Publications by authors named "Lorenzo Rocchi"

98 Publications

Stroke in Patients with Schistosomiasis: Review of Cases in Literature.

Can J Infect Dis Med Microbiol 2022 25;2022:3902570. Epub 2022 Jul 25.

Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.

Introduction: Cerebral vascular comorbidities may occur in patients with schistosomiasis, as described in case reports. We have summarized general clinical and neurological features in patients with stroke associated with schistosomiasis, through a review of case reports in the literature. A total of eight case reports were retrieved. The mean age of patients was 36.42 ± 16.7 (19 to 56 years), four females, three males, and one anonymous sex. Eosinophilia was the most frequent feature at presentation, followed by cardiac abnormalities, confusion, fever, ataxia, hemiplegia, headache, urticaria, dysphasia, and memory impairment. Patients usually present with watershed infarction or intracranial vasculitis. In one case, extracranial carotid arteries presented with inflammation and stenosis. The patient's serology was positive on admission in five cases. Full neurological recovery was reported in three cases, and partial improvement in another three. In two cases, information on neurological outcomes was incomplete. Stroke in schistosomiasis can be caused by haemodynamic impairment, direct lesion to the arterial wall, vasa vasorum obliterative endarteritis, contiguity with a focus of inflamed tissue, or inflammatory intimal damage. Schistosomiasis needs to be included in the differential diagnosis of stroke in people living or coming back from endemic areas.

Conclusions: Further studies addressing the noncommunicable comorbidity issues related to this condition are needed.
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http://dx.doi.org/10.1155/2022/3902570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343201PMC
July 2022

How Do I Find Clues About Where Myoclonus Is Originating?

Mov Disord Clin Pract 2022 Jul 13;9(5):721-722. Epub 2022 Jun 13.

Department of Medical Sciences and Public Health University of Cagliari Cagliari Italy.

Myoclonus is defined as a brief and jerky shock-like involuntary movement caused by abrupt muscle contraction or sudden cessation of ongoing muscular activity. Myoclonus can be generated by abnormal activity in different parts of the nervous system, both peripheral and central, including cortical and subcortical structures. According to the presumed neural generator, myoclonus is classified as cortical, subcortical (including myoclonus-dystonia and brainstem/reticular myoclonus), spinal (including segmental spinal and propriospinal myoclonus), and peripheral. The identification of myoclonus subtypes, and therefore its potential source, is clinically important because it can guide diagnosis and treatment. In this video lecture (Video), we reviewed how to determine myoclonus origin. We first reviewed the clinical features typical of each myoclonus subtype. We, then, explored the electrophysiological techniques that can aid in the differential diagnosis of myoclonus, based on its origin. In conclusion, we provided a clinical and electrophysiological overview on how to find clues about neural generators of myoclonus.
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http://dx.doi.org/10.1002/mdc3.13472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274365PMC
July 2022

Standard intensities of transcranial alternating current stimulation over the motor cortex do not entrain corticospinal inputs to motor neurons.

J Physiol 2022 Jul 1. Epub 2022 Jul 1.

Department of Bioengineering, Imperial College, London, UK.

Transcranial alternating current stimulation (TACS) is commonly used to synchronize a cortical area and its outputs to the stimulus waveform, but gathering evidence for this based on brain recordings in humans is challenging. The corticospinal tract transmits beta oscillations (∼21 Hz) from the motor cortex to tonically contracted limb muscles linearly. Therefore, muscle activity may be used to measure the level of beta entrainment in the corticospinal tract due to TACS over the motor cortex. Here, we assessed whether TACS is able to modulate the neural inputs to muscles, which would provide indirect evidence for TACS-driven neural entrainment. In the first part of the study, we ran simulations of motor neuron (MN) pools receiving inputs from corticospinal neurons with different levels of beta entrainment. Results suggest that MNs are highly sensitive to changes in corticospinal beta activity. Then, we ran experiments on healthy human subjects (N = 10) in which TACS (at 1 mA) was delivered over the motor cortex at 21 Hz (beta stimulation), or at 7 Hz or 40 Hz (control conditions) while the abductor digiti minimi or the tibialis anterior muscle were tonically contracted. Muscle activity was measured using high-density electromyography, which allowed us to decompose the activity of pools of motor units innervating the muscles. By analysing motor unit pool activity, we observed that none of the TACS conditions could consistently alter the spectral contents of the common neural inputs received by the muscles. These results suggest that 1 mA TACS over the motor cortex given at beta frequencies does not entrain corticospinal activity. KEY POINTS: Transcranial alternating current stimulation (TACS) is commonly used to entrain the communication between brain regions. It is challenging to find direct evidence supporting TACS-driven neural entrainment due to the technical difficulties in recording brain activity during stimulation. Computational simulations of motor neuron pools receiving common inputs in the beta (∼21 Hz) band indicate that motor neurons are highly sensitive to corticospinal beta entrainment. Motor unit activity from human muscles does not support TACS-driven corticospinal entrainment.
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http://dx.doi.org/10.1113/JP282983DOI Listing
July 2022

Does epilepsy contribute to the clinical phenotype of C9orf72 mutation in fronto-temporal dementia?

Epilepsy Behav 2022 Aug 22;133:108783. Epub 2022 Jun 22.

Institute of Neurology, Azienda Ospedaliero Universitaria di Cagliari, Cagliari, Italy; Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.

C9orf72 mutation is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) worldwide. Recently, several reports of patients with FTD who carried the C9orf72 mutation and also manifested epilepsy have been published, since seizures occur in FTD at a higher rate than in the general population, the possible association between epilepsy and C9orf72 mutation remains to be clarified. In the attempt to understand whether epilepsy contributes to the phenotype of the C9orf72 mutation, we compared epilepsy occurrence in patients with FTD who carried the C9orf72 mutation and those who did not. In our sample of 84 patients with FTD, 7.1% of cases reported epilepsy, with no significant differences between subsamples of patients with FTD stratified according to the presence of the C9orf72 mutation or to family history of FTD/parkinsonism/motor neuron disease. Our findings did not support to the possibility that epilepsy represents a characteristic feature of the C9orf72 mutation, as suggested by recent case reports published in the English literature.
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http://dx.doi.org/10.1016/j.yebeh.2022.108783DOI Listing
August 2022

Decreased Frontal Gamma Activity in Alzheimer Disease Patients.

