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Functional Magnetic Resonance Imaging of Personality Switches in a Woman with Dissociative Identity Disorder

Authors:
ionizing radiation. To investigate the neuronal substrate in-
volved in the personality switches of DID, we conducted an
fMRI study on a woman with DID while she was switching
personalities.
METHODS
The subject is a 47-year-old, right-handed, Caucasian
woman. She was a victim of severe childhood physical and
sexual abuse and was diagnosed with DID and PTSD ac-
cording to DSM-IV criteria.
1
The history and diagnosis had
been recognized since her early adulthood, and she had re-
ceived long-term psychotherapy with one of the authors.
A complete description of the study was provided to the
subject, and written informed consent was obtained. We
identified the alter personality that appeared most often
during psychotherapy; it consistently appeared upon re-
quest. Simulations of personality switch were performed to
prepare the patient for the fMRI study. To identify the
switching period, the subject was instructed to press a spe-
cific button when she started to switch and again when she
fully became the alter or returned to the native personality.
The personality switch was confirmed by the observation of
the subject’s long-term psychiatrist during both the simula-
tion and the fMRI study.
A volumetric study was performed according to the
method of Jack and colleagues;
5,6
the fMRI study used scan-
ning methods and data analysis techniques similar to those
reported by Stern and colleagues
7
at Massachusetts General
Hospital. The subject was scanned using a 1.5-T Signa de-
vice (General Electric Co., Milwaukee, Wisconsin; modified
by Advanced NMR Systems, Wilmington, Massachusetts). A
pillow and foam padding were used to minimize head move-
ment. A set of sagittal localizer scans was performed first to
orient 13 contiguous axial oblique slices from vortex to cere-
bellum. Functional scanning used an asymmetrical spin-
echo imaging sequence, which is sensitive to signal-intensity
changes arising from small alterations in blood-oxygen level.
A gradient-echo T2-weighted sequence was performed using
NEUROSCIENCE
Editor: Joseph T. Coyle, MD
Functional Magnetic Resonance Imaging of
Personality Switches in a Woman with
Dissociative Identity Disorder
Guochuan E. Tsai, MD, PhD, Donald Condie, MD, Ming-Ting Wu, MD, and I-Wen Chang, BA
Dissociative identity disorder (DID) is a controversial condi-
tion characterized by fluctuating constellations of affective,
memory, and behavioral symptoms that are associated with
a changing sense of personal identity.
1
Clinically, DID is of-
ten associated with posttraumatic stress disorder (PTSD).
Psychodynamically, it is considered rooted in childhood trau-
matic experiences and is usually an extreme form of defense
against overwhelming abuse.
Researchers have recently reported hippocampal volume
to be decreased in persons with PTSD secondary to child-
hood abuse.
2
The hippocampus is sensitive to stress and ov-
erarousal,
2
which individuals with DIDlike those with
PTSDoften encounter in early life. We performed a volu-
metric study of the hippocampus in a patient with comorbid
DID and PTSD for comparison with the literature on PTSD.
Very little is known about the brain substrate involved in
DID, particularly the mechanism of personality switch. Neu-
rophysiological study of DID is limited due to the dynamic
nature of the disorder. Although measurable neurophysio-
logical differences among personalities in DID have been re-
ported, the results have been inconsistent and often mixed.
3
Unlike other brain mapping techniques, functional mag-
netic resonance imaging (fMRI) has high temporal and spa-
tial resolution,
4
so it is an ideal tool to study neuropsychiat-
ric disorders with dynamic symptoms, such as DID. And
with fMRIin contrast to procedures such as positron emis-
sion tomography and single photon emission tomography
a subject can be studied repeatedly without the concern of
119
Supported in part by a NARSAD Young Investigator Award and a
Stanley Foundation Research Award (Dr. Tsai).
Reprint requests: Guochuan Tsai, MD, PhD, Laboratory of Molecu-
lar and Psychiatric Neuroscience, Mailman Research Center,
McLean Hospital, 115 Mill St., Belmont, MA 02478.
q 1999 President and Fellows of Harvard College
Harvard Review of Psychiatry 1999;7:119–122.
the BOLD (blood oxygen level–dependent) technique (TE 5
70 ms, TR 5 2 ms, flip angle 5 90°, acquisition matrix 5 64
3 128).
