scholarly journals Mapping of long-term cognitive and motor deficits in pediatric cerebellar brain tumor survivors into a cerebellar white matter atlas

2021 ◽  
Author(s):  
Frederik Grosse ◽  
Stefan Mark Rueckriegel ◽  
Ulrich-Wilhelm Thomale ◽  
Pablo Hernáiz Driever
Keyword(s):  
Brain Tumor ◽  
Executive Function ◽  
Cognitive Function ◽  
White Matter ◽  
Cerebellar Nuclei ◽  
Motor Deficits ◽  
Deep Cerebellar Nuclei ◽  
Cerebellar White Matter ◽  
Lesion Symptom Mapping

Abstract Purpose Diaschisis of cerebrocerebellar loops contributes to cognitive and motor deficits in pediatric cerebellar brain tumor survivors. We used a cerebellar white matter atlas and hypothesized that lesion symptom mapping may reveal the critical lesions of cerebellar tracts. Methods We examined 31 long-term survivors of pediatric posterior fossa tumors (13 pilocytic astrocytoma, 18 medulloblastoma). Patients underwent neuronal imaging, examination for ataxia, fine motor and cognitive function, planning abilities, and executive function. Individual consolidated cerebellar lesions were drawn manually onto patients’ individual MRI and normalized into Montreal Neurologic Institute (MNI) space for further analysis with voxel-based lesion symptom mapping. Results Lesion symptom mapping linked deficits of motor function to the superior cerebellar peduncle (SCP), deep cerebellar nuclei (interposed nucleus (IN), fastigial nucleus (FN), ventromedial dentate nucleus (DN)), and inferior vermis (VIIIa, VIIIb, IX, X). Statistical maps of deficits of intelligence and executive function mapped with minor variations to the same cerebellar structures. Conclusion We identified lesions to the SCP next to deep cerebellar nuclei as critical for limiting both motor and cognitive function in pediatric cerebellar tumor survivors. Future strategies safeguarding motor and cognitive function will have to identify patients preoperatively at risk for damage to these critical structures and adapt multimodal therapeutic options accordingly.

Postsynaptic mechanisms underlying long-term depression of GABAergic transmission in neurons of the deep cerebellar nuclei

1996 ◽  
Vol 76 (1) ◽  
pp. 59-68 ◽  
Author(s):  
W. Morishita ◽  
B. R. Sastry
Keyword(s):  
Synaptic Transmission ◽  
Gabaa Receptor ◽  
Cell Voltage ◽  
Cerebellar Nuclei ◽  
Neuronal Membrane ◽  
Gamma Aminobutyric Acid ◽  
Deep Cerebellar Nuclei ◽  
Long Term Depression ◽  
In Cells

1. The mechanisms underlying long-term depression (LTD) of gamma-aminobutyric acid-A (GABAA) receptor-mediated synaptic transmission induced by 10-Hz stimulation of the inhibitory afferents were investigated using perforated and whole cell voltage-clamp recordings from neurons of the deep cerebellar nuclei (DCN). 2. LTD of inhibitory postsynaptic currents (IPSCs) was reliably induced when the 10-Hz stimulation was delivered under current-clamp conditions where the postsynaptic neuronal membrane was allowed to depolarize. 3. Currents elicited by local applications of the GABAA receptor agonist, 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol hydrochloride (THIP) were also depressed during LTD. 4. LTD could be induced heterosynaptically and did not require the activation of GABAA receptors during the 10-Hz stimulation. 5. In cells loaded with QX-314 and superfused with media containing 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonovaleric acid (APV), a series of depolarizing pulses (50 mV, 200 ms) induced a sustained depression of the IPSC. However, this was not observed in cells recorded with high bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA)-containing pipette solutions or when they were exposed to the L-type Ca2+ channel antagonist, nitrendipine. 6. The 10-Hz-induced LTD was also inhibited by BAPTA and was significantly reduced when DCN cells were loaded with microcystin LR or treated with okadaic acid, both inhibitors of protein phosphatases. 7. These results indicate that increases in postsynaptic [Ca2+] and phosphatase activity can reduce the efficacy of GABAA receptor-mediated synaptic transmission.

