Publications by authors named "Pavel Hok"

26 Publications

  • Page 1 of 1

Cortical somatosensory processing after botulinum toxin therapy in post-stroke spasticity.

Medicine (Baltimore) 2021 Jun;100(25):e26356

Department of Neurology, Palacký University Olomouc and University Hospital Olomouc.

Abstract: In dystonic and spastic movement disorders, abnormalities of motor control and somatosensory processing as well as cortical modulations associated with clinical improvement after botulinum toxin A (BoNT-A) treatment have been reported, but electrophysiological evidence remains controversial. In the present observational study, we aimed to uncover central correlates of post-stroke spasticity (PSS) and BoNT-A-related changes in the sensorimotor cortex by investigating the cortical components of somatosensory evoked potentials (SEPs). Thirty-one chronic stroke patients with PSS of the upper limb were treated with BoNT-A application into the affected muscles and physiotherapy. Clinical and electrophysiological evaluations were performed just before BoNT-A application (W0), then 4 weeks (W4) and 11 weeks (W11) later. PSS was evaluated with the modified Ashworth scale (MAS). Median nerve SEPs were examined in both upper limbs with subsequent statistical analysis of the peak-to-peak amplitudes of precentral P22/N30 and postcentral N20/P23 components. At baseline (W0), postcentral SEPs were significantly lower over the affected cortex. At follow up, cortical SEPs did not show any significant changes attributable to BoNT-A and/or physiotherapy, despite clear clinical improvement. Our results imply that conventional SEPs are of limited value in evaluating cortical changes after BoNT-A treatment and further studies are needed to elucidate its central actions.
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http://dx.doi.org/10.1097/MD.0000000000026356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238289PMC
June 2021

Botulinum toxin injection changes resting state cerebellar connectivity in cervical dystonia.

Sci Rep 2021 Apr 15;11(1):8322. Epub 2021 Apr 15.

Department of Neurology, University Hospital Olomouc, I. P. Pavlova 6, 77900, Olomouc, Czech Republic.

In cervical dystonia, functional MRI (fMRI) evidence indicates changes in several resting state networks, which revert in part following the botulinum neurotoxin A (BoNT) therapy. Recently, the involvement of the cerebellum in dystonia has gained attention. The aim of our study was to compare connectivity between cerebellar subdivisions and the rest of the brain before and after BoNT treatment. Seventeen patients with cervical dystonia indicated for treatment with BoNT were enrolled (14 female, aged 50.2 ± 8.5 years, range 38-63 years). Clinical and fMRI examinations were carried out before and 4 weeks after BoNT injection. Clinical severity was evaluated using TWSTRS. Functional MRI data were acquired on a 1.5 T scanner during 8 min rest. Seed-based functional connectivity analysis was performed using data extracted from atlas-defined cerebellar areas in both datasets. Clinical scores demonstrated satisfactory BoNT effect. After treatment, connectivity decreased between the vermis lobule VIIIa and the left dorsal mesial frontal cortex. Positive correlations between the connectivity differences and the clinical improvement were detected for the right lobule VI, right crus II, vermis VIIIb and the right lobule IX. Our data provide evidence for modulation of cerebello-cortical connectivity resulting from successful treatment by botulinum neurotoxin.
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http://dx.doi.org/10.1038/s41598-021-87088-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050264PMC
April 2021

Multiparametric Quantitative MRI in Neurological Diseases.

Front Neurol 2021 8;12:640239. Epub 2021 Mar 8.

Department of Neurology, Goethe University, Frankfurt, Germany.

Magnetic resonance imaging (MRI) is the gold standard imaging technique for diagnosis and monitoring of many neurological diseases. However, the application of conventional MRI in clinical routine is mainly limited to the visual detection of macroscopic tissue pathology since mixed tissue contrasts depending on hardware and protocol parameters hamper its application for the assessment of subtle or diffuse impairment of the structural tissue integrity. Multiparametric quantitative (q)MRI determines tissue parameters quantitatively, enabling the detection of microstructural processes related to tissue remodeling in aging and neurological diseases. In contrast to measuring tissue atrophy via structural imaging, multiparametric qMRI allows for investigating biologically distinct microstructural processes, which precede changes of the tissue volume. This facilitates a more comprehensive characterization of tissue alterations by revealing early impairment of the microstructural integrity and specific disease-related patterns. So far, qMRI techniques have been employed in a wide range of neurological diseases, including in particular conditions with inflammatory, cerebrovascular and neurodegenerative pathology. Numerous studies suggest that qMRI might add valuable information, including the detection of microstructural tissue damage in areas appearing normal on conventional MRI and unveiling the microstructural correlates of clinical manifestations. This review will give an overview of current qMRI techniques, the most relevant tissue parameters and potential applications in neurological diseases, such as early (differential) diagnosis, monitoring of disease progression, and evaluating effects of therapeutic interventions.
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http://dx.doi.org/10.3389/fneur.2021.640239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982527PMC
March 2021

The Central Effects of Botulinum Toxin in Dystonia and Spasticity.

Toxins (Basel) 2021 02 17;13(2). Epub 2021 Feb 17.

Department of Neurology, Faculty of Medicine and Dentistry, University Hospital Olomouc, Palacký University Olomouc, 779 00 Olomouc, Czech Republic.

In dystonic and spastic movement disorders, however different in their pathophysiological mechanisms, a similar impairment of sensorimotor control with special emphasis on afferentation is assumed. Peripheral intervention on afferent inputs evokes plastic changes within the central sensorimotor system. Intramuscular application of botulinum toxin type A (BoNT-A) is a standard evidence-based treatment for both conditions. Apart from its peripheral action on muscle spindles, a growing body of evidence suggests that BoNT-A effects could also be mediated by changes at the central level including cerebral cortex. We review recent studies employing electrophysiology and neuroimaging to investigate how intramuscular application of BoNT-A influences cortical reorganization. Based on such data, BoNT-A becomes gradually accepted as a promising tool to correct the maladaptive plastic changes within the sensorimotor cortex. In summary, electrophysiology and especially neuroimaging studies with BoNT-A further our understanding of pathophysiology underlying dystonic and spastic movement disorders and may consequently help develop novel treatment strategies based on neural plasticity.
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http://dx.doi.org/10.3390/toxins13020155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922085PMC
February 2021

Very late complications of oncotherapy in glioblastoma patients: A case series.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2021 Feb 22. Epub 2021 Feb 22.