Ann Neurol 2022 Jun 17. Epub 2022 Jun 17.

Experimental Neuropsychophysiology Laboratory, Department of Behavioral and Clinical Neurology, Santa Lucia Foundation, Scientific Institute for Research and Health Care, Rome, Italy.

Objective: In Alzheimer disease (AD) animal models, synaptic dysfunction has recently been linked to a disorder of high-frequency neuronal activity. In patients, a clear relation between AD and oscillatory activity remains elusive. Here, we attempt to shed light on this relation by using a novel approach combining transcranial magnetic stimulation and electroencephalography (TMS-EEG) to probe oscillatory activity in specific hubs of the frontoparietal network in a sample of 60 mild-to-moderate AD patients.

Methods: Sixty mild-to-moderate AD patients and 21 age-matched healthy volunteers (HVs) underwent 3 TMS-EEG sessions to assess cortical oscillations over the left dorsolateral prefrontal cortex, the precuneus, and the left posterior parietal cortex. To investigate the relations between oscillatory activity, cortical plasticity, and cognitive decline, AD patients underwent a TMS-based neurophysiological characterization and a cognitive evaluation at baseline. The latter was repeated after 24 weeks to monitor clinical evolution.

Results: AD patients showed a significant reduction of frontal gamma activity as compared to age-matched HVs. In addition, AD patients with a more prominent decrease of frontal gamma activity showed a stronger impairment of long-term potentiation-like plasticity and a more pronounced cognitive decline at subsequent follow-up evaluation at 24 weeks.

Interpretation: Our data provide novel evidence that frontal lobe gamma activity is dampened in AD patients. The current results point to the TMS-EEG approach as a promising technique to measure individual frontal gamma activity in patients with AD. This index could represent a useful biomarker to predict disease progression and to evaluate response to novel pharmacological therapies. ANN NEUROL 2022.
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http://dx.doi.org/10.1002/ana.26444DOI Listing
June 2022

Action Selection and Motor Decision Making: Insights from Transcranial Magnetic Stimulation.

Brain Sci 2022 May 12;12(5). Epub 2022 May 12.

Department of Clinical Neurophysiology, Kuopio University Hospital, University of Eastern Finland, 70211 Kuopio, Finland.

In everyday life, goal-oriented motor behaviour relies on the estimation of the rewards/costs associated with alternative actions and on the appropriate selection of movements. Motor decision making is defined as the process by which a motor plan is chosen among a set of competing actions based on the expected value. In the present literature review we discuss evidence from transcranial magnetic stimulation (TMS) studies of motor control. We focus primarily on studies of action selection for instructed movements and motor decision making. In the first section, we delve into the usefulness of various TMS paradigms to characterise the contribution of motor areas and distributed brain networks to cued action selection. Then, we address the influence of motivational information (e.g., reward and biomechanical cost) in guiding action choices based on TMS findings. Finally, we conclude that TMS represents a powerful tool for elucidating the neurophysiological mechanisms underlying action choices in humans.
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http://dx.doi.org/10.3390/brainsci12050639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139261PMC
May 2022

Does Olfactory Dysfunction Correlate with Disease Progression in Parkinson's Disease? A Systematic Review of the Current Literature.

Brain Sci 2022 Apr 19;12(5). Epub 2022 Apr 19.

Department of Medical Sciences and Public Health, Institute of Neurology, University of Cagliari, SS 554 km 4.500, 09042 Cagliari, Italy.

Background: Loss of olfaction is a well-established early feature of Parkinson's disease (PD). Although olfactory dysfunction has been widely described as a prodromal feature of PD in the literature, whether it can be considered a biomarker of PD progression is still a matter of debate.

Objective: The aim of this work is to define the possible relationship between the progression of olfactory dysfunction and other putative clinical hallmarks of PD over time, through a systematic review of the current literature.

Methods: We conducted a systematic review of the literature on PubMed from inception to March 2022. We included only longitudinal studies conducted on patients with diagnosis of idiopathic PD who underwent olfactory function testing at baseline and repeated it at least once during follow-up.

Results: Among 5740 records identified through database searching, nine longitudinal studies met full criteria and underwent data extraction.

Conclusions: Olfaction seemed to decrease over time, albeit with a degree of fluctuation. Moreover, smell detection ability seems to deteriorate more rapidly in the early phase of disease, indicating a possible association with disease progression. More studies are needed to better understand the role of olfaction as a biomarker of PD progression over time.
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http://dx.doi.org/10.3390/brainsci12050513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139278PMC
April 2022

Extension Block Pinning Vs Single Kirshner Wiring To Treat Bony Mallet Finger. A Retrospective Study.

Acta Biomed 2022 03 10;92(S3):e2021535. Epub 2022 Mar 10.

Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy. Università Cattolica del Sacro Cuore, Roma, Italia..

Background And Aim: Bony Mallet Finger or Mallet Fracture is a common injury of the hand, which follows a forced flexion of the extended distal interphalangeal joint, that leads to a bony avulsion of the distal phalanx. Depending on fracture extension and dislocation, those lesions can either be treated conservatively or surgically. Several surgical options have been described in the literature. The aim of this study is to compare retrospectively two percutaneous pinning techniques: the extension block technique according to Ishiguro vs an original single Kirshner wiring (Umbrella technique).

Methods: Between January 1998 and December 2019, among all patients treated surgically for a Mallet Fracture with either the Ishiguro' and the Umbrella technique, 98 have been included in this study. All patients have been assessed one year after surgery using the Crawford method.

