Nov. 2011, Volume 8, No. 11 (Serial No. 84), pp.

647660 Journal of US-China Medical Science, ISSN 1548-6648, USA

DA VID

PUBLISHING

The FMRI Correlates of Psychological Complexes: Exploring the Neurobiology of Internal Conflict
Leon Petchkovsky1, 2, Michael Petchkovsky2, 3, Philip Morris2, 4, Paul Dickson2, Danielle T. Montgomery2, Jonathan Dwyer2, Patrick Burnett2 and Mark Strudwick5
1. Department of Psychiatry, University of Queensland, Australia 2. Pinniger Clinic, Robina, Queensland, Australia 3. Quirk-Ability Gallery, Church St Parramatta, Australia 4. Department of Psychiatry, Bond University, Robina Queensland, Australia 5. FMRI Unit, Wesley Hospital Brisbane, Australia Abstract: Objective: Internal conflict is a common feature of subjective life, but its neurobiology is poorly understood. A century ago, Jung discovered that subjects, asked to respond quickly to stimulus words presented serially from a standard list, would occasionally produce unusual associations with emotional and physiologically disturbances, at odds with their usual conscious stance. From such responses, complexes could be inferred. Complexes were thought to feature in psychosis, neurosis, deviant behaviors like criminality and the psychopathology of everyday life. Method: Jungs 100 Word Association Test adapted for fMRI conditions was performed in a 4 Tesla fMRI Unit with 12 normal subjects, yielding 14 scans. Words were presented at 20 second intervals. Two lots of 339 volumes (36 slices per volume) were acquired per subject. A generic complex response was mapped by contrasting all complexed responses against neutral. Results: SPM5 analysis of complexed responses revealed a pattern of bilaterally symmetrical activity, well above the FWE/FDR threshold (Z scores ranging from 4.77 to 5.58), in anterior insulae, medial prefrontal (SMA and middle cingulate), lateral prefrontal (Brocas), and mid -temporal regions. Conclusions: Internal conflict has a biological substrate. The pattern involves internal negotiations at three levels; cortico-limbic, antero-posterior (prefrontal versus post-frontal), and interhemispheric. Both insulae are involved. This pattern is similar to the resonance circuitry described by Siegel and colleagues as central to empathy and our sense of self and other. Key words: Psychological complexes, resonance circuit, Carl Jung, internal conflict, fMRI, Dan Siegel. .

1. Introduction
Over 100 years ago, Jung [1], with his Word Association Test (WAT), and Freud [2], with his free association technique, examined the associative process in their patients inner lives. Jung, bringing a physiological psychology approach, noticed that when a person presented with a word from a standard list is asked to respond as quickly as possible with the first word that comes to mind, most responses tend to be bland and neutral, but every so often there are long
Corresponding author: Leon Petchkovsky, PhD, associate professor, research fields: functional neurobiology of psychodynamic processes. E-mail: leon.petchkovsky@gmail.com.

pauses, often with unusual behavioural and semantic features (the so-called complex indicators which include idiosyncratic word responses and body movements), and physiological disturbances (heart rate, breathing rate, skin conductance). Such responses typically organize around themes. From these responses, a map of psychological hot spots can be built. Jung called these affect-bound thematic nodes the complexes. But more importantly, both he and Freud viewed complexed reactions as evidence of internal conflict, a state in which a sense of self collides with internal opposition. Attempts, by Jeffrey Satinover MD [3] in the early 80s, to look at the neurobiological underpinnings of the complexes, using QEEG, proved inconclusive. QEEG

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The FMRI Correlates of Psychological Complexes: Exploring the Neurobiology of Internal Conflict

and ERP data analysis was then insufficiently advanced. 1.1 Jung on the Complexes It is worth going back to Jungs original descriptions. He was impressed by the way complexes seemed to over-ride volition and conscious intention. [complexes] are psychic entities which are outside the control of the conscious mind.always contain something like a conflictare the sore spots, the betes noires, the skeletons in the cupboard which we do not like to remember but still come back to mind unbidden in the most unwelcome fashion.experience shows that complexes are infinitely varied, yet careful comparison reveals a relatively small number of typical primary forms [4]. Jungs WAT investigations in schizophrenia (or dementia praecox as it was called then) revealed affective as well as cognitive dimensions, leading him to wonder about the role of complexes across a spectrum of conditions, ranging from psychosis, dissociative disorder, psychological trauma, through to everyday life. the average speed of the reactions and their qualities, was a relatively subsidiary result compared with the way in which the method was disturbed by the autonomous behaviour of the psyche.it was then that I discovered the feeling-toned complexes, which had always been registered before as failures to react. p 95.fundamentally there is no difference in principle between a fragmentary personality and a complexp 97.whether such small psychic fragments are also capable of a consciousness of their own is still an unanswered question.dream psychology shows us as plainly as could be wished how complexes appear in personified form..We observe the same phenomenon in certain psychoses when the complexes get loud and appear as voices having a thoroughly personal character.p 98.the aetiology of their origin is frequently a so-called trauma[or]a moral conflict. complexes are in truth the living units of

