Publications by authors named "Verity M McClelland"

15 Publications

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EEG measures of sensorimotor processing and their development are abnormal in children with isolated dystonia and dystonic cerebral palsy.

Neuroimage Clin 2021 Jan 19;30:102569. Epub 2021 Jan 19.

Children's Neurosciences Department, Evelina London Children's Hospital, Guy's and St Thomas NHS Foundation Trust, London SE1 7EH, United Kingdom. Electronic address:

Dystonia is a disorder of sensorimotor integration associated with abnormal oscillatory activity within the basal ganglia-thalamo-cortical networks. Event-related changes in spectral EEG activity reflect cortical processing but are sparsely investigated in relation to sensorimotor processing in dystonia. This study investigates modulation of sensorimotor cortex EEG activity in response to a proprioceptive stimulus in children with dystonia and dystonic cerebral palsy (CP). Proprioceptive stimuli, comprising brief stretches of the wrist flexors, were delivered via a robotic wrist interface to 30 young people with dystonia (20 isolated genetic/idiopathic and 10 dystonic CP) and 22 controls (mean age 12.7 years). Scalp EEG was recorded using the 10-20 international system and the relative change in post-stimulus power with respect to baseline was calculated for the alpha (8-12 Hz) and beta (14-30 Hz) frequency bands. A clear developmental profile in event-related spectral changes was seen in controls. Controls showed a prominent early alpha/mu band event-related desynchronisation (ERD) followed by an event-related synchronisation (ERS) over the contralateral sensorimotor cortex following movement of either hand. The alpha ERD was significantly smaller in the dystonia groups for both dominant and non-dominant hand movement (ANCOVA across the 3 groups with age as covariate: dominant hand F(2,47) = 4.45 p = 0.017; non-dominant hand F(2,42) = 9.397 p < 0.001. Alpha ERS was significantly smaller in dystonia for the dominant hand (ANCOVA F(2,47) = 7.786 p = 0.001). There was no significant difference in ERD or ERS between genetic/idiopathic dystonia and dystonic CP. CONCLUSION: Modulation of alpha/mu activity by a proprioceptive stimulus is reduced in dystonia, demonstrating a developmental abnormality of sensorimotor processing which is common to isolated genetic/idiopathic and acquired dystonia/dystonic CP.
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http://dx.doi.org/10.1016/j.nicl.2021.102569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044718PMC
January 2021

Abnormal microscale neuronal connectivity triggered by a proprioceptive stimulus in dystonia.

Sci Rep 2020 11 27;10(1):20758. Epub 2020 Nov 27.

Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RX, UK.

We investigated modulation of functional neuronal connectivity by a proprioceptive stimulus in sixteen young people with dystonia and eight controls. A robotic wrist interface delivered controlled passive wrist extension movements, the onset of which was synchronised with scalp EEG recordings. Data were segmented into epochs around the stimulus and up to 160 epochs per subject were averaged to produce a Stretch Evoked Potential (StretchEP). Event-related network dynamics were estimated using a methodology that features Wavelet Transform Coherency (WTC). Global Microscale Nodal Strength (GMNS) was introduced to estimate overall engagement of areas into short-lived networks related to the StretchEP, and Global Connectedness (GC) estimated the spatial extent of the StretchEP networks. Dynamic Connectivity Maps showed a striking difference between dystonia and controls, with particularly strong theta band event-related connectivity in dystonia. GC also showed a trend towards higher values in dystonia than controls. In summary, we demonstrate the feasibility of this method to investigate event-related neuronal connectivity in relation to a proprioceptive stimulus in a paediatric patient population. Young people with dystonia show an exaggerated network response to a proprioceptive stimulus, displaying both excessive theta-band synchronisation across the sensorimotor network and widespread engagement of cortical regions in the activated network.
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http://dx.doi.org/10.1038/s41598-020-77533-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695825PMC
November 2020

Application of Machine Learning Using Decision Trees for Prognosis of Deep Brain Stimulation of Globus Pallidus Internus for Children With Dystonia.

