Korhan Buyukturkoglu | Columbia University (original) (raw)

Papers by Korhan Buyukturkoglu

BackgroundPrior studies in multiple sclerosis (MS) support reliability of telehealth-delivered co... more BackgroundPrior studies in multiple sclerosis (MS) support reliability of telehealth-delivered cognitive batteries, although, to date, none have reported predictive external validity, i.e., relationships of cognitive test performance to neural correlates across administration modalities. In this study we aimed to compare brain-behavior relationships, using the Symbol Digit Modalities Test (SDMT), the most reliable and sensitive cognitive measure in MS, measured from patients seen via telehealth versus in-person.MethodsSDMT was administered to individuals with MS either in-person (N=60, mean age=39.7) or remotely via video conference (N=51, mean age=47.4). Magnetic resonance imaging (MRI) data was collected in 3-Tesla scanners. Using 3D-T1 images cerebral, cortical, deep gray, cerebral white matter and thalamic nuclei volumes were calculated. Using a meta-analysis approach with an interaction term for participant group, individual regression models were run for each MRI measure havin...

Multiple Sclerosis and Related Disorders

Background: Prior studies in multiple sclerosis (MS) support reliability of telehealth-delivered ... more Background: Prior studies in multiple sclerosis (MS) support reliability of telehealth-delivered cognitive batteries, although, to date, none have reported relationships of cognitive test performance to neural correlates across administration modalities. In this study we aimed to compare brain-behavior relationships, using the Symbol Digit Modalities Test (SDMT), the most reliable and sensitive cognitive measure in MS, measured from patients seen via telehealth versus in-person. Methods: SDMT was administered to individuals with MS either in-person (N=60, mean age=39.7) or remotely via video conference (N=51, mean age=47.4). Magnetic resonance imaging (MRI) data was collected in 3-Tesla scanners. Using 3-dimensional T1 images cerebral, cortical, deep gray, cerebral white matter and thalamic nuclei volumes were calculated. Using a meta-analysis approach with an interaction term for participant group, individual regression models were run for each MRI measure having SDMT scores as the outcome variable in each model. In addition, the correlation and average difference between In-person and Remote group associations across the MRI measures were calculated. Finally, for each MRI variable I 2 score was quantified to test the heterogeneity between the groups. Results: Administration modality did not affect the association of SDMT performance with MRI measures. Brain tissue volumes showing high associations with the SDMT scores in one group also showed high associations in the other (r = 0.83; 95% CI = [0.07, 0.86]). The average difference between the In-person and the Remote group associations was not significant (β Remoteβ In-person = 0.14, 95% CI = [-0.04, 0.34]). Across MRI measures, the average I 2 value was 14%, reflecting very little heterogeneity in the relationship of SDMT performance to brain volume. Conclusion: We found consistent relationships to neural correlates across in-person and remote SDMT administration modalities. Hence, our study extended the findings of the previous studies demonstrating the feasibility of remote administration of the SDMT.

MS and Related Disorders, 2002

Background: Memory dysfunction is common in multiple sclerosis (MS); mechanistic understanding of... more Background: Memory dysfunction is common in multiple sclerosis (MS); mechanistic understanding of its causes is lacking. Large-scale network resting-state functional connectivity (RSFC) is sensitive to memory dysfunction. Objective: We derived and tested summary metrics of memory network RSFC. Methods: Cognitive data and 3T magnetic resonance imaging (MRI) scans were collected from 235 MS patients and 35 healthy controls (HCs). Index scores were calculated as RSFC within (anteriority index, AntI) and between (integration index, IntI) dorsomedial anterior temporal and medial temporal memory subnetworks. Group differences in index expression were evaluated. Associations between index scores and memory/non-memory cognition were evaluated; relationships between T2 lesion volume (T2LV) and index scores were assessed. Results: Index scores were related to memory and T2LV in MS patients, who showed marginally elevated AntI relative to HC (p = 0.06); no group differences were found for IntI. Better memory was associated with higher AntI (β = 0.15, p = 0.018) and IntI (β = 0.16, p = 0.014). No associations were found for non-memory cognition. Higher T2LV was associated with higher AntI and IntI; exploratory mediation analysis revealed significant inconsistent mediation, that is, higher index scores partially suppressed the negative association between T2LV and memory. Conclusion: Summary, within-subject metrics permit replication and circumvent challenges of traditional (incommensurate) RSFC variables to advance development of mechanistic models of memory dysfunction in MS.

