Browsing by Subject "MOTOR CORTEX"

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  • Ojala, Juhani; Vanhanen, Jukka; Harno, Hanna; Lioumis, Pantelis; Vaalto, Selja; Kaunisto, Mari A.; Putaala, Jukka; Kangasniemi, Marko; Kirveskari, Erika; Mäkelä, Jyrki P.; Kalso, Eija (2022)
    Objectives Central poststroke pain (CPSP), a neuropathic pain condition, is difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) targeted to the primary motor cortex (M1) can alleviate the condition, but not all patients respond. We aimed to assess a promising alternative rTMS target, the secondary somatosensory cortex (S2), for CPSP treatment. Materials and Methods This prospective, randomized, double-blind, Sham-controlled three-arm crossover trial assessed navigated rTMS (nrTMS) targeted to M1 and S2 (10 sessions, 5050 pulses per session at 10 Hz). Participants were evaluated for pain, depression, anxiety, health-related quality of life, upper limb function, and three plasticity-related gene polymorphisms including Dopamine D2 Receptor (DRD2). We monitored pain intensity and interference before and during stimulations, and at one month. A conditioned pain modulation test was performed using the cold pressor test. This assessed the efficacy of the descending inhibitory system, which may transmit TMS effects in pain control. Results We prescreened 73 patients, screened 29, and included 21, of whom 17 completed the trial. NrTMS targeted to S2 resulted in long-term (from baseline to one-month follow-up) pain intensity reduction of >= 30% in 18% (3/17) of participants. All stimulations showed a short-term effect on pain (17-20% pain relief), with no difference between M1, S2, or Sham stimulations, indicating a strong placebo effect. Only nrTMS targeted to S2 resulted in a significant long-term pain intensity reduction (15% pain relief). The cold pressor test reduced CPSP pain intensity significantly (p = 0.001), indicating functioning descending inhibitory controls. The homozygous DRD2 T/T genotype is associated with the M1 stimulation response. Conclusions S2 is a promising nrTMS target in the treatment of CPSP. The DRD2 T/T genotype might be a biomarker for M1 nrTMS response, but this needs confirmation from a larger study.
  • Kortteenniemi, Aaron; Ortega-Alonso, Alfredo; Javadi, Amir-Homayoun; Tolmunen, Tommi; Ali-Sisto, Toni; Kotilainen, Tuukka; Wikgren, Jan; Karhunen, Leila; Velagapudi, Vidya; Lehto, Soili M. (2020)
    Background Transcranial direct current stimulation (tDCS), a putative treatment for depression, has been proposed to affect peripheral metabolism. Metabolic products from brain tissue may also cross the blood-brain barrier, reflecting the conditions in the brain. However, there are no previous data regarding the effect of tDCS on circulating metabolites. Objective To determine whether five daily sessions of tDCS modulate peripheral metabolites in healthy adult men. Methods This double-blind, randomized controlled trial involved 79 healthy males (aged 20-40 years) divided into two groups, one receiving tDCS (2 mA) and the other sham stimulated. The anode was placed over the left dorsolateral prefrontal cortex and the cathode over the corresponding contralateral area. Venous blood samples were obtained before and after the first stimulation session, and after the fifth stimulation session. Serum levels of 102 metabolites were determined by mass spectrometry. The results were analysed with generalised estimating equations corrected for the family-wise error rate. In addition, we performed power calculations estimating sample sizes necessary for future research. Results TDCS-related variation in serum metabolite levels was extremely small and statistically non-significant. Power calculations indicated that for the observed variation to be deemed significant, samples sizes of up to 11,000 subjects per group would be required, depending on the metabolite of interest. Conclusion Our study found that five sessions of tDCS induced no major effects on peripheral metabolites among healthy men. These observations support the view of tDCS as a safe treatment that does not induce significant changes in the measured peripheral metabolites in healthy male subjects.
