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1.
Hum Brain Mapp ; 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35792001

RESUMO

The network of brain structures engaged in motor sequence learning comprises the same structures as those involved in tremor, including basal ganglia, cerebellum, thalamus, and motor cortex. Deep brain stimulation (DBS) of the ventrointermediate nucleus of the thalamus (VIM) reduces tremor, but the effects on motor sequence learning are unknown. We investigated whether VIM stimulation has an impact on motor sequence learning and hypothesized that stimulation effects depend on the laterality of electrode location. Twenty patients (age: 38-81 years; 12 female) with VIM electrodes implanted to treat essential tremor (ET) successfully performed a serial reaction time task, varying whether the stimuli followed a repeating pattern or were selected at random, during which VIM-DBS was either on or off. Analyses of variance were applied to evaluate motor sequence learning performance according to reaction times (RTs) and accuracy. An interaction was observed between whether the sequence was repeated or random and whether VIM-DBS was on or off (F[1,18] = 7.89, p = .012). Motor sequence learning, reflected by reduced RTs for repeated sequences, was greater with DBS on than off (T[19] = 2.34, p = .031). Stimulation location correlated with the degree of motor learning, with greater motor learning when stimulation targeted the lateral VIM (n = 23, ρ = 0.46; p = .027). These results demonstrate the beneficial effects of VIM-DBS on motor sequence learning in ET patients, particularly with lateral VIM electrode location, and provide evidence for a role for the VIM in motor sequence learning.

2.
Sci Rep ; 11(1): 19521, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593887

RESUMO

School closures have a negative impact on physical and mental well-being, and education, of children and adolescents. A surveillance programme to detect asymptomatic SARS-CoV-2 infection could allow schools to remain open, while protecting the vulnerable. We assessed the feasibility of a programme employing gargle samples and pool testing of individually extracted RNA using rRT-qPCR in a primary and a secondary school in Germany, based on programme logistics and acceptance. Twice a week, five participants per class were selected to provide samples, using an algorithm weighted by a risk-based priority score to increase likelihood of case detection. The positive response rate was 54.8% (550 of 1003 pupils). Logistics evaluation revealed the rate-limiting steps: completing the regular pre-test questionnaire and handing in the samples. Acceptance questionnaire responses indicated strong support for research into developing a surveillance programme and a positive evaluation of gargle tests. Participation was voluntary. As not all pupils participated, individual reminders could lead to participant identification. School-wide implementation of the programme for infection monitoring purposes would enable reminders to be given to all school pupils to address these steps, without compromising participant anonymity. Such a programme would provide a feasible means to monitor asymptomatic respiratory tract infection in schools.


Assuntos
COVID-19/diagnóstico , COVID-19/prevenção & controle , Surtos de Doenças/prevenção & controle , Monitoramento Epidemiológico , Instituições Acadêmicas/estatística & dados numéricos , Adolescente , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19/estatística & dados numéricos , Criança , Estudos de Viabilidade , Alemanha/epidemiologia , Humanos , Pandemias , Saliva/virologia , Estudantes/estatística & dados numéricos , Inquéritos e Questionários
3.
JMIR Res Protoc ; 10(5): e28673, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-33979297

RESUMO

BACKGROUND: School closures are a widely implemented strategy for limiting infection spread in the current COVID-19 pandemic. The negative impact of school closures on children and young people is increasingly apparent, however. OBJECTIVE: We aim to evaluate the feasibility of an infection monitoring program in schools to enable targeted quarantining to replace school closures. The program is currently being implemented in two model schools in Magdeburg, Germany, within the framework of the Study of Coronavirus Outbreak Prevention in Magdeburg Schools (Studie zur Ausbruchsvermeidung von Corona an Magdeburger Schulen [STACAMA]). METHODS: Five pupils per class are pseudorandomly selected twice a week and asked to provide a gargle sample over a 16-week evaluation period. RNA is extracted from each sample individually in a laboratory and pooled according to school class for real-time reverse transcription polymerase chain reaction (rRT-PCR) analysis. Immediate individual sample testing will be carried out in the case of a positive pool test. Individual RNA extraction prior to pooling and application of rRT-PCR result in high test sensitivity. Testing will be performed in strict adherence to data protection standards. All participating pupils will receive a 16-digit study code, which they will be able to use to access their test. RESULTS: When the study commenced on December 2, 2020, 520 (52%) pupils and their families or guardians had consented to study participation. The study was suspended after four test rounds due to renewed school closures resulting from rising regional infection incidence. Testing resumed when schools reopened on March 8, 2021, at which time consent to participation was provided for 54% of pupils. We will quantitatively and qualitatively evaluate the logistics and acceptability of the program. CONCLUSIONS: The findings from this study should inform the design of infection surveillance programs in schools based on gargle samples and a PCR-based pool testing procedure, enabling the identification of aspects that may require adaptation before large-scale implementation. Our focus on each step of the logistics and on the experiences of families should enable a robust assessment of the feasibility of such an approach. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28673.