the unconscious psyche.that is why Freud became the real discoverer of the unconscious in psychology.the via regia to the unconscious, however, is not the dream, but the complex, which is the architect of the dreams and symptoms [5] 1.2 Our Aims Primarily, we wanted to describe the neurobiological correlates of complexed responses. Since there are different types of complexes, as well as individual differences between subjects, we wanted initially to delineate a generic complex response, by pooling all responses with complex indicators. This might give a baseline from which to modify experimental protocols, allowing discrimination between different kinds of complexes (e.g., Oedipal versus death complexes etc), investigate the role of complexes in a range of pathological conditions (i.e., PTSD, behaviour disorders, personality disorders, depression schizophrenia and mania), and generate more reliable therapy outcome measures. Availability of a 4 Tesla fMRI unit at the Wesley Hospital Brisbane, and funding from the International Association of Analytical Psychology (IAAP) Research Funding Committee, allowed us to proceed. 1.3 Subjects These were 13 volunteers: 7 males, 6 females, 12 R handed, 1 L handed, ages 26 to 63, all healthy adult mental health professionals (psychologists; psychiatrists, psychotherapists, counsellors, Jungian Analysts) affiliated with the Australian and New Zealand Society of Jungian Analysts (ANZSJA). Two volunteers repeated the test after a 12 month interval. 1.4 Ethics Recruitment was by word of mouth invitations to ANZSJA Members and Affiliates, e-mail invitations via the ANZSJA mailing list, public announcements at ANZSJA AGMs (2005, 2006) and ANZSJA-sponsored Professional Development Seminars.

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Clearance was obtained from the Ethics Committees of ANZSJA, the University of Queensland, and the Wesley Hospital Brisbane (the site of the fMRI Unit). Confidentiality measures were in place. Investigators were concerned about the unsettling nature of elicitation of complexed responses. As safety net, volunteers could have, on request, intensive de-briefing sessions (60 minutes) with a choice of senior Consultants. In a pre-procedure interview, Subjects were given Information for Volunteers forms, and Metals Check and Interim Medical Examination as prescribed by Wesley Hospital fMRI protocols. Written Informed Consent was obtained after the procedure had been fully explained.

2. Experimental Protocols
2.1 The Word Association Procedure Itself The fMRI process requires each subject hold their head still throughout. Our fMRI Unit technical advisors stressed that vocalisation can spoil imaging. We therefore modified the classical procedure accordingly. Volunteers were told that every 20 seconds, a new word from a standard list of 100 words would appear on a video screen (in two blocks of 50 words each with a 5 minute rest period for the magnet to cool). Instead of vocalising their response, volunteers would press a finger-button just as soon as they had completed saying their response mentally, then hand-write the response word on a moving scroll. Volunteers received a prior 5 minute practice session. The Standard English version Zurich Institute 100 Word WAT List [6] was used. An English translation of Kasts WAT Guidelines [7], and Meiers text on the WAT [8] informed procedure. Complex indicators, as detailed in the WAT Guidelines [7] include: (1) Any reaction time 0.4 sec greater than Median (the 50st slowest response). Jung used this as cut-off point, rather than 1 SD >Mean.

The high values [of extreme responses] influence the otherwise quite low average values in a most disturbing and possibly quite misleading manner. ....By [using Median plus 0.4] the influence of the excessively high values is eliminated. [9]. (2) Incorrect reproductions on repeat WAT (not done here because of logistics constraints) (3) Semantic Indicators (a) No reaction (b) Repetition of stimulus word (c) clang reactions (e.g., big-pig) (d) Disconnected reactions, e.g., subject gives the name of an object in the room unconnected with the stimulus word. (e) Responding with several words. (f) Neologisms, colloquialisms, profanities (g) Stereotypies (use of the same response repeatedly). (4) Behavioural indicators (a) Mimic, movement, laughter (b) Stuttering or mispronunciation (5) Self reported complexes. Identifying and Selecting Complexed Responses in individuals. After each session, investigator discussed responses with subject, marked responses subject felt were disturbing, identified semantic complex indicators (as described in the Zurich WAT protocol) and invited further comment. Within each WAT response, we identified several variably overlapping groups. Time Delay (TD) Group (0.4 seconds above Median). Self Reported Complex (SR) Group. Semantic Indicators Group (SI). Pooled (Complex) or Generic set. The sum of TD SR and SI responses. Neutral (Simple) Group. All remaining responses below median time, excluding any response that followed immediately after either a TD or SR response

