Publications by authors named "Francesca Zidda"

6 Publications

  • Page 1 of 1

Structural white and gray matter differences in a large sample of patients with Posttraumatic Stress Disorder and a healthy and trauma-exposed control group: Diffusion tensor imaging and region-based morphometry.

Neuroimage Clin 2020 12;28:102424. Epub 2020 Sep 12.

Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany; Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany. Electronic address:

Differences in structural white and gray matter in survivors of traumatic experiences have been related to the development and maintenance of Posttraumatic Stress Disorder (PTSD). However, there are very few studies on diffusion tensor imaging and region based morphometry comparing patients with PTSD to two control groups, namely healthy individuals with or without trauma experience. It is also unknown if differences in white and gray matter are associated. In this cross-sectional study, we examined white- and gray matter differences between 44 patients with PTSD, 49 trauma control and 61 healthy control subjects. We compared the groups applying Tract-Based Spatial Statistics (TBSS) for a whole brain white matter analysis as well as region of interest analyses for white and gray matter. First, trauma control subjects in comparison to patients with PTSD and healthy control subjects showed significantly a) higher fractional anisotropy (FA) in the left corticospinal tract and inferior fronto-occipital fasciculus than patients with PTSD, b) higher FA in the left inferior fronto-occipital-, right inferior- and right superior longitudinal fasciculi, c) higher FA in the forceps minor and d) higher volume of the left and right anterior insulae. Second, we show significant correlations between the FA in the forceps minor and the gray matter volume in the left and right anterior insulae. Third, the mean FA value in the forceps minor correlated negatively with symptom severity of PTSD and depression as well as trait anxiety, whereas the gray matter volume in the left anterior insula correlated negatively with symptom severity in PTSD. Our findings underline the importance of brain structures critically involved in emotion regulation and salience mapping. While previous studies associated these processes primarily to functional and task-based differences in brain activity, we argue that morphometrical white and gray matter differences could serve as targets in neuroscientifically-informed prevention and treatment interventions for PTSD.
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http://dx.doi.org/10.1016/j.nicl.2020.102424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511745PMC
September 2020

Peripheral input and phantom limb pain: A somatosensory event-related potential study.

Eur J Pain 2020 08 22;24(7):1314-1329. Epub 2020 May 22.

Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Background: Following amputation, nearly all amputees report nonpainful phantom phenomena and many of them suffer from chronic phantom limb pain (PLP) and residual limb pain (RLP). The aetiology of PLP remains elusive and there is an ongoing debate on the role of peripheral and central mechanisms. Few studies have examined the entire somatosensory pathway from the truncated nerves to the cortex in amputees with PLP compared to those without PLP. The relationship among afferent input, somatosensory responses and the change in PLP remains unclear.

Methods: Transcutaneous electrical nerve stimulation was applied on the truncated median nerve, the skin of the residual limb and the contralateral homologous nerve in 22 traumatic upper-limb amputees (12 with and 10 without PLP). Using somatosensory event-related potentials, the ascending volley was monitored from the brachial plexus, the spinal cord, the brainstem and the thalamus to the primary somatosensory cortex.

Results: Peripheral input could evoke PLP in amputees with chronic PLP (7/12), but not in amputees without a history of PLP (0/10). The amplitudes of the somatosensory components were comparable between amputees with and without PLP. In addition, evoked potentials from the periphery through the spinal, subcortical and cortical segments were not significantly associated with PLP.

Conclusions: Peripheral input can modulate PLP but seems insufficient to cause PLP. These findings suggest the multifactorial complexity of PLP and different mechanisms for PLP and RLP.

Significance: Peripheral afferent input plays a role in PLP and has been assumed to be sufficient to generate PLP. In this study we found no significant differences in the electrical potentials generated by peripheral stimulation from the truncated nerve and the skin of the residual limb in amputees with and without PLP. Peripheral input could enhance existing PLP but could not cause it. These findings indicate the multifactorial complexity of PLP and an important role of central processes in PLP.
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http://dx.doi.org/10.1002/ejp.1579DOI Listing
August 2020

White matter correlates of contextual pavlovian fear extinction and the role of anxiety in healthy humans.

Cortex 2019 12 20;121:179-188. Epub 2019 Sep 20.

Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany.

