Functional Brain Network Topology of ALS Patients as Evident In Disability

Amyotrophic Lateral Sclerosis (ALS) can be regarded as one of the most fatal neurodegenerative diseases and is characterised by affecting the upper and lower motor neurons. Notably, all motor functions are gradually overruled and barely survive past 3 years after the onset of ALS symptoms. Reports confirm increasing loss of network structure in patients with ALS and this network of impaired connectivity spreads over time.

Definition of Neuroimaging

Neuroimaging is the use of varied techniques to either directly or indirectly image the structure and function of the nervous system.
Functional brain imaging is the study of human brain function based on analysis of data acquired using brain imaging modalities such as Electroencephalography (EEG), Magnetoencephalography (MEG), functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET) or Optical Imaging.
Going by the potential for investigation of both brain structure and function, advanced neuroimaging methods give significant opportunities to improve diagnosis, guide prognosis, and direct future treatment strategies in ALS.

Electroencephalography (EEG)

It is a test that detects electrical activity in the human brain using small, flat metal disks known as electrodes that are attached to the scalp. The brain cells then communicate through electrical impulses that are active all the time. The electrodes are able to detect brainwave and the EEG machine amplifies signals and records them in a wave pattern on a computer screen
It is used in identification of problems in the electrical activity of the brain that may be associated with particular neurological disorders such as ALS. In its working, the measurements given by an EEG are used in ascertaining or elimination of certain conditions such as seizure disorders and head injury. The recorded wave forms show the cortical electrical activity. EEG is significantly small and is measured in microvolts (mV).

The use of EEG as an approach in analysis possesses a number of significant advantages over other techniques. For instance, when compared to fMRI, EEG has the upper hand because:

• It is a direct measure of neuronal activity.
• It allows time-frequency analysis of this activity.
• It is also barely impacted on by head motion.
• It can more readily be used with challenging patient populations such as ALS patients.
• The hardware and maintenance costs involved are significantly low.
• The high temporal resolution enables the study of dynamic processes involved in brain diseases such as ALS.

What is the Functional Network of the brain?

It basically refers to how the brain is wired, that is, how neurons connect with other neurons. In the case where a neuron dies, the neuron it was connected to has to reconnect to another neuron.

The advancement in science and technology has enabled perception of the human brain as a complex system of interacting units. The organization of networks in the brain can be distinguished by use of a number of metrics that facilitate approximation of functional integration and segregation and quantification of centrality of brain regions.

The alterations to the network topology have been identified for several neurological disorders such as ALS as well as psychiatric disorders. These changes consist of focal loss of grey and white matter and reductions in white matter tract integrity, changes in neural networks, metabolism and receptor distribution in the brain.

Studies on Functional Network Topology of ALS patients

ALS is known to be a result of continuous impairment in a fixed set of motor neuron connections, loss of activity in these neurons and therefore causing disability. The neuroimaging studies that have been carried out have criticized this belief owing to the fact that the disease can spread widely along numerous non-motor neuron links too. Thus, the principle that ALS is a representation of the outcome of widespread and progressive impairment of a defined set of motor connections is discredited.

Even more importantly, studies done in the past have given the idea that alteration in the network composition of the brain takes place in patients with ALS. This consequently causes functional and structural degeneration of neuronal connections and as a result the brain’s neuronal network is re-arranged. Observations have been made indicating that structural motor network degeneration suggests spread of ALS along functional connections of the motor network.

There is hope in the study of ALS since advanced neuroimaging techniques have facilitated the non-invasive investigation of structural and functional brain organization. These modern methods as it stands are assisting in the pathology and physiology of the neurodegenerative disease.

The employment of neuroimaging techniques has aided in clarifying the fundamental mechanisms that are associated with the development, spread and progression of ALS. A recent study that was conducted has also reinforced the utilization of resting-state EEG a potential biomarker for ALS. This implied that a pathologic interference of the network can be established in the initial stage of the neurological disorder. However, there is need to address methodological issues that may influence both network reconstruction and connectivity estimation.

In the recent past, research has shown that patients with ALS possess a distinct functional brain network in comparison to otherwise healthy people. This has been established by studies that have seen the difference and can be heavily linked with disability. ALS involves the loss of neurons and this translates to continuous re-wiring of the motor neurons. When this takes place, the process is compelled and anomalous which can be attributed to disease disability. The findings obtained from this research have supported research done prior that observed change in the brains of ALS patients. From the monitoring, it was evident that the changes in the brain’s neuronal network can facilitate the evaluation of ALS as a disease and it probable progression over time.

A study that was aimed at gathering information on EEG functional network topology associated with disability in ALS patients was recently conducted. Researchers mobilized and analyzed 21 patients with ALS with an average age of 66 are various stages of impairment. They also extended the analysis to 16 age-matched persons by making use of two distinct EEG parameters. This was in order to compare the outcome of the ALS patients to the age-matched healthy controls. The objective was to find out if ALS is associated with changes in the neuronal network of the brain and whether the re-organization was linked to disability. A hypothesis was formulated that functional network topology is perturbed in ALS and that the re-organization is linked to disability.

Results Analysis

The resulting analysis showed that, for a fact, ALS patients have a disparate brain network arrangement in comparison to healthy individuals. This disparity was notably correlated with disability. This outcome suggested that the topology of resting-state functional networks in ALS is affected by the disease in relation to disability. In addition, the results demonstrated that EEG analysis can be useful tool when it comes to aiding in the monitoring and evaluation of the clinical status of patients with ALS.

As had been earlier hypothesized, findings implied that ALS changes the brain network topology which thus exhibits a tendency to deviate from normal, probably optimal organization. ALS shows signs of affecting extra-motor brain regions, an outcome that matches the idea that pathological perturbations are rarely confined to a single locus.

Researchers further observed that studies that had been carried out in the past displayed a direct relation between disability and disease progression. Even more interesting, this observed correlation between the network organization and the disease disability gave the idea that there was probability of monitoring progression of ALS based on EEG analysis. The structural and functional connectivity degeneration in ALS go hand in hand and the resultant pathogenic process affects the functional and structural network organization of the brain.

Most neuroimaging studies have shortcomings, such as a small number of patients, inadequate clinical characterization of patients, absence of adequate controls, and scarcity of longitudinal assessments. With advanced research, future studies will be undertaken using a bigger group of ALS patients in a bid to confirm the results from this particular study. In addition, studies involving research teams’ collaborations and standardized assessments will overcome these limitations and provide further insight into the development and progression of ALS. In spite of the above results being promising, the perception of how the brain’s functional networks are perturbed in ALS patients and how this can be related to disability is unclear.

On an interesting note, a similar shift towards a more decentralized functional brain network topology has been previously established in Parkinson’s disease and Multiple Sclerosis. Also, functional networks in epilepsy patients that respond to vagal nerve stimulation reorganize towards a more centralized topology. These deductions suggest that there is a probable prevalent pathway in neurological disorders.

Although EEG has been used widely to assess brain disorders, it has not been utilized broadly to evaluate the functional network changes brought about by ALS. The detection of a distinctive EEG network properties stands as a difficult undertaking in the early stages of ALS. Hence, it can be speculated that EEG functional network topology is associated with disability in patients of ALS. EEG therefore still has an important role in the study of ALS.