Department of Pathology and Laboratory of Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic.

Background: Stroke-like syndrome is defined as a rare, delayed complication of brain oncotherapy. Cases with more favorable brain cancer diagnoses and longer life expectancy have been previously reported, but here we present, for the first time, three long-term survivors of glioblastoma with stroke-like syndromes.

Methods And Results: Three young or middle-aged patients underwent tumor resection and chemoradiotherapy. They received regular clinical and imaging follow-up with stable neurological status and no signs of tumor recurrence. They exhibited varied signs and symptoms (motor and sensory deficits, aphasia, memory and cognitive disorders, seizures, and headache) accompanied by imaging abnormalities. Stroke-like syndromes developed within 2-5 days and resolved in 2-6 weeks. Diffusion-weighted MRI and T2 brain perfusion abnormalities were demonstrated in all patients. In addition, there was focal T1 MRI contrast enhancement due to blood-brain barrier disruption. In addition to tumor recurrence, classic stroke, encephalitis, metabolic and mitochondrial disorders, and post-seizure swelling should be excluded. The imaging indicated intensive MRI scanning and symptomatic medication (steroids supplemented by antiepileptics, vasoactive agents, etc.) for judicious management. With respect to the course, an invasive procedure was still considered an option.

Conclusion: All stroke-like syndromes are diagnoses of exclusion. To avoid misinterpretation of imaging findings as glioblastoma recurrence and avert recall oncotherapy or redundant interventions, better understanding of delayed complications of brain tumor therapy is crucial.
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http://dx.doi.org/10.5507/bp.2021.012DOI Listing
February 2021

Contemporary clinical neurophysiology applications in dystonia.

J Neural Transm (Vienna) 2021 04 16;128(4):509-519. Epub 2021 Feb 16.

1st Department of Neurology, Masaryk University Medical School and St. Anne University Hospital, Brno, Czech Republic.

The complex phenomenological understanding of dystonia has transcended from the clinics to genetics, imaging and neurophysiology. One way in which electrophysiology will impact into the clinics are cases wherein a dystonic clinical presentation may not be typical or a "forme fruste" of the disorder. Indeed, the physiological imprints of dystonia are present regardless of its clinical manifestation. Underpinnings in the understanding of dystonia span from the peripheral, segmental and suprasegmental levels to the cortex, and various electrophysiological tests have been applied in the course of time to elucidate the origin of dystonia pathophysiology. While loss of inhibition remains to be the key finding in this regard, intricacies and variabilities exist, thus leading to a notion that perhaps dystonia should best be gleaned as network disorder. Interestingly, the complex process has now spanned towards the understanding in terms of networks related to the cerebellar circuitry and the neuroplasticity. What is evolving towards a better and cohesive view will be neurophysiology attributes combined with structural dynamic imaging. Such a sound approach will significantly lead to better therapeutic modalities in the future.
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http://dx.doi.org/10.1007/s00702-021-02310-6DOI Listing
April 2021

[Aphasia associated with lacunar infarctions].

Nervenarzt 2021 Aug 16;92(8):802-808. Epub 2021 Feb 16.

Klinik für Neurologie, Goethe-Universität Frankfurt, Schleusenweg 2-16, 60528, Frankfurt, Deutschland.

Background: Typical lacunar syndromes do not include aphasia but aphasia has been reported in rare atypical lacunar syndromes.

Objective: Description of the phenomenology and of affected fiber tracts.

Material And Methods: Case series of three patients with lacunar stroke as evidenced by magnetic resonance imaging. Identification of affected fiber tracts via fiber tracking from coregistered lesion sites in brains of two healthy participants.

Results: The lacunar strokes that produced aphasia were located in the very lateral territory of perforating branches of the middle cerebral artery and extended along the external capsule into its most rostrodorsal aspect. Even though the cortex, thalamus and most parts of the basal ganglia were unaffected, patients exhibited a mild to moderate nonfluent aphasia with syntactic deficits. Fiber tracking revealed that in contrast to the nonaphasic control patient with a neighboring lacunar stroke, the aphasic patient strokes involved particularly fibers of the left arcuate fascicle as well as fibers of the frontostriatal and frontal aslant tracts.

Conclusion: Left lateral lacunar stroke can cause clinically relevant aphasia through disruption of speech-relevant fiber tracts.
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http://dx.doi.org/10.1007/s00115-021-01072-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342334PMC
August 2021

Modulation of the human sensorimotor system by afferent somatosensory input: evidence from experimental pressure stimulation and physiotherapy.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2020 Dec 13;164(4):371-379. Epub 2020 Nov 13.

Department of Neurology, Faculty of Medicine and Dentistry, Palacky University Olomouc, and University Hospital Olomouc, Czech Republic.

