Differences in Brain Structure and Functional Connectivity During Memory Processing in Posttraumatic Stress Disorder

Shin-Eui Park; Jae-hee Chung; Jong-Il Park; Jong-Chul Yang

doi:10.30773/pi.2025.0104

Psychiatry Investig > Volume 23(3); 2026 > Article

Park, Chung, Park, and Yang: Differences in Brain Structure and Functional Connectivity During Memory Processing in Posttraumatic Stress Disorder

Original Article

Psychiatry Investigation 2026;23(3):298-307.

Published online: March 6, 2026

DOI: https://doi.org/10.30773/pi.2025.0104

Differences in Brain Structure and Functional Connectivity During Memory Processing in Posttraumatic Stress Disorder

Shin-Eui Park^1,^*

, Jae-hee Chung^2,^3,^*

, Jong-Il Park^2,³

, Jong-Chul Yang^2,³

¹Division of High-Tech Medical Devices, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Republic of Korea

²Department of Psychiatry, Jeonbuk National University Medical School, Jeonju, Republic of Korea

³Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea

Correspondence: Jong-Chul Yang, MD, PhD Department of Psychiatry, Jeonbuk National University Medical School, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Republic of Korea Tel: +82-63-250-2580, Fax: +82-63-275-3157, E-mail: yangjc@jbnu.ac.kr

^* These authors contributed equally to this work.

Received March 28, 2025 Revised May 6, 2025 Accepted May 26, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

This study aimed to investigate the association between changes in brain volumes and memory task-based functional connectivity (FC) patterns in patients with posttraumatic stress disorder (PTSD) compared to healthy controls (HCs).

Methods

This study employed voxel-based morphometry and task-based functional magnetic resonance imaging using memory task to examine alterations in brain volume density and FC within and between relevant brain regions involved in memory processes such as encoding and retrieval.

Results

PTSD patients exhibited increased brain volumes in the right cerebellum (Cb) in the gray matter (GM) region compared to HCs. Analysis of FC patterns revealed that both groups exhibited similar connectivity patterns, but PTSD patients displayed higher and more extensive interregional connectivity relative to HCs. During the memory encoding process, PTSD patients exhibited higher FC linked to the Cb in the right postcentral gyrus, left precentral gyrus (PrCG), left orbito frontal gyrus (OFG), and superior frontal gyrus, while demonstrating lower connectivity in the right hippocampus. In the memory retrieval period, PTSD patients showed higher FC in the right middle frontal gyrus, left middle occipital gyrus, left OFG, right inferior parietal gyrus, and right PrCG, along with lower FC in the right/left inferior frontal gyrus and right superior parietal gyrus. Additionally, a negative correlation was observed between PTSD symptom severity and local GM volumes in the right Cb. However, no significant correlation was found with FC.

Conclusion

Our findings provide insights into the specific alterations in brain structure and connectivity associated with PTSD, contributing to a better understanding of the underlying neural mechanisms of PTSD.

Keywords: Posttraumatic stress disorder, Cerebellum, Task-based functional connectivity, Voxel-based morphometry, Memory task.

INTRODUCTION

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric condition that can develop in individuals who have experienced or witnessed traumatic events. PTSD is characterized by a range of symptoms, including intrusive memories, hyperarousal, avoidance behaviors, and negative alterations in cognition and mood [1]. Among these symptoms, disturbances in memory processes have been recognized as a significant feature of PTSD [2].

Memory dysfunction in PTSD is commonly observed in both the encoding and retrieval phases of memory, resulting in impairments in the formation and retrieval of traumatic and non-traumatic memories [3]. These memory disturbances contribute to the persistent re-experiencing of traumatic events, difficulty in emotional regulation, and the maintenance of PTSD symptoms [4].

In recent years, neuroimaging techniques have provided valuable insights into the neural underpinnings of PTSD-related memory dysfunction [2]. Among these techniques, functional magnetic resonance imaging (fMRI) has emerged as a powerful tool to investigate the functional connectivity (FC) of brain networks during memory tasks [5]. FC refers to the temporal synchronization and coordination of brain regions during task performance or rest, reflecting the communication and integration of neural networks.

Previous studies [6-9] have revealed alterations in FC patterns associated with memory process in individuals with PTSD, implicating disrupted interactions between key brain regions involved in memory processes. These alterations involve regions such as the amygdala, hippocampus (Hipp), prefrontal cortex, and the default mode network, which are crucial for memory encoding, consolidation, and retrieval [2,6-9]. Understanding the specific alterations in memory task-based FC in PTSD patients can shed light on the underlying neural mechanisms of memory dysfunction and potentially guide the development of targeted interventions. Furthermore, such investigations may also contribute to the identification of potential biomarkers for early detection and monitoring of treatment response in PTSD.