Long-term depression of IPSPs in rat deep cerebellar nuclei

Neuroreport ◽  
1993 ◽  
Vol 4 (6) ◽  
pp. 719-722 ◽  
Author(s):  
Wade Morishita ◽  
Bhagavatula R. Sastry
Keyword(s):  
Cerebellar Nuclei ◽  
Deep Cerebellar Nuclei ◽  
Long Term Depression

scholarly journals Altered brain metabolism contributes to executive function deficits in school-aged children born very preterm

2020 ◽  
Vol 88 (5) ◽  
pp. 739-748 ◽  
Author(s):  
Barbara Schnider ◽  
◽  
Ruth Tuura ◽  
Vera Disselhoff ◽  
Bea Latal ◽  
...  
Keyword(s):  
Executive Function ◽  
Preterm Birth ◽  
White Matter ◽  
Brain Metabolism ◽  
School Age ◽  
Very Preterm ◽  
Brain Metabolite ◽  
Frontal White Matter ◽  
Executive Function Deficits

Abstract Background Executive function deficits in children born very preterm (VPT) have been linked to anatomical abnormalities in white matter and subcortical brain structures. This study aimed to investigate how altered brain metabolism contributes to these deficits in VPT children at school-age. Methods Fifty-four VPT participants aged 8–13 years and 62 term-born peers were assessed with an executive function test battery. Brain metabolites were obtained in the frontal white matter and the basal ganglia/thalami, using proton magnetic resonance spectroscopy (MRS). N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, glutamate + glutamine (Glx)/Cr, and myo-Inositol (mI)/Cr were compared between groups and associations with executive functions were explored using linear regression. Results In the frontal white matter, VPT showed lower Glx/Cr (mean difference: −5.91%, 95% CI [−10.50, −1.32]), higher Cho/Cr (7.39%, 95%-CI [2.68, 12.10]), and higher mI/Cr (5.41%, 95%-CI [0.18, 10.64]) while there were no differences in the basal ganglia/thalami. Lower executive functions were associated with lower frontal Glx/Cr ratios in both groups (β = 0.16, p = 0.05) and higher mI/Cr ratios in the VPT group only (interaction: β = −0.17, p = 0.02). Conclusion Long-term brain metabolite alterations in the frontal white matter may be related to executive function deficits in VPT children at school-age. Impact Very preterm birth is associated with long-term brain metabolite alterations in the frontal white matter. Such alterations may contribute to deficits in executive function abilities. Injury processes in the brain can persist for years after the initial insult. Our findings provide new insights beyond structural and functional imaging, which help to elucidate the processes involved in abnormal brain development following preterm birth. Ultimately, this may lead to earlier identification of children at risk for developing deficits and more effective interventions.

Long-Term Recreational Cannabis Use Is Associated With Lower Executive Function and Processing Speed in a Pilot Sample of Older Adults

2021 ◽  
pp. 089198872110491
Author(s):  
Katie Stypulkowski ◽  
Rachel E. Thayer
Keyword(s):  
Older Adults ◽  
Working Memory ◽  
Executive Function ◽  
Cognitive Function ◽  
Processing Speed ◽  
Bimodal Distribution ◽  
Cannabis Use ◽  
Short Term ◽  
Small Pilot Study

More older adults are using cannabis for recreational and/or medical purposes, but most studies examining cognitive function and cannabis use do not include older adults. The current small pilot study sought to compare cognitive function and emotional functioning among adults age 60 and older who were regular, primarily recreational cannabis users ( n = 28) and nonusers ( n = 10). A bimodal distribution was observed among cannabis users such that they had either initiated regular use more recently (“short-term” users; ≤7 years, n = 13) or earlier in life (“long-term” users; ≥19 years, n = 15). Nonusers, short-term, and long-term users were not different in depression, anxiety, or emotion regulation, or alcohol use. Nonusers scored significantly higher than long-term users in executive function. Short-term users scored significantly higher than long-term users in executive function, processing speed, and general cognition. Additionally, greater recent cannabis use frequency was negatively associated with working memory. The current findings suggest that short-term recreational cannabis use does not result in differences in cognitive performance compared to nonusers, which may indicate that short-term use is relatively benign in older adults. However, longer duration of use is associated with poorer processing speed and executive functioning, and more recent cannabis use is associated with poorer working memory, which may impact older adults’ overall cognitive functioning.

scholarly journals Cognitive Function and White Matter Changes Associated with Renal Transplantation