Peripheral afferent input is critical for human motor control and motor learning. Both skin and deep muscle mechanoreceptors can affect motor behaviour when stimulated. Whereas some modalities such as vibration have been employed for decades to alter cutaneous and proprioceptive input, both experimentally and therapeutically, the central effects of mechanical pressure stimulation have been studied less frequently. This discrepancy is especially striking when considering the limited knowledge of the neurobiological principles of frequently used physiotherapeutic techniques that utilise peripheral stimulation, such as reflex locomotion therapy. Our review of the available literature pertaining to pressure stimulation focused on transcranial magnetic stimulation (TMS) and neuroimaging studies, including both experimental studies in healthy subjects and clinical trials. Our search revealed a limited number of neuroimaging papers related to peripheral pressure stimulation and no evidence of effects on cortical excitability. In general, the majority of imaging studies agreed on the significant involvement of cortical motor areas during the processing of pressure stimulation. Recent data also point to the specific role of subcortical structures, such as putamen or brainstem reticular formation. A thorough comparison of the published results often demonstrated, however, major inconsistencies which are thought to be due to variable stimulation protocols and statistical power. In conclusion, localised peripheral sustained pressure is a potent stimulus inducing changes in cortical activation within sensory and motor areas. Despite historical evidence for modulation of motor behaviour, no direct link can be established based on available fMRI and electrophysiological data. We highlight the limited amount of research devoted to this stimulus modality, emphasise current knowledge gaps, present recent developments in the field and accentuate evidence awaiting replication or confirmation in future neuroimaging and electrophysiological studies.
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http://dx.doi.org/10.5507/bp.2020.052DOI Listing
December 2020

Changes in oxygen saturation and the retinal nerve fibre layer in patients with optic neuritis associated with multiple sclerosis in a 6-month follow-up.

Acta Ophthalmol 2020 Dec 12;98(8):841-847. Epub 2020 May 12.

Department of Ophthalmology, Faculty of Medicine and Dentistry, University Hospital, Palacký University Olomouc, Olomouc, Czech Republic.

Purpose: Optic neuritis (ON) is an inflammatory demyelinating disorder of the optic nerve, which can be the first manifestation of multiple sclerosis (MS). The main goal was to assess changes in the retinal nerve fibre layer (RNFL) and in retinal oxygen saturation [arterial (AS), venous (VS) and arterio-venous (A-V) difference] in the affected and unaffected eye.

Methods: Fifty patients with ON due to MS within 3 months of onset of symptoms were enrolled (17 males, mean age 35.3). All patients were examined at baseline (V1) and after 6 months (V2) using optical coherence tomography (OCT) to get RNFL values; automatic retinal oximetry to obtain saturation values; and ultrasound to exclude arterial stenosis, and orbital colour Doppler imaging was performed in the ophthalmic artery.

Results: At V1, AS was significantly increased in affected eye compared to unaffected eye (99.5% versus 98.0%, p = 0.03). Significant decrease in A-V difference from baseline was detected in both eyes for ON eye: 32.0% versus 29.0%, p = 0.004; for fellow eye: 31.4% versus 30.0%, p = 0.04. We did not observe any changes in retinal vessel diameter. There were no changes observed in blood flow in ophthalmic artery. At V1, there were no significant differences in RNFL, and significant loss of RNFL was confirmed in the affected eye at V2 (95 μm versus 86 μm, p = 0.0002) and in comparison with the fellow eye (86 μm versus 94 μm, p = 0.0002). There were no correlations between RNFL and saturation values at V1, although at V2, there was a negative correlation between the RNFL and AS (Spearman's rho = -0.480, p = 0.003) and between the RNFL and VS (rho = -0.620, p = 0.00007).

Conclusion: Retinal oximetry is altered in both eyes in MS patients with unilateral ON. During the course of the disease, the retinal oxygen consumption decreases to a different degree in each eye and this change is not completely followed by changes in the RNFL thickness, suggesting either sub-clinical ON or systemic effects in the clinically unaffected eye. Since this is the first and initial longitudinal evaluation of the saturation changes in MS patients, the clinical value of these findings needs to be deeper evaluated in the future studies.
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http://dx.doi.org/10.1111/aos.14463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754403PMC
December 2020

Multimodal Quantitative MRI Reveals No Evidence for Tissue Pathology in Idiopathic Cervical Dystonia.

Front Neurol 2019 27;10:914. Epub 2019 Aug 27.

Department of Neurology, Goethe University, Frankfurt, Germany.

While in symptomatic forms of dystonia cerebral pathology is by definition present, it is unclear so far whether disease is associated with microstructural cerebral changes in idiopathic dystonia. Previous quantitative MRI (qMRI) studies assessing cerebral tissue composition in idiopathic dystonia revealed conflicting results. Using multimodal qMRI, the presented study aimed to investigate alterations in different cerebral microstructural compartments associated with idiopathic cervical dystonia . Mapping of T, T, , and proton density (PD) was performed in 17 patients with idiopathic cervical dystonia and 29 matched healthy control subjects. Statistical comparisons of the parametric maps between groups were conducted for various regions of interest (ROI), including major basal ganglia nuclei, the thalamus, white matter, and the cerebellum, and voxel-wise for the whole brain. Neither whole brain voxel-wise statistics nor ROI-based analyses revealed significant group differences for any qMRI parameter under investigation. The negative findings of this qMRI study argue against the presence of overt microstructural tissue change in patients with idiopathic cervical dystonia. The results seem to support a common view that idiopathic cervical dystonia might primarily resemble a functional network disease.
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http://dx.doi.org/10.3389/fneur.2019.00914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719627PMC
August 2019

Differential Effects of Sustained Manual Pressure Stimulation According to Site of Action.

Front Neurosci 2019 17;13:722. Epub 2019 Jul 17.

Department of Neurology, University Hospital Olomouc, Olomouc, Czechia.