Frontiers in Behavioral Neuroscience, 2021

Background: The current pilot study was designed to examine the association between hippocampal γ... more Background: The current pilot study was designed to examine the association between hippocampal γ-aminobutyric acid (GABA) concentration and episodic memory in older individuals, as well as the impact of two major risk factors for Alzheimer’s disease (AD)—female sex and Apolipoprotein ε4 (ApoE ε4) genotype—on this relationship.Methods: Twenty healthy, community-dwelling individuals aged 50–71 (11 women) took part in the study. Episodic memory was evaluated using a Directed Forgetting task, and GABA+ was measured in the right hippocampus using a Mescher-Garwood point-resolved magnetic resonance spectroscopy (MRS) sequence. Multiple linear regression models were used to quantify the relationship between episodic memory, GABA+, ApoE ɛ4, and sex, controlling for age and education.Results: While GABA+ did not interact with ApoE ɛ4 carrier status to influence episodic memory (p = 0.757), the relationship between GABA+ and episodic memory was moderated by sex: lower GABA+ predicted worse m...

Multiple Sclerosis Journal, 2019

Background: Individuals with multiple sclerosis (MS) frequently present with depression and anxie... more Background: Individuals with multiple sclerosis (MS) frequently present with depression and anxiety, as well as cognitive impairment, challenging clinicians to disentangle interrelationships among these symptoms. Objective: To identify cognitive functions associated with anxiety and depression in MS. Methods: Mood and cognition were measured in 185 recently diagnosed patients (Reserve Against Disability in Early Multiple Sclerosis (RADIEMS) cohort), and an independent validation sample (MEM CONNECT cohort, n = 70). Partial correlations evaluated relationships of cognition to anxiety and depression controlling for age, sex, education, and premorbid verbal intelligence. Results: In RADIEMS cohort, lower anxiety was associated with better nonverbal memory ( rp = –0.220, p = 0.003) and lower depression to better attention/processing speed ( rp = –0.241, p = 0.001). Consistently, in MEM CONNECT cohort, lower anxiety was associated with better nonverbal memory ( rp = –0.271, p = 0.028) an...

Journal of neurology, neurosurgery, and psychiatry, Jan 26, 2017

To investigate global and lobular cerebellar volumetries in patients with progressive multiple sc... more To investigate global and lobular cerebellar volumetries in patients with progressive multiple sclerosis (MS), testing the contribution of cerebellar lobular atrophy to both motor and cognitive performances. Eighty-two patients with progressive MS and 46 healthy controls (HC) were enrolled in this cross-sectional study. Clinical evaluation included motor and cognitive testing: Expanded Disability Status Scale, cerebellar Functional System score, Timed 25-Foot Walk Test, 9-Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT) and California Verbal Learning Test II (CVLT). Cerebellar volumes were automatically obtained using the Spatially Unbiased Infratentorial Toolbox. A hierarchical multiple linear regression analysis was performed to assess the relationship between MRI variables of supratentorial and cerebellar damage (grey matter fraction, T2 lesion volume, metrics of cerebellar atrophy and cerebellar lesion volume) and motor/co...