4.
Neurosci Biobehav Rev ; 126: 146-158, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33737103

RESUMO

Extensive neuroanatomical connectivity between the anterior thalamic nuclei (ATN) and hippocampus and neocortex renders them well-placed for a role in memory processing, and animal, lesion, and neuroimaging studies support such a notion. The deep location and small size of the ATN have precluded their real-time electrophysiological investigation during human memory processing. However, ATN electrophysiological recordings from patients receiving electrodes implanted for deep brain stimulation for pharmacoresistant focal epilepsy have enabled high temporal resolution study of ATN activity. Theta frequency synchronization of ATN and neocortical oscillations during successful memory encoding, enhanced phase alignment, and coupling between ATN local gamma frequency activity and frontal neocortical and ATN theta oscillations provide evidence of an active role for the ATN in memory encoding, potentially integrating information from widespread neocortical sources. Greater coupling of a broader gamma frequency range with theta oscillations at rest than during memory encoding provides additional support for the hypothesis that the ATN play a role in selecting local, task-relevant high frequency activity associated with particular features of a memory trace.


Assuntos
Núcleos Anteriores do Tálamo , Neocórtex , Animais , Eletroencefalografia , Hipocampo , Humanos , Memória
5.
Front Neurosci ; 14: 591777, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33335470

RESUMO

Regaining communication abilities in patients who are unable to speak or move is one of the main goals in decoding brain waves for brain-computer interface (BCI) control. Many BCI approaches designed for communication rely on attention to visual stimuli, commonly applying an oddball paradigm, and require both eye movements and adequate visual acuity. These abilities may, however, be absent in patients who depend on BCI communication. We have therefore developed a response-based communication BCI, which is independent of gaze shifts but utilizes covert shifts of attention to the left or right visual field. We recorded the electroencephalogram (EEG) from 29 channels and coregistered the vertical and horizontal electrooculogram. Data-driven decoding of small attention-based differences between the hemispheres, also known as N2pc, was performed using 14 posterior channels, which are expected to reflect correlates of visual spatial attention. Eighteen healthy participants responded to 120 statements by covertly directing attention to one of two colored symbols (green and red crosses for "yes" and "no," respectively), presented in the user's left and right visual field, respectively, while maintaining central gaze fixation. On average across participants, 88.5% (std: 7.8%) of responses were correctly decoded online. In order to investigate the potential influence of stimulus features on accuracy, we presented the symbols with different visual angles, by altering symbol size and eccentricity. The offline analysis revealed that stimulus features have a minimal impact on the controllability of the BCI. Hence, we show with our novel approach that spatial attention to a colored symbol is a robust method with which to control a BCI, which has the potential to support severely paralyzed people with impaired eye movements and low visual acuity in communicating with their environment.

6.
Clin Neurophysiol ; 131(2): 414-419, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31877491

RESUMO

OBJECTIVE: The pedunculopontine nucleus (PPN) has been proposed as a new deep brain stimulation (DBS) target for the treatment in idiopathic Parkinson's syndrome (IPS) and progressive supranuclear palsy (PSP). In IPS, levodopa has been shown to induce alpha activity in the PPN, indicating a possible physiological role for these oscillations in movement control. Despite shared clinical features, the PPN is more severely affected in PSP than IPS. Here we investigated neuronal oscillations in the PPN in PSP and the influence of levodopa and movement. METHODS: Local field potentials were recorded bilaterally from the PPN of 4 PSP patients at rest, with levodopa and during self-paced leg movements. RESULTS: During rest, levodopa administration was associated with significantly increased alpha and reduced gamma activity in the PPN. Without levodopa, continuous movements were associated with reduced alpha and beta power. These differences between oscillatory power during movement and resting state were not observed with levodopa administration. CONCLUSION: In PSP the changes in neuronal oscillations in the PPN region on levodopa administration are similar to those reported in IPS. The enhancement of lower frequency oscillations in the PPN is possibly influenced by a dopaminergic activation of the striatal pathway and a reduced pallidal inhibition. SIGNIFICANCE: Levodopa influences neuronal oscillations at low and high frequencies in the PPN region in Parkinsonian disorders.


