White Matter Integrity and Chronic Poststroke Upper Limb Function: An ENIGMA Stroke Recovery Analysis.

BACKGROUND: Integrity of the corticospinal tract (CST) is an important biomarker for upper limb motor function following stroke. However, when structurally compromised, other tracts may become relevant for compensation or recovery of function. METHODS: We used the ENIGMA Stroke Recovery data set, a multicenter, retrospective, and cross-sectional collection of patients with upper limb impairment during the chronic phase of stroke to test the relevance of tracts in individuals with less and more severe (laterality index of CST fractional anisotropy ≥0.25) CST damage in an observational study design. White matter integrity was quantified using fractional anisotropy for the CST, the superior longitudinal fascicle, and the callosal fibers interconnecting the primary motor cortices between hemispheres. Optic radiations served as a control tract as they have no a priori relevance for the motor system. Pearson correlation was used for testing correlation with upper limb motor function (Fugl-Meyer upper extremity). RESULTS: From 1235 available data sets, 166 were selected (by imaging, Fugl-Meyer upper extremity, covariates, stroke location, and stage) for analyses. Only individuals with severe CST damage showed a positive association of fractional anisotropy in both callosal fibers interconnecting the primary motor cortices (r[21]=0.49; P=0.025) and superior longitudinal fascicle (r[21]=0.51; P=0.018) with Fugl-Meyer upper extremity. CONCLUSIONS: Our data support the notion that individuals with more severe damage of the CST depend on residual pathways for achieving better upper limb outcome than those with less affected CST.

Contemporary clinical neurophysiology applications in dystonia.

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.

[Aphasia associated with lacunar infarctions]. / Aphasien bei lakunären Hirninfarkten.

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.

Low-Frequency Oscillations Code Speech during Verbal Working Memory.

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.SIGNIFICANCE STATEMENT 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.

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

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.

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

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.

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

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.

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

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.

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

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.

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.

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.

Interhemispheric parietal cortex connectivity reflects improvement in post-stroke spasticity due to treatment with botulinum toxin-A.

In post-stroke spasticity (PSS), effective treatment with botulinum neurotoxin (BoNT) is associated with transient decrease in activation of the ipsilesional superior parietal lobule (SPL) and intraparietal sulcus (IPS). We hypothesized that this would be reflected in changes in resting-state functional connectivity (rsFC) of the SPL/IPS. Our aim was therefore to assess rsFC of the ipsilesional SPL/IPS in chronic stroke patients with hemiparesis both with and without PSS and to explore the relationship between SPL/IPS rsFC and PSS severity. To this end, fourteen chronic stroke patients with upper limb weakness and PSS (the PSS group) and 8 patients with comparable weakness but no PSS (the control group) underwent clinical evaluation and 3 fMRI examinations, at baseline (W0) and 4 and 11 weeks after BoNT (W4 and W11, respectively). Seed-based rsFC of the atlas-based SPL and IPS was evaluated using a group×time interaction analysis and a correlation analysis with PSS severity (modified Ashworth scale), integrity of the ipsilesional somatosensory afferent pathway (evoked potential N20 latency), and age. In the PSS group, transient improvement in PSS was associated with increase in rsFC between the ipsilesional IPS and the contralesional SPL at W4. The interhemispheric connectivity was negatively correlated with PSS severity at baseline and with PSS improvement at W4. We propose adaptation of the internal forward model as the putative underlying mechanism and discuss its possible association with increased limb use, diminished spastic dystonia, or improved motor performance, as well as its potential contribution to the clinical effects of BoNT.

Polypharmacy in patients with multiple sclerosis and the impact on levels of care and therapy units.

Background: The aim of this study was to examine the societal costs of polypharmacy in patients with multiple sclerosis (MS). We therefore focused on the association between the number of medications on the level of care (LOC), the German classification of the need for care, and the number of therapy sessions (TTU). Methods: In addition to demographic information and medication, 101 MS patients performed the Multiple Sclerosis Health Resource Utilization Survey (MS-HRS). Medications were subdivided into a total number of medications (TD), MS-related medication [MSD, i.e., disease-modifying drugs (DMDs) and symptomatic treatment (SD)], and medication for comorbidities (CDs). Multivariate linear regression models were performed to estimate if the amount of each medication type affects LOC or TTU. Results: Polypharmacy appeared in 54 patients at the time of the survey. The relative risk (RR) of LOC 1 increased significantly by 2.46 (p = 0.001) per TD and by 2.55 (p = 0.004) per MSD, but not per CD (RR 1.44; p = 0.092). The effect of RR on MSD was driven by SD (RR 2.2; p = 0.013) but not DMD (RR 2.6; p = 0.4). RR of MSD remained significant for LOC 2 (1.77; p = 0.009) and LOC 3/4 (1.91; p = 0.015), with a strong trend in RR of SD, but not DMD. TTU increased significantly per MSD (p = 0.012), but not per TD (p = 0.081) and CD (p = 0.724). Conclusion: The number of MSDs is related to the likelihood of a higher level of care and the number of therapy sessions and is therefore a good indication of the extent of the societal costs.