Sustained pressure stimulation of the body surface has been used in several physiotherapeutic techniques, such as reflex locomotion therapy. Clinical observations of global motor responses and subsequent motor behavioral changes after stimulation in certain sites suggest modulation of central sensorimotor control, however, the neuroanatomical correlates remain undescribed. We hypothesized that different body sites would specifically influence the sensorimotor system during the stimulation. We tested the hypothesis using functional magnetic resonance imaging (fMRI) in thirty healthy volunteers (mean age 24.2) scanned twice during intermittent manual pressure stimulation, once at the right lateral heel according to reflex locomotion therapy, and once at the right lateral ankle (control site). A flexible modeling approach with finite impulse response basis functions was employed since non-canonical hemodynamic response was expected. Subsequently, a clustering algorithm was used to separate areas with differential timecourses. Stimulation at both sites induced responses throughout the sensorimotor system that could be mostly separated into two anti-correlated subsystems with transient positive or negative signal change and rapid adaptation, although in heel stimulation, insulo-opercular cortices and pons showed sustained activation. In direct voxel-wise comparison, heel stimulation was associated with significantly higher activation levels in the contralateral primary motor cortex and decreased activation in the posterior parietal cortex. Thus, we demonstrate that the manual pressure stimulation affects multiple brain structures involved in motor control and the choice of stimulation site impacts the shape and amplitude of the blood oxygenation level-dependent response. We further discuss the relationship between the affected structures and behavioral changes after reflex locomotion therapy.
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http://dx.doi.org/10.3389/fnins.2019.00722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650750PMC
July 2019

Low-Frequency Oscillations Code Speech during Verbal Working Memory.

J Neurosci 2019 08 13;39(33):6498-6512. Epub 2019 Jun 13.

Department of Neurology, Goethe University, 60528 Frankfurt, Germany,

The way the human brain represents speech in memory is still unknown. An obvious characteristic of speech is its evolvement over time. During speech processing, neural oscillations are modulated by the temporal properties of the acoustic speech signal, but also acquired knowledge on the temporal structure of language influences speech perception-related brain activity. This suggests that speech could be represented in the temporal domain, a form of representation that the brain also uses to encode autobiographic memories. Empirical evidence for such a memory code is lacking. We investigated the nature of speech memory representations using direct cortical recordings in the left perisylvian cortex during delayed sentence reproduction in female and male patients undergoing awake tumor surgery. Our results reveal that the brain endogenously represents speech in the temporal domain. Temporal pattern similarity analyses revealed that the phase of frontotemporal low-frequency oscillations, primarily in the beta range, represents sentence identity in working memory. The positive relationship between beta power during working memory and task performance suggests that working memory representations benefit from increased phase separation. Memory is an endogenous source of information based on experience. While neural oscillations encode autobiographic memories in the temporal domain, little is known on their contribution to memory representations of human speech. Our electrocortical recordings in participants who maintain sentences in memory identify the phase of left frontotemporal beta oscillations as the most prominent information carrier of sentence identity. These observations provide evidence for a theoretical model on speech memory representations and explain why interfering with beta oscillations in the left inferior frontal cortex diminishes verbal working memory capacity. The lack of sentence identity coding at the syllabic rate suggests that sentences are represented in memory in a more abstract form compared with speech coding during speech perception and production.
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http://dx.doi.org/10.1523/JNEUROSCI.0018-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697399PMC
August 2019

Botulinum Toxin Modulates Posterior Parietal Cortex Activation in Post-stroke Spasticity of the Upper Limb.

Front Neurol 2019 9;10:495. Epub 2019 May 9.

Department of Neurology, Palacký University and University Hospital, Olomouc, Czechia.

Post-stroke spasticity (PSS) is effectively treated with intramuscular botulinum toxin type A (BoNT-A), although the clinical improvement is likely mediated by changes at the central nervous system level. Using functional magnetic resonance imaging (fMRI) of the brain, this study aims to confirm and locate BoNT-A-related changes during motor imagery with the impaired hand in severe PSS. Temporary alterations in primary and secondary sensorimotor representation of the impaired upper limb were expected. Thirty chronic stroke patients with upper limb PSS undergoing comprehensive treatment including physiotherapy and indicated for BoNT treatment were investigated. A change in PSS of the upper limb was assessed with the modified Ashworth scale (MAS). fMRI and clinical assessments were performed before (W0) and 4 weeks (W4) and 11 weeks (W11) after BoNT-A application. fMRI data were acquired using 1.5-Tesla scanners during imagery of finger-thumb opposition sequences with the impaired hand. At the group level, we separately modeled (1) average activation at each time point with the MAS score and age at W0 as covariates; and (2) within-subject effect of BoNT-A and the effect of time since W0 as independent variables. Comprehensive treatment of PSS with BoNT-A significantly decreased PSS of the upper limb with a maximal effect at W4. Task-related fMRI prior to treatment (W0) showed extensive activation of bilateral frontoparietal sensorimotor cortical areas, bilateral cerebellum, and contralesional basal ganglia and thalamus. After BoNT-A application (W4), the activation extent decreased globally, mostly in the bilateral parietal cortices and cerebellum, but returned close to baseline at W11. The intra-subject contrast revealed a significant BoNT-A effect, manifesting as a transient decrease in the activation of the ipsilesional intraparietal sulcus and superior parietal lobule. We demonstrate that BoNT-A treatment of PSS of the upper limb is associated with transient changes in the ipsilesional posterior parietal cortex, possibly resulting from temporarily altered sensorimotor upper limb representations.
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http://dx.doi.org/10.3389/fneur.2019.00495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521800PMC
May 2019

Changes in sensorimotor network activation after botulinum toxin type A injections in patients with cervical dystonia: a functional MRI study.

Exp Brain Res 2018 Oct 3;236(10):2627-2637. Epub 2018 Jul 3.

Department of Neurology, University Hospital and Faculty of Medicine and Dentistry of Palacký University, I. P. Pavlova 6, 775 20, Olomouc, Czech Republic.