  • Pauls, K. Amande M.; Korsun, Olesia; Nenonen, Jukka; Nurminen, Jussi; Liljeström, Mia; Kujala, Jan; Pekkonen, Eero; Renvall, Hanna (2022)
    Exaggerated subthalamic beta oscillatory activity and increased beta range cortico-subthalamic synchrony have crystallized as the electrophysiological hallmarks of Parkinson's disease. Beta oscillatory activity is not tonic but occurs in 'bursts' of transient amplitude increases. In Parkinson's disease, the characteristics of these bursts are altered especially in the basal ganglia. However, beta oscillatory dynamics at the cortical level and how they compare with healthy brain activity is less well studied. We used magnetoencephalography (MEG) to study sensorimotor cortical beta bursting and its modulation by subthalamic deep brain stimulation in Parkinson's disease patients and age-matched healthy controls. We show that the changes in beta bursting amplitude and duration typical of Parkinson's disease can also be observed in the sensorimotor cortex, and that they are modulated by chronic subthalamic deep brain stimulation, which, in turn, is reflected in improved motor function at the behavioural level. In addition to the changes in individual beta bursts, their timing relative to each other was altered in patients compared to controls: bursts were more clustered in untreated Parkinson's disease, occurring in 'bursts of bursts', and re-burst probability was higher for longer compared to shorter bursts. During active deep brain stimulation, the beta bursting in patients resembled healthy controls' data. In summary, both individual bursts' characteristics and burst patterning are affected in Parkinson's disease, and subthalamic deep brain stimulation normalizes some of these changes to resemble healthy controls' beta bursting activity, suggesting a non-invasive biomarker for patient and treatment follow-up.
  • Liljeström, Mia; Kujala, Jan; Stevenson, Claire; Salmelin, Riitta (2015)
  • Rodionov, Andrei; Savolainen, Sarianna; Kirveskari, Erika; Mäkelä, Jyrki P.; Shulga, Anastasia (2020)
    Recovery of lower-limb function after spinal cord injury (SCI) is dependent on the extent of remaining neural transmission in the corticospinal pathway. The aim of this proof-of-concept pilot study was to explore the effects of long-term paired associative stimulation (PAS) on leg muscle strength and walking in people with SCI. Five individuals with traumatic incomplete chronic tetraplegia (>34 months post-injury, motor incomplete, 3 females, mean age 60 years) with no contraindications to transcranial magnetic stimulation (TMS) received PAS to one or both legs for 2 months (28 sessions in total, 5 times a week for the first 2 weeks and 3 times a week thereafter). The participants were evaluated with the Manual Muscle Test (MMT), AIS motor and sensory examination, Modified Asworth Scale (MAS), and the Spinal Cord Independence Measure (SCIM) prior to the intervention, after 1 and 2 months of PAS, and after a 1-month follow-up. The study was registered at (NCT03459885). During the intervention, MMT scores and AIS motor scores increased significantly (p = 0.014 and p = 0.033, respectively). Improvements were stable in follow-up. AIS sensory scores, MAS, and SCIM were not modified significantly. MMT score prior to intervention was a good predictor of changes in walking speed (Radj2 = 0.962). The results of this proof-of-concept pilot study justify a larger trial on the effect of long-term PAS on leg muscle strength and walking in people with chronic incomplete SCI.
  • Lukasik, Karolina M.; Lehtonen, Minna; Salmi, Juha; Meinzer, Marcus; Joutsa, Juho; Laine, Matti (2018)
    The effects of transcranial direct current stimulation (tDCS) on dorsolateral prefrontal cortex functions, such as working memory (WM), have been examined in a number of studies. However, much less is known about the behavioral effects of tDCS over other important WM-related brain regions, such as the ventrolateral prefrontal cortex (VLPFC). In a counterbalanced within-subjects design with 33 young healthy participants, we examined whether online and offline single-session tDCS over VLPFC affects WM updating performance as measured by a digit 3-back task. We compared three conditions: anodal, cathodal and sham. We observed no significant tDCS effects on participants' accuracy or reaction times during or after the stimulation. Neither did we find any differences between anodal and cathodal stimulation. Largely similar results were obtained when comparing subgroups of high- and low-performing participants. Possible reasons for the lack of effects, including individual differences in responsiveness to tDCS, features of montage, task and sample characteristics, and the role of VLPFC in WM, are discussed.