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since a strong complexed response can sometimes persevere to the next word presentation. 2.2 Imaging Images were acquired with a 4 Tesla Bruker Medspec system installed at the Wesley Hospital, Brisbane. As this system was not fitted with a whole body RF transmit coil, an actively detunable transverse electromagnetic (TEM) head coil was used for RF transmission and reception [10]. Head movement was limited by using foam inserts within the head coil. Functional imaging was performed using a T2* weighted EPI sequence (TR: 3000 ms; TE: 30 ms; flip angle: 90 ; 64 64 image matrix; 3.6 3.6 3 mm resolution; 0.6 mm gap). The problems of geometric and intensity distortions inherent to echo-planar imaging (EPI) were addressed by using the point spread function (PSF) approach outlined by Zeng and Constable [11]. 339 volumes of 36 slices were acquired for full brain coverage, 5 volumes being discarded before a analysis to allow steady-state 3D tissue magnetisation to be reached. Prior to fMRI acquisition, high-resolution

College London, http://www.fil.ion.ac.uk). Complex responses were contrasted with neutral ones. Data were then analysed voxel by voxel in two stages of a mixed effects model using classical inference [12]. Low- and high-pass filtering was applied, the former using an AR1 model and the latter a 128 sec window. In the second-stage analysis that treated participants as a random effect, individual contrast images were entered in a group level t-test. The resulting t-values were transformed into corresponding Z-scores. The whole brain SPMs were height and extent thresholded using an alpha level better than .0001 and a minimum of 5 contiguous voxels, respectively FWE (Family Wise Error) and FDR (False Discovery Rate) < .05 thresholds were also applied. [13] 3.2 Image Display SPM data was also used as a base to generate 3-D images with a range of innovative imaging softwares including Drishti [14], because for the purpose of generating images of the complex response, we saw advantages imposing in displaying a gradated graphic For representation of BOLD activation, rather than arbitrary statistical thresholds. visualisation purposes a normalised T1 scan at 1mm voxel size from one subject, taken concurrently with the fMRI datasets, was processed with the BET (Brain Extraction Tool) [15] software package to remove non-brain matter from the image. SPM5 generated second stage (group) analysis data contrasting pooled complexes with neutral responses was scaled up and resampled with cubic smoothing using MATLAB array transforms to voxel dimensions matching the T1 image, with care to maintain coregistration of images. Both volumes (saved in uncompressed format) were treated as raw data (ignoring header information) and imported into Drishti. Suitable transfer functions applied to the volumes colour-mapped voxel values revealing fMRI results superimposed on the anatomical image for three dimensional display.

(0.9

mm3)

MP-RAGE

T1-weighted image (TR: 1500 ms; TE: 3.35 ms; flip angle: 8 ; TI: 700 ms; 225 256 image matrix) was acquired to facilitate co-registration of fMRI data for anatomic visualisation of activation foci.

3. Results
Of our total 15 scans, one was discarded because of image distortion from dental fillings. 14 scans from 12 subjects remained. 3.1 FMRI Data Analysis A haemodynamic response function (HRF) was fitted to the onsets for the word presentations. Functional image data were realigned, normalised to Talairach/MNI atlas space, and smoothed with a 8 mm isotropic Gaussian kernel in Statistical Parametric Mapping 5 (SPM5) (Wellcome Department of Imaging Neuroscience, Institute of Neurology, University

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3.3 Findings This paper reports on the generic complex pattern; SPM5 2nd level analysis core group findings for the

contrast between all pooled complex versus all neutral (COMPLEX>NEUTRAL) over the first 3 seconds (Fig. 1 and Table 1), and then over the entire 20 second epoch.

