CHAPTER 1 INTRODUCTION
3. Neuroplasticity
3.3. TMS studies
The coupling within and between networks should be able to reconfigure dynamically in order to support ongoing processing demands. Transcranial magnetic stimulation (TMS) can be used to modulate cortical activity and can therefore be applied to explore electrical network dynamics (Eldaief et al., 2011). EEG is an ideal technique for the investigation of TMS‟ influences on networks. It enables
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the assessment of both spatial and spectral changes in network interactions, which is crucial for examining frequency-specific effects of TMS.TMS is a suitable tool to study changes within and across cortical networks. Repetitive TMS (rTMS) can induce transitory alterations in local cortical activity. Therefore, by stimulating a cortical target region it should be possible to stimulate its connections. Local stimulation to a network node is supposed to propagate transsynaptically to distant but interconnected nodes with high spatial specificity (Paus, 2005; Hampson & Hoffman, 2010a). Indeed, previous fMRI studies have shown that rTMS affects not only stimulated areas but also other nodes from the same functional network (Hubl et al., 2008; Grefkes & Fink, 2011). Hence, TMS can be used as a non-invasive approach with which to study human cerebral plasticity.
Different stimulation protocols have been proposed. Depending on the protocol, TMS can induce either an increase or a reduction of neural activity and a facilitation or suppression of corresponding behavior. Single-pulse paradigms were shown to induce a strong facilitation of spontaneous and visual-evoked spiking activity shortly after the TMS-pulse, which was followed by the subsequent suppression of activity (Moliadze et al., 2003). Another stimulation paradigm, paired-pulse TMS, involves the application of a conditioning stimulus pulse prior to the test stimulus delivered. It has been extensively studied in the motor cortex. The main principle of this stimulation is the alteration of the motor evoked potential (MEP) with the conditioning stimulus. This permits us to infer that there is a functional interaction between the target of the conditioning stimulus and the location of the test stimulus. Another important stimulation method is rTMS, which involves the delivery of trains of TMS pulses, to produce changes in cortical excitability that persist beyond the duration of stimulus. The exact mechanisms leading to alterations in excitability are unknown, but they are believed to involve processes similar to synaptic long-term potentiation and long-term-depression (Fitzgerald et al., 2003;
Thickbroom, 2007).
More recently, Huang et al. (2005) developed a patterned repetitive stimulation protocol to rapidly induce long-lasting changes in cortical plasticity. The classic theta-burst rTMS stimulation (TBS) paradigm consists of three pulses at 50 Hz, repeated every 200 msec (i.e. at 5 Hz). In the continuous protocol, a 40 second train of uninterrupted theta-burst stimulation is applied, resulting in a decrease in MEP amplitude of over 40%, with suppression persisting for as long as 60 min. In the intermittent theta-burst protocol, a 2 second train of theta-burst stimulation is repeated every 10 seconds. The MEP amplitude in the experiment of Huang et al. (2005) was increased by up to 75%, with the facilitation lasting for about 15-20 minutes (Huang et al., 2005; Nyffeler et al., 2006). EEG studies have suggested that theta-burst effects on evoked responses persisted for up to 90 minutes longer than for conventional rTMS protocols (Shafi et al., 2013).
In general, the effects of TBS on neuroplasticity were shown to depend on several factors including stimulation parameters: the strength of the magnetic flux, the shape of stimulation coil, intensity, inter-burst frequency, the frequency of pulses within each pulse (Goldsworthy et al., 2012); the distance and angle between the coil and the cortical surface; the region of stimulation, neural architecture of the stimulated neural tissue and its baseline activity (Nyffeler et al., 2008; Capotosto et al., 2012). Yet,
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relatively little is known about the precise effects of TBS on neural activity and on neuronal networks. It was suggested that the balance between synchronization and desynchronization of neural assemblies might be affected by TBS (Schindler et al., 2008). Indeed, Schindler at al. (2008) showed that TBS is associated with increased neuronal synchronization in the cerebral hemisphere ipsilateral to the stimulation site relative to the unstimulated hemisphere.Numerous studies have reported that the application of TMS in patients with brain disease can modulate brain activity (Bolognini et al., 2009; Song et al., 2011; Tanaka et al., 2011). Murase et al.
(2004) assessed the impact of interhemispheric inhibition from the unaffected hemisphere to the affected hemisphere by evaluating the amplitude of the conditioned motor evoked potential (MEP) in the double-pulse trial relative to the amplitude of the test MEP when test stimulus was measured alone (Murase et al., 2004). In normal subjects, the amount of transcallosal inhibition from the „resting‟
hemisphere to the „active‟ hemisphere initially decreased and then became facilitative just before the movement onset (stimulation of one hemisphere apparently led to a larger response in contralateral stimulation); however, in stroke patients, interhemispheric inhibition remained significant. Furthermore, the degree of interhemispheric inhibition to the lesioned cortex was correlated with a slower performance on a finger-tapping task. These results led the authors to a conclusion that inhibition from the unaffected hemisphere might actually inhibit motor activity in the lesioned hemisphere after stroke.
Since TMS provides a means of modulating cortical activity in a noninvasive, safe and targeted manner, it has a great potential to be used as a therapeutic tool. Indeed, Grefkes et al. (2011) demonstrated that therapeutic interventions with TMS had a corrective effect on pathological connectivity not only at the stimulation site but also among distant brain regions (Grefkes & Fink, 2011). Ackerley et al. (2010) reported improvement of grip-lift behavior in stroke patients with affected upper-limb function after combined training and contralateral TBS (Ackerley et al., 2010). Although early results are promising, the application of these approaches in the therapeutic realm is still in its preliminary stages (Shafi et al., 2013).
Taken together, TMS is a useful tool to modulate and to study neuronal activity within functional networks. However, it remains unclear whether and how the effects of TMS on subjects‟ behavior can be predicted. An insight into the changes of neural communication induced by TMS might be of great value to enable us to understand and predict the variable behavioral effects across subjects (Hampson
& Hoffman, 2010b; Vanneste et al., 2011).
In Rizk et al. (submitted) we investigated influences of continuous TBS (cTBS) on network coherence and on behavior in a group of healthy young participants. We hypothesized that cTBS would influence network coherence in specific frequencies. We also expected to find a neural correlate (in at least some of the spectral changes) in the behavioral effects of stimulation.