Kayako Matsuo1,2, Jun Inoue3, Toshiki Iwabuchi4, and Hidenori Yamasue5
1Center for Research Collaboration and Support, Dokkyo Medical University, Tochigi, Japan, 2Department of Psychiatry, Hamamatsu University School of Medicine (former), Hamamatsu, Japan, 3Department of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan, 4Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan, 5Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan
Synopsis
We found a negative correlation between brain
activity estimates of two conditions, daily recognition and trauma memory
remembering, that reflected altered responses in PTSD. We conducted two
task-fMRI runs for 9 patients with PTSD and the matched controls employing a script-driven
imagery task. A region-of-interest analysis revealed a negative correlation
between a hyperarousal subscale of psychological assessment and the activity
estimate in the hippocampus in the daily recognition whereas a positive
correlation in the trauma memory remembering. When computing voxel-based correlations
between the activity estimates of the two conditions, extensive negative
correlations emerged around the hippocampus in patients.
INTRODUCTION:
Posttraumatic stress disorder (PTSD) would
alter brain responses and create a new pattern of activation. We aimed to
characterize the altered pattern of activation in PTSD using fMRI. The second
scan after a treatment of eye movement desensitization and reprocessing (EMDR) 1 was also conducted to observe how the treatment resolved the alteration. In a
standard analysis, we typically apply a general linear model (GLM) to examine
which task activates a brain location more extensively than other tasks. However,
such a standard GLM method may have a disadvantage of failing to capture other
types of features including a negative correlation between two tasks.METHODS:
Nine patients with PTSD (DSM-5 diagnosed) and
nine age- and gender-matched controls (M/F=2/7) participated in the study after
giving a written informed consent (approved by the institutional review board).
Six out of the 9 patients also attended the second scan after the EMDR
treatment (average 339.3 days of interval). A set of neuropsychological
assessments including the Impact of Event Scale-Revised (IES-R-J) was conducted
to patients. A 3-Tesla MRI was used to perform a BOLD fMRI with TR 2000 ms, TE
22 ms , flip angle 90 deg, FOV 192 mm, matrix 64 x 64, 45 axial-oblique slices,
slice thickness 3 mm, interleaved, with no inter-slice space and 270 volumes. We
adopted a script-driven imagery task 2 to conduct two runs of fMRI that
presented two types of scripts respectively: patients’ own traumatic memory (Trauma
task) and tooth-brushing movement as a daily activity (Tooth task). Both tasks contained
blocks of the listening to a narration (Nar) and those of the remembering of it
(Rem). After a standard preprocessing procedure, contrast estimates of Tooth
Nar, Tooth Rem, Trauma Nar and Trauma Rem (against signals in blocks of a
fixation) were computed individually using SPM12 (University College London, UK).
We conducted a regression analysis to find locations whose activation was
correlated to a score of the neuropsychological assessments and defined regions
of interest (ROIs)
with a diameter of 20 mm
. We observed the correlations between the activity estimates
in the ROIs and the subscale scores of the assessments.RESULTS:
The ROI analysis revealed a negative
correlation between a hyperarousal subscale of the IES-R-J and activity
estimates in the hippocampus in the Tooth Nar contrast, as well as a positive
correlation between the same subscale and the estimates in the Trauma Rem (Fig.
1). This suggested that the estimates in the hippocampus would have negative
correlations between the Tooth Nar and the Trauma Rem. To confirm this deduction,
we computed correlations of activity estimates themselves by a voxel-based
manner between the Tooth Nar and the Trauma Rem. We confirmed the negative
correlation, which extended widely including the hippocampus, the amygdala, the
insula and other temporal structures in patients (Fig. 2).DISCUSSION:
The brain responses of PTSD manifested in a
way that patients who had an intense suppression of brain activation during
daily recognition (Tooth Nar) showed an intense activation during trauma memory
remembering (Trauma Rem), and vice versa. The EMDR apparently reduced the negative
correlations (Fig. 2).
The hippocampus was specifically remarked
because it is a center of memory consolidation 3 and involved in altered cognition in PTSD 4. Actually, the involvement
of the hippocampus in fMRI studies has been not necessarily clear and demonstrated
a heterogeneity across studies 5-6. The heterogeneity might be explained by the negative
correlation that we found because previous studies typically examined differences
in the magnitude of activation between conditions and failed to detect the other
types of relationships including negative correlation.
Clinically, the negative correlation seems relevant
to the “Windows of Tolerance” model 7-8. The “Window of Tolerance” refers to an optimum zone in
which patients can efficiently function. Patients with PTSD often experience
two extremes, hyperarousal (e.g., anger) and hypoarousal (e.g., dissociation),
both of which are assumed to be outside the optimum zone 8. If the negative
correlation reflected the alteration of these extremes, the magnitude of the
flip might have a possibility for us to use it as an estimation of the patients’
responses to the treatment as well as the prognosis, which deserves a further investigation.CONCLUSIONS:
A feature of the brain response pattern in
PTSD was found in the negative correlation of the activity estimates between
the daily recognition and the trauma memory remembering. If a patient
suppressed the activity in the hippocampus during the daily recognition, the
activity during the trauma memory remembering would be enhanced, and vice
versa. The negative correlation might have a relationship with frequent alterations
of patients’ psychiatric states between hyperarousal and hypoarousal.Acknowledgements
This
study was supported by the Grant-in-Aid for Challenging Exploratory Research
(KAKENHI #15K13140) of the Japan Society for the Promotion of Science (JSPS).References
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