Fregni F, Pascual-Leone ATechnology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS. Nat Clin Pract Neurol 3:383-393

Harvard Medical School and the Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Nature Clinical Practice Neurology (Impact Factor: 7.64). 08/2007; 3(7):383-93. DOI: 10.1038/ncpneuro0530
Source: PubMed


In neurology, as in all branches of medicine, symptoms of disease and the resulting burden of illness and disability are not simply the consequence of the injury, inflammation or dysfunction of a given organ; they also reflect the consequences of the nervous system's attempt to adapt to the insult. This plastic response includes compensatory changes that prove adaptive for the individual, as well as changes that contribute to functional disability and are, therefore, maladaptive. In this context, brain stimulation techniques tailored to modulate individual plastic changes associated with neurological diseases might enhance clinical benefits and minimize adverse effects. In this Review, we discuss the use of two noninvasive brain stimulation techniques--repetitive transcranial magnetic stimulation and transcranial direct current stimulation--to modulate activity in the targeted cortex or in a dysfunctional network, to restore an adaptive equilibrium in a disrupted network for best behavioral outcome, and to suppress plastic changes for functional advantage. We review randomized controlled studies, in focal epilepsy, Parkinson's disease, recovery from stroke, and chronic pain, to illustrate these principles, and we present evidence for the clinical effects of these two techniques.

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    • "After stroke, high frequency (4 5 Hz) or low frequency ( r1 Hz) rTMS may be used to increase ipsilesional or decrease contralesional excitability respectively. Given recent evidence of functional S1–S1 connections mediated by the CC in the human brain (Brodie et al., 2014), theoretically either of these rTMS approaches could be used to reestablish the balance of interhemispheric excitability after stroke (Fregni and Pascual-Leone, 2007; Nowak et al., 2009). The majority of previous rTMS studies have focused on modulation of M1 excitability. "
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    ABSTRACT: Emerging evidence indicates impairments in somatosensory function may be a major contributor to motor dysfunction associated with neurologic injury or disorders. However, the neuroanatomical substrates underlying the connection between aberrant sensory input and ineffective motor output are still under investigation. The primary somatosensory cortex (S1) plays a critical role in processing afferent somatosensory input and contributes to the integration of sensory and motor signals necessary for skilled movement. Neuroimaging and neurostimulation approaches provide unique opportunities to non-invasively study S1 structure and function including connectivity with other cortical regions. These research techniques have begun to illuminate casual contributions of abnormal S1 activity and connectivity to motor dysfunction and poorer recovery of motor function in neurologic patient populations. This review synthesizes recent evidence illustrating the role of S1 in motor control, motor learning and functional recovery with an emphasis on how information from these investigations may be exploited to inform stroke rehabilitation to reduce motor dysfunction and improve therapeutic outcomes. Copyright © 2015. Published by Elsevier Ltd.
    Neuropsychologia 07/2015; DOI:10.1016/j.neuropsychologia.2015.07.007 · 3.30 Impact Factor
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    • "The mechanisms by which tDCS induces changes across different levels of the nervous system may involve membrane polarization and, consequently, the modulation of neuronal activity (Hunter et al. 2013). The current model of tDCS effects is based on cortico–cortical interactions, with some subcortical components (e.g., ACC and thalamic nuclei) in these circuits (Fregni and Pascual-Leone 2007). However, sensory systems have both feed-forward and feedback networks that integrate afferent information and circuits of self-regulation to optimize the perception of a given stimulus (Hunter et al. 2013) and that might contribute to sensory modulation by tDCS. "
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    ABSTRACT: Physiological and exogenous factors are able to adjust sensory processing by modulating activity at different levels of the nervous system hierarchy. Accordingly, transcranial direct current stimulation (tDCS) may use top-down mechanisms to control the access for incoming information along the neuroaxis. To test the hypothesis that brain activation induced by tCDS is able to initiate top-down modulation and that chronic stress disrupts this effect, 60-day-old male Wistar rats (n = 78) were divided into control; control + tDCS; control + sham-tDCS; stress; stress + tDCS; and stress + sham-tDCS. Chronic stress was induced using a restraint stress model for 11 weeks, and then, the treatment was applied over 8 days. BDNF levels were used to assess neuronal activity at spinal cord, brainstem, and hippocampus. Mechanical pain threshold was assessed by von Frey test immediately and 24 h after the last tDCS-intervention. tDCS was able to decrease BDNF levels in the structures involved in the descending systems (spinal cord and brainstem) only in unstressed animals. The treatment was able to reverse the stress-induced allodynia and to increase the pain threshold in unstressed animals. Furthermore, there was an inverse relation between pain sensitivity and spinal cord BDNF levels. Accordingly, we propose the addition of descending systems in the current brain electrical modulation model.
    Experimental Brain Research 02/2015; 233(5). DOI:10.1007/s00221-015-4212-1 · 2.04 Impact Factor
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    • "This effect is because of the less resistive current pathways in the higher conductive regions and has not been mentioned before. An interesting question, raised in many tDCS experiments, is whether weak direct currents introduced to big electrodes positioned at the head surface can have therapeutic effects (Fregni and Pascual-Leone 2007). It has been demonstrated that an electric field of about 140 μV mm −1 is sufficient to enhance the firing rate of neurons (Francis et al 2003). "
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