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Frontotemporal dementia (FTD) is a neurodegenerative condition with devastating consequences which has not received due attention, and as such, we currently have no effective treatment for it. Despite their similarities, FTD is less common than Alzheimer’s disease, but its impact is more damaging as it has an earlier onset, and it is highly heritable. Because of its symptoms are usually associate with old age, e.g., unusual behaviors, emotional problems, trouble in communication, or difficulty with walking, its early on set is often illusive. In addition, its clinical heterogeneity and overlap with other neurodegenerative and psychiatric disorders, further complicates its diagnosis. Even though, fluid biomarkers are measured in CSF and blood (plasma or serum) for early detection and can be used in differentiating FTD from Alzheimer’s disease (AD), or even identifying pre-symptomatic patients of familial cases, there is presently no curative or palliative treatment for FTD.
Progress in imaging and neuromodulation offers promises in advancing our understanding of the basis of FTD that could guide our efforts for a more reliable diagnosis and treatment of this disease. It is expected that more targeted treatments will emerge from these new understandings to the point of revising clinical criteria for FTD.
Among the existing technologies for treatment of neuropsychiatric disorders, transcranial magnetic stimulation (TMS) has shown promises in many disorders. Given the successful record of TMS with disorders like depression, OCD, anxiety, etc., several studies have been carried out and assessed its ability in discerning the function of GABAergic and glutamatergic circuits, which culprits in AD and FTD [Padovani].
As GABAergic and glutamatergic circuits are implicated in these conditions, it is important to show that they are both altered in FTD patients [Sun, Benousi] and in pre-symptomatic carriers of a pathogenic mutation for FTD [Gazzina]. As FTD is characterized by a series of symptoms, including personality and behavioral disturbances, language deficits, and impairment of executive functions, and that TMS has been successful in treating patients with these symptoms, scientists have explored and demonstrated the TMS potential to help place the role of these neuro transmitters in proper context. Especially, as they correlate with both positive and negative neuropsychiatric symptoms and with disease progression. Furthermore, since recently TMS has shown much higher efficacy when guided by functional imaging, we have explored these potentials in the past few years using resting-state fMRI or rsfMRI as guidance.
All strong aspects of our innovative therapeutic approach for treatment of psychiatric disorders come together in improving clinical symptoms in patients with FTD. Our experience in using non‐invasive brain stimulation has shown promising results on language processing in patients with Autism, ADHD, and primary progressive aphasia (PPA). We have shown that multiple sessions of TMS demonstrate cumulative and long‐lasting after‐effects in patients with various symptoms of FTD, mediated by the modulation of cortical plasticity. As such, we offer fMRI-guided TMS to FTD patients as it is capable of revealing reliable biomarkers based on rsfMRI to both guide treatment and monitor intervention outcomes, particularly in the pre-symptomatic phases of the disease. This means that fMRI-guided TMS, which is already capable of assessing performance of specific cortical circuits in the central nervous system, can extend such benefit to FTD patients as well. Because of its non-invasive nature and in contrast with pharmacological treatments, we have been able to develop fMRI-guided TMS protocols to assess and modify, non‐invasively, the function of many different mechanisms including GABAergic and glutamatergic circuits, whose malfunctioning are a trademark of FTD. This makes fMRI-guided TMS an effective technique for diagnosis and treatment for FTD.
1. Padovani A, Benussi A, Di Lorenzo F, et al. Sensitivity and specificity of transcranial magnetic stimulation for differential diagnosis of Alzheimer’s disease and frontotemporal dementia. Alzheimer’s Dement. 2017;13:P695-P696
2. Benussi A, Alberici A, Ferrari C, et al. The impact of transcranial magnetic stimulation on diagnostic confidence in patients with Alzheimer disease. Alzheimers Res Ther. 2018;10:94.
3. Sun B, Halabisky B, Zhou Y, Palop JJ, Yu G, Mucke L, Gan L. Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer’s Disease. Cell Stem Cell. 2009 Dec 4;5(6):624-33. doi: 10.1016/j.stem.2009.10.003. PMID: 19951690; PMCID: PMC2823799.
4. González-García N, Armony JL, Soto J, Trejo D, Alegría MA, Drucker-Colín R. Effects of rTMS on Parkinson’s disease: a longitudinal fMRI study. Journal of neurology. 2011 Jul 1;258(7):1268-80.
5. Gazzina S, Benussi A, Premi E, et al. Neuroanatomical correlates of transcranial magnetic stimulation in presymptomatic Granulin Mutation Carriers. Brain Topogr. 2018;31:488-497
6. Overbeek G, Gawne TJ, Reid MA, Kraguljac NV, Lahti AC. A multimodal neuroimaging study investigating resting-state connectivity, glutamate and GABA at 7 T in first-episode psychosis. J Psychiatry Neurosci. 2021 Dec 21;46(6):E702-E710. doi: 10.1503/jpn.210107. PMID: 34933941; PMCID: PMC8695527.
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Neurotherapeutix is the leading clinic for functional imaging guided transcranial magnetic stimulation (TMS), a safe, innovative, and non-invasive methodology for treating a wide range of acute and chronic mental disorders and brain injuries. Our advanced fMRI technology allows us to map the brain for the… Learn More »
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