Front Neurol 2020 Aug;11:825

Children's Neurosciences Department, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

Background: While Deep Brain Stimulation (DBS) of the Globus pallidus internus is a well-established therapy for idiopathic/genetic dystonia, benefits for acquired dystonia are varied, ranging from modest improvement to deterioration. Predictive biomarkers to aid DBS prognosis for children are lacking, especially in acquired dystonias, such as dystonic Cerebral Palsy. We explored the potential role of machine learning techniques to identify parameters that could help predict DBS outcome.

Methods: We conducted a retrospective study of 244 children attending King's College Hospital between September 2007 and June 2018 for neurophysiological tests as part of their assessment for possible DBS at Evelina London Children's Hospital. For the 133 individuals who underwent DBS and had 1-year outcome data available, we assessed the potential predictive value of six patient parameters: sex, etiology (including cerebral palsy), baseline severity (Burke-Fahn-Marsden Dystonia Rating Scale-motor score), cranial MRI and two neurophysiological tests, Central Motor Conduction Time (CMCT) and Somatosensory Evoked Potential (SEP). We applied machine learning analysis to determine the best combination of these features to aid DBS prognosis. We developed a classification algorithm based on Decision Trees (DTs) with k-fold cross validation for independent testing. We analyzed all possible combinations of the six features and focused on acquired dystonias.

Results: Several trees resulted in better accuracy than the majority class classifier. However, the two features that consistently appeared in top 10 DTs were CMCT and baseline dystonia severity. A decision tree based on CMCT and baseline severity provided a range of sensitivity and specificity, depending on the threshold chosen for baseline dystonia severity. In situations where CMCT was not available, a DT using SEP alone provided better than the majority class classifier accuracy.

Conclusion: The results suggest that neurophysiological parameters can help predict DBS outcomes, and DTs provide a data-driven, highly interpretable decision support tool that lends itself to being used in clinical practice to help predict potential benefit of DBS in dystonic children. Our results encourage the introduction of neurophysiological parameters in assessment pathways, and data collection to facilitate multi-center evaluation and validation of these potential predictive markers and of the illustrative decision support tools presented here.
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http://dx.doi.org/10.3389/fneur.2020.00825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115974PMC
August 2020

Abnormal patterns of corticomuscular and intermuscular coherence in childhood dystonia.

Clin Neurophysiol 2020 04 4;131(4):967-977. Epub 2020 Feb 4.

Medical Research Council Brain Network Dynamics Unit and Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom. Electronic address:

Objective: Sensorimotor processing is abnormal in Idiopathic/Genetic dystonias, but poorly studied in Acquired dystonias. Beta-Corticomuscular coherence (CMC) quantifies coupling between oscillatory electroencephalogram (EEG) and electromyogram (EMG) activity and is modulated by sensory stimuli. We test the hypothesis that sensory modulation of CMC and intermuscular coherence (IMC) is abnormal in Idiopathic/Genetic and Acquired dystonias.

Methods: Participants: 11 children with Acquired dystonia, 5 with Idiopathic/Genetic dystonia, 13 controls (12-18 years). CMC and IMC were recorded during a grasp task, with mechanical perturbations provided by an electromechanical tapper. Coherence patterns pre- and post-stimulus were compared across groups.

Results: Beta-CMC increased post-stimulus in Controls and Acquired dystonia (p = 0.001 and p = 0.010, respectively), but not in Idiopathic/Genetic dystonia (p = 0.799). The modulation differed between groups, being larger in both Controls and Acquired dystonia compared with Idiopathic/Genetic dystonia (p = 0.003 and p = 0.022). Beta-IMC increased significantly post-stimulus in Controls (p = 0.004), but not in dystonia. Prominent 4-12 Hz IMC was seen in all dystonia patients and correlated with severity (rho = 0.618).

