Towards dynamical network biomarkers in neuromodulation of episodic migraine

Computational methods have complemented experimental and clinical neursciences and led to improvements in our understanding of the nervous systems in health and disease. In parallel, neuromodulation in form of electric and magnetic stimulation is gaining increasing acceptance in chronic and intractable diseases. In this paper, we firstly explore the relevant state of the art in fusion of both developments towards translational computational neuroscience. Then, we propose a strategy to employ the new theoretical concept of dynamical network biomarkers (DNB) in episodic manifestations of chronic disorders. In particular, as a first example, we introduce the use of computational models in migraine and illustrate on the basis of this example the potential of DNB as early-warning signals for neuromodulation in episodic migraine.Comment: 13 pages, 5 figure

Transcranial Electric Stimulation Entrains Cortical Neuronal Populations in Rats

Low intensity electric fields have been suggested to affect the ongoing neuronal activity in vitro and in human studies. However, the physiological mechanism of how weak electrical fields affect and interact with intact brain activity is not well understood. We performed in vivo extracellular and intracellular recordings from the neocortex and hippocampus of anesthetized rats and extracellular recordings in behaving rats. Electric fields were generated by sinusoid patterns at slow frequency (0.8, 1.25 or 1.7 Hz) via electrodes placed on the surface of the skull or the dura. Transcranial electric stimulation (TES) reliably entrained neurons in widespread cortical areas, including the hippocampus. The percentage of TES phase-locked neurons increased with stimulus intensity and depended on the behavioral state of the animal. TES-induced voltage gradient, as low as 1 mV/mm at the recording sites, was sufficient to phase-bias neuronal spiking. Intracellular recordings showed that both spiking and subthreshold activity were under the combined influence of TES forced fields and network activity. We suggest that TES in chronic preparations may be used for experimental and therapeutic control of brain activity

Human middle temporal cortex, perceptual bias, and perceptual memory for ambiguous three-dimensional motion

When faced with inconclusive or conflicting visual input human observers experience one of multiple possible perceptions. One factor that determines perception of such an ambiguous stimulus is how the same stimulus was perceived on previous occasions, a phenomenon called perceptual memory. We examined perceptual memory of an ambiguous motion stimulus while applying transcranial magnetic stimulation (TMS) to the motion-sensitive areas of the middle temporal cortex (hMT+). TMS increased the predominance of whichever perceptual interpretation was most commonly reported by a given observer at baseline, with reduced perception of the less favored interpretation. This increased incidence of the preferred percept indicates impaired long-term buildup of perceptual memory traces that normally act against individual percept biases. We observed no effect on short-term memory traces acting from one presentation to the next. Our results indicate that hMT+ is important for the long-term buildup of perceptual memory for ambiguous motion stimuli

Transcranial magnetic stimulation as a new tool to control pain perception.

Treatment for chronic pain is frequently unsuccessful or characterized by side-effects. The high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been suggested in the management of refractory chronic pain. Various studies have shown that HF-rTMS sessions of long-duration applied at primary motor cortex induce pain relief through mechanisms of plastic changes. Efficacy of rTMS mostly depends on stimulation parameters, but this aspect requires better characterization. A rationale to target other cortical areas exists. Current data are promising, but a careful analysis of stimulation settings and maintenance treatment design are need

The effects of transcranial static magnetic fields stimulation over the supplementary motor area on anticipatory postural adjustments

We investigated the influence of transcranial static magnetic field stimulation (tSMS) over the supplementary motor area (SMA) on anticipatory postural adjustments (APAs), in which the activation of the postural muscles of the legs and trunk that control standing posture precedes the activation of the prime mover muscles during rapid shoulder flexion movement. Eighteen subjects performed a self-paced rapid shoulder flexion task before, during, and after tSMS. Electromyogram (EMG) activity was recorded from the deltoid anterior (AD) as the prime mover muscle and the biceps femoris (BF) as the postural muscle during the task. The EMG latency difference (ΔEMG onset) between the two muscles was calculated by subtracting the EMG burst onset of the BF from that of the AD. The ΔEMG onset was significantly shortened, but center-of-pressure parameters were not affected after tSMS stimulation. These findings suggest that tSMS applied over the SMA could inhibitively modulate APAs function

Modeling transcranial magnetic stimulation from the induced electric fields to the membrane potentials along tractography-based white matter fiber tracts