  • Pohjonen, Markus; Savolainen, Sarianna; Arokoski, Jari; Shulga, Anastasia (2021)
    Objectives: Earlier studies have shown how chronic spinal cord injury (SCI) patients have benefitted from paired associative stimulation (PAS), consisting of high-frequency peripheral nerve stimulation (PNS) and high-intensity transcranial magnetic stimulation (TMS). Since high-frequency PNS is poorly characterized, its therapeutic effect without TMS should be evaluated. We tested the effect of PNS combined with motor imagery in chronic SCI patients using the same parameters of PNS as in earlier PAS-based studies that also used TMS. Methods: Five patients with chronic incomplete SCI and tetraplegia received a 6-week treatment of PNS combined with motor imagery to the weaker upper limb. Patients were evaluated with Manual Muscle Testing (MMT), hand function tests (Box and block, grip and pinch strength dynamometry), and spasticity. Results: There was no significant change in hand function tests or spasticity. MMT values improved significantly immediately after the PNS period (0.59 +/- 0.17, p = 0.043) and in the 1-month follow-up visit (0.87 +/- 0.18, p = 0.043). However, improvement of MMT values was weaker than in chronic tetraplegic patients in a corresponding PAS study that used identical PNS stimulation but also included the TMS component omitted here (Tolmacheva et al., 2019a, Clin Neurophysiol Pract). Conclusions: The lack of effect on functional hand tests with the protocol presented here suggests that the synergistic effect of PNS and TMS components is essential for the full therapeutic effect previously observed with PAS intervention. The moderate improvement of the MMT score suggests the possible usefulness of PNS and motor imagery for some of those tetraplegic SCI patients who have contraindications to TMS. Significance: These results add to the understanding of the PAS therapeutic mechanism by highlighting the importance of dual stimulation for achieving the full therapeutic effect of long-term PAS with a high-frequency PNS component. (C) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.
  • Pohjonen, Markus; Nyman, Anna-Lena; Kirveskari, Erika; Arokoski, Jari; Shulga, Anastasia (2022)
    Paired associative stimulation (PAS) with high-frequency peripheral nerve stimulation (PNS), called “high-PAS”, induces motor-evoked potential (MEP) potentiation in healthy subjects and improves muscle activity and independence in incomplete spinal cord injury patients. Data on optimal PNS intensity in PAS are scarce. In a high-PAS protocol, PNS intensity is defined as “minimal intensity required to produce F-responses”. We sought to further refine this definition and to investigate how PNS intensity affects PAS outcome. Two experiments were performed on 10 healthy subjects where MEP amplitude change was measured 0, 30, and 60 min after PAS. In the first experiment, the intensity required to achieve 7/10 persistence of F-responses was used to define PNS intensity level. In the second experiment, we used the intensity required to achieve 1/10 persistence (“baseline”). In addition, we applied this intensity at + 25%, − 25%, and − 50% levels. In the first experiment, PAS did not produce significant MEP potentiation. In the second experiment, PAS produced statistically significant MEP potentiation, with PNS intensity of “baseline” and “baseline − 25%” levels but not at + 25% or − 50% levels. In conclusion, for PAS utilizing high-frequency PNS, the intensity required to achieve 1/10 F-response persistence or the intensity 25% lower produces significant MEP potentiation in healthy subjects.
  • Tolmacheva, Aleksandra; Savolainen, Sarianna; Kirveskari, Erika; Brandstack, Nina; Mäkelä, Jyrki P.; Shulga, Anastasia (2019)
    Objectives Long-term paired associative stimulation (PAS) is a non-invasive combination of transcranial magnetic stimulation and peripheral nerve stimulation and leads to improved hand motor function in individuals with incomplete traumatic tetraplegia. Spinal cord injuries (SCIs) can also be induced by neurological diseases. We tested a similar long-term PAS approach in patients with nontraumatic neurological SCI. Methods In this case series five patients with nontraumatic tetraplegia received PAS to the weaker upper limb 3 to 5 times per week for 6 weeks. Patients were evaluated with manual muscle testing (MMT) before and immediately after therapy and at the 1- and 6-month follow ups. Patients were also evaluated for spasticity, hand mechanical and digital dynamometry, pinch, and Box and Blocks tests. Results All patients had improved MMT values at all post-PAS evaluations. The mean±standard error MMT increase was 1.44±0.37 points (p=0.043) immediately after PAS, 1.57±0.4 points (p=0.043) at the 1-month follow-up, and 1.71±0.47 points (p=0.043) at the 6-month follow up. The pinch, digital dynamometry values, and Box and Blocks test results also improved in all patients. Conclusions Long-term PAS may be a safe and effective treatment for improving hand function in patients with nontraumatic tetraplegia. Significance This is the first report demonstrating the therapeutic potential of PAS for neurological SCI.