Assuntos
Antiparkinsonianos/farmacologia , Ondas Encefálicas , Levodopa/farmacologia , Movimento , Núcleo Tegmental Pedunculopontino/fisiopatologia , Paralisia Supranuclear Progressiva/fisiopatologia , Idoso , Antiparkinsonianos/uso terapêutico , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Núcleo Tegmental Pedunculopontino/efeitos dos fármacos , Paralisia Supranuclear Progressiva/tratamento farmacológico
7.
J Neural Eng ; 16(6): 066010, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31416059

RESUMO

OBJECTIVE: Convolutional neural networks (CNNs) have proven successful as function approximators and have therefore been used for classification problems including electroencephalography (EEG) signal decoding for brain-computer interfaces (BCI). Artificial neural networks, however, are considered black boxes, because they usually have thousands of parameters, making interpretation of their internal processes challenging. Here we systematically evaluate the use of CNNs for EEG signal decoding and investigate a method for visualizing the CNN model decision process. APPROACH: We developed a CNN model to decode the covert focus of attention from EEG event-related potentials during object selection. We compared the CNN and the commonly used linear discriminant analysis (LDA) classifier performance, applied to datasets with different dimensionality, and analyzed transfer learning capacity. Moreover, we validated the impact of single model components by systematically altering the model. Furthermore, we investigated the use of saliency maps as a tool for visualizing the spatial and temporal features driving the model output. MAIN RESULTS: The CNN model and the LDA classifier achieved comparable accuracy on the lower-dimensional dataset, but CNN exceeded LDA performance significantly on the higher-dimensional dataset (without hypothesis-driven preprocessing), achieving an average decoding accuracy of 90.7% (chance level = 8.3%). Parallel convolutions, tanh or ELU activation functions, and dropout regularization proved valuable for model performance, whereas the sequential convolutions, ReLU activation function, and batch normalization components reduced accuracy or yielded no significant difference. Saliency maps revealed meaningful features, displaying the typical spatial distribution and latency of the P300 component expected during this task. SIGNIFICANCE: Following systematic evaluation, we provide recommendations for when and how to use CNN models in EEG decoding. Moreover, we propose a new approach for investigating the neural correlates of a cognitive task by training CNN models on raw high-dimensional EEG data and utilizing saliency maps for relevant feature extraction.


Assuntos
Atenção/fisiologia , Mapeamento Encefálico/métodos , Eletroencefalografia/métodos , Redes Neurais de Computação , Feminino , Humanos , Masculino
8.
J Neuroeng Rehabil ; 16(1): 72, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186029

RESUMO

BACKGROUND: Central drop foot is a common problem in patients with stroke or multiple sclerosis (MS). For decades, it has been treated with orthotic devices, keeping the ankle in a fixed position. It has been shown recently that semi-implantable functional electrical stimulation (siFES) of the peroneal nerve can lead to a greater gait velocity increase than orthotic devices immediately after being switched on. Little is known, however, about long-term outcomes over 12 months, and the relationship between quality of life (QoL) and gait speed using siFES has never been reported applying a validated tool. We provide here a report of short (3 months) and long-term (12 months) outcomes for gait speed and QoL. METHODS: Forty-five consecutive patients (91% chronic stroke, 9% MS) with central drop foot received siFES (Actigait®). A 10 m walking test was carried out on day 1 of stimulation (T1), in stimulation ON and OFF conditions, and repeated after 3 (T2) and 12 (T3) months. A 36-item Short Form questionnaire was applied at all three time points. RESULTS: We found a main effect of stimulation on both maximum (p < 0.001) and comfortable gait velocity (p < 0.001) and a main effect of time (p = 0.015) only on maximum gait velocity. There were no significant interactions. Mean maximum gait velocity across the three assessment time points was 0.13 m/s greater with stimulation ON than OFF, and mean comfortable gait velocity was 0.083 m/s faster with stimulation ON than OFF. The increase in maximum gait velocity over time was 0.096 m/s, with post hoc testing revealing a significant increase from T1 to T2 (p = 0.012), which was maintained but not significantly further increased at T3. QoL scores showed a main effect of time (p < 0.001), with post hoc testing revealing an increase from T1 to T2 (p < 0.001), which was maintained at T3 (p < 0.001). Finally, overall absolute QoL scores correlated with the absolute maximum and comfortable gait speeds at T2 and T3, and the increase in overall QoL scores correlated with the increase in comfortable gait velocity from T1 to T3. Pain was reduced at T2 (p < 0.001) and was independent of gait speed but correlated with overall QoL (p < 0.001). CONCLUSIONS: Peroneal siFES increased maximal and comfortable gait velocity and QoL, with the greatest increase in both over the first three months, which was maintained at one year, suggesting that 3 months is an adequate follow-up time. Pain after 3 months correlated with QoL and was independent of gait velocity, suggesting pain as an independent outcome measure in siFES for drop foot.