Brain function is a complex phenomenon influenced by various factors. Neuronal cell density refers to the number of neurons present in a specific area of the brain. The brain consists of billions of neurons that communicate with each other through intricate networks. Also, there are many neuroimaging studies [10-12] explored association between changes of brain volumes and FC.

The present study aims to investigate association between changes of brain volumes and memory task-based FC patterns in PTSD patients using voxel-based morphometry (VBM) and fMRI by employing memory tasks that engage different memory processes, such as encoding and retrieval. We aim to elucidate the specific alterations in FC within and between relevant brain regions affected by abnormal brain volume density in patients with PTSD compared to healthy controls (HCs).

Findings from this study have the potential to advance our understanding of the neural correlates between brain volume difference and its effect to memory dysfunction in PTSD and may inform the development of novel therapeutic approaches for alleviating memory-related symptoms in this population. Furthermore, this research may contribute to the broader field of neuroimaging and help uncover mechanisms underlying memory processes in healthy individuals as well.

In summary, investigating brain volume changes and memory task-based FCs in PTSD patients has the potential to uncover critical insights into the neuronal cell defects and its association to memory dysfunction derived from PTSD symptomatology. The findings may pave the way for innovative interventions aimed at improving memory function and overall well-being in individuals affected by PTSD.

METHODS

Subjects

We recruited seventeen patients and 17 control subjects. However, due to poor MRI data quality, 8 individuals were excluded from the analysis. Finally, thirteen PTSD patients (mean age, 27.92±10.09 years) and 13 HC (mean age, 29.08±9.40 years) (Mann-Whitney U test, p=0.687) diagnosed by a psychiatrist based on the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) criteria were included in this study (Table 1). All participants were right-handed (chi-square test, p>0.999) and took the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) [13]. The CAPS-5 is a validated tool utilized in the assessment of the severity, validity, and improvement of PTSD symptoms as outlined by the DSM-5. Each PTSD symptom is evaluated using separate 5-point rating scales for frequency and intensity, ranging from 0 to 4. Participants with CAPS-5 scores below 40 were excluded from the subsequent analysis. Before undergoing MRI, all volunteers received a thorough explanation of all experimental procedures and each provided written informed consent. Participants in both groups showed no abnormalities on physical and neurological examinations. Also, all the experimental procedures and methods were performed in accordance with the relevant guidelines and regulations approved by the IRB-JBUH (Jeonbuk National University Hospital IRB number 2019-07-016).

In addition, clinical characteristics of the PTSD group were assessed. The mean duration of illness was 49.7 months (range, 6-125 months). Trauma types varied across individuals and included childhood peer bullying (n=6), sexual assault (n=1), physical abuse by family members (n=1), motor vehicle accidents (n=3), military-related assault (n=1), and the traumatic loss of a close acquaintance (n=1). All participants were prescribed antidepressants, including escitalopram (n=4, 10-20 mg), sertraline (n=4, 50-100 mg), desvenlafaxine (n=3, 50- 100 mg), vortioxetine (n=1, 10 mg), fluvoxamine (n=1, 100 mg), and mirtazapine (n=1, 15 mg). Concomitant use of anxiolytics, hypnotics, and antipsychotics was also observed, including etizolam (n=4, 0.25-0.75 mg), zolpidem (n=2, 10-12.5 mg), aripiprazole (n=2, 2-4 mg), and others (e.g., trazodone [n=1, 25 mg], clonazepam [n=1, 0.5 mg], alprazolam [n=1, 0.25 mg]).

Inclusion criteria

1) Participants who met DSM-5 criteria for PTSD.

2) Age of participants were between 20 and 60 years.

3) All participants have an education above middle school (more than 9 years: middle school in Korea).

4) Right-handed.

Exclusion criteria

1) History of head trauma.

2) History of cardiovascular or endocrine disease.

3) Psychiatric illness other than PTSD.

4) Presence of magnetically active object in the body.

Data acquisition

All participants were subjected to neuroimaging using a 3 tesla Magnetom Verio MR Scanner (Siemens Medical Solutions) equipped with an 8-channel birdcage head coil. Highresolution T1-weighted images were obtained through a threedimensional magnetization prepared rapid acquisition gradient echo (3D MP-RAGE) sequence, employing the following acquisition parameters: repetition time (TR) of 1,900 ms, echo time (TE) of 2.35 ms, a field-of-view (FOV) of 22×22 cm², matrix size of 256×256, one excitation (NEX), and a slice thickness of 1 mm. Functional images were acquired utilizing a gradient-echo echo planar imaging technique, with the subsequent acquisition settings: TR of 2,000 ms, TE of 30 ms, flip angle of 90°, FOV of 22×22 cm², matrix size of 64×64, one NEX, 25 slices, and a slice thickness of 5 mm without a slice gap.

