The neural basis of cognitive deficits in adults with Sickle Cell Disease: a task-based fMRI study
Poster No:
220
Submission Type:
Abstract Submission
Authors:
Nahom Mossazghi1, Karim Helmet2, Sossena Wood3
Institutions:
1Carnegie Mellon University, PIttsburgh, PA, 2University of Pittsburgh, Pittsburrgh, PA, 3Carnegie Mellon University, Pittsburgh, PA
First Author:
Co-Author(s):
Introduction:
Sickle Cell Disease (SCD) is a genetic blood disorder caused by a mutation in the beta-globin gene, impairing oxygen delivery and neurovascular function(Kato, 2018). This dysfunction leads to severe neurological complications, including strokes, silent cerebral infarcts, and progressive cognitive decline(Jones, 2023; Portela, 2022). Cognitive flexibility, a critical component of executive function that enables individuals to adapt to changing tasks and environments, is notably impaired in SCD(Mizuno et al., 2023). Prior work suggests that the frontoparietal network, particularly the prefrontal cortex, supports cognitive flexibility, yet how SCD disrupts these circuits remains unclear(Clayden, 2023; Mizuno et al., 2023). To our knowledge, we are the first to use task-based neuroimaging to examine this disruption. In this study, we used the Digit Symbol Substitution Task (DSST), a standard measure of cognitive flexibility, during fMRI to characterize brain activation patterns(Jaeger, 2018). We hypothesize that SCD leads to reduced activation in the frontoparietal network, with compensatory recruitment of additional regions explaining the observed deficits in cognitive flexibility.
Methods:
Participants [5 controls, aged 25.8 ± 2.68; 5 SCD patients, aged 34 ± 7.09] completed demographic information prior to scanning. In our customized DSST paradigm (Fig. 1), a reference table pairs digits with symbols. Participants view a digit-symbol prompt and press distinct keys to indicate whether the pair is congruent (matches the reference table) or incongruent (does not match), thereby engaging cognitive flexibility through varied digit-symbol combinations. Imaging was conducted on a Siemens 3T MRI scanner, acquiring T1-weighted MPRAGE for anatomical structures and two DSST runs for task-related activation [TR = 1.031 s, TE = 0.03 s, slice thickness = 2 mm, spacing = 2 mm]. Behavioral data were analyzed in Python using descriptive statistics (mean accuracy and response times) and performed t-tests to assess significance. fMRI data were preprocessed with fMRIPrep (motion correction, normalization, smoothing). First-level GLM analyses modeled BOLD responses for each condition, followed by second-level group comparisons.
·DSST Task Structure
Results:
We found that adults with SCD show slightly higher DSST accuracy than controls (Fig. 2a) [patients vs. controls: combined 96.16% ± 3.13 vs 93.97 ± 5.38%; congruent 96.76 ± 2.70% vs 95.06 ± 3.83%; incongruent 95.59 ± 4.08 vs 93.16 ± 9.52%], p > 0.05 and comparable response times [combined 1.66 ± 0.70s vs 1.66 ± 0.57s; congruent 1.53 ± 0.66s vs 1.56 ± 0.53s; incongruent 1.79 ± 0.71s vs 1.78 ± 0.59s], p > 0.05. fMRI GLM analyses for the Congruent > Incongruent contrast reveal distinct activation patterns between controls and patients with SCD. In controls, congruent trials show significant activations in posterior regions, including the occipital lobe and parietal cortex, while incongruent activations are widespread across the frontal and parietal cortices. In patients with SCD, congruent activations are reduced and limited to smaller frontal regions, whereas incongruent activations are more pronounced, particularly in the parietal cortex.
·DSST Task Performance and fMRI Contrast Analysis
Conclusions:
Although behavioral performance was similar, fMRI analysis revealed that participants with SCD engaged distinct neural circuits compared to controls. Reduced activation during congruent tasks and widespread recruitment of cognitive control regions during incongruent tasks in the SCD group suggest reliance on alternative compensatory strategies. This is the first study to employ task-based neuroimaging to examine circuit-level differences in adults with SCD. Our results partially support our hypothesis, showing lower parietal but greater frontal activation in SCD. We are planning to continue recruitment in our ongoing study to increase our sample size and determine if these results are consistent or if pronounced behavioral deficits and altered neural activation patterns emerge.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Higher Cognitive Functions:
Executive Function, Cognitive Control and Decision Making 2
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI)
Keywords:
Cognition
Computational Neuroscience
Cortex
Degenerative Disease
DISORDERS
MRI
Neurological
Other - Sickle Cell Disease; Executive Function; Task-based fMRI;
1|2Indicates the priority used for review
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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
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Provide references using APA citation style.
2. Clayden, J. D. (2023). Structural connectivity mediates the relationship between blood oxygenation and cognitive function in sickle cell anemia. Blood Advances, 7(11), 2297–2308.
3. Couette, M. (2023). Early strokes are associated with more global cognitive deficits in adults with sickle cell disease. Journal of Clinical Medicine, 12(4).
4. Jaeger, J. (2018). Digit symbol substitution test. Journal of Clinical Psychopharmacology, 38(5), 513–519.
5. Jones, R. S. (2023). Silent infarction in sickle cell disease is associated with brain volume loss in excess of infarct volume. Frontiers in Neurology, 14.
6. Jorgensen, D. R. (2017). Disease severity and slower psychomotor speed in adults with sickle cell disease. Blood Advances, 1(21), 1790–1795.
7. Kato, G. J. (2018, March). Sickle cell disease. In Nature Reviews Disease Primers (Vol. 4). Nature Publishing Group.
8. Mizuno, A. (2023). Low thalamic activity during a digit-symbol substitution task is associated with symptoms of subjective cognitive decline. Frontiers in Psychiatry, 14.
9. Portela, G. T. (2022). Comprehensive assessment of cognitive function in adults with moderate and severe sickle cell disease. American Journal of Hematology, 97(9), E344–E346.
10. Sundd, P. (2018). Pathophysiology of sickle cell disease. Annual Review of Pathology: Mechanisms of Disease, 14, 263–292.