The history and usage of TMS:

TMS is often considered an excellent alternative to other methods of

neuromodulation including those that utilise electrical stimulation. Despite these methods

(that include Transcranial Alternating Current Stimulation or Transcranial Direct Current

Stimulation (tDCS)) being developed after the introduction of TMS, the level of spatial

specificity and the mechanism of action of this method has ensured that it has remained a

popular choice in both research and clinical environments. It is generally regarded as a safe

method of producing a transient modulation of areas of the brain (providing safety

guidelines are accurately followed).

TMS as a method of neuro-modulation was first proposed by Barker and colleagues

in 1985 (Barker, Jalinous, & Freeston, 1985). During a TMS procedure a wire coil is placed

against the scalp, as a current is passed through the coil. This in turn produces a magnetic

field that passes through the skull with relatively little resistance, which can reach up to 50 –

60 mm into the outer layer of the brain. As the magnetic field passes into the participants

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current in turn acts by depolarising the neurons this then can induce transient physiological

changes (either excitatory or inhibitory). This subsequently can be used to induce temporary

behavioural changes in the participant (Horvath, Perez, Forrow, Fregni, & Pascual-Leone,

2011). The coils that are used often take the shape of a figure of 8, however the first to be

used was a simple circular coil whose level of spatial specificity was particularly low. In

addition to these figure of 8 coils other shaped coils have also been designed to allow for

the stimulation of deeper brain structures. These deeper brain stimulation coils include H

coils (Roth, Zangen, & Hallett, 2002), double cone coils (Lontis, Voigt, & Struijk, 2006) as well

as the theoretically proposed C coils (Davey & Riehl, 2006) and circular crown coils (Deng,

Peterchev, & Lisanby, 2008). As we wished to only stimulate superficial layers of the cortex

with a good level of focality, the coils that we used in this investigation were the standard

figure of 8 shaped coils.

Over the years, since its conception TMS has become one of the preferred methods

of neuro-modulation. This is because after years of development and fine-tuning it can now

be used effectively alongside EEG recording (Ilmoniemi & Kičić, 2010), PET scanning

(Siebner, Peller, & Lee, 2008) or functional Magnetic Resonance Imaging (fMRI) (Bohning et

al., 1999; Ruff, Driver, & Bestmann, 2009), with only a few issues (again, providing guidelines

are followed). The method has received widespread use as an experimental way of

determining the nature of causal relationships between functional brain activity and

behaviour. This usage has led it to become an invaluable tool in cognitive neuroscientific

research.

Perhaps the greatest potential application of TMS however comes in the medical

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et al., 2007). Other protocols have also been shown to be successful in the treatment of

otherwise drug resistant depression (Avery et al., 2010; Blumberger et al., 2018; Chung,

Hoy, & Fitzgerald, 2015; George et al., 2000; Kolbinger, Hoflich, Hufnagel, Moller, & Kasper,

1995; Lisanby et al., 2009; Loo, McFarquhar, & Mitchell, 2008). TMS as a treatment of

depression has recently become widespread and has been deemed successful enough to be

approved for use by the Food and Drug Administration (FDA) in the United States of America

(Horvath, Mathews, Demitrack, & Pascual-Leone, 2010). Similarly it has also received

approval by the NHS as a tool to treat painful migraines and cluster headaches (Ahmed,

Goadsby, Bhola, Reinhold, & Bruggenjurgen, 2015; Brüggenjürgen, Baker, Bhogal, & Ahmed,

2016).It has been proposed that TMS protocols could also have other uses in medical

settings. This includes the treatment of OCD (Greenberg et al., 1997), relieving the effects of

some brain injuries (Paxman, Stilling, Mercier, & Debert, 2018) or strokes (Naeser et al.,

2005) and alleviating some of the symptoms associated with schizophrenia (Jin et al., 2005).

It should be noted however that the findings on its efficacy in terms of these treatments

often appears mixed, especially for the treatment of schizophrenia and OCD respectively

(McIntosh et al., 2004; Sarkhel, Sinha, & Praharaj, 2010). As a result its widespread use in

the treatment of these conditions has yet to become a reality. However further

investigations of this method could look to ascertain other uses, and perhaps even the

emergence of other potential treatments for conditions that we have yet to consider.

TMS can be applied in a number of different ways. Single-pulse TMS involves a

protocol in which pulses are presented in isolation or separated by a very long delay

(Gagliardo et al., 2007; Pascual-Leone, Walsh, & Rothwell, 2000). Repetitive TMS involves

pulses that are rapidly repeated in a series of “trains” (Avery et al., 2010; George et al.,

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Stimulation, in which repetitive TMS trains are punctuated by brief pauses. This results in

repeated TMS pulses, whereby blocks of trains are presented at a frequency of ~ 5 Hz, thus

mimicking typical theta frequency (Blumberger et al., 2018; Di Lazzaro et al., 2008; Huang,

Edwards, Rounis, Bhatia, & Rothwell, 2005; Suppa et al., 2016). Finally Paired Associative

Stimulation (PAS) in which pairs of stimuli are separated by a variable interval (Buch et al.,

2011; Chiappini, Silvanto, Hibbard, Avenanti, & Romei, 2018; Rizzo et al., 2011; Rizzo et al.,

2009; Romei, Chiappini, Hibbard, & Avenanti, 2016; Stefan, Kunesch, Cohen, Benecke, &

Classen, 2000). Each of these methods have slightly different effects on the brain and also

have a different level of safety concerns. The following sections will look to discuss these

common TMS protocols, as well as the one that we intend to make use of in the current

investigation.