BACKGROUND:Trauma-related intrusive memories (TR-IMs) are core symptoms of posttraumatic stress disorder (PTSD). Prior research links reexperiencing symptoms with resting-state functional coupling between the right dorsolateral prefrontal cortex (dlPFC) and right hippocampus (HPC). However, prior work has not examined whether this negative coupling relates to TR-IMs or has differentiated between the anterior and posterior HPC (aHPC/pHPC). This study examined relationships of TR-IM frequency and properties with resting-state negative coupling between the right dlPFC and right aHPC/pHPC in symptomatic trauma-exposed individuals with TR-IMs. METHODS:Participants (N = 109; 88 female) completed 2 weeks of ecological momentary assessments capturing TR-IM frequency and properties (intrusiveness, emotional intensity, vividness, visual properties, and reliving). Using resting-state functional magnetic resonance imaging, participant-specific 4-mm spheres were placed at the right dlPFC voxel most anticorrelated with the right aHPC/pHPC. Quasi-Poisson and linear mixed-effect models assessed relationships of TR-IM frequency and properties with right dlPFC-right aHPC/pHPC anticorrelation. RESULTS:TR-IM emotional intensity was positively associated with right dlPFC-aHPC connectivity, while vividness and visual properties correlated with right dlPFC-pHPC connectivity. These associations remained significant after controlling for PTSD symptom severity and time since trauma. No significant associations emerged between TR-IM frequency, intrusiveness, or reliving and anticorrelation with either hippocampal subregion. CONCLUSIONS:This study provides novel insights into the neural correlates of TR-IMs, highlighting the relevance of intrinsic negative coupling between the right dlPFC and aHPC/pHPC to their phenomenology. Further research on this circuit could advance understanding of component processes of trauma reexperiencing, a severe and treatment-refractory PTSD symptom.

Trauma-related intrusive memories (TR-IMs) possess unique phenomenological properties that contribute to adverse post-traumatic outcomes, positioning them as critical intervention targets. However, transdiagnostic treatments for TR-IMs are scarce, as their underlying mechanisms have been investigated separate from their unique phenomenological properties. Extant models of more general episodic memory highlight dynamic hippocampal-cortical interactions that vary along the anterior-posterior axis of the hippocampus (HPC) to support different cognitive-affective and sensory-perceptual features of memory. Extending this work into the unique properties of TR-IMs, we conducted a study of eighty-four trauma-exposed adults who completed daily ecological momentary assessments of TR-IM properties followed by resting-state functional magnetic resonance imaging (rs-fMRI). Spatiotemporal dynamics of anterior and posterior hippocampal (a/pHPC)-cortical networks were assessed using co-activation pattern analysis to investigate their associations with different properties of TR-IMs. Emotional intensity of TR-IMs was inversely associated with the frequency and persistence of an aHPC-default mode network co-activation pattern. Conversely, sensory features of TR-IMs were associated with more frequent co-activation of the HPC with sensory cortices and the ventral attention network, and the reliving of TR-IMs in the “here-and-now” was associated with more persistent co-activation of the pHPC and the visual cortex. Notably, no associations were found between HPC-cortical network dynamics and conventional symptom measures, including TR-IM frequency or retrospective recall, underscoring the utility of ecological assessments of memory properties in identifying their neural substrates. These findings provide novel insights into the neural correlates of the unique features of TR-IMs that are critical for the development of individualized, transdiagnostic treatments for this pervasive, difficult-to-treat symptom.