The subject wore headphones, and the instructions for
switching personalities or guided imagination were played
to her on a tape. As in the simulation session, she heard the
instruction of personality switch, “switch to . . . now.” As soon
as she pressed the button to indicate that she had fully
switched to the alter (native) personality, she was instructed
to switch back to the native (alter) personality. FMRI studies
were performed while she was switching back and forth be-
tween native and alter personalities. To control for volitional
changes, a guided imagination of an irrelevant personality
using a closely matched but emotionally neutral narrative
was performed using recorded instruction, as described by
Cahill and colleagues
8
(see Table 1). To determine test-retest
reliability, the subject was rescanned 4 weeks after the ini-
tial study. The psychiatrist participated in the fMRI scan-
ning procedures to ensure the clinical safety of the subject.
After motion correction, the personality switch–induced
changes in fMRI signal intensity were assessed using a
voxel-by-voxel nonparametric analysis procedure to com-
pare the images acquired during personality switching to
those of the originating personality state.
7
Kolmogorov-
Smirnov statistics were computed for each voxel to assess
the point(s) of maximal difference between the two esti-
mated distribution functions during the control (either na-
tive or alter personality) state and the experimental (switch)
phase (see Figure 1).
RESULTS
The total intracranial volume of the subject (1397.71 cm
3
)
was within normal range. The hippocampal volume (right,
1.09 cm
3
; left, 1.15 cm
3
), however, was significantly smaller
than reported values for normal female adults
6
obtained by
the same technique (right, 2.8 6 0.1 cm
3
; left, 2.5 6 0.1 cm
3
);
it was similar to the volume found in persons with Alzhei-
mers disease, who have significant loss of hippocampal
tissue.
5
In the initial investigation we performed three personal-
ity-switch studies, with a total of 12 cycles of switching from
the native to the alter personality and back again. The
switch phase from native personality to alter averaged 27.6
6 3.0 seconds (mean6standard error); from alter back to na-
tive personality, 32.3 6 2.2 seconds.
FMRI demonstrated changes of brain activity during per-
sonality switches (see Figure 1). The switch from native to
alter personality involved bilateral hippocampal inhibition
(less activity during switching than in the native state), with
inhibition stronger on the right side (Figure 1A,B). The right
parahippocampal and medial temporal regions were also in-
hibited (Figure 1A), as were small regions of the substantia
nigra (Figure 1A) and globus pallidus (Figure 1B). In con-
trast, the switch back toward the native personality involved
only right hippocampal activation (i.e., more activity during
switching than in the native state) (Figure 1C).
No significant activation or inhibition was observed in
other brain regions during either direction of personality
switch. The guided imagination of an irrelevant personality
did not evoke a significant change of fMRI signal. The re-
scanning results were similar to those of the initial study.
DISCUSSION
We found bilateral reduction of hippocampal volume in this
subject with comorbid PTSD and DID, consistent with the
reported reduction of hippocampal volume in patients with
PTSD secondary to childhood trauma.
9
In addition, fMRI
during volitionally induced personality switch showed
changes in hippocampal and medial temporal activity corre-
lated with the switch, suggesting that personality switch
may result from changes in hippocampal and temporal func-
tion. These findings are consistent with the few existing neu-
rophysiological studies of DID,
10–12
in which single photon
emission computed tomography and electroencephalogra-
phy have revealed changes in temporal regions between dif-
ferent personalities in persons with this disorder.
Animal studies and human clinical evidence suggest that
stress has long-term effects on the brain regions involved in
memory, particularly the hippocampus.
2,9
In this subject, re-
duced hippocampal volume may be relevant to the attenua-
tion of hippocampal activity during personality switch to-
ward the alter personality.