Fig. 1 First 3 seconds, SPM. Table 1 First 3 seconds; p-values adjusted for search volume. Set-level
P 0.000 c 10

Cluster level
p corrected 0.000

Voxel

level
T 12.69 10.67 9.21 11.20 9.39 9.30 10.10 8.00 7.88 9.59 9.91 9.27 8.75 9.15 8.76 8.08 8.75 8.64 6.74 Z 5.69 5.32 5.04 5.46 5.07 5.06 5.24 4.73 4.62 5.13 5.06 5.05 4.93 5.02 4.93 4.75 4.93 4.90 4.35 puncorr 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.00 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000

MNI Co-ordinates
Mmm mmm mmm -44 -54 -47 -47 -65 -65 -29 -47 -43 -0 54 65 54 43 36 36 -4 58 -29 14 15 4 -29 -32 -25 22 25 15 14 7 -40 -29 25 29 25 11 22 22 22 14 32 -11 -7 -11 -0 -4 -0 45 49 -7 -7 4 4

Anatomy

KE p uncorr p FWEcorrected p FDRcorrected 101 0.000 0.000 0.002 0.008 40 0.000 0.001 0.007 0.007 58 0.000 0.003 0.057 0.045 21 7 22 0.000 0.001 0.000 0.005 0.007 0.007 0.014 32 0.000 0.008 0.014 0.033 28 15 5 0.000 0.000 0.003 0.014 0.016 0.228 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.001

BA 9 L peri-Brocas BA 44 L peri-Brocas BA 9 L peri-Brocas BA22 L supTemp BA21 LmidTemp BA21 LmidTemp BA13 L insula BA47 L inf Frontal BA13 L insula BA 32 cingulate BA6 R DLPFC BA21 R midTemp BA21 R midTemp BA47 R ant insula and peri-Brocas BA44 R peri-Brocas

-11 BA47 R perei-Brocas 61 11 -18 BA6 SMA BA45 peri-Brocas BA47 peri-Brocas

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In Tables 1 and 2, and throughout our discussion, we have used the term peri-Brocas to refer to the assemblage of prefrontal Brodmann areas that feature so prominently in our findings (BA 44 (pars triangularis), BA 45 (pars opercularis), BA 47 (pars orbitalis), and the lower part of BA 9). The most striking feature of the results is the bilateral symmetry of the BOLD pattern. In the first 3 seconds, activity well above the FWE FDR threshold is seen in (1) L and R peri-Brocas area BA44/45, Z= 5.69 and 5.02 respectively, (2) L and R Middle temporal lobe Z = 5.46 and 5.05 respectively,

(3) L and R middle cingulate/SMA Z = 5.13 and 4.93 respectively, and L and R anterior insula, Z = 5.24 and 5.02 respectively (See Fig. 1, Table 1). There is a horizontal/interhemispheric symmetry at this stage, except for a small area in R prefrontal region at 54, 7, 49 (R precentral Area 6), which stands out on its own, 7 voxels, Z = 5.06, FWE corrected p < 0.001. As one can see from the above, the parallel activation in the Right hemisphere is only slightly weaker, but becomes more so as time goes on. R peri-Broca and R middle temporal activity drop out, as we shall see in the 20 second scan (Fig. 2, Table 2).

Fig. 2 Total 20 second epoch. Table 2

Set-level P 0.000 C 5

Total 20 seconds; p-values adjusted for search volume.

Cluster level pcorrected 0.000 KE 59 Voxel level T 11.76 7.25 10.92 10.05 9.47 8.44 9.51 8.76 8.67 8.83 7.94 8.33 7.23 Z 5.56 4.51 5.41 5.29 5.10 4.55 5.11 4.95 4.91 4.95 4.71 4.82 4.50 Talairach Co-ordinates puncorr mmm mmm mmm 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 -47 -47 54 -0 4 11 -61 -54 -54 -32 -36 32 -11 14 4 4 14 7 18 -32 -22 -29 22 14 29 11 22 32 47 43 54 47 -0 -11 -7 -4 -4 4 0 Anatomy

puncorr pFWEcorrected pFDRcorrected 0.000 0.000 0.107 0.000 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001

BA9 L peri-Brocas BA 9 BA6 L peri-Brocas R DLPFC

0.000 0.000

8 69

0.001 0.000

0.001 0.003 0.008 0.020

BA32 SMA & cingulate BA 6 SMA BA6 SMA BA22 L Mid temporal BA22 L Mid temporal BA22 L Midtemporal BA13 L ant insula BA13 L ant iinsula BA13 R ant insula L head caudate

