Neurological Healthy Controls Research Articles

Second formant transitions for acoustic analysis to differentiate among dementia types

Recent evidence indicates that acoustic features associated with emotional prosody in speech may be an inexpensive, non-invasive method for differentiating among dementia types. In particular, frequency measures in the speech of people with dementia have been associated with listeners’ perception of emotional prosody. The purpose of this study was to determine if second formant (F2) transition information would enhance these differentiations. Prerecorded speech samples of Cookie Theft picture descriptions from 10 individuals with dementia of the Alzheimer’s type (DAT), 5 with vascular dementia (VaD), 9 with MCI, and 10 neurologically healthy controls (NHC) were obtained from the DementiaBank. Nine words that had initial obstruent consonants that occurred at least two times in each of the participant groups were selected for measurement. The F2 durations, extents, and slope were measured and analyzed. Across group comparisons revealed no pattern for F2 durations or extents. The fricatives had longer F2 durations than the plosives. Across word comparisons revealed significant differences across the consonant vowel combinations for all three measures. A group by word interaction occurred for the F2 slope with the VaD group exhibiting larger slopes than the other two groups.

Analysis of emotional prosody as a tool for differential diagnosis of cognitive impairments: a pilot research.

This pilot research was designed to investigate if prosodic features from running spontaneous speech could differentiate dementia of the Alzheimer's type (DAT), vascular dementia (VaD), mild cognitive impairment (MCI), and healthy cognition. The study included acoustic measurements of prosodic features (Study 1) and listeners' perception of emotional prosody differences (Study 2). For Study 1, prerecorded speech samples describing the Cookie Theft picture from 10 individuals with DAT, 5 with VaD, 9 with MCI, and 10 neurologically healthy controls (NHC) were obtained from the DementiaBank. The descriptive narratives by each participant were separated into utterances. These utterances were measured on 22 acoustic features via the Praat software and analyzed statistically using the principal component analysis (PCA), regression, and Mahalanobis distance measures. The analyses on acoustic data revealed a set of five factors and four salient features (i.e., pitch, amplitude, rate, and syllable) that discriminate the four groups. For Study 2, a group of 28 listeners served as judges of emotions expressed by the speakers. After a set of training and practice sessions, they were instructed to indicate the emotions they heard. Regression measures were used to analyze the perceptual data. The perceptual data indicated that the factor underlying pitch measures had the greatest strength for the listeners to separate the groups. The present pilot work showed that using acoustic measures of prosodic features may be a functional method for differentiating among DAT, VaD, MCI, and NHC. Future studies with data collected under a controlled environment using better stimuli are warranted.

Blood spinal cord barrier disruption recovers in patients with degenerative cervical myelopathy after surgical decompression: a prospective cohort study

The pathophysiology of degenerative cervical myelopathy (DCM) is characterized by chronic compression-induced damage to the spinal cord leading to secondary harm such as disruption of the blood spinal cord barrier (BSCB). It is therefore the purpose of this study to analyze BSCB disruption in pre- and postoperative DCM patients and to correlate those with the clinical status and postoperative outcome. This prospectively controlled cohort included 50 DCM patients (21 female; 29 male; mean age: 62.9 ± 11.2 years). As neurological healthy controls, 52 (17 female; 35 male; mean age 61.8 ± 17.3 years) patients with thoracic abdominal aortic aneurysm (TAAA) and indication for open surgery were included. All patients underwent a neurological examination and DCM-associated scores (Neck Disability Index, modified Japanese Orthopaedic Association Score) were assessed. To evaluate the BSCB status, blood and cerebrospinal fluid (CSF) samples (lumbar puncture or CSF drainage) were taken preoperatively and in 15 DCM patients postoperatively (4 female; 11 male; mean age: 64.7 ± 11.1 years). Regarding BSCB disruption, CSF and blood serum were examined for albumin, immunoglobulin (Ig) G, IgA and IgM. Quotients for CSF/serum were standardized and calculated according to Reiber diagnostic criteria. Significantly increased preoperative CSF/serum quotients were found in DCM patients as compared to control patients: AlbuminQ (p < .001), IgAQ (p < .001) and IgGQ (p < .001). IgMQ showed no significant difference (T = − 1.15, p = .255). After surgical decompression, neurological symptoms improved in DCM patients, as shown by a significantly higher postoperative mJOA compared to the preoperative score (p = .001). This neurological improvement was accompanied by a significant change in postoperative CSF/serum quotients for Albumin (p = .005) and IgG (p = .004) with a trend of a weak correlation between CSF markers and neurological recovery. This study further substantiates the previous findings, that a BSCB disruption in DCM patients is evident. Interestingly, surgical decompression appears to be accompanied by neurological improvement and a reduction of CSF/serum quotients, implying a BSCB recovery. We found a weak association between BSCB recovery and neurological improvement. A BSCB disruption might be a key pathomechanism in DCM patients, which could be relevant to treatment and clinical recovery.