Assuntos
Terapia por Estimulação Elétrica/instrumentação , Transtornos Neurológicos da Marcha/terapia , Adulto , Eletrodos Implantados , Feminino , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/fisiopatologia , Qualidade de Vida , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/instrumentação , Reabilitação do Acidente Vascular Cerebral/métodos , Resultado do Tratamento
9.
Neuropsychologia ; 129: 171-178, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30951737

RESUMO

Due to an increased crossing of the optic nerve fibers at the optic chiasm in albinism, the visual cortex receives largely monocular input from the contralateral eye. Here we investigated whether this obstruction of binocular integration at the cortical input stage also impacts on interocular information exchange at the high processing level of visual memory. Interocular transfer (IOT) of visual memory retrieval was tested psychophysically after monocular encoding in 8 albinotic participants and 24 healthy controls. The retrieval performance (hit rate, reaction time, d') was determined when using the same or different eye at encoding. To assess the effect of reduced visual acuity (VA) on recognition, we simulated interocular acuity differences (IOA) in two healthy control groups (each n = 8), i.e., with large (VA: 0.89 vs. 0.12) and small simulated interocular difference (VA: 0.25 vs. 0.12), with the latter matched to that observed in the albinotic participants (VA: 0.20 vs. 0.15). A significant decrease in retrieval performance was observed in controls with simulated strongly reduced VA in one eye (p < 0.0001). For the other conditions and groups, including the albinotic participants, no dependence on VA and no significant difference between using the same or different eye was observed. This indicates interocular transfer and hence interocular information exchange in human albinism. These findings thus provide insights into the scope of plasticity of binocular information processing and inter-hemispherical information flow.


Assuntos
Albinismo/fisiopatologia , Plasticidade Neuronal/fisiologia , Quiasma Óptico/fisiopatologia , Reconhecimento Visual de Modelos/fisiologia , Reconhecimento Psicológico/fisiologia , Transtornos da Visão/fisiopatologia , Acuidade Visual/fisiologia , Córtex Visual/fisiopatologia , Adulto , Albinismo/complicações , Humanos , Pessoa de Meia-Idade , Transtornos da Visão/etiologia , Visão Binocular/fisiologia , Visão Monocular/fisiologia , Adulto Jovem
10.
Front Neurol ; 10: 126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30842752

RESUMO

Motor recovery following stroke is believed to necessitate alteration in functional connectivity between cortex and muscle. Cortico-muscular coherence has been proposed as a potential biomarker for post-stroke motor deficits, enabling a quantification of recovery, as well as potentially indicating the regions of cortex involved in recovery of function. We recorded simultaneous EEG and EMG during wrist extension from healthy participants and patients following ischaemic stroke, evaluating function at three time points post-stroke. EEG-EMG coherence increased over time, as wrist mobility recovered clinically, and by the final evaluation, coherence was higher in the patient group than in the healthy controls. Moreover, the cortical distribution differed between the groups, with coherence involving larger and more bilaterally scattered areas of cortex in the patients than in the healthy participants. The findings suggest that EEG-EMG coherence has the potential to serve as a biomarker for motor recovery and to provide information about the cortical regions that should be targeted in rehabilitation therapies based on real-time EEG.