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, May 28, 2017

To investigate the EEG-derived functional connectivity at rest (FCR) patterns of fatigued Multipl... more To investigate the EEG-derived functional connectivity at rest (FCR) patterns of fatigued Multiple Sclerosis (MS) patients in order to find good parameters for a future EEG-Neurofeedback intervention to reduce their fatigue symptoms. We evaluated FCR between hemispheric homologous areas, via spectral coherence between pairs of corresponding left and right bipolar derivations, in the Theta, Alpha and Beta bands. We estimated FCR in 18MS patients with different levels of fatigue and minimal clinical severity and in 11 age and gender matched healthy controls. We used correlation analysis to assess the relationship between the fatigue scores and the FCR values differing between fatigued MS patients and controls. Among FCR values differing between fatigued MS patients and controls, fatigue symptoms increased with higher Beta temporo-parietal FCR (p=0.00004). Also, positive correlations were found between the fatigue levels and the fronto-frontal FCR in Beta and Theta bands (p=0.0002 and ...

Journal of Pediatric Neuroradiology, 2016

Multiple sclerosis (Houndmills, Basingstoke, England), 2017

Memory deficits due to multiple sclerosis (MS) have been variably linked to lower subcortical gre... more Memory deficits due to multiple sclerosis (MS) have been variably linked to lower subcortical grey matter (SCGM) and mesial temporal lobe (MTL) volumes. We investigated which is the better predictor and whether this changes across disease stages. Memory was assessed in 315 patients. Magnetic resonance imaging (MRI) measured volumes of total brain, grey matter, white matter, MTL (hippocampus, amygdala) and SCGM (thalamus, caudate). MTL predicted memory in the total sample and in patients with earlier (<10 years) or later (⩾10 years) relapsing disease. SCGM (specifically thalamus) predicted memory in progressive patients. Neuroanatomical correlates of memory deficits differ across disease stages.

Journal of Neuroimaging, 2021

Background and Purpose: This study aims todetermine the sensitivity of superficial white matter (... more Background and Purpose: This study aims todetermine the sensitivity of superficial white matter (SWM) integrity as a metric to distinguish early multiple sclerosis (MS) patients from healthy controls (HC). Methods: Fractional anisotropy and mean diffusivity (MD) values from SWM bundles across the cortex and major deep white matter (DWM) tracts were extracted from 29 early MS patients and 31 age-and sex-matched HC. Thickness of 68 cortical regions and resting-state functional-connectivity (RSFC) among them were calculated. The distribution of structural and functional metrics between groups were compared using Wilcoxon rank-sum test. Utilizing a machine learning method (adaptive boosting), 6 models were built based on: 1-SWM, 2-DWM, 3-SWM and DWM, 4-cortical thickness, or 5-RSFC measures. In model 6, all features from previous models were incorporated. The models were trained with nested 5-folds cross-validation. Area under the receiver operating characteristic curve (AUC roc) values were calculated to evaluate classification performance of each model. Permutation tests were used to compare the AUC roc values. Results: Patients had higher MD in SWM bundles including insula, inferior frontal, orbitofrontal, superior and medial temporal, and pre-and post-central cortices (p < .05). No group differences were found for any other MRI metric. The model incorporating SWM and DWM features provided the best classification (AUC roc = 0.75). The SWM model provided higher AUC roc (0.74), compared to DWM (0.63), cortical thickness (0.67), RSFC (0.63), and all-features (0.68) models (p < .001 for all). Conclusion: Our results reveal a non-random pattern of SWM abnormalities at early stages of MS even before pronounced structural and functional alterations emerge.

