Neuroimaging-guided rTMS of the left inferior frontal gyrus interferes with repetition priming
Introduction
Neuronal networks employed in single word processing have intensively been investigated using neuroimaging modalities such as O-15-water PET and fMRI (Binder, 1997, Herholz et al., 1996, Price, 2000). A common observation of these studies was the activation of the left inferior frontal gyrus (ifg) in single word processing tasks which involved semantic processing like word generation tasks (Herholz et al., 1996, Petersen et al., 1988, Warburton et al., 1996), word stem completion tasks (Buckner et al., 1995), or semantic decision tasks (Thompson-Schill et al., 1997). Recent studies combining rTMS and functional neuroimaging were able to demonstrate that the anterior ifg is not only involved in semantic processing but is also essential for the correct performance of semantic tasks (Devlin et al., 2003), the exact nature of the ifg's role in semantic processing, however, remains unclear. Early PET studies were able to demonstrate that the intensity of left ifg activation decreases with task repetition, i.e., if the same lists of nouns are used for verb generation repeatedly, and increases again as soon as new word lists are employed (Demb et al., 1995, Raichle et al., 1994). In an fMRI study, Buckner et al. gave strong evidence for the hypothesis that this adaptation of activity in left ifg due to repetition is the neuronal substrate of priming. They were able to demonstrate a decrease in BOLD signal with repetition of a word stem completion task, which was independent of the stimulus modality (visual or auditory) and comprised not only verbs, but also nouns and adjectives. It was further demonstrated (Wagner et al., 2000, Devlin et al., 2003) that priming effects were caused by repeated semantic processing in the anterior ifg (that is, BA45) and by semantic and non-semantic processing in the posterior ifg (BA44). This functional dissociation of BA 44 and 45 has recently been confirmed in a combined neuroimaging and cytoarchitectonic study (Amunts et al., 2004). Wagner et al. proposed the hypothesis of controlled semantic retrieval according to which activity of the left ifg is inversely related to the associative strength between two semantic representations (Wagner et al., 2001). Thus, left ifg activity is employed if semantic associations are weak and task-irrelevant representations compete and interfere with the recovery of task-relevant knowledge. On the other hand, if cue–target associations are strong, semantic knowledge is recovered automatically without ifg activity resulting in semantic repetition priming (Wagner et al., 2000). Since verb-generation tasks elicit the strongest left ifg activation with reproducible priming effects and have been validated across several laboratories in a multi-center PET study (Poline et al., 1996), we used this task in an O-15-water PET activation study to identify the location of maximum activation within the left ifg and employed rTMS to interfere with this maximum left ifg activity once during verb generation with unprimed (new) nouns and once with primed (known) nouns in order to study the question whether the left ifg is essential for performance of that task.
Section snippets
Subjects
We examined 5 male volunteers, aged 38 ± 8.4 years without previous history of neurological or psychiatric disease. All subjects were right-handed as assessed by the Edinburgh handedness inventory (Oldfield, 1971) (Table 1). Informed consent was obtained from all subjects and the study was approved by and performed in accordance with the guidelines of the local ethics committee of the University of Cologne.
PET and MR imaging
PET scans were performed on a CTI/Siemens ECAT EXACT HR scanner in 3D mode (Wienhard et
PET activation
All subjects showed significant activation of the left inferior frontal gyrus as expected. The activation foci which were used for positioning of the stimulation coil are shown in Fig. 1 and Talairach coordinates are given in Table 2. They were located in the anterior part of the left ifg corresponding to the triangular part. In all cases, these activations were located on the convexity of the triangular part, which corresponds to BA45 (Amunts et al., 1999). The induced electric field, with
Discussion
The main finding of this study is the fact that successful interference of left ifg function with rTMS could only be achieved–in the whole group as well as in each single subject–if lists of primed words were used for a verb-generation task. Since the facilitation of associations due to task repetition has been described as priming (Tulving and Schacter, 1990), our data provide evidence for direct interference with repetition priming mechanisms during semantic tasks. They extend results from
Conclusion
The results of this study are compatible with a repetition priming function of the left ifg known as Broca's area, as demonstrated by significantly longer verb-generation latencies during rTMS stimulation over this region after task repetition. This decrease of CBF change as measured with PET or fMRI may not be a direct neurophysiological correlate of priming mechanisms but may reflect a decrease of active inhibition from distant brain regions.
Acknowledgments
This study was supported by Köln Fortune Grant 126/2001 and the Marga und Walter Boll-Stiftung.
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2016, NeuroImage: ClinicalRepetition priming and cortical arousal in healthy aging and Alzheimer's disease
2015, NeuropsychologiaCitation Excerpt :However, impaired repetition priming in patients with AD does not appear to be due primarily to a disruption of this neuromodulatory system, but rather to impairment of neural mechanisms that mediate conceptual priming (e.g., a disruption of the effective interaction between frontal and temporal cortical regions). A number of recent studies have emphasized the critical role of recurrent interactions and neural synchrony between frontal and temporal regions in effective object recognition, repetition priming, and semantic integration (Clarke et al., 2011; Ghuman et al., 2008; Gilbert et al., 2010; Thiel et al., 2005; Wyatte et al., 2012). The unique corticocortical disconnectivity found in AD may serve as an effective model for investigating the basic neural mechanisms mediating these cognitive processes.
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2013, Handbook of Clinical NeurologyCitation Excerpt :Two independent studies confirmed that the left pars triangularis is a necessary node for semantic processing. In one of these studies, offline HF-rTMS impaired the participants’ ability to find a verb that semantically matched a presented noun (Thiel et al., 2005). In the other study, online HF-rTMS worsened performance in a semantic decision involving abstract but not concrete categories (Papagno et al., 2009).
Neural mechanisms of repetition priming of familiar and globally unfamiliar visual objects
2010, Brain ResearchCitation Excerpt :In particular, a significant RS effect was detected in the right inferior frontal cortex (BA 45/47), extending into the anterior insula for both types of objects and the magnitude of this effect was correlated with priming across subjects for both stimulus types (Figs. 4A, D). These results reinforce the findings from prior studies that have reported correlations between prefrontal RS and priming for stimuli repeated within the same task (Bergerbest et al., 2004; Bunzeck et al., 2006; Dobbins et al., 2004; Horner and Henson, 2008; Maccotta and Buckner, 2004; Orfanidou et al., 2006; Thiel et al., 2005; Turk-Browne et al., 2006; Wig et al., 2005). Because the correlation between priming and RS in right inferior frontal/insular cortex was present for the familiar and unfamiliar objects, this region is likely engaged in stimulus and response-independent processes, such as general task set configuration and central response selection processes.