Comment on: Changes in interoceptive processes following brain stimulation by Pollatos, Herbert, Mai & Kammer, 201

Coll, Michel-Pierre

Hobson, Hannah

Penton, Tegan

Philosophical Transactions of the Royal Society B Biological Sciences

Greenwich Academic Literature Archive

Running head: COMMENT ON POLLATOS ET AL., 2016   1   Important methodological issues regarding the use of TMS to investigate interoceptive processing.  Comment on: Changes in interoceptive processes following brain stimulation by Pollatos, Herbert, Mai & Kammer, 2016  Michel-Pierre Colla, Tegan Penton a, Hannah Hobson a*  a.MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, University of London, SE5 8AF  *Correspondance :  Hannah Hobson, DPhil MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, De Crespigny Park, Denmark Hill, London, United Kingdom, SE5 8AF  Tel: +44 20 7848 0936  hannah.hobson@kcl.ac.uk   Conflict of interest  The authors declare no conflict of interest.   Number of words: 1613    COMMENT ON POLLATOS ET AL., 2016  2  In the field of interoception research, one outstanding question is the precise nature of the neural 1 networks underlying interoceptive processing (1). The anterior insula (AI) is a key component of 2 contemporary interoception models (2). However, most evidence implicating the AI in interoceptive 3 processing is correlational and it remains unclear what its precise role in interoception is.  4 This issue was tackled by Pollatos and colleagues (3). Using an inhibitory form of transcranial 5 magnetic stimulation (TMS), continuous theta burst stimulation (cTBS), they aimed to provide causal 6 evidence for the involvement of the AI in interoception. The main results suggest that stimulation 7 aiming to inhibit the AI or the somatosensory cortex disrupted performance, and confidence in this 8 performance, for interoceptive tasks relative to stimulation applied to an occipital control site. The 9 same stimulation also altered the heartbeat evoked potential (HEP), an EEG measure thought to index 10 cortical processing of one’s heartbeats (4). The authors interpreted these findings as the impairment of 11 certain aspects of interoceptive processing following cTBS to the right AI, concluding that “cTBS is 12 an effective tool to investigate the neural network supporting interoceptive processes”.  13 This study should be commended for its originality, the use of a within subject design, and multiple 14 concurrent multimodal measures of interoceptive processing. However, two critical issues cast doubt 15 on the conclusions that can be drawn from these data.  16 Which brain regions were stimulated? 17 The AI is a deep cortical region, positioned behind frontal cortical regions (including the inferior 18 frontal gyrus and operculum). Because of the AI’s neuroanatomical position and depth, it is doubtful 19 that TMS could directly reach this region with the parameters used by Pollatos and colleagues. Whilst 20 anatomically near regions to the AI such as the auditory cortex have been targeted in other areas of 21 research (e.g. using TMS to modulate tinnitus symptoms, 5) it is unclear whether the observed effects 22 are due to stimulation of deeper regions or more lateral association areas that are more likely to be 23 modulated by TMS (e.g. 6, 7).  TMS administered using a figure-of-8 coil is thought to only stimulate 24 brain regions 1.5-3cm below the scalp (8), while insula depth is estimated at 4-5cm (9). Direct 25 stimulation to the cortical depth of the AI may be achieved using double-cone or helmet-shaped coils, 26 COMMENT ON POLLATOS ET AL., 2016  3  although focality of the electrical field is compromised in comparison to superficial cortical 27 stimulation (9).  28 To establish if TMS could reach the AI with the stimulation parameters employed by Pollatos and 29 colleagues, we used the SimNIBS software (10) to run calculations of the electric field induced using 30 these parameters. All parameters and results of this simulation are accessible online 31 (https://osf.io/5qbcs/). As shown in Figure 1, the results of this simulation suggest that with these 32 stimulation parameters, only a negligible portion of the electric field reaches the AI. 33 In their discussion, the authors concede that “there is no guarantee of reaching the anterior insula with 34 a TMS coil positioned over the skull”, but then argue that their pattern of results seems specific 35 enough to say that the anterior part of the insula was indeed targeted. In light of our simulation results, 36 we contend that it is unlikely that AI activity was directly influenced by the stimulation. We therefore 37 suggest two possible reinterpretations of Pollatos and colleagues’ results. Firstly, it is possible that the 38 AI may have been indirectly disrupted via inhibition of cortical regions it is connected to. Indeed, 39 there is evidence that TMS can affect activity of deeper regions through stimulation of connected 40 cortical areas. For example, cTBS to other frontal regions (dorsolateral prefrontal cortex) has been 41 shown to indirectly suppress insula activation through modulation of fronto-insular connectivity (11, 42 see also 12). As direct stimulation of the AI in Pollatos et al.’s experiment was unlikely, one 43 reinterpretation of this data is that worsening of interoceptive performance was the result of indirect 44 modulation of AI activity, via inhibition of more superficial cortical regions.  