Overt Word Reading and Visual Object Naming in Adults with Dyslexia: Electroencephalography Study in Transparent Orthography.

The study aimed to investigate overt reading and naming processes in adult people with dyslexia (PDs) in shallow (transparent) language orthography. The results of adult PDs are compared with adult healthy controls HCs. Comparisons are made in three phases: pre-lexical (150-260 ms), lexical (280-700 ms), and post-lexical stage of processing (750-1000 ms) time window. Twelve PDs and HCs performed overt reading and naming tasks under EEG recording. The word reading and naming task consisted of sparse neighborhoods with closed phonemic onset (words/objects sharing the same onset). For the analysis of the mean ERP amplitude for pre-lexical, lexical, and post-lexical time window, a mixed design ANOVA was performed with the right (F4, FC2, FC6, C4, T8, CP2, CP6, P4) and left (F3, FC5, FC1, T7, C3, CP5, CP1, P7, P3) electrode sites, within-subject factors and group (PD vs. HC) as between-subject factor. Behavioral response latency results revealed significantly prolonged reading latency between HCs and PDs, while no difference was detected in naming response latency. ERP differences were found between PDs and HCs in the right hemisphere's pre-lexical time window (160-200 ms) for word reading aloud. For visual object naming aloud, ERP differences were found between PDs and HCs in the right hemisphere's post-lexical time window (900-1000 ms). The present study demonstrated different distributions of the electric field at the scalp in specific time windows between two groups in the right hemisphere in both word reading and visual object naming aloud, suggesting alternative processing strategies in adult PDs. These results indirectly support the view that adult PDs in shallow language orthography probably rely on the grapho-phonological route during overt word reading and have difficulties with phoneme and word retrieval during overt visual object naming in adulthood.

Brain Sciences Special Issue "Neuromodulation of Cortical Networks in Neurological and Neuropsychiatric Disorders: Potential Clinical Indications and the Biophysiological Impact of Stimulation".

Individuals with neurological and neuropsychiatric disorders face a variety of difficulties that can significantly impact their daily lives [...].

Treated and Untreated Primary Progressive Multiple Sclerosis: Walkthrough Immunological Changes of Monocytes and T Regulatory Cells.

The objective of this study was to investigate regulatory T cells (Tregs) and monocytes; specifically, the expression of CTLA-4 (CD152) and FOXP3+ in CD4+CD25+ Tregs and the expression of CD40+ and CD192+ monocyte subpopulations in subjects with primary progressive multiple sclerosis (PPMS). Immunological analysis was conducted on peripheral blood samples collected from the 28 PPMS subjects (15 treated with ocrelizumab and 13 untreated PPMS subjects) and 10 healthy control subjects (HCs). The blood samples were incubated with antihuman CD14, CD16, CD40, and CD192 antibodies for monocytes and antihuman CD4, CD25, FOXP3, and CTLA-4 antibodies for lymphocytes. The study results showed that in comparison to HCs both ocrelizumab treated (N = 15) and untreated (N = 13) PPMS subjects had significantly increased percentages of CTLA-4+ and FOXP3+ in CD4+CD25+ Tregs. Further, ocrelizumab treated PPMS subjects, compared to the untreated ones, had significantly decreased percentages of CD192+ and CD40+ nonclassical monocytes. Increased percentages of CTLA-4+ and FOXP3+ in CD4+CD25+ Tregs in both ocrelizumab treated and untreated PPMS subjects indicates the suppressive (inhibitory) role of Tregs in abnormal immune responses in PPMS subjects. Decreased percentages of CD40+, CD192+, and CD14+CD16++ monocytes for treated compared to untreated PPMS subjects suggests a possible role for ocrelizumab in dampening CNS inflammation.

Exploring Neurophysiological Mechanisms and Treatment Efficacies in Laryngeal Dystonia: A Transcranial Magnetic Stimulation Approach.