As the global prevalence of trauma rises, there is a growing need for accessible and scalable treatments for trauma-related disorders like posttraumatic stress disorder (PTSD). Trauma-related intrusive memories (TR-IMs) are a central PTSD symptom and a target of exposure-based therapies, gold-standard treatments that are effective but resource-intensive. This study examined whether a brief ecological momentary assessment (EMA) protocol assessing the phenomenology of TR-IMs could reduce intrusion symptoms in trauma-exposed adults. Participants (N=131) experiencing at least 2 TR-IMs per week related to a DSM-5 criterion A trauma completed a 2-week EMA protocol during which they reported on TR-IM properties three times per day, and on posttraumatic stress symptoms at the end of each day. Longitudinal symptom measurements were entered into linear mixed-effects models to test the effect of Time on TR-IMs. Over the 2-week EMA protocol, intrusion symptom severity (cluster B scores) significantly declined (t = -2.78, p = 0.006), while other symptom cluster scores did not significantly change. Follow-up analyses demonstrated that this effect was specific to TR-IMs (t = -4.02, p < 0.001), and was not moderated by survey completion rate, total PTSD symptom severity, or ongoing treatment. Our findings indicate that implementing an EMA protocol assessing intrusive memories could be an effective trauma intervention. Despite study limitations like its quasi-experimental design and absence of a control group, the specificity of findings to intrusive memories argues against a mere regression to the mean. Overall, an EMA approach could provide a cost-effective and scalable treatment option targeting intrusive memory symptoms.

Trauma-related intrusive memories (TR-IMs) are hallmark symptoms of posttraumatic stress disorder (PTSD), but their neural correlates remain partly unknown. Given its role in autobiographical memory, the hippocampus may play a critical role in TR-IM neurophysiology. The anterior and posterior hippocampi are known to have partially distinct functions, including during retrieval of autobiographical memories. This study aimed to investigate the relationship between TR-IM frequency and the anterior and posterior hippocampi morphology in PTSD. Ninety-three trauma-exposed adults completed daily ecological momentary assessments for fourteen days to capture their TR-IM frequency. Participants then underwent anatomical magnetic resonance imaging to obtain measures of anterior and posterior hippocampal volumes. Partial least squares analysis was applied to identify a structural covariance network that differentiated the anterior and posterior hippocampi. Poisson regression models examined the relationship of TR-IM frequency with anterior and posterior hippocampal volumes and the resulting structural covariance network. Results revealed no significant relationship of TR-IM frequency with hippocampal volumes. However, TR-IM frequency was significantly negatively correlated with the expression of a structural covariance pattern specifically associated with the anterior hippocampus volume. This association remained significant after accounting for the severity of PTSD symptoms other than intrusion symptoms. The network included the bilateral inferior temporal gyri, superior frontal gyri, precuneus, and fusiform gyri. These novel findings indicate that higher TR-IM frequency in individuals with PTSD is associated with lower structural covariance between the anterior hippocampus and other brain regions involved in autobiographical memory, shedding light on the neural correlates underlying this core symptom of PTSD.

AbstractAs the global prevalence of exposure to traumatic events rises, there is a growing need for accessible and scalable treatments for trauma-related disorders like posttraumatic stress disorder (PTSD). Intrusive reexperiencing symptoms, such as trauma-related intrusive memories (TR-IMs), are central to PTSD and a target of gold-standard treatments that are effective but resource-intensive. This study examined whether completing a brief ecological momentary assessment (EMA) protocol assessing the occurrence and phenomenology of TR-IMs was associated with decreases in intrusion symptom severity. Trauma-exposed adults (N = 139) experiencing at least 2 TR-IMs per week related to a DSM-5 criterion A traumatic event completed a 2-week EMA protocol. During this period, they reported on 18 sensory-perceptual and affective qualities of their TR-IMs three times per day and on posttraumatic stress symptom severity at day’s end. Longitudinal symptom measurements were entered into linear mixed-effects models to test the effect of Time on symptom severity. Over the 2-week protocol, intrusion symptom severity decreased, while other symptom cluster scores did not change. Within the intrusion symptoms, this effect was specific to TR-IMs and emotional reactivity to trauma reminders, and was not moderated by survey completion rate, total PTSD symptom severity, ongoing treatment, or time since trauma. This study was quasi-experimental and lacked a control group, therefore no definitive conclusions about clinical utility can be made. Nonetheless, these findings provide preliminary proof-of-principle and warrant future clinical trials assessing the clinical efficacy of EMAs of intrusive trauma memories as a scalable treatment option targeting intrusive memory symptoms.

Intrusive memories (IMs) are a hallmark posttraumatic stress symptom and are characterized by spontaneous, contextually-deficient reliving of sensory details of the index event. Coordinated interactions between the posterior (vs. anterior) hippocampus and occipitoparietal regions have been implicated in the contextually-bound replay of sensory-perceptual features of episodic memory. We examined if the temporal dynamics of these interactions are associated with the spontaneous sensory-rich reliving properties of trauma-related IMs (TR-IMs).