Phenotypic correlates of serum neurofilament light chain levels in amyotrophic lateral sclerosis.

To investigate the relationship between serum levels of the neuroaxonal degeneration biomarker neurofilament light chain (NFL) and phenotype in ALS. Serum NFL (sNFL) concentration was quantified in 209 ALS patients and 46 neurologically healthy controls (NHCs). sNFL was clearly increased in ALS patients and discriminated them from NHCs with AUC = 0.9694. Among ALS patients, females had higher sNFL levels, especially in case of bulbar onset. sNFL was more increased in phenotypes with both upper (UMN) and lower motor neuron (LMN) signs, and particularly in those with UMN predominance, compared to LMN forms. At the same time, primary lateral sclerosis (PLS) had significantly lower levels compared to UMN-predominant ALS (AUC = 0.7667). sNFL correlated negatively with disease duration at sampling and ALSFRS-R score, positively with disease progression rate, differed among King's stages, and was negatively associated with survival. It also correlated with clinical/neurophysiological indices of UMN and LMN dysfunction (Penn UMN Score, LMN score, MRC composite score, active spinal denervation score). On the contrary, sNFL was not associated with cognitive deficits nor with respiratory parameters. Notably, we found a negative correlation between sNFL and estimated glomerular filtration rate (eGFR). We confirm that ALS is characterized by increased sNFL levels, whose main determinant is the rate of degeneration of both UMNs and LMNs. sNFL is a biomarker of only motor, not of extra-motor, disease. The negative correlation with kidney function might reflect varying renal clearance of the molecule and deserves further investigation before introducing sNFL measurement as routine test in clinical care of ALS patients.

Face-to-Face Communication in Aphasia: The Influence of Conversation Partner Familiarity on a Collaborative Communication Task

Aphasia is language impairment due to acquired brain damage. It affects people’s ability to communicate effectively in everyday life. Little is known about the influence of environmental factors on everyday communication for people with aphasia (PWA). It is generally assumed that for PWA speaking to a familiar person (i.e. with shared experiences and knowledge) is easier than speaking to a stranger (Howard, Swinburn, and Porter). This assumption is in line with existing psycholinguistic theories of common ground (Clark, 1996), but there is little empirical data to support this assumption. The current study investigated whether PWA benefit from conversation partner (CP) familiarity during goal-directed communication, and how this effect compared to a group of neurologically healthy controls (NHC). Sixteen PWA with mild to severe aphasia, sixteen matched NHC, plus self-selected familiar CPs participated. Pairs were videotaped while completing a collaborative communication task. Pairs faced identical Playmobile rooms: the view of the other’s room was blocked. Listeners attempted to replicate the 5-item set-up in the instructor’s room. Roles were swapped for each trial. For the unfamiliar condition, participants were paired with another participant’s CP (PWA were matched with another PWA’s CP based on their aphasia profile). The outcomes were canonical measures of communicative efficiency (i.e. accuracy, time to complete, etc.). Results showed different effects in response to the unfamiliar partner for PWA compared to NHC: In the instructor role, PWA showed faster trial times with the unfamiliar partner, but similar accuracy scores in both conditions. NHC, on the other hand, showed similar trial times across CPs, but higher accuracy scores with the unfamiliar partner. In the listener role, PWA showed a pattern more similar to NHC: equal trial times across conditions, and an improvement in accuracy scores with the unfamiliar partner. Results show that conversation partner familiarity significantly affected communication for PWA dyads on a familiar task, but not for NHC. This research highlights the importance of identifying factors that influence communication for PWA and understanding how this effect varies across aphasia profiles. This knowledge will ultimately inform our assessment and intervention of real-world communication.