In contrast to the inhibition seen during the switch to-
ward the alter personality, activation was observed in the
Harvard Rev Psychiatry
July/August 1999
120 Tsai et al
TABLE 1. Instructions for Personality Switch and Guided Imagination
Alter personality Irrelevant personality
Switch to “Guardian” now. Don’t switch.
Imagine that you are an 8-year-old girl named Guardian. Imagine that you are an 8-year-old girl named Player.
You like to watch what happens with [patient’s name]. You like to play with a neighbor girl named Helen.
[Patient’s name] was sexually abused by her father and has been Helen gets along with her father, as in an ordinary family.
very sad throughout her life.
Memory Scale. Scores on all of the subscales were in the av-
erage range. This finding differentiated our subject from pa-
tients with memory disorders. It was also consistent with
the notion that the correlation between deficits in short-term
verbal memory and decreased right-hippocampal volume in
patients with combat-related PTSD does not extend to pa-
tients with PTSD related to childhood abuse.
9,15
Future
study including these clinical, neuropsychological, and
functional-brain-imaging variables will help to delineate the
relationship between PTSD and DID.
Second, in our study personality switching was initiated
by conscious effort. The capacity for volitional elicitation and
reintegration of an alter personality in our subject is not
characteristic of DID patients in general. This volitional pro-
cess may be distinct from spontaneous pathological switch-
ing and cannot be generalized to DID patients who present
only with spontaneous switching. In fact, screening of DID
patients for the study indicated that only a minority of them
could successfully and reliably signal the personality status
and the beginning of a personality switch. The majority,
early in their recovery to personality consolidation, switched
randomly into different alters and failed reliably to report
the change of personality status. Thus, stage of reintegra-
tion recovery may be a relevant study variable and further
limits the generalizability of our findings.
Third, conscious recollection and episodic retrieval are
associated with changes in hippocampal blood flow.
15,16
In
addition, affective and emotional states can affect hippocam-
pal activity. The emotionally neutral, irrelevant personality
control that we performed did not address the issue of differ-
right hippocampus when the subject was returning from the
alter to the native personality. Such activation suggests that
a hippocampus-mediated process is also instrumental in the
subject’s return to the native personality. This adds to the
intriguing possibility that the hippocampus may be involved
in personality switch and dissociation in DID. Activation of
the hippocampus associated with a return to the native per-
sonality suggests a possible neurophysiological basis for an
empirical treatment principle in DIDi.e., consolidating al-
ter personalities by facilitating processing and integration
of early traumatic memories.
In addition to changes in medial temporal and hippocam-
pal activity, nigrostriatal-system inhibition was also asso-
ciated with personality switch (see Figure 1A,B). The hip-
pocampus and associated medial temporal cortical areas
(including entorhinal, perirhinal, and parahippocampal re-
gions) are important neuronal structures for declarative
memory (conscious memory of specific events).
13
The nigro-
striatal system is essential for the gradual, incremental
learning of association (nondeclarative memory).
14
Taken to-
gether, our findings suggest that structures of both declara-
tive memory and nondeclarative memory may be involved in
the personality switches of DID.
Our study has several limitations. First, our subject had
comorbid PTSD and DID; thus our results are not specific for
DID. Clinically, it is difficult to identify a subpopulation of
patients with DID who do not also have symptoms consis-
tent with a diagnosis of PTSD.
Interestingly, our subject was not memory-impaired, as
indicated by a normal score (106) on the general Wechsler
Harvard Rev Psychiatry
Volume 7, Number 2
Tsai et al 121
FIGURE 1. Changes in brain activity during switch between native and alter personalities. The statistical maps comparing the control
phase (native or alter personality) and the switching phase were transformed to 2log(p) maps and translated into a gray scale before being
superimposed over the high-resolution T1-weighted images for anatomic localization. Areas with statistically significant fMRI signal-
intensity changes (p , 0.001) are indicated by arrows. A. Inhibition of right hippocampus, parahippocampus, medial temporal structures,
and substantia nigra during switch from the native to the alter personality (control: native phase). B. Inhibition of the hippocampus
(bilateral, but right side stronger than left) and globus pallidus (right) during switch from the native to the alter personality (control:
native phase). C. Activation of a small region of the right hippocampus during switch from the alter to the native personality (control:
alter phase). R, right; L, left; g, globus pallidus; h, hippocampus; p, parahippocampal gyrus; s, substantia nigra.
ent affective states induced consciously. That is, affectively
charged volitional recall could be contributing to our find-
ings. Different affective states in patients with DID have not
yet been studied with fMRI.