0.000

62

0.000

0.005 0.015 0.015

0.000

24

0.000

0.012 0.040

0.000 0.000

10 12

0.000 0.000

0.024 0.109

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We also analysed the entire group scan as consecutive 3 second segments. After the first 6 seconds, nothing passes the FWE FDR threshold. The results of the 20 second group scan are shown in Fig. 2 and Table 2. Bilateral symmetry is less marked over the 20 second span. In order of decreasing salience, the following BOLD responses above the FWE and FDR thresholds are seen. Left peri-Brocas area, 59 voxels at -47 14 22 L BA 9 and 44, and -47 4 32 L BA 9 (Z = 5.56 and 4.51 respectively) 8 voxels at 54 4 47 R BA 6 in the dorsolateral cortex (Z = 5.41) 69 voxels at -0 14 43 (BA 32 SMA and cingulate), 4 7 54 BA6 (SMA) and 11 18 47 BA 6 (SMA). Z scores are respectively 5.29, 5.10, and 4.55. 62 voxels at -61 -32 -0, -54 -29 -11, -54 -29 -7 (all L Middle Temp). Z = 5.11, 4.95, 4.91. 24 voxels at -32 22 -4 and -36 14 -4 (BA 13 L ant insula) score at Z = 4.95 and 4.71 and -32 10 voxels at 32 29 4 (BA 13, R ant insula) Z = 4.82. Below the FWE threshold (0.109) but above the FDR threshold (0.001), we also note activity at -11 11 0, L head of caudate, corresponding with the fixation of attention that is part of the experience of striking a complex. Comparing the pattern over 20 seconds with the initial 3 second pattern, we note that there is less symmetry. Right peri-Brocas and middle temporal activity is much diminished. However, Right insular activity is a little more prominent, and the midline SMA/cingulated activity noted in the 3 second scan is more extensive. The small but intense 54 4 47 BA6 DLFPC area noted earlier in the 3 second response has intensified further over the following period (From Z = 5.06 to Z = 5.41), and is now the second most intense activation site in the list! The bilateral symmetry of the generic complex response.

Fig. 3

Drishti display.

4. Discussion
4.1 The Sites Involved We have reviewed the literature for findings relevant to the sites that feature in our results and present some of the salient findings below. (1) The peri-Brocas area observed to light up bilaterally in these results is formed by Brodmanns Area 44 (pars triangularis), 45 (pars opercularis), 47 (pars orbitalis), as well as the lower part of BA 9. BA 44 and 45 are traditionally associated with motor speech (and we would expect them to light up as the subject articulates word responses). But we have known for some time, beginning with Fogassi and Rigolazzis work on mirror neurones (16 and 17), that the peri-Brocas area is an important mirror neurone site in primates. (2) Middle and superior temporal areas (BA 21 22). We know that these areas subserve word generation and semantic processing [18]. We would therefore expect them to be active in the complexed situation. But there is a range of studies that suggest that this region (especially superior temporal gyrus BA22) also has a mirror neurone role [19]. (3) The salience of SMA. Why is SMA so prominent? We know that Iacobonis powerful brain electrode recording studies on SMA in 14 subjects during surgery for epilepsy [20] suggest strongly that SMA is a supra-modulator of other mirror neuron sites (peri-Brocas and peri-Wernickes) [16, 17]. Furthermore, a range of other studies suggest SMA is central to a broad range of attention and volition switching tasks [2123]. BOLD activity in our results

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also extends to middle and anterior cingulum, sites closely linked with self-monitoring and self-awareness [48]. (4) Anterior insular activation. Bud Craig [24] provides perhaps the most comprehensive review of contemporary research on insular (and especially anterior insular) cortex (AIC) function and postulates that AIC should be regarded as con-involved with Anterior Cingulum in self-awareness processes, as a substrate for self-representation at each moment of time. There is a strong affective component to this, which is seen in fMRI studies of anterior insular activity in Borderline Personality Disorder [25]. (5) Head of Caudate Activity. When a complex is elicited, the subjective experience has a very intrusive quality. Attention gets fixated. Head of caudate activity is prominent in our findings (12 voxels at -11 11 -0 p <.0001, Z = 4.50 FDR. 001 but below the FWE threshold at .109). We know that caudate activation has been observed in a range of conditions including love states (romantic and maternal). See Bartels and Zeki [26] and a range of studies on obsessional conditions [2729]. (6) Bilateral Symmetry. Why does the generic complex response show so much bilaterally symmetry? Much has been written about left versus right hemispheric function. Australian vision neuroscientist, Jack Pettigrew, was one of the first researchers in this area, and became particularly interested in the role of hemispheric switching in Bipolar Disorder [30]. Perhaps the deepest and most comprehensive contemporary review is that of Iain McGilchrist [31]. In essence, McGilchrist argues that each hemisphere has its own distinctive mode of awareness or consciousness. The right hemisphere develops first (the first 2 to 3 years of life) and processes incoming data (including proprioceptive body field) holistically. It also mediates highly affect-loaded attachment and threat patterns. Right hemispheric over-activity in vertebrates is associated with wariness and depression (the subject as prey). Whereas left hemisphere circuitry