Complement Profiles in Patients with Amyotrophic Lateral Sclerosis: A Prospective Observational Cohort Study.

BackgroundThe complement system has been suggested to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS), a progressive motor neuron disease. In the present study, we compared levels of selected complement markers to clinical outcome in ALS patients.MethodsThis observational, explorative cohort study included 92 ALS patients, 61 neurological controls (NCs) admitted for suspected aneurysmal subarachnoid haemorrhage, and 96 neurologically healthy controls (NHCs). Peripheral blood and cerebrospinal fluid (CSF) were obtained for the measurement of ficolin-1, −2, and −3; collectin-11, MBL, MASP-3, MAP-1, C4, C3, PTX-3, and complement activation products C4c, C3bc, and sC5b-9. We recorded clinical outcomes of ALS patients for 24 to 48 months after inclusion in order to analyse the effects of the complement markers on survival time.ResultsCompared with both control groups, ALS patients exhibited increased collectin-11, C4 and sC5b-9 in plasma, as well as increased ficolin-3 in CSF. Ficolin-2 was significantly decreased in plasma of the ALS patients compared with NHCs, but not with NCs. The concentration of collectin-11, C3 and C3bc correlated negatively with the revised ALS functional rating scale (ALSFRS-R). No association was found between levels of complement markers and survival as estimated by hazard ratios.ConclusionALS patients exhibit aberrant expression of selected mediators of the lectin complement pathway as well as increased activation of the terminal complement pathway, corroborating the notion that the complement system might be involved in the pathophysiology of ALS.

A novel physiologic marker of bulbar motor involvement in amyotrophic lateral sclerosis: Jaw muscle synergy

ObjectiveTo identify a novel physiologic marker of bulbar motor involvement in amyotrophic lateral sclerosis (ALS) based on jaw muscle synergies. MethodsMuscle synergies were extracted from the surface electromyographic recordings of five jaw muscles during speech in 11 individuals at the prodromal or symptomatic stages of bulbar ALS and 10 neurologically-healthy controls, using non-negative matrix factorization. The disrupted muscle synergies in ALS were identified; their efficacy in differentiating individuals with ALS from healthy controls and relation to the previously-reported kinematic and functional speech deficits were determined. ResultsAn antagonist synergy (i.e., masseter × digastric) was significantly disrupted in ALS, which differentiated individuals with ALS from healthy controls with 82% sensitivity and 90% specificity. Such a disruption occurred prodromally and was associated with slowed jaw movement and reduced speaking rate across the range of severity. ConclusionsThe disruption of jaw antagonist synergy in ALS likely reflects the impact of impaired neural drive on the coordinative functioning of bulbar muscles, which may be used to assess bulbar motor involvement. SignificanceJaw antagonist synergy shows promise as a novel physiologic marker of bulbar motor involvement in ALS, which has the potential to serve as a quantitative measurement tool for bulbar assessment.

