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      Disrupted hemodynamic response within dorsolateral prefrontal cortex during cognitive tasks among people with multiple sclerosis-related fatigue

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          Abstract

          Introduction

          Mental fatigue is an early and enduring symptom in persons with autoimmune disease particularly multiple sclerosis (MS). Neuromodulation has emerged as a potential treatment although optimal cortical targets have yet to be determined. We aimed to examine cortical hemodynamic responses within bilateral dorsolateral prefrontal cortex (dlPFC) and frontopolar areas during single and dual cognitive tasks in persons with MS-related fatigue compared to matched controls.

          Methods

          We recruited persons (15 MS and 12 age- and sex-matched controls) who did not have physical or cognitive impairment and were free from depressive symptoms. Functional near infrared spectroscopy (fNIRS) registered hemodynamic responses during the tasks. We calculated oxyhemoglobin peak, time-to-peak, coherence between channels (a potential marker of neurovascular coupling) and functional connectivity (z-score).

          Results

          In MS, dlPFC demonstrated disrupted hemodynamic coherence during both single and dual tasks, as evidenced by non-significant and negative correlations between fNIRS channels. In MS, reduced coherence occurred in left dorsolateral PFC during the single task but occurred bilaterally as the task became more challenging. Functional connectivity was lower during dual compared to single tasks in the right dorsolateral PFC in both groups. Lower z-score was related to greater feelings of fatigue. Peak and time-to-peak hemodynamic response did not differ between groups or tasks.

          Conclusions

          Hemodynamic responses were inconsistent and disrupted in people with MS experiencing mental fatigue, which worsened as the task became more challenging. Our findings point to dlPFC, but not frontopolar areas, as a potential target for neuromodulation to treat cognitive fatigue.

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          Most cited references56

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          The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.

          To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. Validation study. A community clinic and an academic center. Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.
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            Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

            The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.
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              The validity of the Hospital Anxiety and Depression Scale. An updated literature review.

              To review the literature of the validity of the Hospital Anxiety and Depression Scale (HADS). A review of the 747 identified papers that used HADS was performed to address the following questions: (I) How are the factor structure, discriminant validity and the internal consistency of HADS? (II) How does HADS perform as a case finder for anxiety disorders and depression? (III) How does HADS agree with other self-rating instruments used to rate anxiety and depression? Most factor analyses demonstrated a two-factor solution in good accordance with the HADS subscales for Anxiety (HADS-A) and Depression (HADS-D), respectively. The correlations between the two subscales varied from.40 to.74 (mean.56). Cronbach's alpha for HADS-A varied from.68 to.93 (mean.83) and for HADS-D from.67 to.90 (mean.82). In most studies an optimal balance between sensitivity and specificity was achieved when caseness was defined by a score of 8 or above on both HADS-A and HADS-D. The sensitivity and specificity for both HADS-A and HADS-D of approximately 0.80 were very similar to the sensitivity and specificity achieved by the General Health Questionnaire (GHQ). Correlations between HADS and other commonly used questionnaires were in the range.49 to.83. HADS was found to perform well in assessing the symptom severity and caseness of anxiety disorders and depression in both somatic, psychiatric and primary care patients and in the general population.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Methodology
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Data curationRole: InvestigationRole: Methodology
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                5 June 2024
                2024
                : 19
                : 6
                : e0303211
                Affiliations
                [1 ] Recovery & Performance Laboratory, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, Canada
                [2 ] Computer Science, Faculty of Science, Memorial University of Newfoundland, St. John’s, NL, Canada
                NUST: National University of Sciences and Technology, PAKISTAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-4594-0077
                Article
                PONE-D-23-42776
                10.1371/journal.pone.0303211
                11152297
                38837991
                85c93e06-893f-42b8-a848-070fe3374d1b
                © 2024 Baldasso et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 December 2023
                : 21 April 2024
                Page count
                Figures: 6, Tables: 2, Pages: 16
                Funding
                Funded by: Canada Research Chairs, Government of Canada
                Award ID: 2019-00290
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001805, Canada Foundation for Innovation;
                Award ID: 33621
                Award Recipient :
                The research was funded by Canada Research Chairs (Grant Number 2019-00290) and Canada Foundation for Innovation (Grant Number 33621) (MP). The funders were not involved in the conduct of the research.
                Categories
                Research Article
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Immunology
                Autoimmune Diseases
                Multiple Sclerosis
                Biology and Life Sciences
                Immunology
                Clinical Immunology
                Autoimmune Diseases
                Multiple Sclerosis
                Medicine and Health Sciences
                Immunology
                Clinical Immunology
                Autoimmune Diseases
                Multiple Sclerosis
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                Demyelinating Disorders
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                Multiple Sclerosis
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                Neurology
                Neurodegenerative Diseases
                Multiple Sclerosis
                Physical Sciences
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                Classical Mechanics
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                Material Fatigue
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                Anatomy
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