Conclusion: Idiopathic/Genetic and Acquired dystonia share an abnormal low-frequency IMC. In contrast, sensory modulation of beta-CMC differed between the two groups.

Significance: The findings suggest that sensorimotor processing is abnormal in Acquired as well as Idiopathic/Genetic dystonia, but that the nature of the abnormality differs.
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http://dx.doi.org/10.1016/j.clinph.2020.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083222PMC
April 2020

Disease-specific patterns of basal ganglia neuronal activity in Neurodegeneration with Brain Iron Accumulation type I (NBIA-1).

Clin Neurophysiol 2019 06 26;130(6):877-878. Epub 2019 Mar 26.

Complex Motor Disorders Service, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

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http://dx.doi.org/10.1016/j.clinph.2019.03.005DOI Listing
June 2019

Somatosensory Evoked Potentials and Central Motor Conduction Times in children with dystonia and their correlation with outcomes from Deep Brain Stimulation of the Globus pallidus internus.

Clin Neurophysiol 2018 02 24;129(2):473-486. Epub 2017 Nov 24.

Complex Motor Disorder Service, Children's Neurosciences Department, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London SE1 7EH, United Kingdom. Electronic address:

Objectives: To report Somatosensory Evoked Potentials (SEPs) and Central Motor Conduction Times (CMCT) in children with dystonia and to test the hypothesis that these parameters predict outcome from Deep Brain Stimulation (DBS).

Methods: 180 children with dystonia underwent assessment for Globus pallidus internus (GPi) DBS, mean age 10 years (range 2.5-19). CMCT to each limb was calculated using Transcranial Magnetic Stimulation. Median and posterior tibial nerve SEPs were recorded over contralateral and midline centro-parietal scalp. Structural abnormalities were assessed with cranial MRI. One-year outcome from DBS was assessed as percentage improvement in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-m).

Results: Abnormal CMCTs and SEPs were found in 19% and 47% of children respectively and were observed more frequently in secondary than primary dystonia. Of children proceeding to DBS, better outcome was seen in those with normal (n = 78/89) versus abnormal CMCT (n = 11/89) (p = 0.002) and those with normal (n = 35/51) versus abnormal SEPs (n = 16/51) (p = 0.001). These relationships were independent of dystonia aetiology and cranial MRI findings.

Conclusions: CMCTs and SEPs provide objective evidence of motor and sensory pathway dysfunction in children with dystonia and relate to DBS outcome.

Significance: CMCTs and SEPs can contribute to patient selection and counselling of families about potential benefit from neuromodulation for dystonia.
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http://dx.doi.org/10.1016/j.clinph.2017.11.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786451PMC
February 2018

Cortico-muscular coherence enhancement via coherent Wavelet enhanced Independent Component Analysis.

Annu Int Conf IEEE Eng Med Biol Soc 2017 Jul;2017:2786-2789

Functional coupling between the motor cortex and muscle activity is usually detected and characterized using the spectral method of cortico-muscular coherence (CMC) between surface electromyogram (sEMG) and electroencephalogram (EEG) recorded synchronously under motor control task. However, CMC is often weak and not easily detectable in all individuals. One of the reasons for the low levels of CMC is the presence of noise and components unrelated to the considered tasks in recorded sEMG and EEG signals. In this paper we propose a method for enhancing relative levels of sEMG components coherent with synchronous EEG signals via a variant of Wavelet Independent Component Analysis combined with a novel component selection algorithm. The effectiveness of the proposed algorithm is demonstrated using data collected in neurophysiologcal experiments.
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http://dx.doi.org/10.1109/EMBC.2017.8037435DOI Listing
July 2017

The neurophysiology of paediatric movement disorders.

Curr Opin Pediatr 2017 Dec;29(6):683-690

aDivision of Neuroscience, Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London bComplex Motor Disorder Service, Children's Neurosciences Department, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust cDepartment of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

Purpose Of Review: To demonstrate how neurophysiological tools have advanced our understanding of the pathophysiology of paediatric movement disorders, and of neuroplasticity in the developing brain.