Finally, our findings could reflect a compensatory re-
sponse of the hippocampal regions to a primary functional
deficit that is not detected by fMRI. Another interpretation
of our results is that the observed change in brain activity
during personality switching reflects the difference between
disparate personalities rather than the process of switching
per se. Since we performed the study for only two personali-
ties, we cannot resolve this issue. A large case series study
might elucidate the common mechanism of switching, if
one exists.
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... These studies have shown regional cerebral blood flow (rCBF) or glucose metabolism (CMRglu) changes in the temporal, parietal (implicated in dissociative and conversion phenomena), and orbitofrontal (likely involved in the integration of the self) cortices, in the hippocampus (involved in memory and in the removal of traumatic events), in the basal ganglia, and in other areas. However, they have reached different, and at times conflicting, conclusions, finding out hyperactivation of brain areas in some cases [12][13][14], and hypoactivation in others [15]. It is also unclear whether these changes involve more often the left or right hemisphere, albeit recent evidence suggests greater damage of the former. ...
... Based on these criteria, we analyzed 61 studies, from which we excluded 48 studies, of which 26 were unrelated to the subject, 6 were case reports/case studies [15,[23][24][25][26][27], 1 was focused on schizophrenia [28], 1 was conducted on adolescents with post-traumatic stress disorder [29], 1 was conducted on healthy subjects [30], 7 used structural neuroimaging techniques [31][32][33][34][35][36][37], and 3 were not focused on dissociative disorders [38][39][40]. We finally included 13 studies published between 2006 and 2022 [14,33,34,[41][42][43][44][45][46][47][48][49][50]. ...
... The hypoactivation of the caudate in dissociative disorders during egocentric tasks has been confirmed by fMRI findings [46], whilst DID patients' caudate nucleus hyperactivates during traumatic identity state condition, in response to personal trauma scripts [34]. The latter can be explained by the fact that the dorsal striatum i.e., caudate nucleus is involved both in the switch between identity states and in the maintenance of the altered identity state [15,41,50,71]. ...
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Background: Dissociative disorders encompass loss of integration in essential functions such as memory, consciousness, perception, motor control, and identity. Nevertheless, neuroimaging studies, albeit scarce, have suggested the existence of particular brain activation patterns in patients belonging to this diagnostic category. The aim of this review is to identify the main functional neuroimaging correlates of dissociative disorders. Methods: we searched the PubMed database to identify functional neuroimaging studies conducted on subjects with a diagnosis of a dissociative disorder, following the PRISMA guidelines. In the end, we included 13 studies in this systematic review, conducted on 51 patients with dissociative identity disorder (DID), 28 subjects affected by depersonalization disorder, 24 with dissociative amnesia, and 6 with other or not specified dissociative disorders. Results: Prefrontal cortex dysfunction seems prominent. In addition, changes in the functional neural network of the caudate are related to alterations of identity state and maintenance of an altered mental status in DID. Another role in DID seems to be played by a dysfunction of the anterior cingulate gyrus. Other regions, including parietal, temporal, and insular cortices, and subcortical areas were reported to be dysfunctional in dissociative disorders. Conclusions: Prefrontal dysfunction is frequently reported in dissociative disorders. Functional changes in other cortical and subcortical areas can be correlated with these diagnoses. Further studies are needed to clarify the neurofunctional correlations of each dissociative disorder in affected patients, in order to identify better tailored treatments.
... Two fMRI case studies have begun to identify brain activity implicated in this transition, also colloquially termed "switching." One study identified differential activity in the hippocampus, parahippocampal gyrus, medial temporal regions, substantia nigra, and globus pallidus, depending on which state the individual was transitioning to (Tsai, Condie, Wu, & Chang, 1999). In another case, researchers implicated pre and postcentral gyrus, nucleus accumbens, and lateral prefrontal cortex in the switching process (Savoy, Frederick, Keuroghlian, Wolk, 2012;. ...