Associations of mitochondrial genomic variation with corticobasal degeneration, progressive supranuclear palsy, and neuropathological tau measures

Mitochondrial health is important in ageing and dysfunctional oxidative phosphorylation (OXPHOS) accelerates ageing and influences neurodegeneration. Mitochondrial DNA (mtDNA) codes for vital OXPHOS subunits and mtDNA background has been associated with neurodegeneration; however, no study has characterised mtDNA variation in Progressive supranuclear palsy (PSP) or Corticobasal degeneration (CBD) risk or pathogenesis. In this case–control study, 910 (42.6% male) neurologically-healthy controls, 1042 (54.1% male) pathologically-confirmed PSP cases, and 171 (52.0% male) pathologically-confirmed CBD cases were assessed to determine how stable mtDNA polymorphisms, in the form of mtDNA haplogroups, were associated with risk of PSP, risk of CBD, age of PSP onset, PSP disease duration, and neuropathological tau pathology measures for neurofibrillary tangles (NFT), neuropil threads (NT), tufted astrocytes (TA), astrocytic plaques (AP), and oligodendroglial coiled bodies (CB). 764 PSP cases and 150 CBD cases had quantitative tau pathology scores. mtDNA was genotyped for 39 unique SNPs using Agena Bioscience iPlex technologies and mitochondrial haplogroups were defined to mitochondrial phylogeny. After adjustment for multiple testing, we observed an association with risk of CBD for mtDNA sub-haplogroup H4 (OR = 4.51, P = 0.001) and the HV/HV0a haplogroup was associated with a decreased severity of NT tau pathology in PSP cases (P = 0.0023). Our study reports that mitochondrial genomic background may be associated with risk of CBD and may be influencing tau pathology measures in PSP. Replication of these findings will be important.

The influence of traumatic brain injury on the allocation of vertical spatial attention

ABSTRACTObjective: Research on impairments of spatial attention has primarily investigated hemispatial neglect in brain-lesioned patients, revealing decrements in the allocation of attention to right versus left egocentric or allocentric hemispace. Whereas head trauma might injure those parts of the brain that allocate vertical attention, little is known about the influence of trauma on the allocation of visuospatial attention in vertical space. Thus, the goal of this study was to learn if chronic moderate-to-severe traumatic brain injury (m/sTBI) alters the allocation of vertical visuospatial attention as assessed by the Attention Network Task (ANT). The ANT assesses the influence of Posner-type spatial cues and distractors using an Eriksen flanker task.Methods: 12 chronic m/sTBI patients and 12 demographically-matched neurologically-healthy controls (HCs) completed a version of the ANT wherein trials were coded for cue and target locations above and below central visual fixation. Trial-wise reaction times (RT) and accuracy were subjected to mixed-model ANOVAs and planned contrasts.Results: These data were subject to secondary analyses, which revealed that across groups, median RTs were significantly faster when targets occurred above than below the central visual fixation (p < .01); however, only HCs’ error rates differed as a function of target altitude. Unlike controls, m/sTBI survivors did not exhibit the anticipated upward error-rate attentional bias.Conclusions: As alteration of spatial attention can be a major cause of disability, present findings suggest that m/sTBI survivors exhibit this loss of normal upward attentional bias. Future studies are need to learn if these patients might benefit from treatment.

Gene expression profiling analysis of locus coeruleus in idiopathic Parkinson's disease by bioinformatics.

This study aimed to explore the underlying molecular mechanisms of idiopathic Parkinson's disease (IPD) by bioinformatics analysis. Gene expression profile GSE34516 was downloaded from the Gene Expression Omnibus. Eight locus coeruleus post-mortem tissue samples derived from four IPD patients and four neurological healthy controls were used to identify the differentially expressed genes (DEGs) by paired t test. Based on the DEGs, principal components were analyzed. The Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway analysis of the genome microarray data were then performed. Finally, protein-protein interaction (PPI) network of the DEGs was constructed. Total 261 DEGs including 195 up-regulated and 66 down-regulated DEGs were identified. Intracellular protein transport and RNA splicing via transesterification reactions were selected as the most two significantly enriched functions. Mismatch repair, N-glycan biosynthesis, spliceosome and nucleotide excision repair were the significantly enriched pathways. In the PPI network, CTSS, CD53, IGSF6, PTPRC and LAPTM5 were the hub nodes. Intracellular protein transport and RNA splicing via transesterification reactions were closely associated with IPD. The DEGs, such as CX3CR1, SLC5A7, CD53 and PTPRC may be the potential targets for IPD diagnosis and treatment.