Results: With both techniques better results have been achieved in younger patients and for those treated early. The umbrella technique seems to have better results in patients with fracture classified as 2b or 2c (Wehbe and Schneider classification), whereas the Ishiguro technique seems more appropriate for patients with a 1b fracture. Complication rate and typology vary depending on the used technique.

Conclusions: The Ishiguro' and the Umbrella technique both lead to good results for the treatment of surgical Mallet Fractures. The choice of the best type of pinning should mainly depend on fracture extension and time elapsed from trauma.
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http://dx.doi.org/10.23750/abm.v92iS3.12484DOI Listing
March 2022

Resurfacing capitate pyrocarbon implant as salvage procedure in several serious outcomes of carpal injuries. Clinical experience and follow-up.

Acta Biomed 2022 03 10;92(S3):e2021536. Epub 2022 Mar 10.

Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy. Università Cattolica del Sacro Cuore, Roma, Italia..

Background And Aim: Resurfacing Capitate Pyrocarbon Implant has been introduced in the surgical practice as an alternative method to restore wrist motion, strength and functions in patients suffering from wrist osteoarthritis. It has already been well described in the literature as a treatment for advanced stages of degenerative wrist diseases which follow scaphoid's and lunate's injuries such as scapho-lunate advanced collapse, scaphoid non-union advanced collapse, and advanced stages of Kienböck disease. Authors extended the use of RCPI to other selected cases of complicated wrist injuries, spreading out from the classic indications for which this device was designed.

Methods: We discuss 8 cases with serious outcomes of carpal injuries treated with Resurfacing Capitate Pyrocarbon Implant as salvage procedure between 2005 and 2013 by the first author of this paper Results: Among the eight particular selected cases, at a mean 4.3 years follow-up (range 2-11) only one was considered a failure and underwent a total wrist arthrodesis, resolving pain after all. The seven other cases reported good results. Range of Motion, Visual Analogue Scale for pain, subjective satisfaction and radiographical outcomes are reported.

Conclusions: As a result of this heterogeneous clinical experience, validated by long-term follow-ups in most cases, we think that the use of a Resurfacing Capitate Pyrocarbon Implant can be suggested as an option in the outcomes of various carpal injuries.
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http://dx.doi.org/10.23750/abm.v92iS3.12486DOI Listing
March 2022

SAFETY AND RELIABILITY OF CARBON-PEEK PLATE FOR THE TREATMENT OF DISTAL RADIUS FRACTURES: A REVIEW OF THE LITERATURE.

Orthop Rev (Pavia) 2021 22;13(2):28362. Epub 2021 Sep 22.

Department of Orthopaedics - Hand Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma - Università Cattolica del Sacro Cuore.

Introduction: Distal radius fractures are one of the most common injuries. Open reduction and internal fixation (ORIF) are the most diffused between surgical treatments. Carbon-fiber reinforced (CFR) polyetheretherketone (PEEK) plates have been proposed to prevent effects linked to stainless steel or titanium alloy traditional plates, such as radio-opacity, mismatch of bone-plate elasticity modulus, corrosion, limited fatigue life, osseointegration.

Objective: This review aims to evaluate the actual safety and reliability of CFR- PEEK plates to treat distal radius fractures.

Methods: Electronic databases PubMed, Google Scholars, and Cochrane Library were searched in December 2020. Eligible studies were published in peer-reviewed journals. Three authors independently selected relevant articles and discussed those. Searching identified 13 titles and abstracts, 11 manuscripts were considered eligible for the full-text analysis. Of these 11 papers, 7 studies were included in our review.

Results: 215 patients were analyzed in this systematic review. The mean age of enrolled patients was 52,8 years. 34% were males and 66% were females. Fractures were classified according to AO/ASIF classification system. We reported 12 cases of complications specific to this device, such as intraoperative plate and screws rupture, erosive flexor tendons synovitis, and loosening.

Conclusion: CFR-PEEK distal radius plates are potentially an alternative to traditional ones. But we believe that the use of this device does not entail a significant advantage in the treatment of distal radius fractures, as safe and low-cost traditional devices are available. Further comparative studies are needed to demonstrate the superiority of carbon devices.
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http://dx.doi.org/10.52965/001c.28362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037658PMC
September 2021

One Year of COVID-19: Lessons Learned in a Hand Trauma Center.

J Clin Med 2022 Apr 13;11(8). Epub 2022 Apr 13.

Orthopedics & Hand Surgery Unit, Department of Orthopedics, Fondazione Policlinico Universitario A. Gemelli, IRCCS-Catholic University of the Sacred Hearth, 00168 Rome, Italy.

2020 will be remembered worldwide as the year of COVID-19 outbreak. The onset of this pandemic abruptly changed everybody's life and, in a particular manner, doctors' lives. Our hand surgery department became rapidly one of the first COVID-19-specialized wards in Italy, impacting considerably the authors' routines and activities. In this paper, the authors focus on how the demographics of patients with hand trauma changed and how they had to modify their activity. The authors retrospectively took into consideration all patients reaching their emergency department (ED) with hand trauma between 9 March 2020 (the day of the beginning of the first lockdown in Italy) and 8 March 2021 and compared them to those who reached the ED in the three previous years. Authors have analyzed the number of patients, their gender and age, the severity of their trauma, where the trauma occurred, the type of lesion, the percentage of patients who underwent surgery, and the percentage of patients who had an emergency admission. In the last year, the number of patients reaching the ED for a hand trauma has been reduced by two thirds (975 patients during the past year), the mean age of those patients has slightly increased, the severity of cases has increased, places of trauma and type of lesions have changed, and, lastly, the percentage of patients needing surgery who were admitted immediately has increased. This paper shows how the type of patients reaching the ED changed and discusses how surgeons evolved and modified their habits in treating those patients during the first lockdown and the year that followed.
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http://dx.doi.org/10.3390/jcm11082163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024795PMC
April 2022

A Critical Investigation of Cerebellar Associative Learning in Isolated Dystonia.