45 Alternatively, affected regions in the ventrolateral prefrontal cortex may make a unique contribution 46 to interoceptive processes (indeed, the frontal opercular regions are also activated during interoception 47 tasks; see 13,14), or to non-interoceptive aspects of interoception tasks. These cortical regions are 48 considered to play an important role in language and decision-making (15,16), disruption to which 49 could feasibly have impacted on the tasks used by Pollatos and colleagues. 50    COMMENT ON POLLATOS ET AL., 2016  4  Are these effects specific to interoception? 51 Without control tasks however, the nature of this disruption is unclear, leading us onto our second 52 point: it is unclear whether affected performance on the interoception tasks was specific to 53 interoception, or reflective of a more general transient cognitive impairment. Future researchers 54 wishing to use similar methods to examine the role of brain regions in interoceptive processing will of 55 course need to consider which control tasks best suit their experimental question, but it is crucial to 56 use a control task that is similar in nature and difficulty to the interoceptive tasks in order to ensure 57 that decrease in performance is not related to alteration of general processes such as attention, 58 memory or sensation. Such tasks include, but are not limited to, time estimation (17), tone perception 59 (18) and tactile perception (19).  60 The absence of a control condition is also problematic for the EEG measures used. Indeed, the authors 61 measured the HEP over right fronto-central sites close to the AI and somatosensory stimulation sites, 62 but further from the occipital control site. It is therefore possible that cTBS over the right fronto-63 central areas altered the electrical brain response of these areas in a non-specific manner. To claim 64 that the disruption of electrocortical potentials caused by the stimulation is specific to the HEP, it is 65 necessary to show that stimulation effects are not generalised to other non-interoceptive evoked 66 potentials (e.g. visual or somatosensory evoked potentials). 67 In conclusion, non-invasive neurostimulation is arguably one of the most informative tools available 68 in cognitive neuroscience and has certainly been underused in the study of interoception. The recent 69 report of Pollatos and colleagues is in this regard an innovative exploratory study. However, we wish 70 to emphasise that stimulating the AI using this technique is a challenging endeavour, and should be 71 carried out with appropriate cautions and control conditions.   72    COMMENT ON POLLATOS ET AL., 2016  5  References 1.  Schulz SM. Neural correlates of heart-focused interoception: a functional magnetic resonance imaging meta-analysis. Philos Trans R Soc Lond B Biol Sci. 2016;371(1708):20160018. 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Terhaar J, Viola FC, Bär KJ, Debener S. Heartbeat evoked potentials mirror altered body perception in depressed patients. Clin Neurophysiol. 2012;123(10):1950–7. Available from: http://dx.doi.org/10.1016/j.clinph.2012.02.086 19.  Ring C, Brener J. Influence of beliefs about heart rate and actual heart rate on heartbeat counting. Psychophysiology. 1996;33(5):541–6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/8854741    COMMENT ON POLLATOS ET AL., 2016  8  Figure Legend Figure 1. Panel A illustrates the EEG electrodes (left) used to select the coil position and orientation (centre) and the resulting surface normalised electric field strength (Norm E, right). Panel B shows  coronal and horizontal slices of the simulation results (left) suggesting that only a negligible portion of the electric field elicited by these stimulation parameters does reach the anterior insula (highlighted in red on the right). 

Important methodological issues regarding the use of TMS to investigate interoceptive processing: a comment on Pollatos et al (2016)

Michel-Pierre Coll

Tegan Penton

Hannah Hobson

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Important methodological issues regarding the use of transcranial magnetic stimulation to investigate interoceptive processing: a Comment on Pollatos
            <i>et al.</i>
            (2016)

http://gala.gre.ac.uk/19511/7/19511%20HOBSON_Important_Methodological_Issues_Regarding_the_use%20of_TMS_2017.pdf

Important methodological issues regarding the use of TMS to investigate interoceptive processing: a comment on Pollatos et al (2016)

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