Alterations in white matter may affect how patients respond to non-invasive electrical brain stimulation


    Tiny changes in the microscopic structure of the human brain may affect how patients respond to an emerging therapy for neurological problems.

    The technique, called non-invasive electrical brain stimulation, involves applying an electrical current to the surface of a patient’s head to stimulate brain cells, altering the patient’s brain activity.

    It is being trialled for a range of neurological problems including recovery from stroke, traumatic brain injury, dementia, and depression, but research to date has found the effects to be inconsistent

    Now, a team led by researchers at Imperial College London has shed more light on why these inconsistencies occur and may provide physical evidence for why some patients respond better than others – because of the fine structure of their brain tissue.

    The new research suggests it may be possible to target the therapy to those patients most likely to benefit.

    They found that differences in the makeup of the brain’s white matter – the tissue deep in the brain and rich in the branching ‘tails’ of nerve cells – were key.

    The research revealed that those who had more connectivity in the regions being stimulated were more likely to respond better to the treatment.

    According to the team, the findings, published in the journal Brain, could help to personalise the non-invasive electrical brain stimulation, targeting the treatment to patients who are most likely to gain clinical benefits.

    Dr Lucia Li, a clinical lecturer in neurology in the Department of Brain Sciences at Imperial College London, and lead author of the study, said:

    “With all the current buzz around brain stimulation for altering brain activity, it’s important to understand who will benefit most from this technique in the clinic.

    “Problems with white matter structure are a feature of a range of different neurological conditions.

    Our study is a step towards more personalised use of brain stimulation, which will improve the outcomes using this technique, as well as reduce the number of people treated un-necessarily.”

    In the study, researchers looked at 24 healthy patients and 35 patients recovering from a moderate or severe traumatic brain injury (TBI).

    Participants performed a task inside an MRI scanner (see ‘The Stop Signal Task’ in notes to editors) while receiving small amounts of electrical current through electrodes on the surface of the scalp or a placebo. They were unable to tell whether they were receiving brain stimulation or not.

    They found that healthy participants who received brain stimulation performed better in the task than when they didn’t receive the treatment.

    For patient with TBI, task performance in response to stimulation varied widely.

    However, when they analysed MRI scans, they found that those participants with highly-connected white matter in the brain region being stimulated responded best to the treatment, and those who had damaged or less-connected regions of white matter showed less improvement.

    They also found that brain stimulation could partially reverse some of the abnormalities in brain activity caused by TBI.

    The team cautions that while more work is needed to confirm the findings, it could mean brain stimulation might prove a useful treatment approach for other neurological conditions with abnormal brain activity as a feature, such as dementia.

    “We found that people with stronger white matter connections in their brain had better improvement with stimulation,” Dr Li explained.

    “This might be an important reason why previous studies have found that some people benefit from stimulation, whilst others don’t and means we can start using brain stimulation in a more personalised way.”

    This shows brain scans

    Tiny changes in the microscopic structure of the human brain may affect how patients respond to an emerging therapy for neurological problems. The image is credited to Lucia Li et al.

    According to the researchers, the study is limited in that in that they only investigated one type of cognitive behaviour and would need to be replicated in other types of behaviour to show if the findings apply more generally.

    In addition, they only stimulated one region of the brain, so they don’t know whether the effects are specific to this region, or whether other regions can be stimulated.

    Dr Li explains the team will now focus on larger studies with more participants to investigate what other factors influence someone’s response to brain stimulation.

    They will also apply the technique to other conditions with abnormalities in brain activity to see if they can alter activity and improve brain function.

    Funding: The work was supported by the Wellcome Trust and the National Institute for Health Research. Patients were predominantly recruited from St Mary’s Hospital (Imperial College Healthcare NHS Trust) and imaged at the Imperial College Clinical Imaging Facility.

    Deep brain stimulation (DBS) is an effective and widely used treatment option for various movement disorders such as Parkinson’s disease (PD), tremor, or dystonia(12).

    Many efforts have been made to study the clinical side effects of chronic stimulation and the peri-procedural risks, also complications are well-characterized (37).

    However, there is limited data available on the potential damage to brain parenchyma through the implanted electrodes and leads in the course of DBS therapy.

    Histopathological autopsy studies on brains of DBS patients have been performed to assess the long-term structural effects of DBS electrodes and leads on brain tissue (813).

    The largest study, examining 26 post-mortem brains of DBS patients, showed only mild to moderate gliosis to DBS lead placement (13).

    Another study analyzed brain tissue of 10 patients treated with DBS up to 7.5 years and found minor axonal changes around the DBS electrode (14).

    Two retrospective studies analyzing postoperative MRI scans (with a maximum of 3 months after DBS surgery) have detected transient white matter changes, whose origin and significance remain uncertain (1516).

    Englot and colleagues found T2 signal hyperintensity surrounding DBS leads on postoperative MRI scans in 6.3% of 239 implants in 133 patients (15).

    The changes were considered to be non-infectious and non-hemorrhagic, but instead as a reactive and inflammatory tissue response.

    They were considered to be transient in nature and could not be correlated to a clinical manifestation of symptoms or worsening of stimulation effects (1516).

    Over the past years, DBS patients in our center underwent MRI imaging during the follow-up for various reasons in addition to immediate postoperative imaging. MRI imaging has been demonstrated to be safe for patients with a (Medtronic®) DBS system, following certain precautions and restrictions (see 17 MRI GUIDELINES for Medtronic Deep Brain Stimulation Systems 2010).

    It can provide excellent anatomical resolution and is routinely being used for postoperative imaging in order to detect complications and to confirm electrode placement (1819). Noticeably, we have observed white matter changes around the electrode lead (for an example see Figure ​Figure1).1).

    This prompted us to assess the occurrence of MRI changes in patients treated with DBS in a retrospective study to obtain more information about potential effects of DBS on brain parenchyma.

    An external file that holds a picture, illustration, etc.
    Figure 1
    Hyperintense signal changes on MRI in a 58-year old patient treated with DBS for Parkinson’s disease. The MRI was conducted about 3 years after STN-DBS surgery. The image shows hyperintense white matter lesions around the upper electrode lead on axial T2 series.

    Imperial College London
    Media Contacts: 
    Ryan O’Hare – Imperial College London
    Image Source:
    The image is credited to Lucia Li et al.

    Original Research: Open access
    “Traumatic axonal injury influences the cognitive effect of non-invasive brain stimulation”. Lucia Li et al.
    Brain. doi:10.1093/brain/awz252


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