Trauma intrusive memories are a hallmark posttraumatic stress symptom. Although decreased hippocampal volume has been implicated in memory and posttraumatic stress disorder (PTSD), with differences between anterior and posterior hippocampal regions, the relation of anterior and posterior hippocampal volumes with trauma intrusive memory (TR-IM) frequency is unknown.

The pituitary adenylate cyclase-activating polypeptide (PACAP) system is implicated in posttraumatic stress disorder (PTSD) and related amygdala-mediated arousal and threat reactivity. PTSD is characterized by increased amygdala reactivity to threat and, more recently, aberrant intrinsic connectivity of the amygdala with large-scale resting state networks, specifically the default mode network (DMN). While the influence of PACAP on amygdala reactivity has been described, its association with intrinsic amygdala connectivity remains unknown. To fill this gap, we examined functional connectivity of resting-state functional magnetic resonance imaging (fMRI) in eighty-nine trauma-exposed adults (69 female) screened for PTSD symptoms to examine the association between blood-borne (circulating) PACAP levels and amygdala-DMN connectivity. Higher circulating PACAP levels were associated with increased amygdala connectivity with posterior DMN regions, including the posterior cingulate cortex/precuneus (PCC/Precun) and left angular gyrus (lANG). Consistent with prior work, this effect was seen in female, but not male, participants and the centromedial, but not basolateral, subregions of the amygdala. Clinical association analyses linked amygdala-PCC/Precun connectivity to anxious arousal symptoms, specifically exaggerated startle response. Taken together, our findings converge with previously demonstrated effects of PACAP on amygdala activity in PTSD-related processes and offer novel evidence for an association between PACAP and intrinsic amygdala connectivity patterns in PTSD. Moreover, these data provide preliminary evidence to motivate future work ascertaining the sex- and subregion-specificity of these effects. Such findings may enable novel mechanistic insights into neural circuit dysfunction in PTSD and how the PACAP system confers risk through a disruption of intrinsic resting-state network dynamics.

BACKGROUND Parkinson's disease mild cognitive impairment (PD-MCI) is frequent and heterogenous. There is no consensus about its influence on subthalamic deep brain stimulation (STN-DBS) outcomes. OBJECTIVE To determine the prevalence of PD-MCI and its subtypes in candidates to STN-DBS. Secondarily, we sought to identify MRI structural markers associated with cognitive impairment in these subgroups. METHODS Baseline data from the French multicentric PREDISTIM cohort were used. Candidates to STN-DBS were classified according to their cognitive performance in normal cognition (PD-NC) or PD-MCI. The latter included frontostriatal (PD-FS) and posterior cortical (PD-PC) subtypes. Between-group comparisons were performed on demographical and clinical variables as well as on T1-weighted MRI sequences at the cortical and subcortical levels. RESULTS 320 patients were included: 167 (52%) PD-NC and 153 (48%) PD-MCI patients. The latter group included 123 (80%) PD-FS and 30 (20%) PD-PC patients. There was no between-group difference regarding demographic and clinical variables. PD-PC patients had significantly lower global efficiency than PD-FS patients and significantly worse performance on visuospatial functions, episodic memory, and language. Compared to PD-NC, PD-MCI patients had cortical thinning and radiomic-based changes in the left caudate nucleus and hippocampus. There were no significant differences between the PD-MCI subtypes. CONCLUSION Among the candidates to STN-DBS, a significant proportion has PD-MCI which is associated with cortical and subcortical alterations. Some PD-MCI patients have posterior cortical deficits, a subtype known to be at higher risk of dementia.

