Relationship between structural abnormalities in the cerebellum and dementia, posttraumatic stress disorder and bipolar disorder

Baldaçara, Leonardo; Borgio, João Guilherme Fiorani; Araújo, Célia Maria de; Nery-Fernandes, Fabiana; Lacerda, Acioly L.T.; Moraes, Walter André dos Santos; Montaño, Maria Beatriz Marcondes Macedo; Rocha, Marlos Vasconcelos; Schoedl, Aline Ferri; Pupo, Mariana; Andreoli, Sérgio Baxter; Miranda‐Scippa, Ângela; Ramos, Luiz Roberto; Mari, Jair J.; Bressan, Rodrigo Affonseca; Jackowski, Andrea Parolin

doi:10.1590/s1980-57642012dn06040003

Cited by 23 publications

(13 citation statements)

References 75 publications

(94 reference statements)

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“…Recent work by Holmes and colleagues also found reduced nodal strength in the cerebellum of PTSD patients, as well as reduced volume and structural covariance (45). Other studies have also reported structural and functional abnormalities in the cerebellum in PTSD (46)(47)(48)(49)(50)(51). Importantly, the cerebellar abnormalities in the current study were evident only during symptom provocation.…”

Section: Figure 4 Effect Of Symptom Provocation On Salience Global Csupporting

confidence: 64%

Salience Network Disruption in US Army Soldiers with PTSD

Abdallah¹,

Averill²,

Ramage

et al. 2018

Preprint

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BACKGROUND: Better understanding of the neurobiology of posttraumatic stress disorder (PTSD) may be critical to developing novel, effective therapeutics. Here, we conducted a data-driven investigation using a well-established, graphbased topological measure of nodal strength to determine the extent of functional dysconnectivity in a cohort of active duty US Army soldiers with PTSD compared to controls.METHODS: 102 participants with (n=50) or without PTSD (n=52) completed functional magnetic resonance imaging (fMRI) at rest and during symptom provocation using subject-specific script imagery. Vertex/voxel global brain connectivity with global signal regression (GBCr), a measure of nodal strength, was calculated as the average of its functional connectivity with all other vertices/voxels in the brain gray matter. RESULTS:In contrast to during resting-state, where there were no group differences, we found a significantly higher GBCr, in PTSD participants compared to controls, in areas within the right hemisphere, including anterior insula, caudalventrolateral prefrontal, and rostral-ventrolateral parietal cortices. Overall, these clusters overlapped with the ventral and dorsal salience networks. Post hoc analysis showed increased GBCr in these salience clusters during symptom provocation compared to resting-state. In addition, resting-state GBCr in the salience clusters predicted GBCr during symptom provocation in PTSD participants but not in controls. CONCLUSION:In PTSD, increased connectivity within the salience network has been previously hypothesized, based primarily on seed-based connectivity findings. The current results strongly support this hypothesis using whole-brain network measure in a fully data-driven approach. It remains to be seen in future studies whether these identified salience disturbances would normalize following treatment.

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Section: Figure 4 Effect Of Symptom Provocation On Salience Global Csupporting

confidence: 64%

Salience Network Disruption in US Army Soldiers with PTSD

Abdallah¹,

Averill²,

Ramage

et al. 2018

Preprint

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“…For example, cerebellar volume has been shown to be lower in adolescents 35 and adults with PTSD, 36,37 with cerebellum volume negatively correlating with PTSD symptoms. Furthermore, meta-analyses of both resting-state 38 and task-based 39 neuroimaging studies indicate hypoactive cerebellar function in PTSD. A recent study found alterations in functional connectivity from distinct cerebellar seeds to brain regions involved in emotional regulation, somatosensory processing and memory retrieval in PTSD, with distinct patterns of cerebellar alterations in the dissociative subtype of PTSD.…”

