Investigating the neural correlates of language production by means of TDCS

Language production is one of the most complex cognitive – motor skills developed by homo sapiens throughout evolution to allow inter-personal and intra-personal communication (Indefrey and Levelt, 2000). A great number of cortical regions have adapted to support this high-speed combination of muscular and mental processes, in order to correctly generate the intended utterances in different contexts and situations. The neural organization of language processing is a thorny matter, that in the last decades has been investigated with a number of different methods ranging from functional imaging (fMRI, PET; see Gernsbacher & Kashack, 2003; Price, 2010; 2012 for reviews) neurophysiology (EEG, ERP, MEG, see Ganushchak et al., 2011 for a review), lesion studies (for a review see Turkeltaub et al., 2011) and non-invasive brain stimulation (such as transcranial magnetic stimulation, TMS, and transcranial direct current stimulation, tDCS, Devlin and Watkins, 2007; Monti et al., 2012 for reviews). Overall these studies have identified specific areas differently involved in language sub-processes (for a review see Price, 2012; Indefrey, 2011). As a new methodology to investigate the relationship between cortical areas and behavioural performance in cognitive tasks, including language, tDCS has been increasingly used in the last decade (Vallar & Bolognini, 2011). This technique relies on a sub-threshold polarization or de-polarization of neurons that leads to a modulation of cortical excitability and plasticity (Nitsche & Paulus, 2011). Due to its ease of application even in clinical settings, the potential of this tool in neuro-scientific investigation seems wide, but there is no precise knowledge of its mechanisms and effects on cognitive functions. The aim of the present study is to test tDCS effects on language production, to explore when this technique can be applied and to deeply investigate the mechanisms that lead to behavioural changes. In particular, since one of the classification criteria in aphasia is verbal fluency, in study 10 1 I investigated the effects of anodal tDCS on a verbal fluency task, aiming at developing a possible protocol to apply on clinical populations. To assess whether stimulation could modulate language production, healthy subjects performed a verbal fluency task both on phonemic and semantic cue immediately after real or sham stimulation. Since this requires the activity of a distributed network, including, among others, the left inferior frontal gyrus (LIFG), the left pre-motor cortex (LPMC), the left inferior and superior temporal gyri (LITG, LSTG) and the bilateral occipital-temporal sulci (Birn et al., 2010), and given that widespread effects of tDCS on functional networks need further clarification, in study 2 I investigated how electrical non-invasive brain stimulation affects cortical excitability by means of a TMS- EEG and tDCS combination, assessing how tDCS modulates cortical excitability and, accordingly, behavioural performance on verbal fluency. An open issue, indeed, is how stimulation enhances the activity of functional networks during task execution. Few recent studies addressed this question, but they generally rely on imaging data (Meinzer et al., 2012, 2013; Holland et al., 2011;). Hence, I tested how cortical excitability is modified after anodal tDCS applied over the LIFG in a functionally connected area, namely the LPMC (BA6) and in a region not involved in verbal fluency, the left superior parietal lobe (LSPL, BA7), and whether these changes could explain the effects of tDCS on task performance. Then, in study 3 and 4 and 5, I tested whether tDCS could be a useful tool to investigate language processes in healthy subjects. In particular, in study 3 and 4 I focused on semantic and phonological interference in picture naming tasks. The functional locus of the semantic interference (SI) effect, indeed, is still not clear (Finkbeiner and Caramazza, 2006; Schnur et al., 2006; 2009; Schnurr and Martin, 2012) and the role of the LIFG and LSTG in this effect is still under debate (Schnur et al., 2006; 2009). To test the different hypotheses underlying SI effect, I investigated the effects of anodal stimulation on the two aforementioned areas in a naming task in which 11 semantic context was manipulated (“blocked naming task”, Belke et al., 2005). Similarly, frontal and temporal regions seem to be involved in the phonological facilitation (PF) effect observed in naming (De Zubicaray et al., 2002; De Zubicaray and McMahon, 2009; Zhao et al., 2012; Damian & Bowers, 2009; Meyer and Schriefers, 1991; Scrhiefers et al., 1990). A picture word interference paradigm (PWI) was then administered after anodal stimulation of the LIFG and LSTG, and the effect of stimulation on PF was assessed. Finally, since proper name retrieval decreases with aging (Evrard et al., 2002), it would be of high interest to develop protocols improving this ability: this is the topic of study 5.