develops later, and processes in a linear rather than gestalt fashion, organized around language, logic and abstractions. At the affective level, left hemisphere is more curious, exploratory, danger-denying, even hypomanic (the subject as predator). McGilchrist associates optimal mind-states with good interhemispheric communication. In our results, peri-Broca, anterior insula, middle and upper temporal gyri, and SMA and cingulate gyri are activated in both hemispheres. Some kind of even-weighted interhemispheric negotiations seems to be involved at least initially in the complexed response? The fact that over the 20 second span, the left hemisphere eventually comes to dominate (at least at the level of the BOLD response) may be a reflection of the psychopathological nature of the complexed response. 4.2 Comparing Study Results with FMRI Patterns Found in Other Conditions Given Jungs linkage of the complexes with psychopathological forms, how do our patterns compare with those founds in various syndromes? A broad review of the field (including lying, PTSD, schizophrenia, attachment and attachment disorders, dissociative states, BPD) follows to see if there are any conditions whose fMRI patterns resembled the ones seen. Lying. The pattern seen in the generic complex response was different to the one described by Kozel [27] in his studies on lying, in which R anterior cingulum preferentially activates and modifies the baseline behaviour of the prefrontal cortex (orbito frontal and dorsolateral) for deceptive purposes. PTSD. Are complexes simply the consequences of psychological trauma? Lanius and colleagues [32, 33] suggest that PTSD is characterized by alternate states of hyperarousal and dissociation. In hyperarousal states, anterior cingulum and Medial Pre-Frontal Cortex are usually underactive, leading to amygdalar overactivity. In dissociation anterior cingulum and medial prefrontal

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cortex are hyperactive, reducing amygdalar activity. Our complexed responses show heightened SMA and cingulate (mainly middle region) activation, suggesting that complexed activity may have a dissociative element, as Jung posited almost a century ago. Dissociative Identity Disorder neurobiology is poorly understood. A single case fMRI study reports substantia nigra and hippocampus changes during switching [34] More recently, Reinders [35] overviews the controversies associated with the DID diagnosis and discusses whether brain imaging studies can distinguish the etiology of DID. The heightened cingulate activity seen in our complexed responses could very well down-modulate amygdalar and hippocampal function towards a more dissociative experience. 4.3 Borderline Personality Disorder Severe neglect and abuse in the first few years of life is a major contributor to Borderline Personality Disorder. In particular the brain circuitry that sustains attachment dynamic seems to be affected. This leads, in Fonagys words, to hyper-responsiveness of the attachment system which makes mentalizing, the capacity to make sense of ourselves and others in terms of mental states, unstable during emotional arousal [36]. This includes anterior insular dysfunction. FMRI studies by Fonagy and colleagues [25] reveal that in social co-operation experiments in patients with borderline Personality Disorder, activity in anterior insula of BPD participants was related only to magnitude of repayment, but not responsive to social input. But more generally, activity in the anterior insula, a region known to respond to norm violations across affective, enteroceptive, economic, and social dimensions, strongly differentiated healthy participants from individuals with BPD. [25] Schizophrenia, viewed by Jung as the annexation of inner life by the complexes, has been the subject of a wide range of functional studies [3638]. A detailed review is beyond the scope of this paper. Gabrieli [39]