2016 ◽  
Vol 43 (1) ◽  
pp. 50-57 ◽  
Author(s):  
Aditi Gupta ◽  
Rebecca J. Lepping ◽  
Alan S.L. Yu ◽  
Rodrigo D. Perea ◽  
Robyn A. Honea ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Executive Function ◽  
Renal Transplantation ◽  
Cognitive Function ◽  
White Matter ◽  
Brain Structure ◽  
White Matter Integrity ◽  
Logical Memory ◽  
Brain White Matter ◽  
With Memory

Background: End-stage renal disease (ESRD) is a disease with an aging population and a high prevalence of cognitive impairment affecting quality of life, health care costs and mortality. Structural changes in the brain with decreased white matter integrity have been observed in ESRD. Understanding the changes in cognition and associated changes in brain structure after renal transplantation can help define the mechanisms underlying cognitive impairment in ESRD. Methods: We conducted a prospective, observational cohort study in ESRD patients listed for renal transplantation and followed them post-transplantation. We assessed their cognitive function with a battery of neuropsychological tests and brain white matter integrity with diffusion tensor imaging (DTI) both before transplant and 3 months after transplant. Results: Eleven patients, aged 56.5 ± 10.7 years, completed the study. Cognitive measures of memory and executive function improved after the transplant, specifically on tests of logical memory I (p = 0.004), logical memory II (p = 0.003) and digit symbol (p < 0.0001). DTI metrics also improved post the transplant with an increase in fractional anisotropy (p = 0.01) and decrease in mean diffusivity (p = 0.004). These changes were more prominent in tracts associated with memory and executive function. Conclusions: Cognitive function, particularly memory and executive function, improve post the transplant with concurrent improvements in white matter integrity in tracts associated with memory and executive function. These data suggest that abnormalities in cognition and brain structure seen in the ESRD population are at least partially reversible.

scholarly journals Ischemic Heart Disease and Cognitive Prognosis in the First Year after Stroke

2020 ◽  
Author(s):  
Michael J O'Sullivan ◽  
Paul Wright
Keyword(s):  
Risk Factors ◽  
Heart Disease ◽  
Executive Function ◽  
Cognitive Function ◽  
White Matter ◽  
Ischemic Heart Disease ◽  
First Year ◽  
One Year ◽  
Moca Score ◽  
Over Time

Importance: Cognitive impairment is the greatest single source of unmet need identified by stroke survivors. Knowledge of the factors that influence cognitive prognosis will lead to better preventive and rehabilitation strategies. Objective: To identify the factors that influence general cognitive function, memory and executive function in the first year after ischemic stroke. Design: Single centre longitudinal observational study. Setting: Hospital stroke service. Participants: A cohort of 179 patients identified within 7 days of first symptomatic ischaemic stroke were enrolled into a longitudinal cognitive study, STRATEGIC. General cognitive function, episodic memory and executive function were assessed in the first three months and again at one year after stroke. Lesion topography was defined by imaging (n=152) performed in the acute period. Cognitive evaluation was repeated at one year in 141 participants. Main Outcome Measures: Montreal Cognitive Assessment (MoCA) score at 1 year. Verbal free recall (Free and Cued Selective Reminding Test) and Digit Symbol Substitution Score provided secondary outcome measures of episodic memory and executive function respectively. Results: At 50+-19 days after stroke, diabetes mellitus and smoking were associated with MoCA score independent of other risk and demographic factors. Lesion vascular territory was independently associated with memory while white matter lesion burden was associated with executive function. In contrast to other risk factors, ischaemic heart disease was associated with change in cognitive scores and MoCA score at one year but not MoCA score at 3 months. IHD was the only factor significantly associated with change over time. This association was significant independent of other factors. Conclusions and Relevance: Associations between post-stroke cognition, and age, diabetes, smoking and white matter lesions, are likely to reflect the general effects of these factors on brain structure and function. These risk factors are not associated with change in cognitive function between 3 months and one year. In contrast, pre-existing ischemic heart disease was associated specifically with change in cognition over time. On average, patients with IHD showed decline in MoCA scores between 3 and 12 months while those free of IHD showed improvement. Intervention for IHD, alongside best-care stroke rehabilitation, merits investigation as a strategy to improve cognitive prognosis after stroke.

scholarly journals Cerebellar white-matter changes in cannabis users with and without schizophrenia