Laryngeal dystonia (LD), known or termed as spasmodic dysphonia, is a rare movement disorder with an unknown cause affecting the intrinsic laryngeal muscles. Neurophysiological studies point to perturbed inhibitory processes, while conventional genetic studies reveal fragments of genetic architecture in LD. The study's aims are to (1) describe transcranial magnetic stimulation (TMS) methodology for studying the functional integrity of the corticospinal tract by stimulating the primary motor cortex (M1) for laryngeal muscle representation and recording motor evoked potentials (MEPs) from laryngeal muscles; (2) evaluate the results of TMS studies investigating the cortical silent period (cSP) in LD; and (3) present the standard treatments of LD, as well as the results of new theoretical views and treatment approaches like repetitive TMS and laryngeal vibration over the laryngeal muscles as the recent research attempts in treatment of LD. Neurophysiological findings point to a shortened duration of cSP in adductor LD and altered cSP duration in abductor LD individuals. Future TMS studies could further investigate the role of cSP in relation to standard laryngological measures and treatment options. A better understanding of the neurophysiological mechanisms might give new perspectives for the treatment of LD.

Transcranial Magnetic Stimulation Measures, Pyramidal Score on Expanded Disability Status Scale and Magnetic Resonance Imaging of Corticospinal Tract in Multiple Sclerosis.

Probing the cortic ospinal tract integrity by transcranial magnetic stimulation (TMS) could help to understand the neurophysiological correlations of multiple sclerosis (MS) symptoms. Therefore, the study objective was, first, to investigate TMS measures (resting motor threshold-RMT, motor evoked potential (MEP) latency, and amplitude) of corticospinal tract integrity in people with relapsing-remitting MS (pwMS). Then, the study examined the conformity of TMS measures with clinical disease-related (Expanded Disability Status Scale-EDSS) and magnetic resonance imaging (MRI) results (lesion count) in pwMS. The e-field navigated TMS, MRI, and EDSS data were collected in 23 pwMS and compared to non-clinical samples. The results show that pwMS differed from non-clinical samples in MEP latency for upper and lower extremity muscles. Also, pwMS with altered MEP latency (prolonged or absent MEP response) had higher EDSS, general and pyramidal, functional scores than pwMS with normal MEP latency finding. Furthermore, the RMT intensity for lower extremity muscles was predictive of EDSS functional pyramidal scores. TMS/MEP latency findings classified pwMS as the same as EDSS functional pyramidal scores in 70-83% of cases and were similar to the MRI results, corresponding to EDSS functional pyramidal scores in 57-65% of cases. PwMS with altered MEP latency differed from pwMS with normal MEP latency in the total number of lesions in the brain corticospinal and cervical corticospinal tract. The study provides preliminary results on the correspondence of MRI and TMS corticospinal tract evaluation results with EDSS functional pyramidal score results in MS.

Expression of CD40 and CD192 in Classical Monocytes in Multiple Sclerosis Patients Assessed with Transcranial Magnetic Stimulation.

Expression of CD40 and CD192 markers in different monocyte subpopulations has been reported to be altered in people with MS (pwMS). Also, functional connectivity of the corticospinal motor system pathway alterations has been proved by transcranial magnetic stimulation (TMS). The study objective was to investigate the expression of CD40 and CD192 in classical (CD14++CD16-), intermediate CD14++CD16+ and non-classical (CD14+CD16++) blood monocyte subpopulations in pwMS, undergoing neurophysiological TMS assessment of the corticospinal tract integrity by recording motor-evoked potentials (MEPs). Radiological examination on lesion detection with MRI was performed for 23 patients with relapsing-remitting MS treated with teriflunomide. Then, immunological analysis was conducted on peripheral blood samples collected from the patients and 10 healthy controls (HC). The blood samples were incubated with anti-human CD14, CD16, CD40 and CD192 antibodies. Next, pwMS underwent neurological testing of functional disability (EDSS) and TMS assessment with recording MEPs from upper and lower extremity muscles. The results show that in comparison to HC subjects, both pwMS with normal and altered MEP findings (prolonged MEP latency or absent MEP response) had significantly decreased surface receptor expression measured (MFIs) of CD192 and increased CD40 MFI in classical monocytes, and significantly increased percentages of classical and total monocytes positive for CD40. Knowing CD40's pro-inflammatory action, and CD192 as a molecule that enables the passing of monocytes into the brain, decreased CD192 in classical monocytes could represent a beneficial anti-inflammatory parameter.

The Cortical Silent Period in the Cricothyroid Muscle as a Neurophysiologic Feature for Dystonia Observation: E-Field-Navigated Transcranial Magnetic (TMS) Study.

