10438 • The Journal of Neuroscience, December 5, 2018 • 38(49):10438–10443 Behavioral/Cognitive Specifying a Causal Role for Angular Gyrus in Autobiographical Memory X Heidi M. Bonnici,1,2,3 XLucy G. Cheke,1,2 Deborah A.E. Green,1,2 Thomas H.M.B. FitzGerald,3,4,5 and XJon S. Simons1,2 1Department of Psychology, University of Cambridge, Cambridge, United Kingdom CB2 3EB, 2Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom CB2 3EB, 3School of Psychology, University of East Anglia, Norwich, United Kingdom NR4 7TJ, 4Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom WC1N 3AR, and 5Max Planck-UCL Centre for Computational Psychiatry and Ageing Research, London, United Kingdom WC1B 5EH Considerable recent evidence indicates that angular gyrus dysfunction in humans does not result in amnesia, but does impair a number of aspects of episodic memory. Patients with parietal lobe lesions have been reported to exhibit a deficit when freely recalling autobio- graphical events from their pasts, but can remember details of the events when recall is cued by specific questions. In apparent contra- diction, inhibitory brain stimulation targeting angular gyrus in healthy volunteers has been found to have no effect on free recall or cued recall of word pairs. The present study sought to resolve this inconsistency by testing free and cued recall of both autobiographical memories and word-pair memories in the same healthy male and female human participants following continuous theta burst stimula- tion (cTBS) of angular gyrus and a vertex control location. Angular gyrus cTBS resulted in a selective reduction in the free recall, but not cued recall, of autobiographical memories, whereas free and cued recall of word-pair memories were unaffected. Additionally, partici- pants reported fewer autobiographical episodes as being experienced from a first-person perspective following angular gyrus cTBS. The findings add to a growing body of evidence that a function of angular gyrus within the network of brain regions responsible for episodic recollection is to integrate memory features within an egocentric framework into the kind of first-person perspective representation that enables the subjective experience of remembering events from our personal pasts. Key words: memory; parietal lobe; recollection; transcranial magnetic stimulation Significance Statement In seeking to understand the role played by the angular gyrus region of parietal cortex in human memory, interpreting the often conflicting findings from neuroimaging and neuropsychology studies has been hampered by differences in anatomical specificity and localization between methods. In the present study, we address these limitations using continuous theta burst stimulation in healthy volunteers to disrupt function of angular gyrus and a vertex control region. With this method, we adjudicate between two competing theories of parietal lobe function, finding evidence that is inconsistent with an attentional role for angular gyrus in memory, supporting instead an account in terms of integrating memory features within an egocentric framework into a first- person perspective representation that enables the subjective experience of remembering. Introduction cortex. Wagner et al. (2005) highlighted the common occurrence Of the network of brain areas associated with episodic memory, of parietal activity in neuroimaging studies of recollection, par- one region to receive considerable attention recently is parietal ticularly in the angular gyrus. This frequency might suggest a critical role in memory function. However, highly accurate mem- ory performance is observed even in patients whose lesions over- Received May 15, 2018; revised Aug. 31, 2018; accepted Sept. 14, 2018. lap closely with the areas activated by healthy participants Author contributions: H.M.B. and J.S.S. designed research; H.M.B., L.G.C., and D.A.E.G. performed research; H.M.B., T.H.M.B.F., and J.S.S. analyzed data; H.M.B., L.G.C., D.A.E.G., T.H.M.B.F., and J.S.S. wrote the paper. performing the same memory tasks (Simons et al., 2008). As ThisworkwassupportedbyaJamesS.McDonnellFoundationScholarAwardtoJ.S.S.Itwascompletedwithinthe such, there is much to understand about the role played by pari- University of Cambridge Behavioural and Clinical Neuroscience Institute, funded by a joint award from the United etal cortex in memory abilities. KingdomMedicalResearchCouncilandtheWellcomeTrust.WethankZoeKourtziandAndrewWelchmanforuseof their TMS system. The authors declare no competing financial interests. Copyright © 2018 Bonnici et al. Correspondence should be addressed to Dr. Jon S. Simons, Department of Psychology, University of Cambridge, This is an open-access article distributed under the terms of the Creative Commons Attribution License Downing Street, Cambridge CB2 3EB, United Kingdom. E-mail: [email protected]. Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in https://doi.org/10.1523/JNEUROSCI.1239-18.2018 any medium provided that the original work is properly attributed. Bonnici et al. • Causal Role for Angular Gyrus in Autobiographical Memory J. Neurosci., December 5, 2018 • 38(49):10438–10443 • 10439 Figure 1. Design of the experiment. Although accurate memory performance can be observed fol- memories, but not word-pair memories, because autobiograph- lowing parietal lesions, memory is not entirely unaffected. Pa- ical recall relies more on subjectively reliving personal events tients with parietal damage have been reported to exhibit (Moscovitch et al., 2016). impairment when freely recalling autobiographical events from We also tested another prediction of the subjective experience their personal pasts, despite their memories appearing intact account: that angular gyrus enables the first-person reexperienc- when recall is cued by specific questions about the events (Berry- ing of past events by integrating memory features within an ego- hill et al., 2007). In addition, although accuracy in identifying the centric framework. Patients with parietal lesions are impaired on context in which stimuli were previously encountered (source egocentric spatial navigation tasks but not allocentric, map-based memory) tends to be unaffected by parietal lesions, participants’ spatial tasks that are sensitive to hippocampal damage (Ciara- confidence in their accurate recollections can be significantly re- melli et al., 2010b). It may be, therefore, that angular gyrus is duced (Simons et al., 2010). Several theories have been proposed responsible for the ability to remember previous events from an to explain these findings, including that free recall and recollec- egocentric, rather than allocentric, viewpoint. If this account is tion confidence are impaired following parietal damage because correct, angular gyrus cTBS should lead to a reduced tendency for of a reduced tendency for memories to capture attention sponta- participants to report experiencing autobiographical memories neously (Cabeza et al., 2008; Ciaramelli et al., 2010a), or that they from a first-person perspective. might reflect a diminished subjective experience of “re-living” personal events (Simons et al., 2010; Moscovitch et al., 2016). Materials and Methods Yazar et al. (2014) attempted to distinguish these accounts using Participants. Twenty-two healthy, right-handed participants (11 female, continuous theta burst stimulation (cTBS) to disrupt angular 11 male) took part in the study (mean age 23.7 years, SD ϭ 3.9 years, ϭ gyrus function in healthy volunteers. The authors tested for range 19–35 years). All had normal or corrected-to-normal vision, greater impairment of free recall than cued recall of word pairs, as had normal hearing, and gave written consent to participation in a man- the attentional account would predict, or greater impairment of ner approved by the Cambridge Psychology Research Ethics Committee. Procedure. All participants were tested on two separate occasions, one source recollection confidence than accuracy, consistent with the week apart, in which one session was the experimental condition (stim- subjective experience account. The results indicated that free re- ulation to the left angular gyrus) and the other session was a control call and cued recall were unaffected by stimulation of angular session (stimulation to vertex). Participants were counterbalanced to gyrus compared with a vertex control location, but that there was receive left angular gyrus or vertex stimulation first. For each session, all selectively reduced confidence in participants’ accurate source participants followed the same procedure (Fig. 1): an autobiographical recollection responses (Yazar et al., 2014). The findings were in- memory (AM) gathering phase, a study phase for the word-pairs task, the terpreted as consistent with the proposal that angular gyrus en- cTBS procedure, followed by the autobiographical memory recall phase ables the subjective experience of remembering (see also Yazar et and the word-pairs test phase. Participants received identical stimulation al., 2017). to the angular gyrus and vertex sites and were blind to the experimental One issue with this interpretation is that the lack of free recall hypotheses. The order of the autobiographical and word-pair memory tasks was counterbalanced across participants to control for any stimu- impairment following angular gyrus cTBS observed by Yazar et lation latency effects.