Paradigm for memory task

Memory task was conducted utilizing two-syllable words with negative emotional content (Figure 1). The brain activation paradigm followed a specific cycle: a resting phase lasting 14 seconds, followed by the first encoding phase lasting 18 seconds, another resting phase of 14 seconds, the first retrieval phase lasting 18 seconds, a subsequent resting phase of 14 seconds, the second encoding phase lasting 18 seconds, another resting phase of 14 seconds, the second retrieval phase lasting 18 seconds, and a final resting phase of 14 seconds. Throughout the rest periods, two fixation crosses were displayed. A set of six different two-syllable words was displayed for 3 seconds each during the encoding phase. Subsequently, during the retrieval phase, the two-syllable words presented during the encoding phase, but without the first consonant, were presented. Then, participants were presented with either new words or the previously presented words from the “encoding” phase. Participants were instructed to press a button if the presented word was recognized as an old word. All word stimuli were presented on a computer monitor employing Superlab Pro software (Cedrus Co.).

Brain volume change analysis

The anatomical images were post-processed using statistical parametric mapping (SPM12) software for VBM analysis following the procedure described in our previous study [14]. Alternating gray matter (GM) and white matter (WM) volumes in both groups were assessed with an independent two-sample t-test with multiple comparisons using family-wise error (FWE) at p<0.05 and cluster size >100 voxels.

Task-based FC analysis

The FC analysis was conducted using the CONN-fMRI FC toolbox (ver. 21a) in conjunction with the SPM12 software. Preprocessing of the data involved several steps. Firstly, slice timing correction was applied using an interleaved acquisition scheme. Subsequently, image realignment was performed to correct for subject motion, with a threshold of 2 mm used to identify and correct for motion artifacts. Field map correction was also applied. The individual T1 images were then co-registered with the functional images. Segmentation of the transformed T1 images into GM, WM, and cerebrospinal fluid was performed using standard SPM tissue probability maps. To reduce spatial noise, the images underwent spatial smoothing using a Gaussian kernel with a full width at half maximum of 8 mm3. For robust detection of functional outliers, a liberal setting was employed, utilizing the 97th percentiles in a normative sample and a global-signal z-value threshold of 9. An anatomical component-based noise correction method (aCompCor) was employed to minimize the impact of noises on the bloodoxygenation-level-dependent (BOLD) signals, including subject motion and identified outlier scans or scrubbing artifacts [15]. Finally, a band-pass filter was applied, restricting the frequency window of the BOLD signals to 0.01-0.1 Hz. Right cerebellum (Cb) (x, y, z=15, -62, -27) observed in VBM analysis was designated as seed region for seed to voxel FC analysis.

Statistical analysis between clinical data and brain volume changes and FC

To analyze the correlation between CAPS-5 scores and different GM volumes and FCs and, Pearson’s correlation coefficient test was performed using the SPSS Statistical software package (version 20.0, IBM Corp.).

RESULTS

Demographic and clinical measurements

Table 1 shows demographic and clinical characteristics of the patients with PTSD and HC. No differences between the two groups were noted in terms of age, sex, handedness and education. The mean scores for CAPS-5 in PTSD patients was 53.92±10.14.

Brain volume difference

There was no significant volume difference in the WM regions between the two groups. However, in the GM regions, patients with PTSD showed increased brain volumes in right Cb (x, y, z=15, -62, -27) when compared to HC (two sample t-test, p-FWE<0.05, cluster size >100 voxel) (Figure 2).

Differences in the FC

The FC patterns derived from the Cb between patients with PTSD and HC are shown in Figure 3 and Table 2. Both groups are characterized by a similar pattern, but have higher and wider interregional connectivity in patients with PTSD than in HC relatively. During memory encoding process, PTSD patients showed relatively higher FCs with the Cb in right the postcentral gyrus (PoCG), left precentral gyrus (PrCG), left orbito frontal gyrus (OFG), and superior frontal gyrus (SFG). On the other hand, there was lower connectivity in right Hipp. In memory retrieval period, there were higher FC in right middle frontal gyrus (MFG), left middle occipital gyrus (MOG), left OFG, right inferior parietal gyrus (IPG), and right PrCG, and lower FC in right/left inferior frontal gyrus (IFG) and right superior parietal gyrus (SPG) in patients with PTSD (one sample t-test, voxel threshold: uncorr. p<0.001, cluster threshold: p-FDR<0.05). In the group difference analysis determined by a two-sample t-test, brain regions including the inferior temporal gyrus (ITG), IPG, SFG, middle cingulate gyrus, and PoCG were identified during the retrieval task only, using threshold-free cluster enhancement with subsequent FWE correction (Figure 4 and Table 3).