The cortical silent period (cSP) is a period of electrical silence following a motor-evoked potential (MEP) in the electromyographic signal recorded from a muscle. The MEP can be elicited by transcranial magnetic stimulation (TMS) over the primary motor cortex site corresponding with the muscle. The cSP reflects the intracortical inhibitory process mediated by GABAA and GABAB receptors. The study aimed to investigate the cSP in the cricothyroid (CT) muscle after applying e-field-navigated TMS over the laryngeal motor cortex (LMC) in healthy subjects. Then, a cSP as a neurophysiologic feature for laryngeal dystonia was observed. We applied a single-pulse e-field-navigated TMS to the LMC over both hemispheres with hook-wire electrodes positioned in the CT muscle in nineteen healthy participants, which triggered the elicitation of contralateral and ipsilateral corticobulbar MEPs. The subjects were engaged in a vocalization task, and then we assessed the following metrics: LMC intensity, peak-to-peak MEP amplitude in the CT muscle, and cSP duration. The results showed that the cSP duration from the contralateral CT muscle was distributed from 40 ms to 60.83 ms, and from the ipsilateral CT muscle, from 40 ms to 65.58 ms. Also, no significant difference was found between the contralateral and ipsilateral cSP duration (t(30) = 0.85, p = 0.40), MEP amplitude in the CT muscle (t(30) = 0.91, p = 0.36), and LMC intensity (t(30) = 1.20, p = 0.23). To conclude, the applied research protocol showed the feasibility of recording LMC corticobulbar MEPs and observing the cSP during vocalization in healthy participants. Furthermore, an understanding of neurophysiologic cSP features can be used to study the pathophysiology of neurological disorders that affect laryngeal muscles, such as laryngeal dystonia.

Confirmation of CD19+ B-Lymphocyte Depletion Prior to Intake of the Second Dose of Ocrelizumab in Multiple Sclerosis Patients.

The aim of the retrospective study was to compare the immunophenotyping of T-lymphocytes, B-lymphocytes, and natural killer cells before the administration of the first and the second dose of ocrelizumab in 22 patients with multiple sclerosis in a three-year period (2019-2021) at the Department of Neurology of the University Hospital of Split. The values of cell immunophenotyping and protein electrophoresis, as well as laboratory parameters, were investigated. There was no significant decrease in serum albumin and globulins before the second dose of ocrelizumab (p > 0,05). A decrease in the number of T-lymphocytes before administration of the second dose of ocrelizumab was observed, but without statistical significance (p = 0.274). Significant depletion occurred in median CD19+ B-lymphocytes (p < 0.001) before the intake of the second dose of ocrelizumab confirming the primary action of ocrelizumab on the B cell lineage.

Assessment of Motor Evoked Potentials in Multiple Sclerosis.

Transcranial magnetic stimulation (TMS) is a noninvasive technique mainly used for the assessment of corticospinal tract integrity and excitability of the primary motor cortices. Motor evoked potentials (MEPs) play a pivotal role in TMS studies. TMS clinical guidelines, concerning the use and interpretation of MEPs in diagnosing and monitoring corticospinal tract integrity in people with multiple sclerosis (pwMS), were established almost ten years ago and refer mainly to the use of TMS implementation; this comprises the magnetic stimulator connected to a standard EMG unit, with the positioning of the coil performed by using the external landmarks on the head. The aim of the present work was to conduct a narrative literature review on the MEP assessment and outcome measures in clinical and research settings, assessed by TMS Methodological characteristics of different TMS system implementations (TMS without navigation, line-navigated TMS and e-field-navigated TMS); these were discussed in the context of mapping the corticospinal tract integrity in MS. An MEP assessment of two case reports, by using an e-field-navigated TMS, was presented; the results of the correspondence between the e-field-navigated TMS with MRI, and the EDSS classifications were presented. Practical and technical guiding principles for the improvement of TMS studies in MEP assessment for MS are discussed, suggesting the use of e-field TMS assessment in the sense that it can improve the accuracy of corticospinal tract integrity testing by providing a more objective correspondence of the neurophysiological (e-field-navigated TMS) and clinical (Expanded Disability Status Scale-EDSS) classifications.

Psychometric properties of the Croatian version of the Multiple Sclerosis Walking Scale (MSWS-12).