Botulinum toxin type A (BoNT) is considered an effective therapeutic option in cervical dystonia (CD). The pathophysiology of CD and other focal dystonias has not yet been fully explained. Results from neurophysiological and imaging studies suggest a significant involvement of the basal ganglia and thalamus, and functional abnormalities in premotor and primary sensorimotor cortical areas are considered a crucial factor in the development of focal dystonias. Twelve BoNT-naïve patients with CD were examined with functional MRI during a skilled hand motor task; the examination was repeated 4 weeks after the first BoNT injection to the dystonic neck muscles. Twelve age- and gender-matched healthy controls were examined using the same functional MRI paradigm without BoNT injection. In BoNT-naïve patients with CD, BoNT treatment was associated with a significant increase of activation in finger movement-induced fMRI activation of several brain areas, especially in the bilateral primary and secondary somatosensory cortex, bilateral superior and inferior parietal lobule, bilateral SMA and premotor cortex, predominantly contralateral primary motor cortex, bilateral anterior cingulate cortex, ipsilateral thalamus, insula, putamen, and in the central part of cerebellum, close to the vermis. The results of the study support observations that the BoNT effect may have a correlate in the central nervous system level, and this effect may not be limited to cortical and subcortical representations of the treated muscles. The results show that abnormalities in sensorimotor activation extend beyond circuits controlling the affected body parts in CD even the first BoNT injection is associated with changes in sensorimotor activation. The differences in activation between patients with CD after treatment and healthy controls at baseline were no longer present.
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http://dx.doi.org/10.1007/s00221-018-5322-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153868PMC
October 2018

The effects of sustained manual pressure stimulation according to Vojta Therapy on heart rate variability.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2018 Sep 23;162(3):206-211. Epub 2018 May 23.

Department of Neurology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic.

Background: The physiotherapeutic technique of Vojta reflex locomotion is often accompanied by various autonomic activity changes and unpleasant sensations. It is unknown whether these effects are specific to Vojta Therapy. Therefore, the aim of this study was to compare changes in cardiac autonomic control after Vojta reflex locomotion stimulation and after an appropriate sham stimulation.

Methods: A total of 28 young healthy adults (20.4 - 25.7 years) were enrolled in this single-blind randomized cross-over study. Participants underwent two modes of 20-minute sustained manual pressure stimulation on the surface of the foot on two separate visits. One mode used manual pressure on the lateral heel, i.e., in a zone employed in the Vojta Therapy (active stimulation). The other mode used pressure on the lateral ankle (control), in an area not included among the active zones used by Vojta Therapy and whose activation does not evoke manifestations of reflex locomotion. Autonomic nervous system activity was evaluated using spectral analysis of heart rate variability before and after the intervention.

Results: The active stimulation was perceived as more unpleasant than the control stimulation. Heart rate variability parameters demonstrated almost identical autonomic responses after both stimulation types, showing either modest increase in parasympathetic activity, or increased heart rate variability with similar contribution of parasympathetic and sympathetic activity.

Conclusion: The results demonstrate changes of cardiac autonomic control in both active and control stimulation, without evidence for a significant difference between the two.
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http://dx.doi.org/10.5507/bp.2018.028DOI Listing
September 2018

Optimization of diffusion-weighted single-refocused spin-echo EPI by reducing eddy-current artifacts and shortening the echo time.

MAGMA 2018 Oct 30;31(5):585-597. Epub 2018 Mar 30.

Brain Imaging Center (BIC), Goethe University Frankfurt, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany.

Objective: The purpose of this work was to optimize the acquisition of diffusion-weighted (DW) single-refocused spin-echo (srSE) data without intrinsic eddy-current compensation (ECC) for an improved performance of ECC postprocessing. The rationale is that srSE sequences without ECC may yield shorter echo times (TE) and thus higher signal-to-noise ratios (SNR) than srSE or twice-refocused spin-echo (trSE) schemes with intrinsic ECC.

Materials And Methods: The proposed method employs dummy scans with DW gradients to drive eddy currents into a steady state before data acquisition. Parameters of the ECC postprocessing algorithm were also optimized. Simulations were performed to obtain minimum TE values for the proposed sequence and sequences with intrinsic ECC. Experimentally, the proposed method was compared with standard DW-trSE imaging, both in vitro and in vivo.

Results: Simulations showed substantially shorter TE for the proposed method than for methods with intrinsic ECC when using shortened echo readouts. Data of the proposed method showed a marked increase in SNR. A dummy scan duration of at least 1.5 s improved performance of the ECC postprocessing algorithm.

Conclusion: Changes proposed for the DW-srSE sequence and for the parameter setting of the postprocessing ECC algorithm considerably reduced eddy-current artifacts and provided a higher SNR.
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http://dx.doi.org/10.1007/s10334-018-0684-xDOI Listing
October 2018

Longitudinal brain activation changes related to electrophysiological findings in patients with cervical spondylotic myelopathy before and after spinal cord decompression: an fMRI study.

Acta Neurochir (Wien) 2018 05 25;160(5):923-932. Epub 2018 Mar 25.

Department of Neurology, Palacký University Olomouc and University Hospital Olomouc, I. P. Pavlova, 185/6, 775 20, Olomouc, Czech Republic.

Background: Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction, potentially leading to severe disability. Abnormal cervical spine magnetic resonance imaging (MRI) and motor evoked potentials (MEPs) are independent predictors of disease progression. Abnormal MRI is accompanied by various activation changes in functional brain MRI (fMRI), whereas preoperative and postoperative fMRI adaptations associated with abnormal preoperative MEP remain unknown.

Methods: Twenty patients (9 males, average age 56.6) with evidence of spinal cord compression on MRI and clinical signs of mild CSM were included. Participants were classified according to their preoperative MEP and underwent three brain fMRI examinations: before surgery, 6, and 12 months after surgery while performing repeated extension-flexion of each wrist.

Results: Functional MRI activation was compared between two subsets of patients, with normal and clearly abnormal MEP (right wrist: 8 vs. 8; left wrist: 7 vs. 9). At baseline, abnormal MEPs were associated with hyperactivation in the cerebellum. At the first follow-up, further hyperactivations emerged in the contralateral sensorimotor cortices and persisted for 1 year. In normal baseline MEP, activation mostly decreased in the ipsilateral sensorimotor cortex postoperatively. The ipsilateral sensorimotor activation after 1-year follow-up correlated with baseline MEP.