Impaired Emotional Prosody Processing in Severe Traumatic Brain Injury: An Event-Related Potential Study

Event Abstract Back to Event Impaired Emotional Prosody Processing in Severe Traumatic Brain Injury: An Event-Related Potential Study Jacqueline A. Rushby1*, Skye McDonald1, Francesca Froreich1, Alana Fisher1 and Jaimi Iredale1 1 University of New South Wales, Psychology, Australia Aims: Impaired communicative competence is well-documented among individuals with a severe traumatic brain injury (TBI). These impairments may in part result from a reduced perception of paralinguistic cues, such as emotional prosody which help inform judgments about another’s emotional state. This study used event-related potentials (ERPs) to examine the neural mechanisms of emotional prosody perception in TBI, within the framework of Schirmer and Kotz’s (2006) model of vocal emotion perception. Methods: Nineteen adults with severe TBI (15 male, age 46.1, education 12.5, average post-traumatic amnesia 66.78 days, average time post-injury 12.5 y), and 18 neurologically-healthy controls (11 males, age 43.9, education 15.4) completed a discrimination task which presented semantically-neutral word pairs from five prosody conditions (happy/happy, angry/angry, neutral/neutral, angry/happy, happy/angry); participants were required to judge the emotional prosody as the ‘same’ or ‘different’ whilst electroencephalogram and accuracy were recorded. Results: Preliminary analyses indicated that ERPs were larger in control compared with TBI participants, and were larger in central than lateral sites for both emotion categories compared with neutral, whereas the converse was found in TBI ,who showed a hemisphere > midline topography, but no topographical differentiation across frontal/posterior regions (F = 4.26, p = .046). This difference was also reflected in reduced accuracy for both emotion conditions for TBI group. Conclusions: TBI participants were not impaired in sensory processing of acoustic cues or recognition of emotional salience in acoustic cues. In regards to cognition and evaluative judgement however, TBI participants showed obvious differences in both ERP morphology, and behavioural outcomes, compared with controls. These findings are consistent with the frontal and posterior poles being more vulnerable to damage in TBI. Keywords: emotion, Prosody, ERP, Severe traumatic brain injury, Sensory Processing* Conference: ASP2013 - 23rd Annual meeting of the Australasian Society for Psychophysiology, Wollongong, Australia, 20 Nov - 22 Nov, 2013. Presentation Type: Oral Presentation Topic: Emotion Citation: Rushby JA, McDonald S, Froreich F, Fisher A and Iredale J (2013). Impaired Emotional Prosody Processing in Severe Traumatic Brain Injury: An Event-Related Potential Study. Conference Abstract: ASP2013 - 23rd Annual meeting of the Australasian Society for Psychophysiology. doi: 10.3389/conf.fnhum.2013.213.00035 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Oct 2013; Published Online: 05 Nov 2013. * Correspondence: Dr. Jacqueline A Rushby, University of New South Wales, Psychology, Randwick, NSW, 2031, Australia, j.rushby@unsw.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jacqueline A Rushby Skye McDonald Francesca Froreich Alana Fisher Jaimi Iredale Google Jacqueline A Rushby Skye McDonald Francesca Froreich Alana Fisher Jaimi Iredale Google Scholar Jacqueline A Rushby Skye McDonald Francesca Froreich Alana Fisher Jaimi Iredale PubMed Jacqueline A Rushby Skye McDonald Francesca Froreich Alana Fisher Jaimi Iredale Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Error-related processing following severe traumatic brain injury: An event-related functional magnetic resonance imaging (fMRI) study