  • Mutanen, Tuomas P.; Kukkonen, Matleena; Nieminen, Jaakko O.; Stenroos, Matti; Sarvas, Jukka; Ilmoniemi, Risto J. (2016)
    Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) often suffers from large muscle artifacts. Muscle artifacts can be removed using signal-space projection (SSP), but this canmake the visual interpretation of the remaining EEG data difficult. We suggest to use an additional step after SSP that we call source-informed reconstruction (SIR). SSP-SIR improves substantially the signal quality of artifactual TMS-EEG data, causing minimal distortion in the neuronal signal components. In the SSP-SIR approach, we first project out the muscle artifact using SSP. Utilizing an anatomical model and the remaining signal, we estimate an equivalent source distribution in the brain. Finally, we map the obtained source estimate onto the original signal space, again using anatomical information. This approach restores the neuronal signals in the sensor space and interpolates EEG traces onto the completely rejected channels. The introduced algorithm efficiently suppresses TMS-related muscle artifacts in EEG while retaining well the neuronal EEG topographies and signals. With the presented method, we can remove muscle artifacts from TMS-EEG data and recover the underlying brain responses without compromising the readability of the signals of interest. (C) 2016 Elsevier Inc. All rights reserved.
  • Komulainen, Emma; Glerean, Enrico; Meskanen, Katarina; Heikkila, Roope; Nummenmaa, Lauri; Raij, Tuukka; Lahti, Jari; Jylhä, Pekka; Melartin, Tarja; Isometsa, Erkki; Ekelund, Jesper (2017)
    The link between neurotransmitter-level effects of antidepressants and their clinical effect remain poorly understood. A single dose of mirtazapine decreases limbic responses to fearful faces in healthy subjects, but it is unknown whether this effect applies to complex emotional situations and dynamic connectivity between brain regions. Thirty healthy volunteers listened to spoken emotional narratives during functional magnetic resonance imaging (fMRI). In an open-label design, 15 subjects received 15 mg of mirtazapine two hours prior to fMRI while 15 subjects served as a control group. We assessed the effects of mirtazapine on regional neural responses and dynamic functional connectivity associated with valence and arousal. Mirtazapine attenuated responses to unpleasant events in the right fronto-insular cortex, while modulating responses to arousing events in the core limbic regions and the cortical midline structures (CMS). Mirtazapine decreased responses to unpleasant and arousing events in sensorimotor areas and the anterior CMS implicated in self-referential processing and formation of subjective feelings. Mirtazapine increased functional connectivity associated with positive valence in the CMS and limbic regions. Mirtazapine triggers large-scale changes in regional responses and functional connectivity during naturalistic, emotional stimuli. These span limbic, sensorimotor, and midline brain structures, and may be relevant to the clinical effectiveness of mirtazapine.
  • Serrien, Deborah; Spape, Michiel (2022)
    Space, time and number are key dimensions that underlie how we perceive, identify and act within the environment. They are interconnected in our behaviour and brain. In this study, we examined interdependencies between these dimensions. To this end, left- and right-handed participants performed an object collision task that required space–time processing and arithmetic tests that involved number processing. Handedness of the participants influenced collision detection with left-handers being more accurate than right-handers, which is in line with the premise that hand preference guides individual differences as a result of sensorimotor experiences and distinct interhemispheric integration patterns. The data further showed that successful collision detection was a predictor for arithmetic achievement, at least in right-handers. These findings suggest that handedness plays a mediating role in binding information processing across domains, likely due to selective connectivity properties within the sensorimotor system that is guided by hemispheric lateralisation patterns.