Correlation between PTSD symptoms and GM volume and FC difference

Figure 5 shows a significant negative correlation between CAPS-5 scores and local GM volumes in right Cb in patients with PTSD (Pearson’s correlation (r)=-0.617, p=0.025). However, there was no significant correlation with FC.

DISCUSSION

The present study aimed to investigate the association between changes in brain volumes and memory task-based FC patterns in patients with PTSD compared to HCs. Our findings revealed several notable results regarding brain volume differences, FC patterns, and the correlation between PTSD symptom severity and brain morphometry. In terms of demographic and clinical characteristics, no significant differences were observed between patients with PTSD and HCs in terms of age, sex, handedness, and education. This suggests that any observed differences in brain measures between the groups are unlikely to be influenced by these demographic factors.

Regarding brain volume differences, our study found increased brain volumes in the right Cb in the GM region of PTSD patients compared to HCs. This finding is consistent with previous research suggesting structural alterations in the Cb in PTSD [16,17]. The Cb is known to play a crucial role in cognitive and emotional processing [18]. Recent research has shown that the Cb plays a role in fear learning and memory [19,20]. Given that PTSD is marked by abnormalities in threat detection and processing [21], this growing body of evidence strongly suggests the involvement of the Cb in the pathophysiology of PTSD. In our result, alterations in cerebellar volume may contribute to the cognitive and emotional dysregulation observed in PTSD [15]. Interestingly, although most previous studies reported decreased cerebellar volumes in PTSD patients, our study found increased GM volumes in the right Cb compared to HCs. A similar pattern of cerebellar enlargement has been reported in adult combat-related PTSD, where volumetric increases were observed particularly in lobules 7b and 8a-b, regions implicated in emotional processing [16]. Consistent with these findings, our results may reflect an early compensatory or maladaptive hypertrophy in response to trauma, which might subsequently be followed by volume reduction associated with symptom progression. Chronic stress-related neuronal loss, impaired neuroplasticity, or neurodegenerative changes could contribute to the observed volume decrease among patients with more severe PTSD symptoms [22]. Similar compensatory-to-degenerative patterns have been described in other stress-related disorders.

Analyzing FC patterns, we found that both the PTSD and HC groups exhibited similar patterns; however, PTSD patients showed higher and more extensive interregional connectivity compared to HCs. During the memory encoding process, PTSD patients displayed higher FC with the Cb in the right PoCG, left PrCG, left OFG, and SFG. This heightened connectivity may indicate compensatory mechanisms or hyperactivation in regions involved in memory encoding [15]. Neurostructural studies have demonstrated that in patients who have experienced trauma, especially those with mild traumatic brain injury, smaller cortical volumes in regions such as the SFG, rostral, and caudal cingulate play a crucial role in predicting the likelihood of developing PTSD symptoms. The SFG is involved in higher cognitive functions, such as working memory, executive control, and attention regulation, which are often impaired in PTSD patients. A study suggests that reduced SFG volume is linked to the difficulty in regulating intrusive memories and cognitive dysfunctions frequently observed in PTSD [23]. Furthermore, Zimmermann et al. [24] observed that the left and right lateral OFG volumes in PTSD patients were significantly smaller than in controls and were negatively correlated with symptom severity. The OFG is associated with emotional regulation, decision-making, and processing of reward-related stimuli. In PTSD, diminished OFG volume may contribute to impaired emotional regulation, which exacerbates the re-experiencing of traumatic events and emotional dysregulation. Taken together, these findings indicate that PTSD patients tend to show smaller cortical volumes in prefrontal regulatory regions, consistent with preclinical work suggesting that prefrontal areas, including the OFG and SFG, play a critical role in the recovery and extinction of threat behaviors. This highlights the importance of these regions in both the emotional and cognitive aspects of PTSD, contributing to a better understanding of how functional and structural changes in the brain contribute to the development and persistence of symptoms. Conversely, lower connectivity was observed in the right Hipp, a region crucial for memory formation [25]. Reduced hippocampal activity in PTSD is also com-mon, and it appears to play an important role in process of fear learning and memory consolidation [26,27]. Our result consistent with previous studies that suggested disrupted hippocampal functioning in PTSD patients during encoding [28,29].

