Our objectives are to simultaneously record high-density EEG and EMG, and to use source analysis to assess the activity and communication in motor and non-motor (underlying cognition) neural networks during rest and during cognitive and motor tasks…
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Final Endpoints:
Discovered ALS biomarker(s) for reliable and early detection, as well as
distinction between different ALS subphenotypes and healthy people based on
differences in ERPs identified using EEG/EMG experiments with subsequent source
localisation.
Secondary outcome
Secondary study outcomes:
• EEG and EMG (anonymised) data sets, for wider research purposes
• Assessing the difference in terms of cortical network dysfunction in the
cognitive domains between different ALS sub-phenotypes and healthy controls
• Cross validation between obtained task-based (ERP) and resting-state
alternations in both motor and cognitive networks.
• Research Publications
Background summary
Amyotrophic Laterals Sclerosis (ALS) or Motor Neuron Disease (MND) is a
terminal neurodegenerative disease, leading to progressive loss of motor
function. Treatment of ALS remains an unresolved challenge despite intensive
research into diagnosis, prognosis and therapy. New therapeutics and the
quality of care after diagnosis can be enhanced by early, more personalised
diagnosis at individual patient level, enabling tailored care and
individualised treatment. To personalise the diagnosis, there is a need for
reliable quantitative biomarkers, for early detection of disease onset and to
distinguish the different subtypes of the disease with different symptoms and
progression rates.
In the motor domain, several biomarkers have been investigated for use in ALS,
e.g. motor unit number index (MUNIX), magnetic resonance imaging (MRI),
electromyography (EMG) and electroencephalography (EEG). However, the
diagnostic utility of these techniques, especially the inexpensive non-invasive
recordings of electrical activity (EEG/EMG) is limited: the biomarkers are not
strongly linked to the neurophysiological mechanisms affected in ALS.
Therefore, it is of interest to distinguish and dissociate the
electrophysiological signatures that reflect sensorimotor network communication
patterns pertaining to each sub-system in function and dysfunction, which in
turn can act as biomarkers. This aim can be achieved with simultaneous EMG/EEG
recordings.
In the cognitive domain, it has been shown that ALS patients may present with
frontotemporal dementia (FTD) (13%), significant cognitive impairment (30%),
and behavioural changes (~50%) that map onto network disruption in
orbitofrontal, frontotemporal, and fronto-striatal neural pathways. From a
pathobiological perspective, there is an overlap between ALS and
neuropsychiatric conditions in population-based studies (~30% of ALS kindreds
have family history of conditions such as schizophrenia) and genomic studies
(4% polygenic overlap between ALS and schizophrenia).
Taken together, this gives a compelling argument in favour of studying the
heterogeneity within ALS in the context of a wider disturbance of different
neural networks, rather than at the level of individual (motor or non-motor)
networks.
Study objective
Our objectives are to simultaneously record high-density EEG and EMG, and to
use source analysis to assess the activity and communication in motor and
non-motor (underlying cognition) neural networks during rest and during
cognitive and motor tasks. These objectives will be achieved by conducting the
resting-state (no task) and task-based event-related potential (ERP) paradigms;
e.g. mismatch negativity (MMN), sustained attention to response task (SART) and
Stroop test. Source localisation methods will be applied on the collected
EEG/EMG data, as well as unsupervised clustering of the measures of network
function.
The key objectives of our project ALS-Electrode are:
1. To cross-sectionally and longitudinally define the disrupted resting-state
networks (in-cluding the communication between the primary motor cortices and
between the frontal-parietal networks), using EEG source and connectivity
analysis; and to identify the motor and cognitive nature of the impairments by
correlates to neuropsychological batteries, motor performance measures and
structural MRI.
2. To identify biomarkers of disruption in non-motor networks associated with
functional neuropsychological tasks using evoked response potentials (ERPs).
This analysis in-cludes behavioural performance measures such as Mismatch
Negativity (MMN), SART, Stroop and oddball tasks, as well as the accompanying
source-localised EEG activity and connectivity that interrogate cognitive
networks (involving frontal dysfunction), against experiment control conditions
(practice and motor effects) and age/gender-matched controls.
3. To identify biomarkers of disruption in motor networks using source-resolved
cortico-muscular communication. The source-space signatures of cortico-muscular
communication *image* and quantify the disruption of broader cortical
projections to the spinal cord during active motor tasks.
In doing so, our aim is to advance understanding of ALS pathology and identify
novel, inexpensively measured biomarkers that can distinguish these
neurodegenerations and their sub-phenotypes from healthy individuals. Such
biomarkers have applications in disease prognostics and measurement of
therapeutic activity of neurotherapeutic candidates. Successful discrimination
of the electrophysiological signatures can be used to diagnose ALS which may be
also useful in terms of better patient care and the development of novel
neuro-motor rehabilitation.
Study design
Observational study, cross-sectional and longitudinal design.
Study burden and risks
Serious risks with low probability: Similar to any recording, there is a remote
risk of electric shock, device malfunction, etc. The device is a CE (Conformité
European) certified regarding the electromagnetic compatibility and electrical
safety for research purposes. The recording system is powered from a battery
and connected to a computer using optical technology (hence, electrically
isolated from the power grid); Consequently, the risks associated to such
incidences are very low, similar to many day-to-day situations.
Transient benign risks with low probability: The risks of the procedures
executed during the experiment set-up and recording are low. The subjects may
show allergic reactions to the recording gels (though this is an exclusion
criteria) that can be managed by medications. This is expected to be extremely
rare, if not beyond the bounds of possibility.
Probable discomforts: The experiments may be boring or tiring for some patients
as it requires remaining in sitting position for more than an hour. People may
need to wash their hair after the experiment. The removal of medicine tapes on
hand and forearm may be painful or uncomfortable for some patients. The
experimenter will use maximum care to minimise such discomforts by allowing
limited mobility to the patient between the recording sessions.
Other Risks: Other risks of participating in the experiment are considered to
be minimal and not greater than the normal life of the participant.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
1. Belong to one cohort of interest
a. ALS patients: definite, probable, probable-laboratory supported or possible
ALS according to the revised El Escorial criteria (Brooks et al., 2000)
b. PMA/PLS patients: patients with clinical diagnosis of PMA or PLS, after
excluding other diseases.
c. Asymptomatic carriers: Carriers of ALS-related gene mutations with no
neurological symptoms associated with ALS
d. Healthy controls: age- and gender-matched to patient groups, intact physical
ability to take part in the experiment
2. Age 18-80 years (inclusive)
3. Capable of thoroughly understanding the study information given; has signed
the informed consent.
Exclusion criteria
Exclusion criteria for all participants:
• Pregnancy
• History of major head trauma
• Any medical condition associated with neuropathy (e.g. diabetes), transient
ischemic attack, stroke, epilepsy, seizure disorder, brain tumours and other
comorbidities (e.g. human immunodeficiency virus)
• Alcohol dependence syndrome, current use of neuroleptic medications or high
dose psychoactive medication
• History of reaction or allergy to recording environments, equipment and the
recording gels
• Tracheostomy, tracheostomal ventilation of any type or frequent need for
(non)-invasive ventilation
Further exclusion criteria for patients:
• Insufficient dominant hand function to perform button pressing (SART/Stroop)
and/or motor tasks
Further exclusion criteria for healthy controls and asymptomatic carriers:
History of neuromuscular, neurological or active psychiatric disease.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL70373.041.19 |