  • Nurmi, Timo; Jaatela, Julia; Vallinoja, Jaakko; Mäenpää, Helena; Piitulainen, Harri (2021)
    Cerebral palsy (CP) is a motor disorder where the motor defects are partly due to impaired proprioception. We studied cortical proprioceptive responses and sensorimotor performance in adolescents with CP and their typically-developed (TD) peers. Passive joint movements were used to stimulate proprioceptors during functional magnetic resonance imaging (fMRI) session to quantify the proprioceptive responses whose associations to behavioral sensorimotor performance were also examined. Twenty-three TD (15 females, age: mean +/- standard deviation 14.2 +/- 2.4 years) and 18 CP (12 females, age: mean +/- standard deviation, 13.8 +/- 2.3 years; 12 hemiplegic, 6 diplegic) participants were included in this study. Participants' index fingers and ankles were separately stimulated at 3 Hz and 1 Hz respectively with pneumatic movement actuators. Regions-of-interest were used to quantify BOLD-responses from the primary sensorimotor (SM1) and secondary (SII) somatosensory cortices and were compared across the groups. Associations between responses strengths and sensorimotor performance measures were also examined. Proprioceptive responses were stronger for the individuals with CP compared to their TD peers in SM1 (p < 0.001) and SII (p < 0.05) cortices contralateral to their more affected index finger. The ankle responses yielded no significant differences between the groups. The CP group had worse sensorimotor performance for hands and feet (p < 0.001). Stronger responses to finger stimulation in the dominant SM1 (p < 0.001) and both dominant and non-dominant SII (p < 0.01, p < 0.001) cortices were associated with the worse hand sensorimotor performance across all participants. Worse hand function was associated with stronger cortical activation to the proprioceptive stimulation. This association was evident both in adolescents with CP and their typically-developed controls, thus it likely reflects both clinical factors and normal variation in the sensorimotor function. The specific mechanisms need to be clarified in future studies.
  • Vainio, Lari; Rantala, Aleksi; Tiainen, Mikko; Tiippana, Kaisa; Komeilipoor, Naeem; Vainio, Martti (2017)
    Previous research has shown that precision and power grip performance is consistently influenced by simultaneous articulation. For example, power grip responses are performed relatively fast with the open-back vowel [a], whereas precision grip responses are performed relatively fast with the close-front vowel [i]. In the present study, the participants were presented with a picture of a hand shaped to the precision or power grip. They were required to pronounce speech sounds according to the front/above perspective of the hand. The results showed that not only the grip performance is affected by simultaneously pronouncing the speech sound but also the production of speech sound can be affected by viewing an image of a grip. The precision grip stimulus triggered relatively rapid production of the front-close vowel [i]. In contrast, the effect related to the power grip stimulus was mostly linked to the vertical dimension of the pronounced vowel since this stimulus triggered relatively rapid production of the back-open vowel [a] and back-mid-open vowel [o] while production of the back-close vowel [u] was not influenced by it. The fact that production of the dorsal consonant [k] or coronal consonant [t] were not influenced by these stimuli suggests that the effect was not associated with a relative front-back tongue shape of the articulation in the absence of changes in any vertical articulatory components. These findings provide evidence for an intimate interaction between certain articulatory gestures and grip types, suggesting that an overlapping visuomotor network operates for planning articulatory gestures and grasp actions.
  • Ylinen, Artturi; Wikman, Patrik; Leminen, Miika; Alho, Kimmo (2022)
    Selective listening to speech depends on widespread networks of the brain, but how the involvement of different neural systems in speech processing is affected by factors such as the task performed by a listener and speech intelligibility remains poorly understood. We used functional magnetic resonance imaging to systematically examine the effects that performing different tasks has on neural activations during selective attention to continuous audiovisual speech in the presence of task-irrelevant speech. Participants viewed audiovisual dialogues and attended either to the semantic or the phonological content of speech, or ignored speech altogether and performed a visual control task. The tasks were factorially combined with good and poor auditory and visual speech qualities. Selective attention to speech engaged superior temporal regions and the left inferior frontal gyrus regardless of the task. Frontoparietal regions implicated in selective auditory attention to simple sounds (e. g., tones, syllables) were not engaged by the semantic task, suggesting that this network may not be not as crucial when attending to continuous speech. The medial orbitofrontal cortex, implicated in social cognition, was most activated by the semantic task. Activity levels during the phonological task in the left prefrontal, premotor, and secondary somatosensory regions had a distinct temporal profile as well as the highest overall activity, possibly relating to the role of the dorsal speech processing stream in sub-lexical processing. Our results demonstrate that the task type influences neural activations during selective attention to speech, and emphasize the importance of ecologically valid experimental designs.