... The hippocampus is centrally involved in learning and memory processing (Squire & Zola-Morgan, 1991), and is sensitive to the neurotoxic effects of chronically activated stress hormones (Conrad, 2008). The majority of studies find that the hippocampus is smaller and abnormally shaped in DID groups compared to nonpsychiatric control groups (Chalavi et al., 2015a;Chalavi et al., 2015b;Ehling et al., 2008;Irle, Lange, Sachsse, & Weniger, 2009;Tsai et al., 1999;Vermetten, Schmahl, Lindner, Loewenstein & Bremner, 2006). In addition to group level comparisons, some work has also demonstrated a negative correlation between hippocampal size and dissociative symptom severity in DID samples or mixed samples that include some individuals with DID (Chalavi et al., 2015b;Ehling et al., 2008;Stein, Koverola, Hanna, Torchia & McClarty, 1997). ...
... One of the largest neuroimaging studies of PTSD to date definitively demonstrated smaller hippocampal volume in PTSD versus trauma exposed controls (Logue et al., 2018). As discussed earlier, smaller hippocampal volume has also been demonstrated in DID and dissociative disorder cohorts (Chalavi et al., 2015a;Chalavi et al., 2015b;Ehling et al., 2008;Irle et al., 2009;Tsai et al., 1999;Vermetten et al., 2006;however, c.f., Weniger et al., 2008 for contrasting evidence). Furthermore, hippocampal volume was negatively associated with the severity of trauma history (Chalavi et al., 2015a;Chalavi et al., 2015b). ...
... Chalavi et al. (2015b) and Vermetten et al. (2006) found no significant difference in the CV of total brain parenchyma between DID patients and HC. Tsai, Condie, Wu, and Chang (1999) found that the cortical volume of their DID patient was within normal limits (WNL). The CT of brain LG was observed to be smaller in DID patients (Chalavi et al., 2015b). ...
... Between DID-PTSD participants, PTSD-only, and healthy controls, Weniger et al. (2008) observed that the hippocampus in patients with PTSD-only showed the most reduction in size, whereas the DID-PTSD and the controls did not significantly differ. On fMRI analysis, Tsai et al. (1999) observed bilateral inhibition of the hippocampus in DID-PTSD patients as compared to normal limits. ...
... There was no significant difference seen in the parahippocampal size between participants who recovered from DID and those who did not recover (Ehling et al., 2007). In an fMRI study of a DID patient, Tsai et al. (1999) observed inhibition of the right parahippocampal gyrus during personality switching compared to standard normal individuals. When comparing different personalities in DID patients, Schlumpf et al. (2013) observed an increase in the activation of the parahippocampal gyrus when DID participants were in the dissociated state compared to their basal state. ...
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... Brain imaging studies on dissociative disorders have focused on two issues: the brain imaging correlates of dissociation per se , and the brain imaging diff erences between dissociative patients and normal controls (or other psychiatric patients). Signifi cant brain-imaging diff erences have been found between (a) diff erent types of dissociative parts of the patient's personality in DID patients (Reinders, Nijenhuis, Paans, Korf, Willemsen, & Den Boer, 2006 ; see Nijenhuis,Chapter 38 ,and Lebois et al.,Chapter 24 ,this volume), (b) dissociative responses and nondissociative responses to trauma-related scripts as elements of PTSD patients' responses to triggers (Lanius, Williamson, Boksman, Densmore, Gupta, Neufeld, Gati, & Menon, 2002 ;see Schiavone & Lanius, Chapter 39 , this volume) including comparisons of the dissociative subtype to other types of PTSD (Lanius et al., 2018 ); (c) perfusion before versus perfusion during switching in DID patients ( Tsai, Condie, Wu, & Chang, 1999 ;Savoy et al., 2012 ); and (d) the cerebral perfusion of dissociative patients versus that of normal controls ( Ş ar, Ü nal, K ı z ı ltan, Kundak çı , & Ö zt ü rk, 2001 ; Ş ar, Ü nal, & Ö zt ü rk, 2007 ). ...
