- •A group of European experts reviewed current evidence for therapeutic efficacy of tDCS.
- •Level B evidence (probable efficacy) was found for fibromyalgia, depression and craving.
- •The therapeutic relevance of tDCS needs to be further explored in these and other indications.
Posts Tagged Cortex
Winner of the Brainlab Community Neurosurgery Award, Sandro Krieg, MD, presented his research, Plasticity of Motor Representations in Patients with Brain Lesions: a Navigated TMS Study, during the 2017 American Association of Neurological Surgeons (AANS) Annual Scientific Meeting.
This study investigated the spatial distributions of motor representations in terms of tumor-induced brain plasticity by analyzing navigated transcranial magnetic stimulation (nTMS) motor maps derived from 100 patients with motor eloquently located brain tumors in or adjacent to the precentral gyrus (PrG).
The research evoked 8,774 motor potentials (MEPs) that were elicited in six muscles of the upper and lower extremity by stimulating four gyri in patients with five possible tumor locations. Regarding the MEP frequency of each muscle-gyrus subdivision per patient, the expected frequency was 3.53 (8,774 divided by 100 patients, further divided by six muscles and four gyri). Accordingly, the patient ratio for each subdivision was calculated by defining the per-patient minimum data points as three.
The tumor-location specific patient ratios were higher for frontal tumors in both gyri than for other tumor locations. This suggests that the finger representation reorganization in these frontal gyri, which corresponds to location of dorsal premotor areas, might be due to within-premotor reorganization rather than relocation of motor function from PrG into premotor areas one might expect from the Rolandic tumors. The research indicates that reorganization of the finger motor representations might be limited along the middle-to-dorsal dimension of the dorsal premotor areas (posterior MFG and SFG) and might not cross rostrally from the primary motor cortex (PrG) to the dorsal premotor cortex.
The use of non-invasive brain neurostimulation (NIBS) techniques to treat neurological or psychiatric diseases is currently under development. Fatigue is a commonly observed symptom in the field of potentially treatable pathologies by NIBS, yet very little data has been published regarding its treatment. We conducted a review of the literature until the end of February 2017 to analyze all the studies that reported a clinical assessment of the effects of NIBS techniques on fatigue. We have limited our analysis to repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). We found only 15 studies on this subject, including 8 tDCS studies and 7 rTMS studies. Of the tDCS studies, 6 concerned patients with multiple sclerosis while 6 rTMS studies concerned fibromyalgia or chronic fatigue syndrome. The remaining 3 studies included patients with post-polio syndrome, Parkinson’s disease and amyotrophic lateral sclerosis. Three cortical regions were targeted: the primary sensorimotor cortex, the dorsolateral prefrontal cortex and the posterior parietal cortex. In all cases, tDCS protocols were performed according to a bipolar montage with the anode over the cortical target. On the other hand, rTMS protocols consisted of either high-frequency phasic stimulation or low-frequency tonic stimulation. The results available to date are still too few, partial and heterogeneous as to the methods applied, the clinical profile of the patients and the variables studied (different fatigue scores) in order to draw any conclusion. However, the effects obtained, especially in multiple sclerosis and fibromyalgia, are really carriers of therapeutic hope.
[Abstract] Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS) – Clinical Neurophysiology
A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinson’s disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer’s disease, tinnitus, depression, schizophrenia, and craving/addiction.
The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10–24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode.
It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform tDCS in a therapeutic setting. In addition, the easy management and low cost of tDCS devices allow at home use by the patient, but this might raise ethical and legal concerns with regard to potential misuse or overuse. We must be careful to avoid inappropriate applications of this technique by ensuring rigorous training of the professionals and education of the patients.
Discovery brings with it possible implications for brain regeneration –
In a cross-domain study directed by professor Peter Carmeliet (VIB – KU Leuven), researchers discovered unexpected cells in the protective membranes that enclose the brain, the so called meninges. These ‘neural progenitors’ (stem cells that differentiate into different kinds of neurons) are produced during embryonic development.
These findings show that the neural progenitors found in the meninges produce new neurons after birth, highlighting the importance of meningeal tissue as well as these cells’ potential in the development of new therapies for brain damage or neurodegeneration. A paper highlighting the results is published in the journal Cell Stem Cell.
Scientists’ understanding of brain plasticity, or the ability of the brain to grow, develop, recover from injuries and adapt to changing conditions throughout our lives, has been greatly broadened in recent years. Before the discoveries of the last few decades, neurologists once thought that the brain became ‘static’ after childhood. This dogma has changed, with researchers finding more and more evidence that the brain is capable of healing and regenerating in adulthood, thanks to the presence of stem cells. However, neuronal stem cells were generally believed to only reside within the brain tissue, not in the membranes surrounding it.
The meninges: unappreciated no more
Believed in the past to serve a mainly protective function to dampen mechanical shocks, the meninges have been historically underappreciated by science as having neurological importance in its own right. The data gathered by the team challenges the current idea that neural precursors—or stem cells that give rise to neurons—can only be found inside actual brain tissue.
Prof. Peter Carmeliet notes: “The neuronal stems cells that we discovered inside the meninges differentiate to full neurons, electrically-active and functionally integrated into the neuronal circuit. To show that the stem cells reside in the meninges, we used the extremely powerful single-cell RNA sequencing technique, a very novel top-notch technique, capable of identifying the [complex gene expression signature] nature of individual cells in a previously unsurpassed manner, a première at VIB.”
Following up on future research avenues
When it comes to future leads for this discovery, the scientists also see possibilities for translation into clinical application, though future work is required.
“An intriguing question is whether these neuronal stem cells in the meninges could lead to better therapies for brain damage or neurodegeneration. However, answering this question would require a better understanding of the molecular mechanisms that regulate the differentiation of these stem cells,” says Carmeliet. “How are these meningeal stem cells activated to become different kinds of neurons? Can we therapeutically ‘hijack’ their regeneration potential to restore dying neurons in, for example, Alzheimer’ Disease, Parkinson’s Disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative disorders? Also, can we isolate these neurogenic progenitors from the meninges at birth and use them for later transplantation? These findings open up very exciting research opportunities for the future.”
Moving into unchartered territory is high risk, and can offer high gain, but securing funding for such type of research is challenging. However, Carmeliet’s discoveries were made possible to a large extent by funding through “Opening the Future: pioneering without boundaries”, a recently created Mecenas Funding Campaign for funding of high risk brain research but with potential for breakthrough discoveries, started up by the KU Leuven in 2013 and unique in Flanders.
“Being able to use such non-conventional funding channels is of utmost importance to break new boundaries in research,” says Carmeliet. “This unique Mecenas funding initiative by the KU Leuven is innovative and boundary-breaking by itself. Our entire team is enormously grateful for the opportunities it has created for our investigations”.
Note: Material may have been edited for length and content. For further information, please contact the cited source.
Bifari F et al. Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex. Cell Stem Cell, Published Online November 23 2016. doi: 10.1016/j.stem.2016.10.020