Journal of Neuroimaging, 2021

Background and purpose: People with human immunodeficiency virus (HIV; PWH) present a complex arr... more Background and purpose: People with human immunodeficiency virus (HIV; PWH) present a complex array of immunologic and medical disorders that impact brain structure and metabolism, complicating the interpretation of neuroimaging. This pilot study of well-characterized multi-morbid PWH examined how medical and immunologic factors predicted brain characteristics on proton MR spectroscopy (1H-MRS) and diffusionweighted imaging (DWI). Methods: Eighteen individuals on combination antiretroviral therapy (cART), with mean age of 56 years, underwent medical history review, neuroimaging, and on the day of imaging, blood draw for assay of 20 plasma cytokines and flow cytometric characterization of peripheral blood mononuclear cell subsets. Predictors of n-acetyl aspartate, choline, myoinositol, glutamate/glutamine, fractional anisotropy and mean diffusivity were identified through bivariate correlation; those significant at p < .1000 were advanced to multivariate analysis, with models created for each neuroimaging outcome. Results: Monocyte subsets and diverse cytokines accounted for 16 of 25 (64%) variables predicting 1H-MRS spectra in frontal gray and white matter and basal ganglia; monocyte subsets did not predict any DWI characteristic. In contrast, age, presence of hypertension, and duration of HIV infection accounted for 13 of 25 (52%) variables predicting diffusion characteristics in the corpus callosum, thalamic radiations, and basal ganglia but only 3 of 25 (12%) predictors of 1H-MRS features. Conclusions: 1H-MRS neurometabolites were most often predicted by immunologic factors sensitive to temporal variation, whereas DWI metrics were more often related to longer-term disease state. In multi-morbid cART-era populations, selection and interpretation of neuroimaging modalities should account for complex temporal and pathogenetic influences of immunologic abnormality, disease state, and aging.

Frontiers in Behavioral Neuroscience, 2021

Methods: Twenty healthy, community-dwelling individuals aged 50–71 (11 women) took part in the study. Episodic memory was evaluated using a Directed Forgetting task, and GABA+ was measured in the right hippocampus using a Mescher-Garwood point-resolved magnetic resonance spectroscopy (MRS) sequence. Multiple linear regression models were used to quantify the relationship between episodic memory, GABA+, ApoE ɛ4, and sex, controlling for age and education.

Results: While GABA+ did not interact with ApoE ɛ4 carrier status to influence episodic memory (p = 0.757), the relationship between GABA+ and episodic memory was moderated by sex: lower GABA+ predicted worse memory in women such that, for each standard deviation decrease in GABA+ concentration, memory scores were reduced by 11% (p = 0.001).

Conclusions: This pilot study suggests that sex, but not ApoE ɛ4 genotype, moderates the relationship between hippocampal GABA+ and episodic memory, such that women with lower GABA+ concentration show worse memory performance. These findings, which must be interpreted with caution given the small sample size, may serve as a starting point for larger studies using multimodal neuroimaging to understand the contributions of GABA metabolism to age-related memory decline.

Dietary factors and MRI metrics in early Multiple Sclerosis

Background: Despite significant interest in diet by the MS community, research on this topic is l... more Background: Despite significant interest in diet by the MS community, research on this topic is limited; there are no published studies evaluating associations between diet and neuroimaging in MS. Methods: We utilized baseline data from the RADIEMS cohort of early MS (diagnosed <5.0 years, n=180). Participants underwent brain MRIs to derive normalized total gray and thalamic volumes, T2 lesion volume, and white matter microstructural integrity of normal appearing white matter (NAWM). Participants completed food frequency questionnaires (FFQ) from which we calculated adherence scores to pre-specified dietary patterns including the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. We evaluated intake of the following pre-specified dietary components: fruits, vegetables, legumes, nuts, whole grains, dairy, fried foods, processed meats, and fat intake. We used multivariable-adjusted linear regression to evaluate MRI metrics versus dietary measures. Results: MIND diet score was associated with thalamic volume; individuals in the highest quartile of MIND diet scores had greater thalamic volumes versus those in the lowest quartile (Q4 vs. Q1: 1.03mL; 95%CI: 0.26mL, 1.79mL; p<0.01). For individual food/nutrients, higher intakes of full-fat dairy were associated with lower T2 lesion volumes (Q4 vs. Q1:-0.93mL; 95%CI:-1.51mL,-0.35ml; p<0.01). Higher intakes of marine omega-3 fatty acids were associated with greater NAWM microstructural integrity (Q4 vs. Q1: 0.40; 95%CI: 0.03, 0.76; p = 0.04). Other foods/nutrients were not associated with MRI outcomes. Conclusions: In this first study focused on neuroimaging and diet in MS, we note significant associations in a crosssectional early MS cohort. Longitudinal follow-up of imaging/clinical outcomes will provide additional insights.