Mov Disord 2022 06 21;37(6):1187-1192. Epub 2022 Mar 21.

Department of Clinical and Movement Neurosciences, University College London, London, UK.

Background: Impaired eyeblink conditioning is often cited as evidence for cerebellar dysfunction in isolated dystonia yet the results from individual studies are conflicting and underpowered.

Objective: To systematically examine the influence of dystonia, dystonia subtype, and clinical features over eyeblink conditioning within a statistical model which controlled for the covariates age and sex.

Methods: Original neurophysiological data from all published studies (until 2019) were shared and compared to an age- and sex-matched control group. Two raters blinded to participant identity rescored all recordings (6732 trials). After higher inter-rater agreement was confirmed, mean conditioning per block across raters was entered into a mixed repetitive measures model.

Results: Isolated dystonia (P = 0.517) and the subtypes of isolated dystonia (cervical dystonia, DYT-TOR1A, DYT-THAP1, and focal hand dystonia) had similar levels of eyeblink conditioning relative to controls. The presence of tremor did not significantly influence levels of eyeblink conditioning. A large range of eyeblink conditioning behavior was seen in both health and dystonia and sample size estimates are provided for future studies.

Conclusions: The similarity of eyeblink conditioning behavior in dystonia and controls is against a global cerebellar learning deficit in isolated dystonia. Precise mechanisms for how the cerebellum interplays mechanistically with other key neuroanatomical nodes within the dystonic network remains an open research question. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313805PMC
June 2022

Proactive inhibition is marked by differences in the pattern of motor cortex activity during movement preparation and execution.

J Neurophysiol 2022 04 2;127(4):819-828. Epub 2022 Mar 2.

Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, United Kingdom.

Successful human behavior relies on the ability to flexibly alter movements depending on the context in which they are made. One such context-dependent modulation is proactive inhibition, a type of behavioral inhibition used when anticipating the need to stop or change movements. We investigated how the motor cortex might prepare and execute movements made under different contexts. We used transcranial magnetic stimulation (TMS) in different coil orientations [postero-anterior (PA) and antero-posterior (AP) flowing currents] and pulse widths (120 and 30 µs) to probe the excitability of different inputs to corticospinal neurons while participants performed two reaction time tasks: a simple reaction time task and a stop-signal task requiring proactive inhibition. We took inspiration from state space models to assess whether the pattern of motor cortex activity changed due to proactive inhibition (PA and AP neuronal circuits represent the and axes of a state space upon which motor cortex activity unfolds during motor preparation and execution). We found that the rise in motor cortex excitability was delayed when proactive inhibition was required. State space visualizations showed altered patterns of motor cortex activity (combined PA and AP activity) during proactive inhibition, despite adjusting for reaction time. Overall, we show that the pattern of neural activity generated by the motor cortex during movement preparation and execution is dependent upon the context under which the movement is to be made. Using directional TMS, we find that the human motor cortex flexibly changes its pattern of neural activity depending on the context in which a movement is due to be made. Interestingly, this occurs despite adjusting for reaction time. We also show that state space and dynamical systems models of movement can be noninvasively visualized in humans using TMS, thereby offering a novel method to study these powerful models in humans.
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http://dx.doi.org/10.1152/jn.00359.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957347PMC
April 2022

Incidence of amyotrophic lateral sclerosis in Sardinia, Italy: age-sex interaction and spatial-temporal variability.

Amyotroph Lateral Scler Frontotemporal Degener 2022 Feb 21:1-7. Epub 2022 Feb 21.

Institute of Neurology, University Hospital of Cagliari, Cagliari, Italy.

This study assessed amyotrophic lateral sclerosis (ALS) incidence in Sardinia, Italy, and the combined contribution of age and gender to disease risk. We also checked disease incidence for spatial-temporal variability. : ALS patients from all neurological centers of the study area who had onset during 2010-2019 and fulfilled El Escorial revised diagnostic criteria were included. Incidence was calculated for the overall study area and each province separately. Additive interaction between age and sex on ALS incidence was assessed. : The average crude annual incidence rate was 3.6/100,000 person-years (95% CI, 3.2-4.1), 3.1/100,000 person-years (95% CI, 2.7-3.5) when age-adjusted. Incidence was greater among people aged ≥65 years and men, with the two variables undergoing significant additive interaction. Incidence increased yearly over the study period, with annual incidence correlating with the increasing yearly frequency of people aged ≥65 years, but not with the proportion of incident cases carrying genetic mutations. Stratifying by province, the rates from Oristano and South Sardinia were higher than the rate from Cagliari. ALS patients from areas at different risk were comparable for frequency of clinical/genetic features. : ALS incidence in Sardinia was in the upper part of the European range of variability. We also provided new information about age and sex as risk factors for ALS, showing male sex as a modifier of the effect of aging on ALS incidence. Spatial-temporal variations in ALS incidence correlated to changes in the proportion of the aging population rather than to the distribution of genetic factors.
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http://dx.doi.org/10.1080/21678421.2022.2041670DOI Listing
February 2022

Restless Legs Syndrome: Known Knowns and Known Unknowns.

Brain Sci 2022 Jan 16;12(1). Epub 2022 Jan 16.

Neurology Unit, Parkinson Disease and Movement Disorders Division, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy.

Although restless legs syndrome (RLS) is a common neurological disorder, it remains poorly understood from both clinical and pathophysiological perspectives. RLS is classified among sleep-related movement disorders, namely, conditions characterized by simple, often stereotyped movements occurring during sleep. However, several clinical, neurophysiological and neuroimaging observations question this view. The aim of the present review is to summarize and query some of the current concepts (known knowns) and to identify open questions (known unknowns) on RLS pathophysiology. Based on several lines of evidence, we propose that RLS should be viewed as a disorder of sensorimotor interaction with a typical circadian pattern of occurrence, possibly arising from neurochemical dysfunction and abnormal excitability in different brain structures.
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http://dx.doi.org/10.3390/brainsci12010118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773543PMC
January 2022

Motor Cortical Network Excitability in Parkinson's Disease.