Conclusions: Abnormal corticospinal MEP findings in cervical spondylotic myelopathy were associated with differences in brain activation, which further increased after spinal cord decompression and did not resolve within 12-month follow-up. In summary, surgery may come too late for those patients with abnormal MEP to recover completely despite their mild clinical signs and symptoms.
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http://dx.doi.org/10.1007/s00701-018-3520-1DOI Listing
May 2018

Freezing of gait is associated with cortical thinning in mesial frontal cortex.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2017 Dec 13;161(4):389-396. Epub 2017 Sep 13.

Department of Neurology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic.

Aims: The relationship between freezing of gait (FOG) and regional brain atrophy has been intensively investigated, but it is still not clearly understood. The study objective was to test whether grey matter (GM) atrophy contributes to FOG in Parkinson's disease (PD) using a surface-based algorithm.

Methods: We investigated 21 patients with PD, 11 with FOG and 10 without FOG. Both groups were assessed using a FOG questionnaire and Hoehn and Yahr staging. High resolution T1-weighted brain images were acquired for each subject using a 1.5T MRI scanner. A surface-based method implemented in FreeSurfer was used to quantify the GM atrophy. A vertex-wise and region of interest (ROI) comparison of spatially normalized subject data using a general linear model and the Wilcoxon rank sum test were to assess significant group differences.

Results: Higher global levels of cortical atrophy were detected in freezers, although this was not statistically significant. The vertex-wise analysis revealed significant local reduction in grey matter thickness in the left supplementary motor area, middle/anterior cingulate cortex, temporal pole and right frontal operculum in freezers at P<0.001, uncorrected. The ROI analysis of average thickness confirmed the regional atrophy in bilateral anterior and posterior cingulate cortices. No significant relative regional cortical atrophy was observed in non-freezers.

Conclusion: FOG was associated with regional cortical atrophy, especially in mesial frontal and cingulate cortices. Our findings provide additional evidence that the development of FOG in patients with PD is associated with local structural cortical changes.
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http://dx.doi.org/10.5507/bp.2017.035DOI Listing
December 2017

Modulation of the sensorimotor system by sustained manual pressure stimulation.

Neuroscience 2017 04 14;348:11-22. Epub 2017 Feb 14.

Department of Neurology, Faculty of Medicine and Dentistry, Palacky University Olomouc, I. P. Pavlova 185/6, Olomouc CZ-77520, Czech Republic; Department of Neurology, University Hospital Olomouc, I. P. Pavlova 185/6, Olomouc CZ-77520, Czech Republic. Electronic address:

In Vojta physiotherapy, also known as reflex locomotion therapy, prolonged peripheral pressure stimulation induces complex generalized involuntary motor responses and modifies subsequent behavior, but its neurobiological basis remains unknown. We hypothesized that the stimulation would induce sensorimotor activation changes in functional magnetic resonance imaging (fMRI) during sequential finger opposition. Thirty healthy volunteers (mean age 24.2) underwent two randomized fMRI sessions involving manual pressure stimulation applied either at the right lateral heel according to Vojta, or at the right lateral ankle (control site). Participants were scanned before and after the stimulation when performing auditory-paced sequential finger opposition with their right hand. Despite an extensive activation decrease following both stimulation paradigms, the stimulation of the heel specifically led to an increase in task-related activation in the predominantly contralateral pontomedullary reticular formation and bilateral posterior cerebellar hemisphere and vermis. Our findings suggest that sustained pressure stimulation of the foot is associated with differential short-term changes in hand motor task-related activation depending on the stimulation. This is the first evidence for brainstem modulation after peripheral pressure stimulation, suggesting that the after-effects of reflex locomotion physiotherapy involve a modulation of the pontomedullary reticular formation.
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http://dx.doi.org/10.1016/j.neuroscience.2017.02.005DOI Listing
April 2017

Longitudinal changes of cortical microstructure in Parkinson's disease assessed with T1 relaxometry.

Neuroimage Clin 2017 21;13:405-414. Epub 2016 Dec 21.

Department of Neurology, Goethe University, Frankfurt/Main, Germany; Brain Imaging Center, Goethe University, Frankfurt/Main, Germany.

Background: Histological evidence suggests that pathology in Parkinson's disease (PD) goes beyond nigrostriatal degeneration and also affects the cerebral cortex. Quantitative MRI (qMRI) techniques allow the assessment of changes in brain tissue composition. However, the development and pattern of disease-related cortical changes have not yet been demonstrated in PD with qMRI methods. The aim of this study was to investigate longitudinal cortical microstructural changes in PD with quantitative T1 relaxometry.

Methods: 13 patients with mild to moderate PD and 20 matched healthy subjects underwent high resolution T1 mapping at two time points with an interval of 6.4 years (healthy subjects: 6.5 years). Data from two healthy subjects had to be excluded due to MRI artifacts. Surface-based analysis of cortical T1 values was performed with the FreeSurfer toolbox.

Results: In PD patients, a widespread decrease of cortical T1 was detected during follow-up which affected large parts of the temporo-parietal and occipital cortices and also frontal areas. In contrast, age-related T1 decrease in the healthy control group was much less pronounced and only found in lateral frontal, parietal and temporal areas. Average cortical T1 values did not differ between the groups at baseline ( = 0.17), but were reduced in patients at follow-up ( = 0.0004). Annualized relative changes of cortical T1 were higher in patients vs. healthy subjects (patients: - 0.72 ± 0.64%/year; healthy subjects: - 0.17 ± 0.41%/year,  = 0.007).

Conclusions: In patients with PD, the development of widespread changes in cortical microstructure was observed as reflected by a reduction of cortical T1. The pattern of T1 decrease in PD patients exceeded the normal T1 decrease as found in physiological aging and showed considerable overlap with the pattern of cortical thinning demonstrated in previous PD studies. Therefore, cortical T1 might be a promising additional imaging marker for future longitudinal PD studies. The biological mechanisms underlying cortical T1 reductions remain to be further elucidated.
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http://dx.doi.org/10.1016/j.nicl.2016.12.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226811PMC
November 2017

Evaluation of brain ageing: a quantitative longitudinal MRI study over 7 years.