11.
Conscious Cogn ; 69: 113-132, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30763808

RESUMO

Sudden comprehension-or insight-during problem-solving can enhance learning, but the underlying neural processes are largely unknown. We investigated neural correlates of learning from sudden comprehension using functional magnetic resonance imaging and a verbal problem-solving task. Solutions and "solutions" to solvable and unsolvable verbal problems, respectively, were presented to induce sudden comprehension or continued incomprehension. We found activations of the hippocampus, medial prefrontal cortex (mPFC), amygdala, and striatum during sudden comprehension. Notably, however, mPFC and temporo-parietal neocortical structures rather than the hippocampus were associated with later learning of suddenly comprehended solutions. Moreover, difficult compared to easy sudden comprehension elicited midbrain activations and was associated with successful learning, pointing to learning via intrinsic reward. Sudden comprehension of novel semantic associations may constitute a special case of long-term memory formation primarily mediated by the mPFC, expanding our knowledge of its role in prior-knowledge-dependent memory.


Assuntos
Associação , Compreensão/fisiologia , Hipocampo/fisiologia , Memória de Longo Prazo/fisiologia , Córtex Pré-Frontal/fisiologia , Resolução de Problemas/fisiologia , Adulto , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Semântica , Adulto Jovem
12.
PLoS One ; 13(11): e0207726, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30475854

RESUMO

Glucocorticoid (GC) refractory relapses in patients with multiple sclerosis (MS) or clinically isolated syndrome (CIS), who are in potential need of treatment escalation, are a key challenge in routine clinical practice. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) has been shown to be an endogenous counter-regulator of GC, and potentiates autoimmune-mediated neuroinflammation. In order to evaluate whether MIF levels are elevated in the cerebrospinal fluid (CSF) of MS patients (CSF-MIF), and whether they are higher still during a GC refractory relapse, we compared CSF-MIF concentrations of CIS/MS patients with acute optic neuritis as their first inflammatory episode (ON, n = 20), CIS/MS patients with a stable disease progression/without relapse (CIS/MS w/o, n = 18), and healthy controls (HC, n = 20) using ANOVA. Mean CSF-MIF concentrations in CIS/MS w/o patients were significantly higher than in ON patients and HCs, whereas ON patients and HCs did not differ. A subgroup analysis of the ON group revealed 10 patients to be responsive to GC-treatment (GC-ON) and 10 patients refractory under GC-treatment (rGC-ON). However, mean CSF-MIF concentrations did not differ between GC-ON and rGC-ON cases. We therefore conclude that MIF is not suitable for distinguishing GC responders from non-responders in a group of patients with acute optic neuritis, but it rather mirrors the ongoing inflammation in long-term MS disease progression.


Assuntos
Glucocorticoides/uso terapêutico , Fatores Inibidores da Migração de Macrófagos/líquido cefalorraquidiano , Esclerose Múltipla/complicações , Neurite Óptica/complicações , Neurite Óptica/tratamento farmacológico , Adolescente , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurite Óptica/líquido cefalorraquidiano , Resultado do Tratamento , Adulto Jovem
13.
Front Neurosci ; 12: 761, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30405341

RESUMO

Transcranial electrical stimulation (TES) has been considered a promising tool for improving working memory (WM) performance. Recent studies have demonstrated modulation of networks underpinning WM processing through application of transcranial alternating current (TACS) as well as direct current (TDCS) stimulation. Differences between study designs have limited direct comparison of the efficacy of these approaches, however. Here we directly compared the effects of theta TACS (6 Hz) and anodal TDCS on WM, applying TACS to the frontal-parietal loop and TDCS to the dorsolateral prefrontal cortex (DLPFC). WM was evaluated using a visual 2-back WM task. A within-subject, crossover design was applied (N = 30) in three separate sessions. TACS, TDCS, and sham stimulation were administered in a counterbalanced order, and the WM task was performed before, during, and after stimulation. Neither reaction times for hits (RT-hit) nor accuracy differed according to stimulation type with this study design. A marked practice effect was noted, however, with improvement in RT-hit irrespective of stimulation type, which peaked at the end of the second session. Pre-stimulation RT-hits in session three returned to the level observed pre-stimulation in session two, irrespective of stimulation type. The participants who received sham stimulation in session one and had therefore improved their performance due to practice alone, had thus reached a plateau by session two, enabling us to pool RT-hits from sessions two and three for these participants. The pooling allowed implementation of a within-subject crossover study design, with a direct comparison of the effects of TACS and TDCS in a subgroup of participants (N = 10), each of whom received both stimulation types, in a counterbalanced order, with pre-stimulation performance the same for both sessions. TACS resulted in a greater improvement in RT-hits than TDCS (F(2,18) = 4.31 p = 0.03). Our findings suggest that future work optimizing the application of TACS has the potential to facilitate WM performance.