Mov Disord 2022 04 9;37(4):734-744. Epub 2022 Jan 9.

IRCCS Neuromed, Pozzilli, Italy.

Background: Motor impairment in Parkinson's disease (PD) reflects changes in the basal ganglia-thalamocortical circuit converging on the primary motor cortex (M1) and supplementary motor area (SMA). Previous studies assessed M1 excitability in PD using transcranial magnetic stimulation (TMS)-evoked electromyographic activity. TMS-evoked electroencephalographic activity may unveil broader motor cortical network changes in PD.

Objective: The aim was to assess motor cortical network excitability in PD.

Methods: We compared TMS-evoked cortical potentials (TEPs) from M1 and the pre-SMA between 20 PD patients tested off and on medication and 19 healthy controls (HCs) and investigated possible correlations with bradykinesia.

Results: Off PD patients compared to HCs had smaller P30 responses from the M1s contralateral (M1+) and ipsilateral (M1-) to the most bradykinetic side and increased pre-SMA N40. Dopaminergic therapy normalized the amplitude of M1+ and M1- P30 as well as pre-SMA N40. We found a positive correlation between M1+ P30 amplitude and bradykinesia in off PD patients.

Conclusions: Changes in M1 P30 and pre-SMA N40 in PD suggest that M1 excitability is reduced on both sides, whereas pre-SMA excitability is increased. The effect of dopaminergic therapy and the clinical correlation suggest that these cortical changes may reflect abnormal basal ganglia-thalamocortical activity. TMS electroencephalography provides novel insight into motor cortical network changes related to the pathophysiology of PD. © 2022 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28914DOI Listing
April 2022

Feeling of Ownership over an Embodied Avatar's Hand Brings About Fast Changes of Fronto-Parietal Cortical Dynamics.

J Neurosci 2022 01 3;42(4):692-701. Epub 2021 Dec 3.

Non-invasive Brain Stimulation Unit, IRCCS Santa Lucia Foundation, Rome 00179, Italy.

When we look at our body parts, we are immediately aware that they belong to us and we rarely doubt about the integrity, continuity, and sense of ownership of our body. Despite this certainty, immersive virtual reality (IVR) may lead to a strong feeling of embodiment over an artificial body part seen from a first-person perspective (1PP). Although such feeling of ownership (FO) has been described in different situations, it is not yet understood how this phenomenon is generated at neural level. To track the real-time brain dynamics associated with FO, we delivered transcranial magnetic stimuli over the hand region in the primary motor cortex (M1) and simultaneously recorded electroencephalography (EEG) in 19 healthy volunteers (11 male/8 female) watching IVR renderings of anatomically plausible (full-limb) versus implausible (hand disconnected from the forearm) virtual limbs. Our data show that embodying a virtual hand is temporally associated with a rapid drop of cortical activity of the onlookers' hand region in the M1 contralateral to the observed hand. Spatiotemporal analysis shows that embodying the avatar's hand is also associated with fast changes of activity within an interconnected fronto-parietal circuit ipsilateral to the brain stimulation. Specifically, an immediate reduction of connectivity with the premotor area is paralleled by an enhancement in the connectivity with the posterior parietal cortex (PPC) which is related to the strength of ownership illusion ratings and thus likely reflects conscious feelings of embodiment. Our results suggest that changes of bodily representations are underpinned by a dynamic cross talk within a highly-plastic, fronto-parietal network. Observing an avatar's body part from a first-person perspective (1PP) induces an illusory embodiment over it. What remains unknown are the cortical dynamics underpinning the embodiment of artificial agents. To shed light on the physiological mechanisms of embodiment we used a novel approach that combines noninvasive stimulation of the cortical motor-hand area and whole-scalp electroencephalographic (EEG) recordings in people observing an embodied artificial limb. We found that just before the illusion started, there is a decrease of activity of the motor-hand area accompanied by an increase of connectivity with the parietal region ipsilateral to the stimulation that reflects the ratings of the embodiment illusion. Our results suggest that changes of bodily representations are underpinned by a dynamic cross talk within a fronto-parietal circuit.
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http://dx.doi.org/10.1523/JNEUROSCI.0636-21.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805621PMC
January 2022

Qualitative smell/taste disorders as sequelae of acute COVID-19.

Neurol Sci 2021 Dec 23;42(12):4921-4926. Epub 2021 Sep 23.

Department of Medical Sciences and Public Health, Institute of Neurology, University of Cagliari, Cagliari, Italy.

Background: Qualitative smell/taste disorders (such as phantosmia, parosmia, phantogeusia, and parageusia) have not yet been fully characterized in patients who had COVID-19, whereas quantitative disturbances (i.e., reduction/loss of smell/taste) have been widely investigated.

Objective: To simultaneously assess the presence of both quantitative and qualitative smell/taste dysfunctions in patients who suffered from COVID-19.

Methods: We enrolled 17 consecutive patients who suffered from COVID-19 over the last 6 months and 21 healthy controls, matched for sex and age. After a negative nasopharyngeal swab, the Sniffin' Sticks Test and the Taste Strips were used to assess olfactory and taste function, respectively. At the same time, the presence of phantosmia, parosmia, phantogeusia, and parageusia was investigated with a standardized questionnaire.

Results: Qualitative disturbances of smell and/or taste were found in 6/17 (35.3%) patients. Phantosmia was reported in 2/17 (11.8%) patients and parosmia in 4/17 (23.5%). There were no significant differences in smell test scores between patients who reported phantosmia and/or parosmia and patients who did not. Phantogeusia was described in 3/17 (17.6%) patients, and parageusia was identified in 4/17 (23.5%) patients. All tested patients were normogeusic.