Eur Radiol 2017 Apr 5;27(4):1568-1576. Epub 2016 Jul 5.

Department of Neurology, Goethe University, Frankfurt/Main, Germany.

Objectives: T1 relaxometry is a promising tool for the assessment of microstructural changes during brain ageing. Previous cross-sectional studies demonstrated increasing T1 values in white and decreasing T1 values in grey matter over the lifetime. However, these findings have not yet been confirmed on the basis of a longitudinal study. In this longitudinal study over 7 years, T1 relaxometry was used to investigate the dynamics of age-related microstructural changes in older healthy subjects.

Methods: T1 mapping was performed in 17 healthy subjects (range 51-77 years) at baseline and after 7 years. Advanced cortical and white matter segmentation was used to determine mean T1 values in the cortex and white matter.

Results: The analysis revealed a decrease of mean cortical T1 values over 7 years, the rate of T1 reduction being more prominent in subjects with higher age. T1 decreases were predominantly localized in the lateral frontal, parietal and temporal cortex. In contrast, mean white matter T1 values remained stable.

Conclusions: T1 mapping is shown to be sensitive to age-related microstructural changes in healthy ageing subjects in a longitudinal setting. Data of a cohort in late adulthood and the senescence period demonstrate a decrease of cortical T1 values over 7 years, most likely reflecting decreasing water content and increased iron concentrations.

Key Points: • T1 mapping is sensitive to age-related microstructural changes in a longitudinal setting. • T1 decreases were predominantly localized in the lateral frontal, parietal and temporal cortex. • The rate of T1 reduction was more prominent in subjects with higher age. • These changes most likely reflect decreasing cortical water and increasing iron concentrations.
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http://dx.doi.org/10.1007/s00330-016-4485-1DOI Listing
April 2017

Botulinum toxin treatment of freezing of gait in Parkinson's disease patients as reflected in functional magnetic resonance imaging of leg movement.

Neuro Endocrinol Lett 2016 ;37(2):147-53

Department of Neurology, Palacky University Medical School and University Hospital, Olomouc, Czech Republic.

Background: Freezing of gait (FOG) is a common disabling symptom of (in) Parkinson's disease (PD). The mechanism of FOG is (in) not clearly understood. We investigated the clinical effect and changes of the activity of the sensorimotor system using repeated functional MRI (fMRI) before and after application of botulinum toxin in Parkinson's disease patients with FOG.

Methods: We investigated 20 patients with PD, 10 with FOG and 10 without FOG. PD patients with FOG were treated with intramuscular application of botulinum toxin type A into the tensor fasciae latae muscle bilaterally. The clinical effect of treatment was assessed using FOG questionnaire, "Time up and go" test, UPDRS, Hoehn and Yahr staging, Clinical global impression scale. Activation of the sensorimotor system was studied using BOLD fMRI of the whole brain during repetitive abduction - adduction of each leg interleaved with rest. The clinical (in the FOG group) and imaging (in both groups) examination was repeated after a four-week interval.

Results: In the FOG group, the FOG questionnaire has shown a decline of scores after application of botulinum toxin that suggests possible effect of botulinum toxin on freezing of gait. In fMRI results, both groups manifested reduction of the sensorimotor network activated with leg movement, however, the FOG group also showed increased activation in cerebellar vermis and nuclei, in dorsal pons and in medulla after treatment.

Conclusion: Alleviation of the FOG in PD patients by botulinum toxin seems to be reflected in the functional participation of the cerebellum and its projections as seen by fMRI.
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October 2018

Sensorimotor modulation by botulinum toxin A in post-stroke arm spasticity: Passive hand movement.

J Neurol Sci 2016 Mar 11;362:14-20. Epub 2016 Jan 11.

Department of Neurology, Faculty of Medicine and Dentistry, Palacký University and University Hospital, Olomouc, Czech Republic.

Introduction: In post-stroke spasticity, functional imaging may uncover modulation in the central sensorimotor networks associated with botulinum toxin type A (BoNT) therapy. Investigations were performed to localize brain activation changes in stroke patients treated with BoNT for upper limb spasticity using functional magnetic resonance imaging (fMRI).

Methods: Seven ischemic stroke patients (4 females; mean age 58.86) with severe hand paralysis and notable spasticity were studied. Spasticity was scored according to the modified Ashworth scale (MAS). fMRI examination was performed 3 times: before (W0) and 4 (W4) and 11weeks (W11) after BoNT. The whole-brain fMRI data were acquired during paced repetitive passive movements of the plegic hand (flexion/extension at the wrist) alternating with rest. Voxel-by-voxel statistical analysis using the General Linear Model (GLM) implemented in FSL (v6.00)/FEAT yielded group session-wise statistical maps and paired between-session contrasts, thresholded at the corrected cluster-wise significance level of p<0.05.

Results: As expected, BoNT transiently lowered MAS scores at W4. Across all the sessions, fMRI activation of the ipsilesional sensorimotor cortex (M1, S1, and SMA) dominated. At W4, additional clusters transiently emerged bilaterally in the cerebellum, in the contralesional sensorimotor cortex, and in the contralesional occipital cortex. Paired contrasts demonstrated significant differences W4>W0 (bilateral cerebellum and contralesional occipital cortex) and W4>W11 (ipsilesional cerebellum and SMA). The remaining paired contrast (W0>W11) showed activation decreases mainly in the ipsilesional sensorimotor cortex (M1, S1, and SMA).

Conclusions: The present study confirms the feasibility of using passive hand movements to map the cerebral sensorimotor networks in patients with post-stroke arm spasticity and demonstrates that BoNT-induced spasticity relief is associated with changes in task-induced central sensorimotor activation, likely mediated by an altered afferent drive from the spasticity-affected muscles.
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http://dx.doi.org/10.1016/j.jns.2015.12.049DOI Listing
March 2016

Predictors of poor treatment response to additional CBT in real panic disorder patients: The role of DLPF, orbitofrontal cortex, parietal lobule, frontal eye field and amygdala in PD.