2011 ◽  
Vol 41 (11) ◽  
pp. 2349-2359 ◽  
Author(s):  
N. Solowij ◽  
M. Yücel ◽  
C. Respondek ◽  
S. Whittle ◽  
E. Lindsay ◽  
...  
Keyword(s):  
White Matter ◽  
Cannabinoid Receptors ◽  
Cannabis Use ◽  
Analysis Of Covariance ◽  
Psychotic Symptoms ◽  
White Matter Volume ◽  
Cerebellar White Matter ◽  
Matter Volume ◽  
Mri Scans

BackgroundThe cerebellum is rich in cannabinoid receptors and implicated in the neuropathology of schizophrenia. Long-term cannabis use is associated with functional and structural brain changes similar to those evident in schizophrenia, yet its impact on cerebellar structure has not been determined. We examined cerebellar grey and white matter in cannabis users with and without schizophrenia.MethodSeventeen patients with schizophrenia and 31 healthy controls were recruited; 48% of the healthy group and 47% of the patients were long-term heavy cannabis users (mean 19.7 and 17.9 years near daily use respectively). Cerebellar measures were extracted from structural 3-T magnetic resonance imaging (MRI) scans using semi-automated methods, and examined using analysis of covariance (ANCOVA) and correlational analyses.ResultsCerebellar white-matter volume was reduced in cannabis users with and without schizophrenia compared to healthy non-users, by 29.7% and 23.9% respectively, and by 17.7% in patients without cannabis use. Healthy cannabis users did not differ in white-matter volume from either of the schizophrenia groups. There were no group differences in cerebellar grey matter or total volumes. Total cerebellar volume decreased as a function of duration of cannabis use in the healthy users. Psychotic symptoms and illness duration correlated with cerebellar measures differentially between patients with and without cannabis use.ConclusionsLong-term heavy cannabis use in healthy individuals is associated with smaller cerebellar white-matter volume similar to that observed in schizophrenia. Reduced volumes were even more pronounced in patients with schizophrenia who use cannabis. Cannabis use may alter the course of brain maturational processes associated with schizophrenia.

Effect of immunotherapy and stereotactic radiosurgery on cognitive function and quality of life in long term survivors of metastatic brain malignancies.

2018 ◽  
Vol 36 (7_suppl) ◽  
pp. 125-125
Author(s):  
Naveen Kumar Reddy ◽  
Franklin Brown ◽  
Judith Hess ◽  
Miklos C. Fogarasi ◽  
Veronica Chiang
Keyword(s):  
Quality Of Life ◽  
Executive Function ◽  
Cognitive Function ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Processing Speed ◽  
Whole Brain Radiation ◽  
Brain Radiation

125 Background: Use of whole brain radiation, radiosurgery, targeted therapies, and more recently, immunotherapies have resulted in improved survival for patients with brain metastases. As patients live longer, it is becoming increasingly important to understand the long-term cognitive function (CF) and quality of life (QOL) changes associated with these therapies. Methods: The Yale Gamma Knife Database was searched for patients surviving greater than 2 years after brain metastasis diagnosis. Of 79 patients identified, 19 were willing to participate in study. All participants underwent a single assessment session of cognitive tests that evaluated executive function (TMTa and TMTb), processing speed (COWA), memory (HVLT), and quality of life (FACT-Br). Results: Within the whole group, mean age was 65.5 years (range 50-88), median time from brain metastasis diagnosis to testing was 60 months (range 25.6-120.6). Mean number of lesions treated was 3.8 (range 1-10). Mean total lesion volume treated was 14.1 mm3 (range 0.6 - 39). Only 2 patients were treated with whole brain radiation therapy. Patient scores were compared to validated normative data for their age group. Patients performed worse than normal for their age on TMTb (p < 0.0001), total word recall (p < 0.0001) and discriminative ability (p = 0.0004). Patients performed as expected for age on TMTa, animal naming, FAS, and % retention. A negative correlation was seen between executive function results and QOL (TMTa: r = -0.569, p ≤ 0.05, TMTb: r = -0.484, p ≤ 0.05) and a positive correlation was seen between processing speed results and QOL (r = 0.672, p ≤ 0.001). Conclusions: In patients surviving more than 2 years after diagnosis and successful treatment of brain metastases, this study shows that portions of executive function and memory are worse than expected for their age, while cognitive processing speed is similar to norms. Cognitive function was correlated with QOL; patients with lowered cognitive function reported a lower quality of life. Given this preliminary data, a further study in a larger population is needed to determine if certain treatments preferentially predispose patients to declines in CF and QOL.

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