Do internal representations of movement rely on maintained processing within the left

Although the results from Study 1 and 3 offer substantial support for the proposal that apraxia is attributed to impaired motor imagery due to disruption to the ventro-dorsal pathway, what was less clear was the role of the left IPL. The introduction of this thesis outlined research from both neuroimaging and neuropsychology that suggests the left IPL is the critical juncture where ventral and dorsal processing is combined, forming a fundamental part of the purported ventro-dorsal pathway (Rizzolatti & Matelli, 2003; Buxbaum & Kalénine, 2010; Rizzolatti et al., 2011). However, the role of the left IPL has been questioned, in particular during object-related movement (for example Goldenberg et al., 2007). Using causal neuropsychological and neuromodulation techniques, the second aim of this thesis was to confirm whether internal movement representations attributed to the ventro-dorsal stream are reliant on intact processing within the left IPL. By assessing the necessity of the left IPL in tasks calling upon motor imagery,

it could also be inferred whether it is accurate to suggest these representations are compromised in apraxia.

Lesions to frontal and parietal regions of the visuomotor network often lead to apraxia, with the left IPL being consistently associated with ideomotor apraxia (Haaland et al., 2000; Leiguarda & Marsden, 2000; Goldenberg, 2009). Study 1 and 3 corroborated these findings, as approximately half of the apraxic patients tested had lesions that directly implicated the left IPL, suggesting that damage to this region can affect skilful object manipulation. Lesions to the left IPL have been associated with impaired imitation of hand gestures and with errors during pantomime and actual object-use (Goldenberg & Spatt, 2009; Goldenberg, 2014). However, errors in gesture recognition and pantomime of object-use is also apparent when lesions occur outside of the parietal lobe; reduced understanding of familiar transitive and intransitive gestures and disturbed pantomime of object-use has been associated with disruption to frontal regions including the inferior frontal gyrus, but not damage to inferior parietal regions (Goldenberg et al., 2007; Pazzaglia et al., 2008; Bolthalter et al., 2011). These findings challenge the necessity of the left IPL during motor imagery, particularly during the mental simulation of object-related action.

However, as lesions are often extensive, it cannot be ruled out that the left IPL is indirectly implicated in these patients; if lesioned areas include corticocortical and corticosubcortical connections, communication along the ventro-dorsal pathway may still be disrupted (Leiguarda, 2001; Lewis, 2006). This issue was acknowledged in research associating frontal lesions with impaired object-use. Referring to Study 1 and 3, the patients with lesions external to the left IPL had damage extending into the underlying white matter of frontoparietal regions, and subcortical lesions including the cerebellum, thalamus, and broca’s area. It is therefore possible that the reciprocal connections between the ventral and ventro-dorsal pathway, or the forward projections from parietal to frontal regions, are disconnected. Consequently it remains that the left IPL may be critical during motor imagery. Yet this explanation is not definitive and does not account for theta-burst stimulation over the inferior frontal cortex of healthy participants impairing production of transitive and intransitive gestures, while left IPL stimulation did not affect gesture production (Bolthalter et al., 2011).

Despite apraxic patients in Study 1 and 3 having lesions that may directly or indirectly implicate the left IPL, the causal link between the integrity of this region and maintained motor imagery via the ventro-dorsal stream remained unclear. Using tDCS, Study 2 and 4 assessed the role of the left IPL in greater depth. Any performance changes in motor imagery tasks due to modulating the cortical excitability of the left IPL would heavily reinforce its role in the integration of perception for action. When given the same perceptual task used with apraxic patients in the initial study,

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healthy participants in Study 2 showed increased reaction times during the perception of object manipulation when left parietal cathodal-inhibitory stimulation was applied with a contralateral frontal reference electrode. As performance during functional semantic judgements was unaffected by stimulation, these findings confirm that the left IPL is required during the perception of motoric elements of object-use but not when perceiving non-motoric action representations. This corresponds to neuroimaging studies indicating that simulation of object- related movement activates several visuomotor areas attributed to the ventro-dorsal stream including the left IPL when individuals observe, imagine, and pantomime object-use (Chao & Martin, 2000; Decety et al., 2002; Mozaz et al., 2002; Rizzolatti & Matelli, 2003; Vingerhoets, 2008; Króliczak & Frey, 2009; Vingerhoets et al., 2009; Caspers et al., 2010). Increased left IPL activation is also observed when making perceptual based decisions and prospective action judgements regarding appropriate object-use, which can be disturbed after rTMS is applied to this area (Buccino et al., 2001; Kellenbach et al, 2003; Buccino et al., 2004; Rizzolatti & Craighero, 2004; Boronat et al., 2005; Buxbaum et al., 2006; Canessa et al., 2008; Ishibathi et al., 2011; Wadsworth & Kana, 2011). Alternatively, perception of object function activates inferotemporal regions, with impaired function judgements manifesting after damage to temporal regions in the case of semantic dementia or herpes encephalitis (Sirigu et al., 1991; Buxbaum et al., 1997; Bozeat et al., 2000; Kellenbach et al., 2003; Mahon & Caramazza, 2003; Boronat et al., 2005; Negri et al., 2007; Canessa et al., 2008), Such research suggests that functional semantic representations may similarly be attributed to more ventral and semantic systems.