Section: Discussionmentioning

confidence: 99%

Cerebellar and Prefrontal Cortical Alterations in PTSD: Structural and Functional Evidence

et al. 2018

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Background: Neuroimaging studies have revealed that disturbances in network organization of key brain regions may underlie cognitive and emotional dysfunction in posttraumatic stress disorder (PTSD). Examining both brain structure and function in the same population may further our understanding of network alterations in PTSD. Methods: We used tensor-based morphometry (TBM) and intrinsic connectivity distribution (ICD) to identify regions of altered volume and functional connectivity in unmedicated individuals with PTSD (n=21) and healthy comparison (HC) participants (n=18). These regions were then used as seeds for follow-up anatomical covariance and functional connectivity analyses. Results: Smaller volume in the cerebellum and weaker structural covariance between the cerebellum seed and middle temporal gyrus were observed in the PTSD group. Individuals with PTSD also exhibited lower whole-brain connectivity in the cerebellum, dorsolateral prefrontal cortex (dlPFC) and medial prefrontal cortex (mPFC). Functional connectivity in the cerebellum and grey matter volume in the dlPFC were negatively correlated with PTSD severity as measured by the DSM-5 PTSD checklist (PCL-5; r= −.0.77, r=−0.79). Finally, seed connectivity revealed weaker connectivity within nodes of the central executive network (right and left dlPFC), and between nodes of the default mode network (mPFC and cerebellum) and the supramarginal gyrus, in the PTSD group. Conclusion: We demonstrate structural and functional alterations in PTSD converging on the PFC and cerebellum. Whilst PFC alterations are relatively well established in PTSD, the cerebellum has not generally been considered a key region in PTSD. Our findings add to a growing evidence base implicating cerebellar involvement in the pathophysiology of PTSD.

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“…Finally, accumulating evidence repeatedly demonstrates functional and structural abnormalities in the cerebellum of PTSD patients (34)(35)(36)(37)(38)(39). Moreover, two recent studies have shown reduced functional nodal strength in the cerebellum in PTSD (19,40).…”

Section: Figure 3 the Effects Of Psychotherapy On Executive Connectimentioning

confidence: 96%

Reduced Salience and Enhanced Central Executive Connectivity Following PTSD Treatment

Abdallah

Averill

Ramage

et al. 2018

Preprint

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BACKGROUND:In soldiers with posttraumatic stress disorder (PTSD), symptom provocation was found to induce increased connectivity within the salience network, as measured by functional magnetic resonance imaging (fMRI) and global brain connectivity with global signal regression (GBCr). However, it is unknown whether these GBCr disturbances would normalize following effective PTSD treatment.METHODS: 69 US Army soldiers with (n = 42) and without PTSD (n = 27) completed fMRI at rest and during symptom provocation using subject-specific script imagery. Then, participants with PTSD received 6 weeks (12 sessions) of group cognitive processing therapy (CPT) or present-centered therapy (PCT). At week 8, all participants repeated the fMRI scans. The primary analysis used a region-of-interest approach to determine the effect of treatment on salience GBCr. A secondary analysis was conducted to explore the pattern of GBCr alterations posttreatment in PTSD participants compared to controls. RESULTS:Over the treatment period, PCT significantly reduced salience GBCr (p = .02). Compared to controls, salience GBCr was high pretreatment (PCT, p = .01; CPT, p = .03) and normalized post-PCT (p = .53), but not post-CPT (p = .006). Whole-brain secondary analysis found high GBCr within the central executive network in PTSD participants compared to controls. Post hoc exploratory analyses showed significant increases in executive GBCr following CPT treatment (p = .01). CONCLUSION:The results support previous models relating CPT to central executive network and enhanced cognitive control while unraveling a previously unknown neurobiological mechanism of PCT treatment, demonstrating treatment-specific reduction in salience connectivity during trauma recollection.

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Relationship between structural abnormalities in the cerebellum and dementia, posttraumatic stress disorder and bipolar disorder

Cited by 23 publications

References 75 publications

Salience Network Disruption in US Army Soldiers with PTSD

Salience Network Disruption in US Army Soldiers with PTSD

Cerebellar and Prefrontal Cortical Alterations in PTSD: Structural and Functional Evidence

Reduced Salience and Enhanced Central Executive Connectivity Following PTSD Treatment

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