In the memory retrieval period, PTSD patients demonstrated higher FC in the right MFG, left MOG, left OFG, right IPG, and right PrCG. These regions are involved in attention [30], visual processing [31,32], and cognitive control [33,34], suggesting increased engagement of these areas during memory retrieval in PTSD patients. Conversely, lower FC was observed in the right/left IFG and right SPG, regions associated with executive functions and working memory [35,36]. These abnormalities showed in psychiatric disorders. These findings may reflect impaired executive control processes in PTSD during memory retrieval. Interestingly, during this period, PTSD patients exhibited a shift in FC from the SFG and OFG to the MFG and OFG during the transition from memory encoding to retrieval. This shift may indicate alterations in the neural networks associated with PTSD. During memory encoding, the SFG is involved in various cognitive functions such as working memory and executive control [37], while the OFG plays a crucial role in emotional processing and decision-making [38]. In contrast, during memory retrieval, the MFG is engaged in self-referential processing and memory recall [39], and the OFG continues to be involved in emotion- and reward-related processing [38]. A previous study has demonstrated that PTSD patients show increased FC between the MFG and amygdala compared to HCs and trauma-exposed individuals without PTSD [40]. These distinct changes in FC may be critical in the development of PTSD. The altered connectivity patterns observed in our study likely reflect the brain’s attempt to compensate for emotional and cognitive disruptions caused by PTSD. The brain may reorganize FC by recruiting alternative networks to support memory processes and mitigate the effects of the disorder. Interestingly, the brain regions, including the ITG, IPG, SFG, middle cingulate gyrus, and PoCG, were identified during the memory retrieval task only, suggesting that PTSD patients exhibit altered FC in networks related to memory processing, emotional regulation, and sensory integration. These findings align with previous studies indicating that PTSD is associated with impaired top-down control over memory retrieval, heightened sensitivity to trauma-related cues, and dysregulated sensory processing, potentially contributing to core symptoms such as intrusive thoughts, hypervigilance, and emotional dysregulation. Furthermore, we examined the correlation between PTSD symptoms, as measured by CAPS-5 scores, and brain measures. We found a significant negative correlation between symptom severity and local GM volumes in the right Cb, suggesting that as PTSD symptoms worsened, GM volumes in the Cb decreased. Our result is consistent with previous study reported that there was a significant negative correlation between vermal volume and CAPS total score in patients with PTSD [41]. It could be suggested that the Cb is one of critical brain region that involved in cognitive-emotional processing in the PTSD patient. However, no significant correlation was observed between symptom severity and FC. It is important to note that the lack of correlation with FC might be attributed to the small sample size or other factors not accounted for in this study.

Overall, our findings contribute to the growing body of literature on the neurobiological underpinnings of PTSD. The increased brain volumes in the Cb, along with altered FC patterns during memory encoding and retrieval, provide insights into the specific neural alterations associated with PTSD. These findings suggest that PTSD is characterized by both structural and functional changes in brain regions involved in memory processes. Future studies with larger sample sizes and longitudinal designs are warranted to confirm and expand upon these findings.

Understanding the neurobiological mechanisms underlying PTSD can inform the development of targeted interventions and therapies aimed at alleviating symptoms and improving the quality of life for individuals affected by this debilitating disorder.

There are some limitations in our study. First, one limitation of this study is the small sample size, which limited the use of more advanced statistical models such as random or mixed-effects analyses. In addition, covariation analyses between symptom severity and brain measures require larger samples to ensure statistical power, particularly given the complexity of fMRI data. A larger sample would be needed to replicate our findings as well as to investigate further understand neurobiological mechanism of PTSD. Second, the possibility of medication effects on brain structure and FC could not be excluded. Whether brain changes in PTSD are primary itself or secondary to other unknown reasons needs to be further elucidated.

In conclusion, present study found a significant increasement in GM volume in local region of Cb that showed close association with clinical symptom severity (CAPS-5 scores) among PTSD patients, also this brain volume changes led to abnormality of brain FC during memory processing. These findings suggest that PTSD symptom can lead to structural and functional network alterations in key brain regions, providing insights into the neural mechanisms underlying PTSD and potential implications for future treatment research.

Notes

Availability of Data and Material

The datasets generated or analyzed during the study are available from the corresponding author on reasonable request.

Conflicts of Interest

Jong-Chul Yang, a contributing editor of the Psychiatry Investigation, was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest.