14.
Neuroimage Clin ; 20: 715-723, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30238915

RESUMO

BACKGROUND: Ketamine is receiving increasing attention as a rapid-onset antidepressant in patients suffering from major depressive disorder (MDD) with treatment resistance or severe suicidal ideation. Ketamine modulates several neurotransmitter systems, including norepinephrine via the norepinephrine transporter (NET), both peripherally and centrally. The locus coeruleus (LC), which has high NET concentration, has been attributed to brain networks involved in depression. Thus we investigated the effects of single-dose of racemic ketamine on the LC using resting state functional MRI. METHODS: Fifty-nine healthy participants (mean age 25.57 ±â€¯4.72) were examined in a double-blind, randomized, placebo-controlled study with 7 Tesla MRI. We investigated the resting state functional connectivity (rs-fc) of the LC before and one hour after subanesthetic ketamine injection (0.5 mg/kg), as well as associations between its rs-fc and a common polymorphism in the NET gene (rs28386840). RESULTS: A significant interaction of drug and time was revealed, and post hoc testing showed decreased rs-fc between LC and the thalamus after ketamine administration compared with baseline levels, including the mediodorsal, ventral anterior, ventral lateral, ventral posterolateral and centromedian nuclei. The rs-fc reduction was more pronounced in NET rs28386840 [AA] homozygous subjects than in [T] carriers. CONCLUSIONS: We demonstrated acute rs-fc changes after ketamine administration in the central node of the norepinephrine pathway. These findings may contribute to understanding the antidepressant effect of ketamine at the system level, supporting modes of action on networks subserving aberrant arousal regulation in depression.


Assuntos
Antidepressivos/administração & dosagem , Ketamina/administração & dosagem , Locus Cerúleo/efeitos dos fármacos , Locus Cerúleo/fisiologia , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/genética , Norepinefrina/fisiologia , Adulto , Mapeamento Encefálico , Método Duplo-Cego , Feminino , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , Polimorfismo de Nucleotídeo Único , Adulto Jovem
15.
Nutrients ; 10(8)2018 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-30049983

RESUMO

OBJECTIVE: Diminished blood levels of zinc have been reported to be associated with T-cell-mediated autoimmunity, which has been implicated in multiple sclerosis (MS). We aimed to compare the distribution of serum zinc status in MS patients with that in healthy controls (HCs) and to investigate a potential correlation with clinical state, through analysis of serum zinc concentration in MS patients suffering from different disease subtypes. METHODS: Serum zinc concentrations of 133 patients with relapsing (RMS) and 18 patients with the progressive form of MS (PMS), according to the McDonald criteria of 2010, were measured. Clinical status was quantified using the Expanded Disability Status Scale (EDSS). Zinc concentrations were also determined in the sera of 50 HCs, matched for age and sex at a group level. RESULTS: MS patients showed significantly lower zinc concentrations (mean (SD)) than HCs (12.5 (2.1) µmol/L vs. 14.6 (2.3) µmol/L, p < 0.001). In contrast, we did not find any difference between RMS (12.4 (2.0) µmol/L) and PMS (13.0 (3.0) µmol/L) cases (p = 0.8). Patients receiving disease-modifying treatment showed lower mean (SD) serum zinc levels than untreated cases (12.3 (1.9) µmol/L vs. 13.5 (3.2) µmol/L, p < 0.03). Zinc levels were not related to disease duration, EDSS, annual relapse rate, or the median number of relapses. CONCLUSIONS: The data suggest that a diagnosis of MS is related to lower serum zinc concentrations than in HCs, and concentrations were lower still under disease-modifying therapy. However, zinc levels did not predict disease subtypes or disability status.