  • Schefold, Joerg C.; Bäcklund, Minna; Ala-Kokko, Tero; Zuercher, Patrick; Mukherjee, Rajat; Mistry, Satish; Mayer, Stephan A.; Dziewas, Rainer; Bakker, Jan; Jakob, Stephan M. (2020)
    Introduction: Post-extubation dysphagia is commonly observed in ICU patients and associated with increased aspiration rates, delayed resumption of oral intake/ malnutrition, prolonged ICU and hospital length of stay, decreased quality of life, and increased mortality. Conventional therapeutic approaches are limited. Pharyngeal electrical stimulation (PES) was previously shown to improve swallowing function and airway safety in severely dysphagic tracheostomised stroke patients. Methods: In a multi-center, single-blind, 1:1 randomized controlled study, up to 400 (360 evaluable) mixed emergency adult ICU patients with recent extubation following mechanical ventilation and confirmed oropharyngeal dysphagia will be enrolled at investigational academic ICUs. Primary objective is to evaluate the effectiveness of PES in reducing the severity of unsafe swallows. Patients will be randomized to receive PES (or sham) treatment on 3 consecutive days in addition to best supportive care. Primary endpoint is a composite of 2 endpoints with hierarchy based on clinical priorities: 1) Swallowing safety based on worst penetration-aspiration-scale (PAS) score in series of up to 4 boli using thin stimuli approx. From 24 to 60 hours after treatment completion, converted to a trichotomized ordinal response of safe (PAS 1-3), penetration (PAS 4-5), or aspiration (PAS 6-8). 2) Dysphagia Outcome and Severity Scale scores determined by bedside assessment 7 +/- 1 days after treatment completion. Oropharyngeal dysphagia will be assessed by Fiberoptic Endoscopic Evaluation of Swallowing by blinded study staff. Patients will be followed-up for a maximum of 90 days. Discussion: This study will evaluate the effects of PES on swallowing safety in critically ill ICU patients post mechanical ventilation with oropharyngeal dysphagia.
  • Souza, Victor Hugo; Nieminen, Jaakko O.; Tugin, Sergei; Koponen, Lari M.; Baffa, Oswaldo; Ilmoniemi, Risto J. (2022)
    Background: Transcranial magnetic stimulation (TMS) coils allow only a slow, mechanical adjustment of the stimulating electric field (E-field) orientation in the cerebral tissue. Fast E-field control is needed to synchronize the stimulation with the ongoing brain activity. Also, empirical models that fully describe the relationship between evoked responses and the stimulus orientation and intensity are still missing. Objective: We aimed to (1) develop a TMS transducer for manipulating the E-field orientation electronically with high accuracy at the neuronally meaningful millisecond-level time scale and (2) devise and validate a physiologically based model describing the orientation selectivity of neuronal excitability. Methods: We designed and manufactured a two-coil TMS transducer. The coil windings were computed with a minimum-energy optimization procedure, and the transducer was controlled with our custommade electronics. The electronic E-field control was verified with a TMS characterizer. The motor evoked potential amplitude and latency of a hand muscle were mapped in 3 degrees steps of the stimulus orientation in 16 healthy subjects for three stimulation intensities. We fitted a logistic model to the motor response amplitude. Results: The two-coil TMS transducer allows one to manipulate the pulse orientation accurately without manual coil movement. The motor response amplitude followed a logistic function of the stimulus orientation; this dependency was strongly affected by the stimulus intensity. Conclusion: The developed electronic control of the E-field orientation allows exploring new stimulation paradigms and probing neuronal mechanisms. The presented model helps to disentangle the neuronal mechanisms of brain function and guide future non-invasive stimulation protocols. (C) 2022 The Authors. Published by Elsevier Inc.