Background: Mild cognitive impairment in Parkinson's disease (PD-MCI) is heterogenous and cognitive subtypes have been identified. However, the anatomo-functional bases of each subtype remain partly unknown. Objective: To propose a description of the current literature on neuroimaging findings associated with cognitive subtypes of PD-MCI. Methods: PubMed/Medline, Embase, PsycINFO and the Cochrane Library databases were searched (until April 2021). Studies comparing PD-MCI cognitive subtypes with healthy controls (HC) and PD patients with normal cognition (PD-NC) on any neuroimaging outcome were included. Results: Ten studies met the inclusion criteria. Six used structural MRI methods, two functional MRI methods, one electroencephalography and five positron or single-photon emission tomography. Most studies (n = 8) determined PD-MCI subtypes based on memory impairment and two based on executive impairment. Compared with HC and/or PD-NC, brain modifications were found in PD patients (a) with amnestic MCI and, to a lesser extent, non-amnestic MCI in occipital, parietal and temporal regions, (b) with executive MCI in frontal and striatal regions and (c) with non-executive MCI in posterior cortical regions. Conclusions: Very few neuroimaging studies have considered cognitive heterogeneity that exists within PD-MCI, making it difficult to draw robust conclusions regarding brain modifications associated with specific subtypes. Given the promising potential of neuroimaging methods in both clinical practice and research, further studies are needed to overcome the limitations of the current literature.

Temporal accounts of Developmental Dyslexia (DD) postulate that a timing impairment plays an important role in this learning disorder. However, DD has been associated with timing disorders as well as other motor and cognitive dysfunctions. It is still unclear whether nonverbal timing skills per se may be considered as independent determinants of DD. In this study, we investigated the independent contribution of predictive timing to DD above and beyond the motor and cognitive dysfunctions typically associated with this disorder. Twenty-one children with DD (aged 8-12, nine females) and 27 controls (14 females) were evaluated on perceptual timing, finger tapping, fine motor control, as well as attention and executive tasks. Participants were native French speakers from various socioeconomic backgrounds. The performance of children with DD was poorer than that of controls in most of the tasks. Predictors of DD, as identified by logistic regression modeling, were beat perception and precision in tapping to the beat, which are both predictive timing variables, children's tapping rate, and cognitive flexibility. These data support temporal accounts of DD in which predictive timing impairments partially explain the core phonological deficit, independent from general motor and cognitive functioning, making predictive timing a valuable tool for early diagnosis and remediation of DD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background The "dual syndrome hypothesis" distinguished two subtypes in mild cognitive impairment (MCI) in Parkinson's disease: frontostriatal, characterized by attentional and executive deficits; and posterior cortical, characterized by visuospatial, memory, and language deficits. Objective The aim was to identify resting-state functional modifications associated with these subtypes. Methods Ninety-five nondemented patients categorized as having normal cognition (n = 31), frontostriatal (n = 14), posterior cortical (n = 20), or mixed (n = 30) cognitive subtype had a 3 T resting-state functional magnetic resonance imaging scan. Twenty-four age-matched healthy controls (HCs) were also included. A group-level independent component analysis was performed to identify resting-state networks, and the selected components were subdivided into 564 cortical regions in addition to 26 basal ganglia regions. Global intra- and inter-network connectivity along with global and local efficiencies was compared between groups. The network-based statistics approach was used to identify connections significantly different between groups. Results Patients with posterior cortical deficits had increased intra-network functional connectivity (FC) within the basal ganglia network compared with patients with frontostriatal deficits. Patients with frontostriatal deficits had reduced inter-network FC between several networks, including the visual, default-mode, sensorimotor, salience, dorsal attentional, basal ganglia, and frontoparietal networks, compared with HCs, patients with normal cognition, and patients with a posterior cortical subtype. Similar results were also found between patients with a mixed subtype and HCs. Conclusion MCI subtypes are associated with specific changes in resting-state FC. Longitudinal studies are needed to determine the predictive potential of these markers regarding the risk of developing dementia. (c) 2021 International Parkinson and Movement Disorder Society