Conclusion: Around one-third of patients who recover from COVID-19 may have persistent qualitative dysfunction in smell/taste domains. Detection of phantogeusia in long-term COVID-19 patients represents a further novel finding. Further investigation is needed to better characterize the pathophysiology of phantosmia, parosmia, phantogeusia, and parageusia in patients who had COVID-19.
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http://dx.doi.org/10.1007/s10072-021-05611-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459812PMC
December 2021

Two forms of short-interval intracortical inhibition in human motor cortex.

Brain Stimul 2021 Sep-Oct;14(5):1340-1352. Epub 2021 Sep 1.

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK.

Background: Pulses of transcranial magnetic stimulation (TMS) with a predominantly anterior-posterior (AP) or posterior-anterior (PA) current direction over the primary motor cortex appear to activate distinct excitatory inputs to corticospinal neurons. In contrast, very few reports have examined whether the inhibitory neurons responsible for short-interval intracortical inhibition (SICI) are sensitive to TMS current direction.

Objectives: To investigate whether SICI evaluated with AP and PA conditioning stimuli (CS and CS) activate different inhibitory pathways. SICI was always assessed using a PA-oriented test stimulus (TS).

Methods: Using two superimposed TMS coils, CS and CS were applied at interstimulus intervals (ISI) of 1-5 ms before a TS, and at a range of different intensities. Using a triple stimulation design, we then tested whether SICI at ISI of 3 ms using opposite directions of CS (SICI and SICI) interacted differently with three other forms of inhibition, including SICI at ISI of 2 ms (SICI), cerebellum-motor cortex inhibition (CBI 5 ms) and short-latency afferent inhibition (SAI 22 ms). Finally, we compared the effect of tonic and phasic voluntary contraction on SICI and SICI.

Results: CS produced little SICI at ISIs = 1 and 2 ms. However, at ISI = 3 ms, both CS and CS were equally effective at the same percent of maximum stimulator output. Despite this apparent similarity, combining SICI or SICI with other forms of inhibition led to quite different results: SICI interacted in complex ways with CBI, SAI and SICI, whereas the effect of SICI appeared to be quite independent of them. Although SICI and SICI were both reduced by the same amount during voluntary tonic contraction compared with rest, in a simple reaction time task SICI was disinhibited much earlier following the imperative signal than SICI.

Conclusions: SICI appears to activate a different inhibitory pathway to that activated by SICI. The difference is behaviourally relevant since the pathways are controlled differently during volitional contraction. The results may explain some previous pathological data and open the possibility of testing whether these pathways are differentially recruited in a range of tasks.
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http://dx.doi.org/10.1016/j.brs.2021.08.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460995PMC
November 2021

Reply to: "A Primary Writing Tremor Is a Form of Dystonic Tremor: Is the Debate Settled?"

Mov Disord 2021 08;36(8):1996-1997

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology University College London, London, United Kingdom.

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http://dx.doi.org/10.1002/mds.28695DOI Listing
August 2021

The Expanding Horizon of Neural Stimulation for Hyperkinetic Movement Disorders.

Front Neurol 2021 14;12:669690. Epub 2021 May 14.

Department of Clinical and Movement Neurosciences, University College London, London, United Kingdom.

Novel methods of neural stimulation are transforming the management of hyperkinetic movement disorders. In this review the diversity of approach available is showcased. We first describe the most commonly used features that can be extracted from oscillatory activity of the central nervous system, and how these can be combined with an expanding range of non-invasive and invasive brain stimulation techniques. We then shift our focus to the periphery using tremor and Tourette's syndrome to illustrate the utility of peripheral biomarkers and interventions. Finally, we discuss current innovations which are changing the landscape of stimulation strategy by integrating technological advances and the use of machine learning to drive optimization.
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http://dx.doi.org/10.3389/fneur.2021.669690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160223PMC
May 2021

Chronic post-traumatic volar plate avulsions of the finger proximal interphalangeal joint: A literature review of different surgical techniques.

Orthop Rev (Pavia) 2021 Mar 31;13(1):9058. Epub 2021 Mar 31.

Orthopaedics and Hand Surgery Unit, Department of Orthopaedics, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome; Università Cattolica del Sacro Cuore, Rome, Italy.

Avulsions of the volar plate of the finger proximal interphalangeal joint (PIPJ) following sprains are often undiagnosed in the acute setting. Therefore, the chronic outcomes of this injury are most frequently the object of study and treatment. Different techniques for volar plate chronic avulsion repair are described in the literature. The most used among these are mainly two: the direct suturing with or without the use of bone anchors and the tenodesis techniques with flexor digitalis superficialis (FDS). The aim of this systematic review is to determine outcomes and complications associated with these surgical treatments of post-traumatic volar plate avulsions without phalangeal fractures. An electronic literature research was carried out and pertinent articles were selected. Surgical techniques details, outcomes and complications for direct sutures and tenodesis technique are discussed. Outcomes (Range of motion and pain) seem to be comparable, whereas authors that use the direct suture technique describe more frequently PIPJ flexion contracture complication. From this review of the literature, authors believe that both techniques are available for the repair of chronic injuries of the volar plate of the PIPJ, although direct suturing can be considered as less reproducible.
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http://dx.doi.org/10.4081/or.2021.9058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077280PMC
March 2021

Brainstem Reflexes in Idiopathic Cervical Dystonia: Does Medullary Dysfunction Play a Role?

Mov Disord Clin Pract 2021 Apr 12;8(3):377-384. Epub 2021 Feb 12.

Department of Clinical and Movements Neurosciences, UCL Queen Square Institute of Neurology University College London London United Kingdom.