Author Contributions

Conceptualization: all authors. Formal analysis: Shin-Eui Park. Funding acquisition: Jong-Chul Yang. Methodology: Jong-Chul Yang, Shin-Eui Park. Software: Shin-Eui Park. Writing—original draft: all authors. Writing—review & editing: all authors.

Funding Statement

This paper was supported by Fund of Biomedical Research Institute, Jeonbuk National University Hospital.

Acknowledgments

None

Figure 1.

Activation paradigm of memory task with unpleasant words. In each encoding period, six different two-syllable words, each appearing once, were sequentially presented. In the following retrieval period, the old words presented in encoding period and new words, without the first consonant, were randomly presented.

Figure 2.

Increased gray matter volumes in patients with posttraumatic stress disorder compared to healthy controls (two sample t-test, uncorr. p<0.001, cluster size >100 voxel). L, left; R, right; Cb, cerebellum (x, y, z=15, -62, -27).

Figure 3.

Positive connectivity networks associated with right cerebellum showing increased gray matter volumes in posttraumatic stress disorder (PTSD) patients and health controls during encoding (A and B) and retrieval periods (C and D) (one sample t-test, voxel threshold: uncorr. p<0.001, cluster threshold: p-FDR<0.05).

Figure 4.

Positive connectivity networks associated with the right cerebellum showing increased gray matter volumes in posttraumatic stress disorder (PTSD) patients and healthy controls during the encoding (A and B) and retrieval periods (C and D), as determined by a two-sample t-test.

Figure 5.

The correlation between CAPS-5 scores and brain volume changes of right Cb in patients with PTSD (r²=0.347, p=0.025) (Pearson’s correlation (r)=-0.617). CAPS-5, Clinician-Administered PTSD Scale for DSM-5; Cb, cerebellum; PTSD, posttraumatic stress disorder.

Table 1.

Demographics between patients PTSD and healthy controls

	Patients with PTSD (N=13)	Healthy controls (N=13)	p
Age (yr)	27.92±10.09	29.08±9.40	0.687^*
Sex (male/female)	9/4	11/2	0.352^†
Handedness (right:left:mixed)	13:0:0	13:0:0	>0.999^†
Education (yr)	12.27±2.71	13.69±1.97	0.511^*
Clinician-Administered PTSD Scale for DSM-5	53.92±10.14	-	-

Values are presented as mean±standard deviation.

^* Mann-Whitney U test;

^† chi-square test.

PTSD, posttraumatic stress disorder; -, not applicable.

Table 2.

Group difference in localized functional connectivity during implicit memory task

Brain area	MNI coordinates			Cluster size (>100 voxel)	Maximum t-value	Peak p-uncorr.	Peak p-FDR
Brain area	x	y	z	Cluster size (>100 voxel)	Maximum t-value	Peak p-uncorr.	Peak p-FDR
Seed: right cerebellum	15	-62	-27
Encoding
Healthy control
Hippocampus	34	-6	-22	993	5.00	<0.001	0.007
PTSD
Postcentral gyrus	52	-16	50	2,546	7.22	<0.001	<0.001
PrCG	-36	-12	68	1,624	6.43	<0.001	0.001
OFG	-4	56	-12	1,506	6.70	<0.001	0.001
Superior frontal gyrus	0	54	26	710	3.64	0.001	0.021
Retrieval
Healthy control
Left IFG	-34	34	0	1,717	5.17	<0.001	<0.001
Right IFG	62	14	26	946	6.09	<0.001	0.005
Superior parietal gyrus	22	-60	52	723	4.61	<0.001	0.019
PTSD
Middle frontal gyrus	38	42	38	2,516	6.99	<0.001	<0.001
Middle occipital gyrus	-40	-74	34	1,222	4.87	0.001	0.001
OFG	-6	48	-4	901	4.61	0.001	0.006
Inferior parietal gyrus	34	-48	40	617	5.19	0.001	0.033
PrCG	22	-26	76	613	4.83	0.001	0.033

MNI, Montreal Neurological Institute; FDR, false discovery rate; PTSD, posttraumatic stress disorder; PrCG, precentral gyrus; OFG, orbito frontal gyrus; IFG, inferior frontal gyrus.

Table 3.