proposes base-line over activity of a brain system involved in self-reflection, the so-called default network, which includes medial prefrontal cortex (MPFC) and posterior cingulate cortex/precuneus, for failure to differentiate between internal and external realities. In normals, this deactivates when a task is presented. But in schizophrenia, hyperactivation (reduced task-related suppression) of the default networks and hyperconnectivity with dorsolateral prefrontal cortex may contribute to self-referential misattribution. Sommer et al. (2008) [49] report R anterior Insular activation during verbal hallucinations in schizophrenic patients. By contrast, our complexed responses showed increased midline cortical activity (SMA and medial prefrontal cortex) confined to the central region, i.e., not extending fronto-caudally to the default network regions. However, R anterior insula did show an increase BOLD response. So the complexed pattern has some resemblance to but also some differences from, the one seen in schizophrenia. 4.4 Obsessive Compulsive Disorders Overactive cingulate gyrus error control systems are found in obsessional conditions. The head of the caudate nucleus is over-active during an obsessional experience [43]. This probably has something to do with the involuntary fixation of attention that characterizes it. Whitesides study gives a good overview [29]. Our findings (Table 2) also show caudate activation, just below the FWE threshold, but still within acceptable FDR limits (L head of caudate (12 voxels at -11 11 -0 p < .0001, Z = 4.50 FDR. 001 but FWE .109). This is to be expected, given that the complexed reaction typically rivets the attention [29, 43]. 4.5 Attachment States Attention is also captivated in intense attachment states, and caudate activation has been observed in a range of love states (romantic and maternal) [26]. But the Nucleus accumbens striatum and medial

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prefrontal/sunpraorbital reward pathways that are activated in these studies are not activated in the complex response that we see in this study. Jung understood that complexes did not necessarily all have to have negative affects, but the ones with positive affects (like De Clerambault syndrome, and obsessional love disorders) could be problematic. We would have need a much larger sample if we wanted to select ONLY the positive affect complexes, because they are in a minority compared to the negative affect ones. Social rejection and rejection-related distress studies. A range of studies showed bilateral activation of SMA/dorsal cingulum, and anterior insulae. Slavichs [44] paper reviews rejection-related distress and painful affect fMRI studies, and describes his own research, where subjects were involved in a social stressor computer game under fMRI conditions. The fMRI pattern of activation was very similar to the one we found in a generic complex response; bilateral activation of medial SMA and dorsal cingulum, and bilateral activation of anterior insula. However, the social distress response generated by the complex is much more internally determined. And as the stimulus word and its problematic response get processed in a conflictual manner, the activities seem to be bi-hemispheric, some of them favouring the Left (Temporal lobe, L Prefrontal, L Brocas and operculum, L head of caudate,) some of them favouring the Right ( R SMA, R Insula, R Brodmann 6). Areas involved in self and other awarenesses are also prominent (SMA, pre-SMA area 6, insula). Cross talk would seem to be occurring interhemispherically as well as between areas to do with self and other. 4.6 The Resonance Circuits The term resonance circuits is used by Dan Siegel and his colleagues at UCLA [45] to refer to the brain circuitry responsible for much of our own self awareness. They also allow us to have a sense of the

experience of others, through a process of resonance, and are therefore of vital importance in empathy and relationship processes. The pathways begin at the mirror neurone sites, and project to the insula, which in turn sends signals to subcortical limbic and hind brain areas, receives feed-back, and projects it onto to the middle pre-frontal region. There is accumulating research evidence to support the validity of this mirror neurone/insula/subcortical/middle pre-frontal system as a substrate for relational awareness. Of all the patterns described, the resonance circuit one is the one that most closely matches our findings, in which we see activation of peri-Brocas SMA and Superior Temporal mirror neurone sites, anterior insula, and cingulate gyrus. The only major mirror neurone site missing in our findings is the site at the inferior parietal lobule [16, 17]. That does not survive the FWE and FDR group analysis thresholds. However, we did find heightened activity in this area (at a statistically significant level) in 4 of our individual scans. There may be strong inter individual difference in the recruitment of this site. This similarity makes sense, since the resonance circuits mediate awareness of self and other, and the internal conflict at the heart of the complexed response is precisely a conflict between internal self and internal other. One difference between complexed activity as elicited by the WAT, and resonance circuitry activity in general, needs to be pointed out. The word association test depends upon the subject having acquired language (the left hemispheric development that begins around the 3rd year). But internal conflict precedes verbal capacity. Primordial self versus other awareness begins much earlier in the human infant, as interactions with its caregivers impact on the development of right hemispheric and limbic circuitry, to lay down implicit memory patterns which shape perceptions to do with fear or safe protectors. This is discussed in detail by Seigel [45].