Neuro Endocrinol Lett 2015 ;36(3):269-81

Department of Psychiatry, University Hospital Olomouc, Czech Republic.

Objective: Previous functional brain imaging studies have described various and contradictory activation findings in patients with panic disorder (PD). Our study focused on patients with a chronic PD, who were investigated and treated in a conventional manner, which represents the real PD patients in clinical practice.

Methods: Continuing their medication, patients were included in a six-week cognitive-behavioral therapy (CBT) program in the psychiatry department. At the onset of the study, participants underwent clinical evaluation using standard scales and were examined using fMRI while listening to verbal threat-related stimuli contrasted to neutral words. According to the therapeutic outcome, they were subsequently divided into two groups, responders, and nonresponders and the two groups were mutually compared.

Results: In non-responders compared to responders, we found increased pre-treatment activation in dorsolateral prefrontal cortex bilaterally, left orbitofrontal cortex, left frontal eye field, right parietal lobule and left amygdala. In addition, both groups showed negative fMRI BOLD correlation with BAI improvement and positive correlation with CGI improvement across the ROIs. We suggest that DLPFC over-activation may reveal a lack of cognitive control over emotional processing, which makes subsequent CBT less effective.

Conclusion: Despite several limitations, we found neuroimaging predictors of poor CBT response, under the conditions of standard clinical practice, in real PD patients.
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December 2015

Cortical activity modulation by botulinum toxin type A in patients with post-stroke arm spasticity: real and imagined hand movement.

J Neurol Sci 2014 Nov 16;346(1-2):276-83. Epub 2014 Sep 16.

Department of Neurology, Faculty of Medicine and Dentistry, Palacký University and University Hospital, Olomouc, Czech Republic.

Background: Our aim was to use functional magnetic resonance imaging (fMRI) to compare brain activation changes due to botulinum toxin A (BoNT) application between two chronic stroke patient groups with different degree of weakness treated for upper limb spasticity.

Methods: Fourteen ischemic stroke patients with hand weakness and spasticity were studied. Spasticity was scored by modified Ashworth scale (MAS). FMRI was performed 3 times: before (W0) and 4 (W4) and 11 weeks (W11) after BoNT application. Group A: 7 patients (2 males, 5 females; mean age 59.14 years) with hand plegia, who imagined moving fingers. Group B: 7 age-matched patients (6 males, 1 female; mean age 59.57 years) able to perform sequential finger movement.

Results: BoNT transiently lowered MAS in W4 in both groups. In group A, activation of the frontal premotor cortex dominated and persisted for all three fMRI sessions whereas the ipsilesional cerebellum and cortex bordering bilateral intraparietal sulcus activation changed over time. Between-session contrasts showed treatment-related activation decreases in the mesial occipitoparietal and lateral occipital cortex. In group B, brain activation was markedly reduced after BoNT (W4). Whereas some of these areas manifested only transient reduction and expanded again at W11, in others the reduction persisted.

Conclusion: Study of two age-matched groups with mild and severe weakness demonstrated different effects of BoNT-lowered spasticity on sensorimotor networks. Group A performing movement imagery manifested BoNT-induced reduction of activation in structures associated with visual imagery. Group B performing movement manifested reduced activation extent and reduced activation of structures outside classical motor system, suggestive of motor network normalization.
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http://dx.doi.org/10.1016/j.jns.2014.09.009DOI Listing
November 2014

BoNT-A related changes of cortical activity in patients suffering from severe hand paralysis with arm spasticity following ischemic stroke.

J Neurol Sci 2012 Aug 9;319(1-2):89-95. Epub 2012 Jun 9.

Department of Neurology, Faculty of Medicine and Dentistry, Palacký University and University Hospital, Olomouc, Czech Republic.

Background: Investigations were performed to localize and analyze the botulinum toxin (BoNT-A) related changes of cerebral cortex activation in chronic stroke patients suffering from severe hand paralysis with arm spasticity. Effects on task- related cerebral activation were evaluated by functional magnetic resonance imaging (fMRI).

Methods: 14 patients (5 males, 9 females, mean age 55.3 years) suffering from upper limb post-stroke spasticity were investigated. The change of arm spasticity was assessed by using the modified Ashworth scale (MAS). FMRI sessions were performed before (W0), four weeks (W4) and 11 weeks (W11) after BoNT-A application. Patients were scanned while performing imaginary movement with the impaired hand. Group fMRI analysis included patient age as a covariate.

Results: BoNT-A treatment was effective in alleviation of arm spasticity. Mean MAS was at Week 0: 2.5 (SD 0.53), at Week 4: 1.45 (SD 0.38), at Week 11: 2.32 (SD 0.44). Task-related fMRI prior to the treatment showed extensive activation of bilateral frontoparietal sensorimotor cortical areas, anterior cingulate gyrus, pallidum, thalamus and cerebellum. Effective BoNT-A treatment (W4) resulted in partial reduction of active network volume in most of the observed areas, whereas BoNT-free data (W11) revealed further volume reduction in the sensorimotor network. On direct comparison, significant activation decreases associated with BoNT-A treatment were located in areas outside the classical sensorimotor system, namely, ipsilesional lateral occipital cortex, supramarginal gyrus and precuneus cortex. On comparison of W4 and W11, no activation increases were found, instead, activation further decreased in ipsilesional insular cortex, contralesional superior frontal gyrus and bilateral frontal pole.

Conclusions: Whole brain activation patterns during BoNT-A treatment of post-stroke arm spasticity and further follow up document predominantly gradual changes both within and outside the classical sensorimotor system.
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http://dx.doi.org/10.1016/j.jns.2012.05.008DOI Listing
August 2012
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