Associations of social network structure with cognition and amygdala volume in multiple sclerosis: An exploratory investigation

Background: Humans are inherently social, biologically programmed to connect with others. Social ... more Background: Humans are inherently social, biologically programmed to connect with others. Social connections are known to impact mental and physical health. Objective: The aim of this study was to test whether social network structure is linked to cognition, mood, fatigue, and regional brain volumes in persons with multiple sclerosis (MS). Methods: A questionnaire quantifying individual-level social network structure (size, density, effective size, and constraint), a comprehensive battery of neuropsychological tests, and magnetic resonance imaging (MRI) was administered to 51 persons with relapsing-remitting MS. Linear regressions assessed associations of network variables to cognition, depression, fatigue, and structural brain volumes. Results: Higher network density and constraint, indicating stronger connections among network members, were associated with worse language functions. Conversely, larger network effective size, a measure of non-redundant network members, was associated with better language functions. No relationships of network structure to depression or fatigue were found. Larger network size was related to larger amygdala volume. Conclusion: Findings suggest that social network structure is linked to language function and amygdala volume in persons with MS. Patients with close-knit networks showed worse language function than those with open networks. Longitudinal studies with larger samples are warranted to evaluate potential causal links between social network structure and MS-related cognitive impairment.

Journal of Neurology, 2020

Objective To investigate associations of social support to psychological well-being, cognition, a... more Objective To investigate associations of social support to psychological well-being, cognition, and motor functioning in patients with multiple sclerosis (MS). Secondarily, we were interested in exploring sex differences in these relationships, based on a bioevolutionary theoretical justification. Methods Social support was assessed in 185 recently diagnosed patients (RADIEMS cohort), and in an independent validation sample (MEMCONNECT cohort, n = 62). Patients also completed a comprehensive neurobehavioral evaluation including measures of mental health, fatigue, quality of life, cognition, and motor function. Correlations tested links between social support and these variables, along with potential gender differences. Results In both samples, higher social support was associated with better mental health, quality of life, subjective cogni-tive function, and less fatigue. In the RADIEMS cohort, higher social support was associated with better motor functions, particularly grip strength and gait endurance in women. Conclusions These findings highlight associations of social support to overall psychological health and motor functioning in persons with MS, underlining the potential opportunity of evaluating and promoting social engagement in novel treatment strategies.

Multiple Sclerosis Journal, 2020

Objective: To build a model to predict cognitive status reflecting structural, functional, and wh... more Objective: To build a model to predict cognitive status reflecting structural, functional, and white matter integrity changes in early multiple sclerosis (MS).Methods: Based on Symbol Digit Modalities Test (SDMT) performance, 183 early MS patients were assigned “lower” or “higher” performance groups. Three-dimensional (3D)-T2, T1, diffusion weighted, and resting-state magnetic resonance imaging (MRI) data were acquired in 3T. Using Random Forest, five models were trained to classify patients into two groups based on 1—demographic/clinical, 2—lesion volume/location, 3—local/global tissue volume, 4—local/global diffusion tensor imaging, and 5—whole-brain resting-state-functional-connectivity measures. In a final model, all important features from previ-ous models were concatenated. Area under the receiver operating characteristic curve (AUC) values were calculated to evaluate classifier performance.Results: The highest AUC value (0.90) was achieved by concatenating all important features from neu-roimaging models. The top 10 contributing variables included volumes of bilateral nucleus accumbens and right thalamus, mean diffusivity of left cingulum-angular bundle, and functional connectivity among hubs of seven large-scale networks.Conclusion: These results provide an indication of a non-random brain pattern mostly compromising areas involved in attentional processes specific to patients who perform worse in SDMT. High accuracy of the final model supports this pattern as a potential neuroimaging biomarker of subtle cognitive changes in early MS.