PURPOSE: Walking difficulties in people with multiple sclerosis (pwMS) are one of the most pronounced predictors affecting patients' quality of life. The study objective was to determine the psychometric properties of the Croatian version of the Multiple Sclerosis Walking Scale (MSWS-12) among pwMS in Croatia and to examine the association between MSWS-12 and Depression, Anxiety, and Stress Scale-21 (DASS-21), and Multiple Sclerosis Impact Scale-29 (MSIS-29). MATERIALS AND METHODS: A cross-sectional study included a sample of pwMS (N = 148). Psychometric properties were examined by estimating the validity and reliability of the MSWS-12. The predictive validity of MSWS-12 and demographic and disease-related factors were assessed by a hierarchical regression model using MSIS-29 and DASS-21 as criterion variables. RESULTS: Scale reliability was good for the MSWS-12 scale, expressed by Cronbach's alpha coefficient (α = 0.98). Correlations between MSWS-12 and DASS-21 (0.20-0.27) and between MSWS-12 and MSIS-29 subscales (0.47-0.83) provided initial support for the convergent validity. Factor analysis demonstrated the unidimensional structure of the MSWS-12. CONCLUSIONS: The Croatian version of the MSWS-12 is a reliable, valid, and clinically useful tool for assessing walking impairments in pwMS.Implications for rehabilitationWalking difficulties in people with multiple sclerosis (pwMS) are one of the most pronounced predictors affecting patients' quality of life.Multiple Sclerosis Walking Scale (MSWS-12) is a measure of the disease's impact on walking abilities from the patient's perspective.MSWS-12 is a reliable scale for assessing walking speed, endurance, and gait quality in multiple sclerosis and is validated in several languages (Korean, Italian, Brazilian, and Persian).The Croatian version of the MSWS-12 is a reliable, predictive, and valid tool for screening walking impairments in pwMS.

Symptom-Level Disability Status Assessed with an Electronic Unsupervised Patient-Reported Expanded Disability Status Scale (ePR-EDSS) in Multiple Sclerosis Patients-The Example of Croatia.

The present study aimed to apply an electronic, unsupervised patient-reported Expanded Disability Status Scale (ePR-EDSS) to investigate disability severity in people with multiple sclerosis (pwMS) as a case study in Croatia in 2021, including demographic and comorbidity characteristics and multiple sclerosis (MS) disease-related factors. The cross-sectional study was conducted as an online survey from 4 October 2021 to 31 December 2021. Symptom-level disability status was assessed with ePR-EDSS for MS capturing MS-related disability across the spectrum of severity.The study enrolled 147 pwMS patients, of which 84% were women. The mean age ± standard deviation in the sample was 41.1 ± 11.3, and the mean disease duration was 8.5 ± 7.4 years, with a median EDSS score of 3.0 (range, 0−8). The distribution of the participants according to clinical forms of MS was as follows: 71% had relapsing-remitting MS, 13% had primary progressive MS, 4% had secondary progressive PMS, and 12% did not provide information on their MS type. Twenty-nine point two percent (29.2%) of the participants had comorbidities in addition to MS. EDSS scores indicate significant differences with regard to age (t = −3.51, p < 0.001), gender (χ2 = 8.04, p < 0.01), and immunomodulatory drug use (χ2 = 5.89, p < 0.05). An ePR-EDSS analysis of disability symptoms showed a significant difference in symptoms with regard to strength, sensation, coordination, vision, fatigue, mobility, and overall wellness among MS types. Participants with PPMS and SPMS were older on average, had higher EDSS, and had more pronounced symptoms of disability measured with ePR-EDSS compared to those with RRMS. Application of ePR-EDSS shows it to be a reliable eHealth tool for clinical assessment of pwMS disability status, and future studies should correlate it with standard self-report scales capturing MS symptoms such as fatigue, depression, anxiety, and stress.

The Patho-Neurophysiological Basis and Treatment of Focal Laryngeal Dystonia: A Narrative Review and Two Case Reports Applying TMS over the Laryngeal Motor Cortex.