Regions showing predominant functional connectivity linked to the right Cb between PTSD patients and healthy controls, as determined by a two-sample t-test

Compared groups	Brain area	Side	MNI coordinates			Cluster size (>100 voxel)	TFCE	p-FWE
Compared groups	Brain area	Side	x	y	z	Cluster size (>100 voxel)	TFCE	p-FWE
Seed: right cerebellum		R	15	-62	-27
Retrieval
Healthy control <PTSD	Inferor temporal gyrus	L	-48	-50	-26	53	2,546	<0.001
	Inferor parietal gyrus	L	-44	-36	52	440	1,987	0.002
	Superior frontal gyrus	R	18	10	62	30	1,602	0.012
	Middle sigulate gyrus	L	-8	-2	46	68	1,532	0.024
	Post central gyrus	L	-26	-32	64	49	1,482	0.028

Cb, cerebellum; PTSD, posttraumatic stress disorder; MNI, Montreal Neurological Institute; TFCE, threshold-free cluster enhancement; FWE, family-wise error; R, right; L, left.

REFERENCES

1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed. Arlington: American psychiatric association; 2013.

2. Harnett NG, Goodman AM, Knight DC. PTSD-related neuroimaging abnormalities in brain function, structure, and biochemistry. Exp Neurol 2020;330:113331

3. Brewin CR. Memory processes in post-traumatic stress disorder. Int Rev Psychiatry 2001;13:159-163.

4. Rubin DC, Berntsen D, Bohni MK. A memory-based model of posttraumatic stress disorder: evaluating basic assumptions underlying the PTSD diagnosis. Psychol Rev 2008;115:985-1011.

5. Park HJ, Friston K. Structural and functional brain networks: from connections to cognition. Science 2013;342:1238411

6. Sripada RK, King AP, Garfinkel SN, Wang X, Sripada CS, Welsh RC, et al. Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder. J Psychiatry Neurosci 2012;37:241-249.

7. Patel R, Spreng RN, Shin LM, Girard TA. Neurocircuitry models of posttraumatic stress disorder and beyond: a meta-analysis of functional neuroimaging studies. Neurosci Biobehav Rev 2012;36:2130-2142.

8. Liu Y, Li B, Feng N, Pu H, Zhang X, Lu H, et al. Perfusion deficits and functional connectivity alterations in memory-related regions of patients with post-traumatic stress disorder. PLoS One 2016;11:e0156016

9. Stevens JS, Jovanovic T, Fani N, Ely TD, Glover EM, Bradley B, et al. Disrupted amygdala-prefrontal functional connectivity in civilian women with posttraumatic stress disorder. J Psychiatr Res 2013;47:1469-1478.

10. Li WH, Tang LR, Wang M, Wang JN, Guo T, He Q, et al. Altered gray matter volume and functional connectivity in medial orbitofrontal cortex of bulimia nervosa patients: a combined VBM and FC study. Front Psychiatry 2022;13:963092

11. Park SE, Jeon YJ, Baek HM. Functional and structural brain abnormalities and clinical characteristics of male patients with alcohol dependence. Brain Sci 2023;13:942

12. Cao Z, Yu W, Zhang Z, Xu M, Lin J, Zhang L, et al. Decreased gray matter volume in the frontal cortex of migraine patients with associated functional connectivity alterations: a VBM and rs-FC study. Pain Res Manag 2022;2022:2115956

13. Kim WH, Jung YE, Roh D, Kim D, Kang SH, Chae JH, et al. Reliability and validity of the Korean version of Clinician-Administered Posttraumatic Stress Disorder Scale for DSM-5. J Korean Med Sci 2019;34:e219

14. Park SE, Kim BC, Yang JC, Jeong GW. MRI-based multimodal approach to the assessment of clinical symptom severity of obsessive-compulsive disorder. Psychiatry Investig 2020;17:777-785.

15. Behzadi Y, Restom K, Liau J, Liu TT. A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. Neuroimage 2007;37:90-101.

16. Sussman D, Pang EW, Jetly R, Dunkley BT, Taylor MJ. Neuroanatomical features in soldiers with post-traumatic stress disorder. BMC Neurosci 2016;17:13

17. Holmes SE, Scheinost D, DellaGioia N, Davis MT, Matuskey D, Pietrzak RH, et al. Cerebellar and prefrontal cortical alterations in PTSD: structural and functional evidence. Chronic Stress (Thousand Oaks) 2018;2:2470547018786390

18. Stoodley CJ, Schmahmann JD. Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex 2010;46:831-844.

19. Ernst TM, Brol AE, Gratz M, Ritter C, Bingel U, Schlamann M, et al. The cerebellum is involved in processing of predictions and prediction errors in a fear conditioning paradigm. Elife 2019;8:e46831

20. Lange I, Kasanova Z, Goossens L, Leibold N, De Zeeuw CI, van Amelsvoort T, et al. The anatomy of fear learning in the cerebellum: a systematic meta-analysis. Neurosci Biobehav Rev 2015;59:83-91.