Multiple Sclerosis Journal, 2020

Background: When persons with multiple sclerosis (MS) report memory decline but objective memory ... more Background: When persons with multiple sclerosis (MS) report memory decline but objective memory performance is normal, there is a bias toward believing objective test results.Objective: Investigate whether subjective memory decline or objective memory performance is more related to hippocampal and hippocampal subfield volumes in early MS.Methods: Persons with early MS (n = 185; ⩽5.0 years diagnosed) completed a subjective memory ques-tionnaire; an objective memory composite was derived from four memory tests. Total hippocampal and subfield volumes were derived from high-resolution 3.0 T magnetic resonance images (MRIs). Partial correlations assessed links between hippocampal volumes and both subjective and objective memory, controlling for age, sex, mood, and pre-morbid intelligence quotient (IQ).Results: Lower total hippocampal and CA1 volumes were related to worse subjective memory but not objective memory (controlling for multiple comparisons). Correlations between subjective memory and both CA1 and subiculum were significantly stronger than were correlations between objective memory and these subfields. Patients in the worst tertile of subjective memory complaints (but not objective memory) had lower hippocampal volumes than 35 demographically similar healthy controls.Conclusion: Patient-report is inherently a longitudinal assessment of within-person memory change in everyday life, which may be more sensitive to subtle disease-related changes than cross-sectional objective tests. Findings align with the aging literature.

Neurology, 2020

Objective To test the hypothesis that higher-challenge gait and balance tasks are more sensitive ... more Objective To test the hypothesis that higher-challenge gait and balance tasks are more sensitive than traditional metrics to subtle patient-reported gait dysfunction and future fall risk in early multiple sclerosis (MS).

Methods Persons with early MS (n = 185; ≤5 years diagnosed) reported gait function (MS Walking Scale) and underwent traditional disability metrics (Expanded Disability Status Scale [EDSS], Timed 25 Foot Walk). Patients and healthy controls (n = 50) completed clinically feasible challenge tasks of gait endurance (2-Minute Walk Test), standing balance (NIH Toolbox), and dynamic balance (balance boards; tandem walk on 2 ten-foot boards of different widths, 4.5 and 1.5 in). MRI assessed global and regional brain volumes, total T2 lesion volume (T2LV), infratentorial T2LVs and counts, and cervical cord lesion counts. Falls, near falls, and fall-related injuries were assessed after 1 year. We examined links between all tasks and patient-reported gait, MRI markers, and fall data.

Results Patients performed worse on higher challenge balance, but not gait, tasks compared with healthy controls. Worse patient-reported gait disturbance was associated with worse performance on all tasks, but only dynamic balance was sensitive to mild patient-reported gait difficulty. Balance tasks were more correlated with MRI metrics than were walking tasks or EDSS score. Thirty percent of patients reported either a fall or near fall after 1 year, with poor dynamic balance as the only task independently predicting falls.

Conclusions Balance plays a leading role in gait dysfunction early in MS. Clinically feasible higher-challenge balance tasks were most sensitive to patient-reported gait, MRI disease markers, and risk of future falls, highlighting potential to advance functional outcomes in clinical practice and trials.

Multiple Sclerosis Journal, 2019

BACKGROUND: Individuals with multiple sclerosis (MS) frequently present with depression and anxie... more BACKGROUND:
Individuals with multiple sclerosis (MS) frequently present with depression and anxiety, as well as cognitive impairment, challenging clinicians to disentangle interrelationships among these symptoms.

OBJECTIVE:
To identify cognitive functions associated with anxiety and depression in MS.