Focal laryngeal dystonia (LD) is a rare, idiopathic disease affecting the laryngeal musculature with an unknown cause and clinically presented as adductor LD or rarely as abductor LD. The most effective treatment options include the injection of botulinum toxin (BoNT) into the affected laryngeal muscle. The aim of this narrative review is to summarize the patho-neuro-physiological and genetic background of LD, as well as the standard recommended therapy (BoNT) and pharmacological treatment options, and to discuss possible treatment perspectives using neuro-modulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and vibrotactile stimulation. The review will present two LD cases, patients with adductor and abductor LD, standard diagnostic procedure, treatments and achievement, and the results of cortical excitability mapping the primary motor cortex for the representation of the laryngeal muscles in the assessment of corticospinal and corticobulbar excitability.

Psychometric Properties of the Pittsburgh Sleep Quality Index (PSQI) in Patients with Multiple Sclerosis: Factor Structure, Reliability, Correlates, and Discrimination.

Sleep disturbances and poor sleep are a common complaint in the population with multiple sclerosis (MS) disease. The most commonly reported scale is the Pittsburgh Sleep Quality Index (PSQI), measuring seven components of sleep quality. Yet, till today, the PSQI instrument has not been validated in people with multiple sclerosis (pwMS). The objective of our study was to add precision in sleep quality assessment by investigating the psychometric properties of PSQI (factor structure, reliability, validity based on relations with other variables, cut-off scores) in pwMS. The cross-sectional study included data on a total of 87 patients with MS and 216 control subjects. Demographic information, education level, and MS-related variables were ascertained. Psychometric properties were examined by estimating the validity, including factor structure, metric invariance, and relations with other MS- and non-MS-related variables, reliability, and discrimination ability of the PSQI. The Croatian version of the PSQI had a two-factor structure which demonstrated loading and partial intercept invariance between pwMS and the control group. The global score and both subscales had high internal consistencies (McDonald's omega and Cronbach's alpha coefficients) in pwMS and showed expected relations with demographic and MS-related variables. PwMS differed significantly in the PSQI global score from the control groups, although receiver operating characteristics (ROC) curve analysis did not indicate a clear cut-off point. The PSQI is a reliable and valid scale and can be applied in clinical settings for assessing sleep quality in pwMS.

Information Processing Speed Assessed with Letter Digit Substitution Test in Croatian Sample of Multiple Sclerosis Patients.

Cognitive impairment is a common complaint in people with multiple sclerosis (pwMS). The study objective was to determine the psychometric properties of the letter digit substitution test (LDST) that measures information processing speed and to investigate the impact of relevant predictors of LDST achievement in pwMS. The design was cross-sectional. The study included 87 pwMS and 154 control subjects. The validity of LDST was examined, and a hierarchical regression model was used to explore relevant predictors of LDST success. The LDST had excellent construct validity, as expressed by differences between pwMS and control subjects. Convergent validity of the LDST was supported by a significant moderate correlation with the expanded disability status scale (EDSS) (ρ = -0.36; p < 0.05) and a significantly strong correlation with the multiple sclerosis impact scale (MSIS-29) physical subscale (r = -0.64; p < 0.01). The LDTS score well differentiated the pwMS considering age, education, EDSS, disease duration, comorbidity, and medication therapy. Using the LDST as a criterion variable in pwMS results showed consistent evidence for the age, education, and EDSS impact on LDST performance. The best cut-off score of ≤35 discriminated the control and MS group. LDST proved to be a valid test for assessing information processing speed in pwMS.

Psychometric Properties of the HADS Measure of Anxiety and Depression Among Multiple Sclerosis Patients in Croatia.

Depression and anxiety are common complaints in patients with multiple sclerosis (MS). The study objective was to investigate the factor structure, internal consistency, and correlates of the Croatian version of the Hospital Anxiety and Depression Scale (HADS) in patients with MS. A total of 179 patients with MS and 999 controls were included in the online survey. All subjects completed the HADS and self-administered questionnaires capturing information of demographic, education level, disease-related variables, and the Multiple Sclerosis Impact Scale-29 (MSIS-29). Psychometric properties were examined by estimating the validity, reliability, and factor structure of the HADS in patients with MS. The two HADS subscales (anxiety and depression) had excellent internal consistencies (Cronbach's α value 0.82-0.83), and factor analysis confirmed a two-factor structure. The convergent validity of the HADS subscales appeared to be good due to the significant correlations between HADS and MSIS-29. Receiver operating characteristic (ROC) analysis indicates that the HADS subscales have a significant diagnostic validity for group differentiation. Hierarchical regression analysis using MSIS-29 subscales as criterion variables showed consistent evidence for the incremental validity of the HADS. The HADS is a reliable and valid self-assessment scale in patients with MS and is suggested to be used in clinical monitoring of the psychiatric and psychological status of patients with MS.