Background: Neurophysiological markers in dystonia have so far not been sistematically applied in clinical practice due to limited reproducibility of results and low correlations with clinical findings. Exceptions might be represented by the blink reflex (BR), including its recovery cycle (BRRC) and the trigemino-cervical reflex (TCR) which, compared to other neurophysiological methods, have shown more consistent alterations in cervical dystonia (CD). However, a comparison between the two techniques, and their possible correlation with disease symptoms, have not been thoroughly investigated.

Objectives: To assess the role of BR, BRCC and TCR in the pathophysiology of idiopathic cervical dystonia.

Methods: Fourteen patients and 14 age-matched healthy controls (HC) were recruited. Neurophysiological outcome measures included latency of R1 and R2 components of the BR, R2 amplitude, BRRC, latency and amplitude of P19/N31 complex of TCR. Clinical and demographic features of patients were also collected, including age at disease onset, disease duration, presence of tremor, sensory trick and pain. The Toronto Western Spasmodic Torticollis Rating Scale was used to characterize dystonia.

Results: Compared to HC, CD patients showed increased latency of the BR R2 and decreased suppression of the BRRC. They also showed increased latency of the P19 and decreased amplitude of P19/N31 complex of TCR. The latency of P19 component of TCR was positively correlated with disease duration.

Conclusions: We propose that the increased latency of R2 and P19 observed here might be reflective of brainstem dysfunction, mediated either by local interneuronal excitability changes or by subtle structural damage.
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http://dx.doi.org/10.1002/mdc3.13149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015899PMC
April 2021

Contribution of TMS and TMS-EEG to the Understanding of Mechanisms Underlying Physiological Brain Aging.

Brain Sci 2021 Mar 22;11(3). Epub 2021 Mar 22.

Department of Neuroscience, University of Padua, 35122 Padua, Italy.

In the human brain, aging is characterized by progressive neuronal loss, leading to disruption of synapses and to a degree of failure in neurotransmission. However, there is increasing evidence to support the notion that the aged brain has a remarkable ability to reorganize itself, with the aim of preserving its physiological activity. It is important to develop objective markers able to characterize the biological processes underlying brain aging in the intact human, and to distinguish them from brain degeneration associated with many neurological diseases. Transcranial magnetic stimulation (TMS), coupled with electromyography or electroencephalography (EEG), is particularly suited to this aim, due to the functional nature of the information provided, and thanks to the ease with which it can be integrated with behavioral manipulation. In this review, we aimed to provide up to date information about the role of TMS and TMS-EEG in the investigation of brain aging. In particular, we focused on data about cortical excitability, connectivity and plasticity, obtained by using readouts such as motor evoked potentials and transcranial evoked potentials. Overall, findings in the literature support an important potential contribution of TMS to the understanding of the mechanisms underlying normal brain aging. Further studies are needed to expand the current body of information and to assess the applicability of TMS findings in the clinical setting.
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http://dx.doi.org/10.3390/brainsci11030405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004753PMC
March 2021

Preconditioning Stimulus Intensity Alters Paired-Pulse TMS Evoked Potentials.

Brain Sci 2021 Mar 4;11(3). Epub 2021 Mar 4.

Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.

Motor cortex (M1) paired-pulse TMS (ppTMS) probes excitatory and inhibitory intracortical dynamics by measurement of motor-evoked potentials (MEPs). However, MEPs reflect cortical and spinal excitabilities and therefore cannot isolate cortical function. Concurrent TMS-EEG has the ability to measure cortical function, while limiting peripheral confounds; TMS stimulates M1, whilst EEG acts as the readout: the TMS-evoked potential (TEP). Whilst varying preconditioning stimulus intensity influences intracortical inhibition measured by MEPs, the effects on TEPs is undefined. TMS was delivered to the left M1 using single-pulse and three, ppTMS paradigms, each using a different preconditioning stimulus: 70%, 80% or 90% of resting motor threshold. Corticospinal inhibition was present in all three ppTMS conditions. ppTMS TEP peaks were reduced predominantly under the ppTMS 70 protocol but less so for ppTMS 80 and not at all for ppTMS 90. There was a significant negative correlation between MEPs and N45 TEP peak for ppTMS 70 reaching statistical trends for ppTMS 80 and 90. Whilst ppTMS MEPs show inhibition across a range of preconditioning stimulus intensities, ppTMS TEPs do not. TEPs after M1 ppTMS vary as a function of preconditioning stimulus intensity: smaller preconditioning stimulus intensities result in better discriminability between conditioned and unconditioned TEPs. We recommend that preconditioning stimulus intensity should be minimized when using ppTMS to probe intracortical inhibition.
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http://dx.doi.org/10.3390/brainsci11030326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998341PMC
March 2021

Matriderm dermal substitute in the treatment of post traumatic hand's fingertip tissue loss.

J Cosmet Dermatol 2022 Feb 7;21(2):750-757. Epub 2021 Apr 7.

Orthopaedics & Hand Surgery Unit, Department of Orthopaedics, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.

Introduction: Treatment of fingers tissue loss is particularly challenging as it often necessitates advanced reconstructive techniques such as flaps or grafts, with esthetic and functional results that are not always as good as hoped for, with long healing times. Recently, along with tissue engineering development, numerous types of dermal substitute have been commercialized, with promising possibilities of treatment in finger tissue loss. In the author's unit, Matriderm is the most commonly used dermal substitute. As described by the manufacturer, this scaffold is designed to be covered with a split-thickness skin graft. In using a two-step procedure, the authors realized that in most cases of fingertips injuries, at three weeks follow-up, the wound appeared in an advanced state of healing, which permitted to avoid grafting.

Material And Methods: Between October 2017 and October 2018, 27 fingers have been included in this study. Patients have been divided in two groups: those treated with Matriderm alone (15 fingers) and those who had a skin graft three weeks after the first surgery (12 fingers). At the 6-month follow-up, authors evaluated the esthetic results with the Vancouver Scar Scale (VSS), the functional results with Quick Disability of the Arm, Shoulder and Hand (qDASH) score, and sensibility by the mean of two-point discrimination test (2-PD).