21. Sevenster D, Visser RM, D’Hooge R. A translational perspective on neural circuits of fear extinction: current promises and challenges. Neurobiol Learn Mem 2018;155:113-126.

22. Pittenger C, Duman RS. Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 2008;33:88-109.

23. Stein MB, Yuh E, Jain S, Okonkwo DO, Mac Donald CL, Levin H, et al. Smaller regional brain volumes predict posttraumatic stress disorder at 3 months after mild traumatic brain injury. Biol Psychiatry Cogn Neurosci Neuroimaging 2021;6:352-359.

24. Zimmermann KS, Li CC, Rainnie DG, Ressler KJ, Gourley SL. Memory retention involves the ventrolateral orbitofrontal cortex: comparison with the basolateral amygdala. Neuropsychopharmacology 2018;43:373-383.

25. Opitz B. Memory function and the hippocampus. Front Neurol Neurosci 2014;34:51-59.

26. Carrión VG, Haas BW, Garrett A, Song S, Reiss AL. Reduced hippocampal activity in youth with posttraumatic stress symptoms: an FMRI study. J Pediatr Psychol 2010;35:559-569.

27. Hayes JP, LaBar KS, McCarthy G, Selgrade E, Nasser J, Dolcos F, et al. Reduced hippocampal and amygdala activity predicts memory distortions for trauma reminders in combat-related PTSD. J Psychiatr Res 2011;45:660-669.

28. Cominski TP, Jiao X, Catuzzi JE, Stewart AL, Pang KC. The role of the hippocampus in avoidance learning and anxiety vulnerability. Front Behav Neurosci 2014;8:273

29. Tsoory MM, Vouimba RM, Akirav I, Kavushansky A, Avital A, Richter-Levin G. Amygdala modulation of memory-related processes in the hippocampus: potential relevance to PTSD. Prog Brain Res 2008;167:35-51.

30. Simon SR, Meunier M, Piettre L, Berardi AM, Segebarth CM, Boussaoud D. Spatial attention and memory versus motor preparation: premotor cortex involvement as revealed by fMRI. J Neurophysiol 2002;88:2047-2057.

31. Rangel-Pacheco A, Lew BJ, Schantell MD, Frenzel MR, Eastman JA, Wiesman AI, et al. Altered fronto-occipital connectivity during visual selective attention in regular cannabis users. Psychopharmacology (Berl) 2021;238:1351-1361.

32. Kaufman DA, Keith CM, Perlstein WM. Orbitofrontal cortex and the early processing of visual novelty in healthy aging. Front Aging Neurosci 2016;8:101

33. Germann J, Petrides M. Area 8A within the posterior middle frontal gyrus underlies cognitive selection between competing visual targets. eNeuro 2020;7:ENEURO.0102-20.2020

34. Eayrs JO, Lavie N. Individual differences in parietal and frontal cortex structure predict dissociable capacities for perception and cognitive control. Neuroimage 2019;202:116148

35. Park SE, Kim YH, Yang JC, Jeong GW. Comparative functional connectivity of core brain regions between implicit and explicit memory tasks underlying negative emotion in general anxiety disorder. Clin Psychopharmacol Neurosci 2022;20:279-291.

36. Moon CM, Jeong GW. Functional neuroanatomy on the working memory under emotional distraction in patients with generalized anxiety disorder. Psychiatry Clin Neurosci 2015;69:609-619.

37. du Boisgueheneuc F, Levy R, Volle E, Seassau M, Duffau H, Kinkingnehun S, et al. Functions of the left superior frontal gyrus in humans: a lesion study. Brain 2006;129:3315-3328.

38. Bechara A, Damasio H, Damasio AR. Emotion, decision making and the orbitofrontal cortex. Cereb Cortex 2000;10:295-307.

39. Wagner IC, van Buuren M, Kroes MC, Gutteling TP, van der Linden M, Morris RG, et al. Schematic memory components converge within angular gyrus during retrieval. Elife 2015;4:e09668

40. Liu T, Ke J, Qi R, Zhang L, Zhang Z, Xu Q, et al. Altered functional connectivity of the amygdala and its subregions in typhoon-related post-traumatic stress disorder. Brain Behav 2021;11:e01952

41. Baldaçara L, Jackowski AP, Schoedl A, Pupo M, Andreoli SB, Mello MF, et al. Reduced cerebellar left hemisphere and vermal volume in adults with PTSD from a community sample. J Psychiatr Res 2011;45:1627-1633.