Psychometric properties of the Croatian version of the depression, anxiety, and stress scale-21 and multiple sclerosis impact scale-29 in multiple sclerosis patients.

OBJECTIVES: Depression, anxiety, stress, and physical disabilities are a common complaint in people with multiple sclerosis (MS), and monitoring of these symptoms are based on self-report questionnaires. The objective of this study was to determine psychometric properties of the Croatian version of the Depression, Anxiety, and Stress Scale-21 (DASS-21) and Multiple Sclerosis Impact Scale-29 (MSIS-29) in people with MS. MATERIALS AND METHODS: We included data on 163 people with MS registered in the Association of multiple sclerosis societies of Croatia (AMSSC). Patients' demographic information, education level, and disease-related variables were ascertained. DASS-21 was applied for assessing depression, anxiety, and stress, while MSIS-29 scale was used for assessment of the physical and psychological impact of MS disease. Psychometric properties were examined by estimating the validity and reliability of the DASS-21 and MSIS-29 scale. Predictive validity of DASS-21 subscales and relevant demographic and disease-related variables was examined by the hierarchical regression model. RESULTS: The Croatian version of the three DASS-21 subscales and two MSIS-29 subscales had excellent internal consistencies (Cronbach's alpha coefficients 0.88-0.93) and good convergent validity, as expressed by inter-correlations between DASS-21 and MSIS-29 subscales. Hierarchical regression analysis using MSIS-29 subscales as criterion variables showed consistent evidence for the predictive validity of depression, anxiety, and stress on psychological impact, and predictive validity of age, EDSS, and anxiety on physical impact. CONCLUSIONS: The Croatian versions of DASS-21 and MSIS-29 are reliable and valid scales in people with MS.

Obstructive Sleep Apnea Syndrome: A Preliminary Navigated Transcranial Magnetic Stimulation Study.

PURPOSE: An increase in resting motor threshold (RMT), prolonged cortical silent period duration (CSP), and reduced short-latency afferent inhibition (SAI), confirmed with previous transcranial magnetic stimulation (TMS), suggest decreased cortical excitability in obstructive sleep apnea syndrome (OSAS). The present study included MRI of OSAS patients for navigated TMS assessment of the RMT, as an index of the threshold for corticospinal activation at rest, and SAI as an index of cholinergic neurotransmission. We hypothesize to confirm findings on SAI and RMT with adding precision in the targeting of motor cortex in OSAS. SUBJECTS AND METHODS: After acquiring head MRIs for 17 severe right-handed OSAS and 12 healthy subjects, the motor cortex was mapped with nTMS to assess the RMT and SAI, with motor evoked potentials (MEPs) recorded from the abductor-pollicis brevis (APB) muscle. The 120%RMT intensity was used for the SAI by a paired-pulse paradigm in which the electrical stimulation to the median nerve is followed by magnetic stimulation of the motor cortex at inter-stimulus intervals (ISIs) of 18-28 ms (ISIs18-28). The SAI control condition included a recording of MEPs without peripheral stimulation. Latency and amplitude of MEP at RMT at 120%RMT for eleven different at ISIs18-28 were analyzed. RESULTS: The study showed a significantly lower percentage deviation of MEP amplitude at ISIs(18-28ms) from the control condition between OSAS and healthy subjects (U=44.0, p=0.01). The intensity of stimulation at RMT was significantly higher in OSAS subjects (U=55.0, p=0.04*). Correlation analysis showed that BMI significantly negatively correlated (ρ=-0.47) with MEP amplitude percentage deviation in OSAS patients. CONCLUSION: The nTMS study results in increased RMT, and reduced cortical afferent inhibition in OSAS patients for SAI at ISIs18-28, confirming previous findings of impaired cortical afferent inhibition in OSAS. Future nTMS studies are desirable to elucidate the role of RMT and SAI in diagnostics and treatment of OSAS, and to elucidate the usefulness of nTMS in OSAS research.