Results: All outcomes were overlapping in patients treated with or without skin graft: mean VSS was 2.3, mean qDASH was 13.3, and mean 2-PD was 7.7 mm.

Conclusions: The results obtained allow to consider Matriderm , used also without skin graft coverage, as a valid solution for treatment of fingertip tissue loss.
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http://dx.doi.org/10.1111/jocd.14115DOI Listing
February 2022

The Signature of Primary Writing Tremor Is Dystonic.

Mov Disord 2021 07 30;36(7):1715-1720. Epub 2021 Mar 30.

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology University College London, London, UK.

Background: It has been debated for decades whether primary writing tremor is a form of dystonic tremor, a variant of essential tremor, or a separate entity. We wished to test the hypothesis that primary writing tremor and dystonia share a common pathophysiology.

Objectives: The objective of the present study was to investigate the pathophysiological hallmarks of dystonia in patients affected by primary writing tremor.

Methods: Ten patients with idiopathic dystonic tremor syndrome, 7 with primary writing tremor, 10 with essential tremor, and 10 healthy subjects were recruited. They underwent eyeblink classic conditioning, blink recovery cycle, and transcranial magnetic stimulation assessment, including motor-evoked potentials and short- and long-interval intracortical inhibition at baseline. Transcranial magnetic stimulation measures were also recorded after paired-associative plasticity protocol.

Results: Primary writing tremor and dystonic tremor syndrome had a similar pattern of electrophysiological abnormalities, consisting of reduced eyeblink classic conditioning learning, reduced blink recovery cycle inhibition, and a lack of effect of paired-associative plasticity on long-interval intracortical inhibition. The latter 2 differ from those obtained in essential tremor and healthy subjects. Although not significant, slightly reduced short-interval intracortical inhibition and a larger effect of paired-associative plasticity in primary writing tremor and dystonic tremor syndrome, compared with essential tremor and healthy subjects, was observed.

Conclusions: Our initial hypothesis of a common pathophysiology between dystonia and primary writing tremor has been confirmed. Primary writing tremor might be considered a form of dystonic tremor. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28579DOI Listing
July 2021

Stimulating the deprived motor 'hand' area causes facial muscle responses in one-handers.

Brain Stimul 2021 Mar-Apr;14(2):347-350. Epub 2021 Feb 5.

Institute of Cognitive Neuroscience, University College London, London, United Kingdom.

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http://dx.doi.org/10.1016/j.brs.2021.01.022DOI Listing
February 2021

Transcranial Evoked Potentials Can Be Reliably Recorded with Active Electrodes.

Brain Sci 2021 Jan 22;11(2). Epub 2021 Jan 22.

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.

Electroencephalographic (EEG) signals evoked by transcranial magnetic stimulation (TMS) are usually recorded with passive electrodes (PE). Active electrode (AE) systems have recently become widely available; compared to PE, they allow for easier electrode preparation and a higher-quality signal, due to the preamplification at the electrode stage, which reduces electrical line noise. The performance between the AE and PE can differ, especially with fast EEG voltage changes, which can easily occur with TMS-EEG; however, a systematic comparison in the TMS-EEG setting has not been made. Therefore, we recorded TMS-evoked EEG potentials (TEPs) in a group of healthy subjects in two sessions, one using PE and the other using AE. We stimulated the left primary motor cortex and right medial prefrontal cortex and used two different approaches to remove early TMS artefacts, Independent Component Analysis and Signal Space Projection-Source Informed Recovery. We assessed statistical differences in amplitude and topography of TEPs, and their similarity, by means of the concordance correlation coefficient (CCC). We also tested the capability of each system to approximate the final TEP waveform with a reduced number of trials. The results showed that TEPs recorded with AE and PE do not differ in amplitude and topography, and only few electrodes showed a lower-than-expected CCC between the two methods of amplification. We conclude that AE are a viable solution for TMS-EEG recording.
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http://dx.doi.org/10.3390/brainsci11020145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912161PMC
January 2021

Frequency-dependent modulation of cerebellar excitability during the application of non-invasive alternating current stimulation.

Brain Stimul 2021 Mar-Apr;14(2):277-283. Epub 2021 Jan 20.

Department of Clinical and Movement Neurosciences, Institute of Neurology, University College London, United Kingdom.

Background: it is well-known that the cerebellum is critical for the integrity of motor and cognitive actions. Applying non-invasive brain stimulation techniques over this region results in neurophysiological and behavioural changes, which have been associated with the modulation of cerebellar-cerebral cortex connectivity. Here, we investigated whether online application of cerebellar transcranial alternating current stimulation (tACS) results in changes to this pathway.

Methods: thirteen healthy individuals participated in two sessions of cerebellar tACS delivered at different frequencies (5Hz and 50Hz). We used transcranial magnetic stimulation to measure cerebellar-motor cortex (M1) inhibition (CBI), short-intracortical inhibition (SICI) and short-afferent inhibition (SAI) before, during and after the application of tACS.

Results: we found that CBI was specifically strengthened during the application of 5Hz cerebellar tACS. No changes were detected immediately following the application of 5Hz stimulation, nor at any time point with 50Hz stimulation. We also found no changes to M1 intracortical circuits (i.e. SICI) or sensorimotor interaction (i.e. SAI), indicating that the effects of 5Hz tACS over the cerebellum are site-specific.

Conclusions: cerebellar tACS can modulate cerebellar excitability in a time- and frequency-dependent manner. Additionally, cerebellar tACS does not appear to induce any long-lasting effects (i.e. plasticity), suggesting that stimulation enhances oscillations within the cerebellum only throughout the stimulation period. As such, cerebellar tACS may have significant implications for diseases manifesting with abnormal cerebellar oscillatory activity and also for future behavioural studies.
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http://dx.doi.org/10.1016/j.brs.2021.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970622PMC
October 2021
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