Recent Findings: Delineation of corticospinal tract connectivity using transcranial magnetic stimulation (TMS) is being investigated as a potential biomarker for response to therapy. TMS measures of cortical excitability and neuroplasticity are also being used to investigate the effects of therapy, demonstrating neuroplastic changes that relate to functional improvements. Analyses of evoked potentials and event-related changes in the electroencephalogaphy spectral activity provide growing evidence for the important role of aberrant sensory processing in the pathophysiology of many different movement disorders. Neurophysiological findings demonstrate that children with clinically similar phenotypes may have differing underlying pathophysiology, which in turn may explain differential response to therapy. Neurophysiological parameters can act as biomarkers, providing a means to stratify individuals, and are well suited to provide biofeedback. They therefore have enormous potential to facilitate improvements to therapy.

Summary: Although currently a small field, the role of neurophysiology in paediatric movement disorders is poised to expand, both fuelled by and contributing to the rapidly growing fields of neuro-rehabilitation and neuromodulation and the move towards a more individualized therapeutic approach.
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http://dx.doi.org/10.1097/MOP.0000000000000547DOI Listing
December 2017

Corticomuscular Coherence With Time Lag With Application to Delay Estimation.

IEEE Trans Biomed Eng 2017 03 17;64(3):588-600. Epub 2016 May 17.

Functional coupling between the motor cortex and muscle activity is usually detected and characterized using the spectral method of corticomuscular coherence (CMC). This functional coupling occurs with a time delay, which, if not properly accounted for, may decrease the coherence and make the synchrony difficult to detect. In this paper, we introduce the concept of CMC with time lag (CMCTL), that is the coherence between segments of motor cortex electroencephalogram (EEG) and electromyography (EMG) signals displaced from a central observation point. This concept is motivated by the need to compensate for the unknown delay between coupled cortex and muscle processes. We demonstrate using simulated data that under certain conditions the time lag between EEG and EMG segments at points of local maxima of CMCTL corresponds to the average delay along the involved corticomuscular conduction pathways. Using neurophysiological data, we then show that CMCTL with appropriate time lag enhances the coherence between cortical and muscle signals, and that time lags which correspond to local maxima of CMCTL provide estimates of delays involved in corticomuscular coupling that are consistent with the underlying physiology.
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http://dx.doi.org/10.1109/TBME.2016.2569492DOI Listing
March 2017

EMG rectification has inconsistent effects on coherence analysis even in single motor unit studies.

J Neurophysiol 2014 Mar;111(5):1150

Academic Unit of Clinical Neurophysiology, King's College Hospital, London, United Kingdom; and.

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http://dx.doi.org/10.1152/jn.00801.2013DOI Listing
March 2014

Modulation of corticomuscular coherence by peripheral stimuli.

Exp Brain Res 2012 Jun 24;219(2):275-92. Epub 2012 Apr 24.

Academic Unit of Clinical Neurophysiology, King's College London, London, SE5 9RS, UK.

The purpose of this study was to investigate the effects of peripheral afferent stimuli on the synchrony between brain and muscle activity as estimated by corticomuscular coherence (CMC). Electroencephalogram (EEG) from sensorimotor cortex and electromyogram (EMG) from two intrinsic hand muscles were recorded during a key grip motor task, and the modulation of CMC caused by afferent electrical and mechanical stimulation was measured. The particular stimuli used were graded single-pulse electrical stimuli, above threshold for perception and activating cutaneous afferents, applied to the dominant or non-dominant index finger, and a pulsed mechanical displacement of the gripped object causing the subject to feel as if the object may be dropped. Following electrical stimulation of the dominant index finger, the level of β-range (14-36 Hz) CMC was reduced in a stimulus intensity-dependent fashion for up to 400 ms post-stimulus, then returned with greater magnitude before falling to baseline levels over 2.5 s, outlasting the reflex and evoked changes in EMG and EEG. Subjects showing no baseline β-range CMC nevertheless showed post-stimulus increases in β-range CMC with the same time course as those with baseline β-range CMC. The mechanical stimuli produced similar modulation of β-range CMC. Electrical stimuli to the non-dominant index finger produced no significant increase in β-range CMC. The results suggest that both cutaneous and proprioceptive afferents have access to circuits generating CMC, but that only a functionally relevant stimulus produces significant modulation of the background β-range CMC, providing further evidence that β-range CMC has an important role in sensorimotor integration.
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http://dx.doi.org/10.1007/s00221-012-3087-7DOI Listing
June 2012