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... w 1999 rokupodczas kierowanego przez badacza przełączenia na osobowość alternatywną wykazali obustronne hamowanie hipokampa (silniejsze po stronie prawej), pola przyhipokampowego oraz małych regionów istoty czarnej i gałki bladej. Zdaniem autorów przy przełączeniu z osobowości alternatywnej na natywną (native) prawy hipokamp wykazywał szczególną aktywność, zdecydowanie większą niż w samym stanie natywnym (Tsai et al., 1999). Z kolei Schlumpf i wsp. ...
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... Notably, an fMRI of one patient performed during the process of voluntarily switching between self-states revealed right medial temporal inhibition, suggesting the possibility of temporal lobe involvement in this process. 122 A growing body of recent literature has examined neurobiological differences between DID self-states. For example, one study compared two types of self-states in DID: trauma-fixated self-states that personally identified with, and were highly physiologically reactive to, the individual's traumatic memories and trauma-avoidant selfstates that were amnestic for, or disowned, traumatic experiences. ...
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... Nevertheless, few neuroimaging studies have examined the neuroanatomical correlates of DID. Previous studies examining neuroanatomical alterations in DID mostly focused on subcortical regions (3,(13)(14)(15). However, a recent study by our group (4) has also investigated brain abnormalities in DID on the cortical level using an exploratory approach in a set of 68 predefined cortical areas across the cortex and reported that individuals with DID have significantly reduced gray matter volume in the medial and dorsolateral prefrontal cortex, the anterior cingulate, the insular cortex, inferior parietal areas, and in several regions within the temporal lobe (4). ...
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Objective: To examine the two constitutes of cortical volume (CV), that is, cortical thickness (CT) and surface area (SA), in individuals with dissociative identity disorder (DID) with the view of gaining important novel insights into the underlying neurobiological mechanisms mediating DID. Methods: This study included 32 female patients with DID and 43 matched healthy controls. Between-group differences in CV, thickness, and SA, the degree of spatial overlap between differences in CT and SA, and their relative contribution to differences in regional CV were assessed using a novel spatially unbiased vertex-wise approach. Whole-brain correlation analyses were performed between measures of cortical anatomy and dissociative symptoms and traumatization. Results: Individuals with DID differed from controls in CV, CT, and SA, with significantly decreased CT in the insula, anterior cingulate, and parietal regions and reduced cortical SA in temporal and orbitofrontal cortices. Abnormalities in CT and SA shared only about 3% of all significantly different cerebral surface locations and involved distinct contributions to the abnormality of CV in DID. Significant negative associations between abnormal brain morphology (SA and CV) and dissociative symptoms and early childhood traumatization (0 and 3 years of age) were found. Conclusions: In DID, neuroanatomical areas with decreased CT and SA are in different locations in the brain. As CT and SA have distinct genetic and developmental origins, our findings may indicate that different neurobiological mechanisms and environmental factors impact on cortical morphology in DID, such as early childhood traumatization.
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Volumes of the right and left anterior temporal lobes and hippocampal formations were measured from magnetic resonance images in 52 healthy volunteers, aged 20-40 years. Subjects were selected by age, sex, and handedness to evaluate possible effect of these variables. Data were normalized for variation in total intracranial volume between individuals. Right-left asymmetry in the volumes of the anterior temporal lobes and hippocampal formations was a normal finding. The anterior temporal lobe of the non-dominant (right) hemisphere was larger than the left by a small (mean right-left difference, 2.3 cm3) but statistically significant amount (P less than .005) in right-handed subjects. No significant effect of age or sex was seen in normalized right or left anterior temporal lobe volume. The right hippocampal formation was larger than the left for all subjects by a small (mean right-left difference, 0.3 cm3) but statistically significant amount (P less than .001). No effect of age, sex, or handedness was seen in normalized hippocampal formation volumes.
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