Objective. Transcranial magnetic stimulation (TMS) is a promising non-invasive tool for modulating the brain activity. Despite the widespread therapeutic and diagnostic use of TMS in neurology and psychiatry, its observed response remains hard to predict, limiting its further development and applications. Although the stimulation intensity is always maximum at the cortical surface near the coil, experiments reveal that TMS can affect deeper brain regions as well. Approach. The explanation of this spread might be found in the white matter fiber tracts, connecting cortical and subcortical structures. When applying an electric field on neurons, their membrane potential is altered. If this change is significant, more likely near the TMS coil, action potentials might be initiated and propagated along the fiber tracts towards deeper regions. In order to understand and apply TMS more effectively, it is important to capture and account for this interaction as accurately as possible. Therefore, we compute, next to the induced electric fields in the brain, the spatial distribution of the membrane potentials along the fiber tracts and its temporal dynamics. Main results. This paper introduces a computational TMS model in which electromagnetism and neurophysiology are combined. Realistic geometry and tissue anisotropy are included using magnetic resonance imaging and targeted white matter fiber tracts are traced using tractography based on diffusion tensor imaging. The position and orientation of the coil can directly be retrieved from the neuronavigation system. Incorporating these features warrants both patient- and case-specific results. Significance. The presented model gives insight in the activity propagation through the brain and can therefore explain the observed clinical responses to TMS and their inter- and/or intra-subject variability. We aspire to advance towards an accurate, flexible and personalized TMS model that helps to understand stimulation in the connected brain and to target more focused and deeper brain regions

Operator Safety and Field Focality in Aluminum Shielded Transcranial Magnetic Stimulation

partially_open4noThis paper aims at verifying the effectiveness of the transcranial magnetic stimulation treatment when a passive shield is introduced for the nursing staff safety. The analysis is developed through a modeling approach, splitting the solution of the field problem into two successive steps. The Duke anatomical model of the Virtual Family dataset is used to model both the patient head and the operator body. The investigations are performed by considering stimulators equipped with a circular spiral coil or a figure-of-eight shaped (FoE or butterfly) winding. The addition of the shield slightly reduces the induced electric field values, while increasing the field focality in the patient brain (especially with the circular coil), preserving the effectiveness of the treatment, anyway. On the operators' side, the presence of a passive conductive shield significantly reduces the exposure levels.partially_openZucca, Mauro; Bottauscio, Oriano; Chiampi, Mario; Zilberti, LucaZucca, Mauro; Bottauscio, Oriano; Chiampi, Mario; Zilberti, Luc

Value and efficacy of transcranial direct current stimulation in the rehabilitation of neurocognitive disorders: A critical review since 2000.

open3siNon-invasive brain stimulation techniques, including transcranial direct current stimulation (t-DCS) have been used in the rehabilitation of cognitive function in a spectrum of neurological disorders. The present review outlines methodological communalities and differences of t-DCS procedures in neurocognitive rehabilitation. We consider the efficacy of tDCS for the management of specific cognitive deficits in four main neurological disorders by providing a critical analysis of recent studies that have used t-DCS to improve cognition in patients with Parkinson’s Disease, Alzheimer’s Disease, Hemi-spatial Neglect and Aphasia. The evidence from this innovative approach to cognitive rehabilitation suggests that tDCS can influence cognition. However, the results show a high variability between studies both on the methodological approach adopted and the cognitive functions aspects. The review also focuses both on methodological issues such as technical aspects of the stimulation ( electrodes position and dimension; current intensity; duration of protocol) and on the inclusion of appropriate assessment tools for cognition. A further aspect considered is the best timing to administer tDCS: before, during after cognitive rehabilitation. We conclude that more studies with shared methodology are needed to have a better understanding of the efficacy of tDCS as a new tool for rehabilitation of cognitive disorders in a range of neurological disordersopenCappon, D; Jahanshahi, M; Bisiacchi, PCappon, Davide; Jahanshahi, M; Bisiacchi, Patrizi

Can tDCS enhance treatment of aphasia after stroke?

Background: Recent advances in the application of transcranial direct current stimulation (tDCS) in healthy populations have led to the exploration of the technique as an adjuvant method to traditional speech therapies in patients with post-stroke aphasia. Aims: The purpose of the review is: (i) to review the features of tDCS that make it an attractive tool for research and potential future use in clinical contexts; (ii) to describe recent studies exploring the facilitation of language performance using tDCS in post-stroke aphasia; (iii) to explore methodological considerations of tDCS that may be key to understanding tDCS in treatment of aphasia post stroke; and (iv) to highlight several caveats and outstanding questions that need to be addressed in future work. Main Contribution: This review aims to highlight our current understanding of the methodological and theoretical issues surrounding the use of tDCS as an adjuvant tool in the treatment of language difficulties after stroke. Conclusions: Preliminary evidence shows that tDCS may be a useful tool to complement treatment of aphasia, particularly for speech production in chronic stroke patients. To build on this exciting work, further systematic research is needed to understand the mechanisms of tDCS-induced effects, its application to current models of aphasia recovery, and the complex interactions between different stimulation parameters and language rehabilitation techniques. The potential of tDCS is to optimise language rehabilitation techniques and promote long-term recovery of language. A stimulating future for aphasia rehabilitation