The necessity of the left IPL during motor imagery is reinforced by the results found in Study 4. This study used classic mental rotation tasks that have consistently been shown to rely on motor or visual imagery depending on task demands (Bonda et al., 1995; Corballis, 1997; Overney et al., 2005; Overney & Blanke, 2009). During left parietal cathodal-inhibitory and right parietal anodal-excitatory stimulation accuracy of hand mental rotation was enhanced compared to left parietal anodal-excitatory and right parietal cathodal-inhibitory stimulation, indicating that disturbance of interhemispheric interactions between the parietal lobes could modulate motor imagery. Reaction times were also reduced during unilateral left parietal cathodal-inhibitory stimulation with a contralateral frontal reference. Unilateral right parietal cathodal-inhibitory or anodal-excitatory stimulation did not affect motor mental rotation performance. Unlike a previous rTMS study that found stimulation of the left or right supramarginal gyrus affected hand laterality performance (Pelgrims et al., 2009), the modulatory effects found in Study 4 are consistent with evidence that apraxic symptoms predominantly occur after damage to the left hemisphere. This suggests that motor imagery is left lateralised but may recruit right parietal regions that are supplementary but not essential (Sirigu et al., 1996; Buxbaum et al., 2005; Niessen et al., 2014). Further, the selective impairment of manipulation judgements during tDCS of the left IPL

confirms that additional frontal and white matter disruption is not necessary to disturb object-use perception as deduced by Vingerhoets and colleagues (2011).

Combined, the findings from both experiments in Study 4 indicate that modulation of the left IPL affects intransitive motor mental rotation. Similarly to object-related movement, several ventro- dorsal visuomotor areas, in particular left parietal regions, are active during the mental rotation of body parts (Bonda et al., 1995; Kosslyn et al., 1998; Rizzolatti & Matelli, 2003; Haaland et al., 2004; Fogassi & Luppino, 2005; Johnson-Frey et al., 2005; Muhlau et al., 2005; Overney et al., 2005). In accordance with neuroimaging data, impaired motor mental rotation is observed when lesions implicate the left parietal regions (Sirigu et al., 1996; Sirigu & Duhamel, 2001; Tomasino et al., 2003a; Tomasino et al., 2003b; Overney & Blanke, 2009), whereas right parietal damage has been shown to impact visual mental rotation whilst motor mental rotation remains normal (Bricolo et al., 1990; Rumiati et al., 2001; Tomasino et al., 2003b).

Overall, the results from Study 2 and 4 directly attribute the left IPL with the perception of transitive object-related action and intransitive mental rotation of hand gestures, corroborating a wealth of neuroimaging and neuropsychological data implicating the left IPL in transitive and intransitive movement (Decety et al., 1994; Decety, 1996; Sirigu et al., 1996; Rizzolatti & Craighero, 2004; Rumiati et al., 2004; Lewis, 2006; Frey, 2007; Vingerhoets et al., 2008; Kalénine et al., 2010; Niessen et al., 2014). These results support the proposal of an additional sub-stream of the visual pathways model important for the integration of perception for action. Further, the lack of effect of tDCS when the right hemisphere was stimulated indicates that motor imagery is left hemisphere dominant. The modulatory effects of tDCS also compliment the lesion data from Study 1 and 3 that suggests direct or indirect disturbance of the left IPL is associated with deficits during the perception and execution of skilled object-related movement. That said, regions external to the left IPL, such as the right parietal lobe or inferior frontal gyrus, may still be integral to internal movement representations via the ventro-dorsal stream, but for different reasons. For example, while the left IPL might form the critical juncture where perception and action are integrated to enable the generation and selection of the appropriate movement gesture, it is feasible that the production of this gesture and inhibition of inappropriate gestures calls upon inferior frontal regions (Decety et al., 1997; Goldenberg et al., 2007). Overall, the results obtained from the neuromodulation studies confirm that when tDCS is applied to the parietal cortex, motor imagery can be modulated. To date, this has seldom been explored and therefore offers unique evidence for the potential of tDCS to assess the cognitive aspects of motor control. Importantly, these studies offer direct evidence for the role of the left IPL during skilled movement representations via the ventro-dorsal sub-stream.

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