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4.7 Limitations. There are Power issues in a study of this kind. The modest number of subjects puts it firmly in the class of pilotstudy. It will need replication. Even at the pilot level, there are many confounding variables. There were some inter-individual differences in fMRI responses (scattered single voxels) detected on t-test comparisons between first and second test results for the two subjects who repeated the fMRI WAT, even though the broader patterns were similar. Some subjects seemed to recruit limbic pathways more vigorously than others. We also noted that some subjects self-reported complexes corresponded closely with their delayed ones (possibly indicating greater self-awareness?), whereas others showed greater divergence. This probably has to do with the subjects capacity for self-reflectiveness or mindfulness (some subjects had much more personal psychoanalysis than others). A separate study to examine the relationship in subjects between deviations in coherence of self-reported and delayed responses and amount of personal analysis is in progress. Other confounding variables included the groups self-selected nature, gender differences, age, culture, prior psychotherapy, differences between types of complexes, individual differences in complex response patterns. Further studies are needed to address this. Furthermore, presentation of words on a screen departs from the standard WAT protocol (verbal presentation by examiner in the room). Yet this may have advantages. Individual differences between examiners are thereby eliminated. The experience is also less confrontational than the standard WAT format. But salience still emerges despite this weaker testing, and despite the noise of confounding variables. Physiological data (GSR, pulsometer, ECG, EEG) would have been a useful supplement, as would the reproduction test component of the standard WAT protocol.

A separate functional connectivity analysis study (Dynamic Causal Modelling in the SPM protocol) is in progress, to be published as an additional finding.

5. Conclusions
In essence, there is considerable similarity between the complexed response pattern and that of the resonance circuits. Lateral prefrontal and middle temporal regions light up bilaterally, as do both insulae, and then both medial prefrontal regions. Over the 20 second span, the right hemisphere tends to be favoured in the mesial sites, but most activity shifts to the left hemisphere. But the initial bilaterality suggests that complexed response involves cross-hemispheric negotiations. There is also an antero-posterior gradient that warrants comment. We know that the mid-line areas implicated in the so-called default network described by Gabrieli and Raichle [41, 46] are both rostral (anterior cingulum and MPFC) and caudal (Posterior cingulum, cuneus, precuneus) to the complexed response (dorsal cingulum) that we see. We also know that default network activity may correlate with background sense of self. The generic complex pattern does not include the default network, suggesting that the BOLD patterns that we see here in the mid-line may relate more to a salient sense of self in the present moment (see Bud Craigs discussion [24] of the contribution of anterior insula to sense of time), or even a sense of internal otherness. 5.1 Internal Self, Internal Other The robust consistency of fMRI patterning reported sustains the notion that the metapsychological concept of complex has neurobiological underpinnings. This has implications for psychodynamic assessment and diagnosis, as well as the tracking of treatment. While a detailed discussion is outside the scope of this report, we present the follow tentative considerations. The various self functions, which feel so central, seem to use a scattered range of sites. Fosatti [47]

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points to R dorso-medial prefrontal cortex as one main area mediating self reference. Ochsner et al. [48] see MPFC as central in supporting processes of mental state attribution to self or other. Other investigators like Gabrieli [41] include more caudal midline systems like the default network posterior cingulum and pre-cuneus. Agency and its associated functions may involve more rostral and ventral prefrontal cortex (executive function and impulse control), as well as dorso-lateral prefrontal cortex (controlling emotions processing ambiguity), and anterior and dorsal cingulate detecting conflict [49]. The Left Dorso Lateral Prefrontal Cortex (DLPFC) is thought to be a site that mediates self-reflective awareness, and insight, as well as executive ego function, and recent QEEG research on lucid dreaming shows high 50 Hz gamma activity in left DLPFC during lucid dreaming states [50]. Any concept or function of self must posit otherness necessarily. But otherness is not limited to the world outside the skin. While the literature on mirror neurone sites deals mainly with brain events in relationship to external others, the elicitation of a complex, especially under the visual presentation protocol described (where the presence of external other is minimized, relative to the internal other), seems to be more about internal conflict. Our findings demonstrate that there is a functional brain pattern associated with this inner conflict. A small, anomalous, but highly activated Right Dorsolateral Prefrontal Cortex area at 54, 4, 47 (8 voxels, R BA 6 Z = 5.41) breaks the resemblance to the resonance circuitry. What to make of it? If Left DLPFC mediates reflective self-awareness, could its homologue in the Right hemisphere mediate awareness of an internal otherness, somehow at odds with ones self? It would be delightfully ironic if in the brain, internal other proves more localized than internal self.

McMahon of the Centre for Advanced imaging, Uni of Queensland, for their help. We also thank the Grants Committee of the International Association of Analytical Psychology for their kind moral and financial support.

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