Assuntos
Esclerose Múltipla Crônica Progressiva/sangue , Esclerose Múltipla Recidivante-Remitente/sangue , Zinco/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Avaliação da Deficiência , Regulação para Baixo , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/diagnóstico , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto Jovem
16.
Brain Behav ; 8(7): e01007, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29877060

RESUMO

BACKGROUND: Affective stimulation entails changes in brain network patterns at rest, but it is unknown whether exogenous emotional stimulation has a prolonged effect on the temporal dynamics of endogenous cortical arousal. We therefore investigated differences in cortical arousal in the listener following stimulation with different attachment-related narratives. METHODS: Resting-state EEG was recorded from sixteen healthy subjects for ten minutes each with eyes closed: first at baseline and then after passively listening to three affective narratives from strangers about their early childhood experiences (prototypical for insecure-dismissing, insecure-preoccupied, and secure attachment). Using the VIGALL 2.1 algorithm, low or high vigilance stages in consecutive EEG segments were classified, and their dynamic profile was analyzed. Questionnaires assessed the listeners' emotional response to the content of the narrative. RESULTS: As a general effect of preceding affective stimulation, vigilance following the stimulation was significantly elevated compared to baseline rest, and carryover effects in dynamic vigilance profiles were observed. A difference between narrative conditions was revealed for the insecure-dismissing condition, in which the decrease in duration of high vigilance stages was fastest compared to the other two conditions. The behavioral data supported the observation that especially the insecure narratives induced a tendency in the listener to affectively disengage from the narrative content. DISCUSSION: This study revealed carryover effects in endogenous cortical arousal evoked by preceding affective stimulation and provides evidence for attachment-specific dynamic alterations of brain states and individual differences in emotional reactivity.


Assuntos
Nível de Alerta/fisiologia , Percepção Auditiva/fisiologia , Encéfalo/fisiologia , Eletroencefalografia/métodos , Narração , Apego ao Objeto , Adulto , Algoritmos , Mapeamento Encefálico , Emoções , Feminino , Alemanha , Humanos , Masculino , Valores de Referência , Descanso , Inquéritos e Questionários
17.
Front Neurol ; 9: 1075, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30619038

RESUMO

Background: Cerebrospinal fluid (CSF) markers of disease in patients with radiologically isolated syndrome (RIS) are the subject of intense investigation, because they have the potential to enhance our understanding of the natural disease course and provide insights into similarities and differences between RIS and other multiple sclerosis (MS) disease identities. Methods: Here we compared neurofilament light chain (NFL) and progranulin (PGRN) levels in the CSF in RIS patients with levels in patients with different subtypes of MS and healthy controls (HC) using Kruskal-Wallis one-way analysis of variance. Results: Median CSF NFL concentrations in RIS patients did not differ to those in HC and clinically isolated syndrome (CIS) patients, but were significantly lower than in relapsing remitting (RRMS) and primary progressive (PPMS) MS patients. In contrast, RIS patients exhibited higher median CSF PGRN levels than HC and showed no significant differences compared with CIS, RRMS, and PPMS cases. Conclusion: We postulate that elevated PGRN values in the CSF of RIS patients might indicate inflammatory and repair activity prior to axonal disintegration.