Correlation between retinal oxygen saturation and the haemodynamic parameters of the ophthalmic artery in healthy subjects.

PURPOSE: The aim of the study was to obtain the values of oxygen saturation in retinal vessels and ophthalmic blood flow parameters in a healthy Caucasian population and assess whether the oximetry parameters are affected by the flow rate or the vascular resistance. METHODS: The spectrophotometric retinal oximetry and colour Doppler imaging (CDI) of retinal vessels were successfully performed with 52 healthy subjects (average age 29.7 ± 5.6 years). The retinal oximeter simultaneously measures the wavelength difference of haemoglobin oxygen saturation in retinal arterioles and venules. The arteriolar and venular saturation in both eyes was measured. The peak systolic (PSV) end diastolic (EDV) velocities, resistive (RI) and pulsatility (PI) indices were obtained for both eyes using CDI in the ophthalmic artery. A paired t-test and two sample t-tests were used for statistical analyses. The correlation was assessed using the Pearson coefficient correlation. RESULTS: The mean oxygen saturation level was 96.9 ± 3.0% for the retinal arterioles and 65.0 ± 5.1% for the retinal venules. The A-V difference was 31.8 ± 4.6%. The mean of the measured haemodynamic parameters was PSV 46.6 ± 9.4 cm/s, EDV 12.0 ± 3.5 cm/s, PI 1.68 ± 0.38 and RI 0.74 ± 0.05. No significant difference in oxygen saturation and haemodynamic parameters was found between the left and the right eyes or the dominant and non-dominant eye. The oximetry and ultrasound values were sex independent. The Pearson correlation coefficient demonstrated a significant yet weak negative correlation between A-V difference and RI (r = -0.321, p = 0.020). CONCLUSIONS: A negative correlation between A-V difference and resistance index was observed, suggesting that reduced oxygen consumption may reflect the increased vascular tone of the ophthalmic vessels, which is likely determined by autoregulatory mechanisms.

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

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.

The Central Effects of Botulinum Toxin in Dystonia and Spasticity.

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.

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

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.

Changes in Brain Responses to Music and Non-music Sounds Following Creativity Training Within the "Different Hearing" Program.

The "Different Hearing" program (DHP) is an educational activity aimed at stimulating musical creativity of children and adults by group composing in the classroom, alternative to the mainstream model of music education in Czechia. Composing in the classroom in the DHP context does not use traditional musical instruments or notation, instead, the participants use their bodies, sounds originating from common objects as well as environmental sounds as the "elements" for music composition by the participants' team, with the teacher initiating and then participating and coordinating the creative process, which ends with writing down a graphical score and then performing the composition in front of an audience. The DHP methodology works with a wide definition of musical composition. We hypothesized that the DHP short-term (2 days) intense workshop would induce changes in subjective appreciation of different classes of music and sound (including typical samples of music composed in the DHP course), as well as plastic changes of the brain systems engaged in creative thinking and music perception, in their response to diverse auditory stimuli. In our study, 22 healthy university students participated in the workshop over 2 days and underwent fMRI examinations before and after the workshop, meanwhile 24 students were also scanned twice as a control group. During fMRI, each subject was listening to musical and non-musical sound samples, indicating their esthetic impression with a button press after each sample. As a result, participants' favorable feelings toward non-musical sound samples were significantly increased only in the active group. fMRI data analyzed using ANOVA with post hoc ROI analysis showed significant group-by-time interaction (opposing trends in the two groups) in the bilateral posterior cingulate cortex/precuneus, which are functional hubs of the default mode network (DMN) and in parts of the executive, motor, and auditory networks. The findings suggest that DHP training modified the behavioral and brain response to diverse sound samples, differentially changing the engagement of functional networks known to be related to creative thinking, namely, increasing DMN activation and decreasing activation of the executive network.

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

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.

Multiparametric Quantitative MRI in Neurological Diseases.

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.

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

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.