Rectification of the EMG is an unnecessary and inappropriate step in the calculation of Corticomuscular coherence.

J Neurosci Methods 2012 Mar 17;205(1):190-201. Epub 2011 Nov 17.

Academic Unit of Clinical Neurophysiology, King's College Hospital, Denmark Hill, London SE5 9RS, UK.

Corticomuscular coherence (CMC) estimation is a frequency domain method used to detect a linear coupling between rhythmic activity recorded from sensorimotor cortex (EEG or MEG) and the electromyogram (EMG) of active muscles. In motor neuroscience, rectification of the surface EMG is a common pre-processing step prior to calculating CMC, intended to maximize information about action potential timing, whilst suppressing information relating to motor unit action potential (MUAP) shape. Rectification is believed to produce a general shift in the EMG spectrum towards lower frequencies, including those around the mean motor unit discharge rate. However, there are no published data to support the claim that EMG rectification enhances the detection of CMC. Furthermore, performing coherence analysis after the non-linear procedure of rectification, which results in a significant distortion of the EMG spectrum, is considered fundamentally flawed in engineering and digital signal processing. We calculated CMC between sensorimotor cortex EEG and EMG of two hand muscles during a key grip task in 14 healthy subjects. CMC calculated using unrectified and rectified EMG was compared. The use of rectified EMG did not enhance the detection of CMC, nor was there any evidence that MUAP shape information had an adverse effect on the CMC estimation. EMG rectification had inconsistent effects on the power and coherence spectra and obscured the detection of CMC in some cases. We also provide a comprehensive theoretical analysis, which, along with our empirical data, demonstrates that rectification is neither necessary nor appropriate in the calculation of CMC.
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http://dx.doi.org/10.1016/j.jneumeth.2011.11.001DOI Listing
March 2012

Glutaric aciduria type 1 presenting with epilepsy.

Dev Med Child Neurol 2009 Mar;51(3):235-9

Evelina Children's Hospital, Guy's and St Thomas' NHS Trust, London, UK.

Glutaric aciduria type 1 (GA-1, OMIM 608801) is an autosomal-recessive disorder resulting from a deficiency of glutaryl-CoA dehydrogenase (GCDH). Clinical expression usually involves an acute encephalopathic episode in infancy, followed by the development of severe dystonia-dyskinesia. Other presentations include mild developmental delay, macrocephaly, and subdural haematoma. Seizures may occur with the acute encephalopathy but are unusual in the long term, unless motor or cognitive difficulties are severe. We report a 6-year-old female who was referred with recurrent epileptic seizures that proved difficult to control with first-line anticonvulsants. There was no history of encephalopathy. She had no neurological or developmental abnormalities. The electroencephalogram was profoundly abnormal with slow background and mixed multifocal and generalized spike-and-wave discharges. Seizures deteriorated on valproic acid. Cranial magnetic resonance imaging showed widened Sylvian fissures. Metabolic investigations revealed GA-1. She has improved on a low-protein diet, carnitine, levetiracetam, and lamotrigine. This is the first report of epileptic seizures as the sole presenting feature of GA-1 and it potentially adds to the clinical spectrum of this disorder. Furthermore, the case emphasizes the role of metabolic investigation when first- or second-line treatment of epilepsy is unsuccessful.
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http://dx.doi.org/10.1111/j.1469-8749.2008.03240.xDOI Listing
March 2009