18.
Int J Neuropsychopharmacol ; 20(11): 909-918, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29099972

RESUMO

Background: The increasing use of ketamine as a potential rapid-onset antidepressant necessitates a better understanding of its effects on blood pressure and heart rate, well-known side effects at higher doses. For the subanesthetic dose used for depression, potential predictors of these cardiovascular effects are important factors influencing clinical decisions. Since ketamine influences the sympathetic nervous system, we investigated the impact of autonomic nervous system-related factors on the cardiovascular response: a genetic polymorphism in the norepinephrine transporter and gender effects. Methods: Blood pressure and heart rate were monitored during and following administration of a subanesthetic dose of ketamine or placebo in 68 healthy participants (mean age 26.04 ±5.562 years) in a double-blind, randomized, controlled, parallel-design trial. The influences of baseline blood pressure/heart rate, gender, and of a polymorphism in the norepinephrine transporter gene (NET SLC6A2, rs28386840 [A-3081T]) on blood pressure and heart rate changes were investigated. To quantify changes in blood pressure and heart rate, we calculated the maximum change from baseline (ΔMAX) and the time until maximum change (TΔMAX). Results: Systolic and diastolic blood pressure as well as heart rate increased significantly upon ketamine administration, but without reaching hypertensive levels. During administration, the systolic blood pressure at baseline (TP0Sys) correlated negatively with the time to achieve maximal systolic blood pressure (TΔMAXSys, P<.001). Furthermore, women showed higher maximal diastolic blood pressure change (ΔMAXDia, P<.001) and reached this peak earlier than men (TΔMAXDia, P=.017) at administration. NET rs28386840 [T] carriers reached their maximal systolic blood pressure during ketamine administration significantly earlier than [A] homozygous (TΔMAXSys, P=.030). In a combined regression model, both genetic polymorphism and TP0Sys were significant predictors of TΔMAXSys (P<.0005). Conclusions: Subanesthetic ketamine increased both blood pressure and heart rate without causing hypertensive events. Furthermore, we identified gender and NET rs28386840 genotype as factors that predict increased cardiovascular sequelae of ketamine administration in our young, healthy study population providing a potential basis for establishing monitoring guidelines.


Assuntos
Analgésicos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Ketamina/farmacologia , Adulto , Análise de Variância , Método Duplo-Cego , Feminino , Seguimentos , Genótipo , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/genética , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Polimorfismo Genético/genética , Fatores Sexuais , Adulto Jovem
19.
Front Hum Neurosci ; 11: 358, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28775684

RESUMO

Cross-frequency coupling (CFC) between slow and fast brain rhythms, in the form of phase-amplitude coupling (PAC), is proposed to enable the coordination of neural oscillatory activity required for cognitive processing. PAC has been identified in the neocortex and mesial temporal regions, varying according to the cognitive task being performed and also at rest. PAC has also been observed in the anterior thalamic nucleus (ATN) during memory processing. The thalamus is active during the resting state and has been proposed to be involved in switching between task-free cognitive states such as rest, in which attention is internally-focused, and externally-focused cognitive states, in which an individual engages with environmental stimuli. It is unknown whether PAC is an ongoing phenomenon during the resting state in the ATN, which is modulated during different cognitive states, or whether it only arises during the performance of specific tasks. We analyzed electrophysiological recordings of ATN activity during rest from seven patients who received thalamic electrodes implanted for treatment of pharmacoresistant focal epilepsy. PAC was identified between theta (4-6 Hz) phase and high frequency band (80-150 Hz) amplitude during rest in all seven patients, which diminished during engagement in tasks involving an external focus of attention. The findings are consistent with the proposal that theta-gamma coupling in the ATN is an ongoing phenomenon, which is modulated by task performance.

20.
Hum Brain Mapp ; 38(8): 4064-4077, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28513104

RESUMO

A salience network (SN) anchored in the anterior insula (AI) and dorsal anterior cingulate cortex (dACC) plays a key role in switching between brain networks during salience detection and attention regulation. Previous fMRI studies have associated expectancy behaviors and SN activation with novelty seeking (NS) and reward dependence (RD) personality traits. To address the question of how functional connectivity (FC) in the SN is modulated by internal (expectancy-related) salience assignment and different personality traits, 68 healthy participants performed a salience expectancy task using functional magnetic resonance imaging, and psychophysiological interaction analysis (PPI) was conducted to determine salience-related connectivity changes during these anticipation periods. Correlation was then evaluated between PPI and personality traits, assessed using the temperament and character inventory of 32 male participants. During high salience expectancy, SN-seed regions showed reduced FC to visual areas and parts of the default mode network, but increased FC to the central executive network. With increasing NS, participants showed significantly increasing disconnection between right AI and middle cingulate cortex when expecting high-salience pictures as compared to low-salience pictures, while increased RD also predicted decreased right dACC and caudate FC for high salience expectancy. Our findings suggest a direct link between personality traits and internal salience processing mediated by differential network integration of the SN. SN activity and coordination may therefore be moderated by novelty seeking and reward dependency personality traits, which are associated with risk of addiction. Hum Brain Mapp 38:4064-4077, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Antecipação Psicológica/fisiologia , Encéfalo/fisiologia , Comportamento Exploratório/fisiologia , Vias Neurais/fisiologia , Personalidade/fisiologia , Recompensa , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Testes Neuropsicológicos , Fatores Sexuais , Adulto Jovem
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