BACKGROUND:The 'dual syndrome' hypothesis states that two cognitive subtypes can be distinguished in mild cognitive impairment in Parkinson's disease (PD-MCI): a frontostriatal one, characterized by attentional and/or executive deficits, and a posterior cortical one, characterized by visuospatial, memory and/or language deficits. The latter type has been associated with a higher risk of earlier development of PD dementia. The functional bases of these subtypes remain partly unknown.OBJECTIVE:To identify EEG modifications associated with PD-MCI subtypes.METHODS:75 non-demented PD patients underwent a comprehensive neuropsychological assessment and a high-density EEG. They were classified as having normal cognition (PD-NC; n = 37), PD-MCI with a frontostriatal subtype (PD-FS; n = 11) or PD-MCI with a posterior cortical subtype (PD-PC; n = 27). Two EEG analyses were performed: (a) spectral powers quantification and (b) functional connectivity analysis.RESULTS:PD-FS patients displayed spectral and functional EEG alterations, namely (a) higher powers in the theta and delta bands, (b) lower powers in the beta2 band and (c) lower functional connectivity in the beta2 band compared to PD-NC and PD-PC patients. These alterations were mainly located in the frontal, limbic and parietal regions. There were no significant differences between PD-NC and PD-PC.CONCLUSION:EEG alterations previously reported in PD-MCI may only concern the frontostriatal subtype, and not the posterior-cortical subtype. This provides evidence for the dual syndrome hypothesis and emphasizes the importance of identifying PD-MCI subtypes. It also shows the promising potential of EEG to discriminate between PD-MCI subtypes.

Context: Cognitive impairments are common in patients with Parkinson's disease (PD) and are heterogeneous in their presentation. The "dual syndrome hypothesis" suggests the existence of two distinct subtypes of mild cognitive impairment (MCI) in PD: a frontostriatal subtype with predominant attentional and/or executive deficits and a posterior cortical subtype with predominant visuospatial, memory, and/or language deficits. The latter subtype has been associated with a higher risk of developing dementia. Objective: The objective of this study was to identify structural modifications in cortical and subcortical regions associated with each PD-MCI subtype. Methods: One-hundred and fourteen non-demented PD patients underwent a comprehensive neuropsychological assessment as well as a 3T magnetic resonance imaging scan. Patients were categorized as having no cognitive impairment (n = 41) or as having a frontostriatal (n = 16), posterior cortical (n = 25), or a mixed (n = 32) MCI subtype. Cortical regions were analyzed using a surface-based Cortical thickness (CTh) method. In addition, the volumes, shapes, and textures of the caudate nuclei, hippocampi, and thalami were studied. Tractometric analyses were performed on associative and commissural white matter (WM) tracts. Results: There were no between-group differences in volumetric measurements and cortical thickness. Shape analyses revealed more abundant and more extensive deformations fields in the caudate nuclei, hippocampi, and thalami in patients with posterior cortical deficits compared to patients with no cognitive impairment. Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) were also observed in the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the striato-parietal tract, and the anterior and posterior commissural tracts. Texture analyses showed a significant difference in the right hippocampus of patients with a mixed MCI subtype. Conclusion: PD-MCI patients with posterior cortical deficits have more abundant and more extensive structural alterations independently of age, disease duration, and severity, which may explain why they have an increased risk of dementia.

BACKGROUND:Anxiety is frequent in Parkinson's disease (PD) and has a negative impact on disease symptoms and quality of life. The underlying mechanisms remain largely unknown. The aim of this study was to identify anatomical and functional changes associated to PD-related anxiety by comparing the volume, shape and texture of the amygdala, the cortical thickness as well as the functional connectivity (FC) of the fear circuit in patients with and without clinically relevant anxiety.METHODS:Non-demented PD patients were recruited, and anxiety was quantified using the Parkinson Anxiety Scale. Structural MRI was used to compare cortical thickness and amygdala structure and resting-state functional MRI to compare FC patterns of the amygdala and resting-state functional networks in both groups.RESULTS:We included 118 patients: 34 with (A+) and 84 without (A-) clinically relevant anxiety. Clusters of cortical thinning were identified in the bilateral fronto-cingulate and left parietal cortices of the A+ group. The texture and the shape of the left amygdala was different in the A+ group but the overall volume did not differ between groups. FC between the amygdala and the whole brain regions did not differ between groups. The internetwork resting-state FC was higher between the "fear circuit" and salience network in the A+ group.CONCLUSION:Anxiety in PD induces structural modifications of the left amygdala, atrophy of the bilateral fronto-cingulate and the left parietal cortices, and a higher internetwork resting-state FC between the fear circuit and the salience network.