Continuous monitoring of one's performance is invaluable for guiding behavior towards successful goal attainment by identifying deficits and strategically adjusting responses when performance is inadequate. In the present study, we exploited the advantages of event-related functional magnetic resonance imaging (fMRI) to examine brain activity associated with error-related processing after severe traumatic brain injury (sTBI). fMRI and behavioral data were acquired while 10 sTBI participants and 12 neurologically-healthy controls performed a task-switching cued-Stroop task. fMRI data were analyzed using a random-effects whole-brain voxel-wise general linear model and planned linear contrasts. Behaviorally, sTBI patients showed greater error-rate interference than neurologically-normal controls. fMRI data revealed that, compared to controls, sTBI patients showed greater magnitude error-related activation in the anterior cingulate cortex (ACC) and an increase in the overall spatial extent of error-related activation across cortical and subcortical regions. Implications for future research and potential limitations in conducting fMRI research in neurologically-impaired populations are discussed, as well as some potential benefits of employing multimodal imaging (e.g., fMRI and event-related potentials) of cognitive control processes in TBI.

A Multivariate Approach To Reveal Biomarker Signatures for Disease Classification: Application to Mass Spectral Profiles of Cerebrospinal Fluid from Patients with Multiple Sclerosis

Mass spectral profiles from cerebrospinal fluid (CSF) are used as input to a novel multivariate approach to select features responsible for the separation of patients with multiple sclerosis (MS) from control groups. Our targeted statistical approach makes it possible to systematically remove features in the spectral fingerprints masking the components expressing the disease pattern. The low molecular weight CSF proteome from 54 patients with MS and a range of other neurological diseases (OND), as well as neurological healthy controls (NHC), is analyzed in replicates using mass spectral profiling. Statistically validated partial least-squares discriminant analysis (PLS-DA) models are created as a first step to separate the groups. Using the group membership as a target, the most discriminatory projection in the multivariate space spanned by the spectral profiles is revealed. From the resulting target-projected component, the spectral regions most significantly contributing to group separation are identified using the nonparametric discriminating variable (DIVA) test together with the so-called selectivity ratio (SR) plot. Our approach is general and can be applied for other diseases and instrumental techniques as well.

Midregional Proenkephalin A and N-terminal Protachykinin A are decreased in the cerebrospinal fluid of patients with dementia disorders and acute neuroinflammation

Midregional Proenkephalin A (MR-PENK A) and N-terminal Protachykinin A (NT-PTA) are stable fragments of the precursor peptides for enkephalins and substance P, respectively. We measured MR-PENK A and NT-PTA concentrations by sensitive chemiluminescence immunoassays in cerebrospinal fluid (CSF) of 19 neurologically healthy controls (NHC), 28 patients with other neurologic disorders (OND), 70 patients with dementia disorders (38 Alzheimer's disease [AD], 8 dementia with Lewy bodies [DLB], 12 frontotemporal dementia [FTD], and 12 patients with vascular dementia [VD]), and 16 patients with acute neuroinflammation (AN). Median concentrations of NT-PTA were decreased in all patient groups compared to NHC showing significant differences between patients with NHC and AN ( p < 0.001), OND and AN ( p < 0.001), FTD and AN ( p < 0.01) and pAD and AN ( p < 0.05). Median MR-PENK A levels were lower in patients with OND, dementia disorders (including AD, FTD, DLB and VD) and AN compared to NHC subjects, although this differences did not reach statistical significance ( p > 0.05). A maximum difference of both proneuropeptide fragments was found between NHC subjects and patients with AN, with a more than 2fold decrease in median NT-PTA and a 1.5fold decrease in median MR-PENK A levels. Concentrations of both proneuropeptide fragments were positively correlated in all patients ( r = 0.77, p < 0.001). Our results indicate alterations of the cerebral PENK A- and PTA-system in both, dementia and acute neuroinflammatory disorders. These neuropeptide systems seem to be highly correlated in healthy and pathological status.