METHODS:
Mood and cognition were measured in 185 recently diagnosed patients (Reserve Against Disability in Early Multiple Sclerosis (RADIEMS) cohort), and an independent validation sample (MEM CONNECT cohort, n = 70). Partial correlations evaluated relationships of cognition to anxiety and depression controlling for age, sex, education, and premorbid verbal intelligence.

RESULTS:
In RADIEMS cohort, lower anxiety was associated with better nonverbal memory (rp = -0.220, p = 0.003) and lower depression to better attention/processing speed (rp = -0.241, p = 0.001). Consistently, in MEM CONNECT cohort, lower anxiety was associated with better nonverbal memory (rp = -0.271, p = 0.028) and lower depression to better attention/processing speed (rp = -0.367, p = 0.002). Relationships were unchanged after controlling for T2 lesion volume and fatigue.

CONCLUSION:
Consistent mood-cognition relationships were identified in two independent cohorts of MS patients, suggesting that cognitive correlates of anxiety and depression are separable. This dissociation may support more precise models to inform treatment development. Treatment of mood symptoms may mitigate effects on cognition and/or treatment of cognition may mitigate effects on mood.

Multiple Sclerosis and Related Disorders

MS and Related Disorders, 2002

Frontiers in Behavioral Neuroscience, 2021

Multiple Sclerosis Journal, 2019

Journal of neurology, neurosurgery, and psychiatry, Jan 26, 2017

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, May 28, 2017

Journal of Pediatric Neuroradiology, 2016

Multiple sclerosis (Houndmills, Basingstoke, England), 2017

Journal of Neuroimaging, 2021

Frontiers in Behavioral Neuroscience, 2021

Dietary factors and MRI metrics in early Multiple Sclerosis

Associations of social network structure with cognition and amygdala volume in multiple sclerosis: An exploratory investigation

Journal of Neurology, 2020

Multiple Sclerosis Journal, 2020

Neurology, 2020

Multiple Sclerosis Journal, 2019

OBJECTIVE:
To identify cognitive functions associated with anxiety and depression in MS.

Background: Prior studies in multiple sclerosis (MS) support reliability of telehealth-delivered ... more Background: Prior studies in multiple sclerosis (MS) support reliability of telehealth-delivered cognitive batteries, although, to date, none have reported predictive external validity, i.e., relationships of cognitive test performance to neural correlates across administration modalities. In this study we aimed to compare brain-behavior relationships, using the Symbol Digit Modalities Test (SDMT), the most reliable and sensitive cognitive measure in MS, measured from patients seen via telehealth versus in-person.
Methods: SDMT was administered to individuals with MS either in-person (N=60, mean age=39.7) or remotely via video conference (N=51, mean age=47.4). Magnetic resonance imaging (MRI) data was collected in 3-Tesla scanners. Using 3D-T1 images cerebral, cortical, deep gray, cerebral white matter and thalamic nuclei volumes were calculated. Using a meta-analysis approach with an interaction term for participant group, individual regression models were run for each MRI measure having SDMT as the outcome variable in each model. In addition, the correlation and average difference between In-person and Remote group effect sizes across the MRI measures were calculated. Finally, for each MRI variable I2 score was quantified to test the heterogeneity between the groups.
Results: Administration modality did not affect the association of SDMT with MRI measures. Brain tissue volumes showing high associations with the SDMT in one group also showed high associations in the other (r = 0.83; 95% CI = [0.07, 0.86]). The average difference between the In- person and the Remote group effect sizes was not significant (bRemote - bIn-person = 0.14, 95% CI = [-0.04, 0.34]). Across MRI measures, the average I2 value was 14%, reflecting very little heterogeneity in the relationship of SDMT to brain volume.
Conclusion: We found consistent relationships to neural correlates across in-person and remote SDMT administration modalities. Hence, our study can be considered a step towards providing predictive external validity to remote administration of the SDMT in MS.