishnamurthy ◽

Lisa Krishnamurthy ◽

Krish Sathian ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Signal To Noise Ratio ◽

Inferior Frontal Gyrus ◽

Area Under The Curve ◽

Control Group ◽

Post Intervention ◽

Or Education ◽

Behavioral Measures ◽

Causal Pathway

OBJECTIVES/SPECIFIC AIMS: Parkinson’s disease (PD) is a condition that affects over a million Americans, and despite current medical therapies, the progression of the disease results in impaired generation of internally timed or guided (IG) movements. To address this loss of motor function, previous rehabilitation therapies have focused on remediating the affected striatal-thalamic-cortical circuits (STC), primarily thought to be responsible in generating timed motor patterns. However, given the disease leads to the cell death of dopaminergic cells that are essential for proper STC function, we propose a motor therapy aimed at utilizing a compensatory parallel cerebellar-thalamic-cortical (CTC) pathway, recruited to perform externally guided (EG) movements, in which gait initiation is driven from sensory input. Our previous study has shown efficacy in our novel argentine tango therapy and improves behavioral measures above the relevant MCID threshold, but it has not been established that the CTC are in the causal pathway that are responsible for these changes. Using neural measures from task fMRI, we have begun to characterize networks that have changed and quantify any associations with behavioral metrics. METHODS/STUDY POPULATION: Patients were randomly assigned to an IG (n=18), EG (n=18), or education contact control (n=14). Participants were assessed preintervention and postintervention for behavioral motor and cognitive measures and neurophysiologically with task based fMRI. In the task, participants performed a foot tapping task under both IG (tap their foot in previously learned rhythm) or EG (tap immediately after receiving a tactile cue on their hand) conditions. The fMRI data were preprocessed using AFNI and registered to MNI standard space. The brainnetome atlas was applied and the average time series of each region of interest (ROI) was used to increase the signal to noise ratio. The activation of these ROI with respect to the stimulus was modeled using GLM, and we estimated the area under the curve during the task blocks. A 1-way ANOVA analysis on these betas were performed between the pre and the post intervention time points and the ROIs that were above a significance of 0.95 were identified and corrected for multiple comparisons. The change in beta in all ROIs for each individual were calculated and then correlated with the changes in the behavioral data, to see which changes in ROI areas matched the best with the behavioral changes. RESULTS/ANTICIPATED RESULTS: The EG group showed significant changes only in the EG task in 2 areas—inferior frontal gyrus and inferior temporal sulcus. Correlating to the cognitive behavioral measures show reduced error from the Inferior frontal gyrus (corr>0.5) best reflect changes in observed. There were no changes to either the STC or the CTC pathways. The IG group showed no changes behaviorally and showed no changes neurally as well. The control group showed no changes behaviorally, but neuronally certain DMN nodes, such as the precuneus and inferior temporal regions showed a significant change for both tasks. DISCUSSION/SIGNIFICANCE OF IMPACT: Addressing the damaged STC pathway directly through IG therapy may not be effective. The EG therapy may not be able to enhance the STC pathway. However, the therapy appears to utilize new areas in the frontal regions and correlates with positively with changes in spatial memory and balance tasks. Contrary to our hypothesis the CTC circuit was not upregulated for performance of the IG or EG task, but therapy may have enhanced recruitment of other cognitively engaged areas. The educational control group interestingly showed changes in the DMN network, which has been shown to be linked to attention during tasks blocks.

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