Pavlovian contextual fear extinction is viewed as an important mechanism for behavioral adaptation in everyday life, including challenging situations of stress and anxiety. It has frequently been shown to relate to the function of brain areas like the hippocampus and medial prefrontal cortex (mPFC), while the role of structural properties, like white matter tracts in these regions, has been less studied. We employed diffusion tensor imaging to determine structural white matter connectivity (cingulum and uncinate fasciculus) correlates of contextual pavlovian fear extinction indicators measured through functional magnetic resonance imaging, skin conductance responses (SCRs) and self-reports of valence, arousal and contingency in 93 healthy individuals. Higher fractional anisotropy values in the hippocampal cingulum were significantly related to higher SCRs during extinction of contextual conditioned responses (explained variance: 11.2%) as an indicator of extinction deficits on the level of physiological arousal. However, FA was neither related to any of the other fear extinction measures, nor did we find associations with functional extinction responses in the hippocampus or mPFC. Trait anxiety was a significant moderator of the SCR-hippocampal cingulum association (explained variance: 32.09%). The data add evidence for a critical role of the hippocampal formation in contextual pavlovian extinction, and, together with the strong effect of trait anxiety, may have implications for the development of anxiety disorders where contextual extinction learning deficits are observed.
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http://dx.doi.org/10.1016/j.cortex.2019.08.020DOI Listing
December 2019

Resting-state connectivity alterations during transient global amnesia.

Neuroimage Clin 2019 23;23:101869. Epub 2019 May 23.

Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address:

While the pathophysiology of transient global amnesia (TGA) is not understood, due to the specific nature of the clinical deficits, transient dysfunction in the medial temporal lobe, especially in the hippocampus, is assumed; however, concomitant disturbances in other brain regions and in executive function have been postulated. In this study, a cohort of 16 patients was prospectively recruited from the emergency department for resting-state functional MRI (fMRI) during the acute stage of TGA, as confirmed by a standardized neuropsychological assessment. Twenty age- and sex-matched controls, as well as twenty patients with a history of TGA, were recruited for comparison. Functional data were processed using independent component analysis (ICA), allowing the complete automatic (data-driven) identification of spontaneous network dynamics. We documented a severe disturbance in anterograde episodic long-term memory in all patients. Group-based ICA of resting-state data in acute TGA patients versus that of controls and patients with a past TGA episode demonstrated reduced FC mainly of structures belonging to the executive network (EN), but also the hippocampus, confirming its pathophysiological involvement in the disorder, as well as areas belonging to the salience network and other subcortical regions. No significant differences were found when comparing connectivity in patients with a history of TGA and controls. Our findings strengthen previous empirical and theoretical accounts of hippocampal and executive dysfunction in TGA. The disruption of frontal, parietal and insular control regions, together with disruption in the hippocampus, provides a new interpretation for the pathophysiology and neuropsychological profile of this neurological disorder on a large-scale network level.
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http://dx.doi.org/10.1016/j.nicl.2019.101869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543172PMC
June 2020

Default mode network connectivity of fear- and anxiety-related cue and context conditioning.

Neuroimage 2018 01 16;165:190-199. Epub 2017 Oct 16.

Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany; Department of Psychology, Faculty for Social Sciences, University of Mannheim, Germany. Electronic address:

Classical fear conditioning is an important mechanism to adequately respond and adapt to environmental threats and has been related to the development of fear and anxiety. Both cue and context conditioning have been studied but little is known about their relation to relevant resting state networks. The default mode network (DMN) has been reported to be involved in affective learning and described as facilitating a state of readiness in responding to environmental changes. We examined resting state brain connectivity patterns of the default mode network (DMN) in 119 healthy volunteers. Specifically, we carried out correlation analyses between the DMN and skin conductance responses (SCRs) as well as arousal, valence and contingency ratings during learning. In addition, we examined the role of trait anxiety. Two different DMN patterns were identified in which stronger connectivity was linked to lower differential SCRs during fear and anxiety learning. One was related to cue conditioning and involved the amygdala and the medial prefrontal cortex, and one was associated with context conditioning and included the hippocampal formation and sensorimotor areas. These results were replicated in an independent sample. Functional connectivity of the DMN with these key regions at rest was also predictive of trait anxiety but this association could not be replicated in the second sample. We showed that DMN connectivity is differently associated with cued versus contextual learning mechanisms. Uncovering individual differences in baseline network connectivity of the DMN with these key regions might lead to a better understanding of fear and anxiety. Such findings could indeed help to identify vulnerability factors linked to network alterations at rest with dysregulation of learning processes involved in the pathophysiology of stress and anxiety disorders.
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http://dx.doi.org/10.1016/j.neuroimage.2017.10.024DOI Listing
January 2018

Oxytocin differentially modulates pavlovian cue and context fear acquisition.

Soc Cogn Affect Neurosci 2017 06;12(6):976-983

Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Fear acquisition and extinction have been demonstrated as core mechanisms for the development and maintenance of mental disorders, with different contributions of processing cues vs contexts. The hypothalamic peptide oxytocin (OXT) may have a prominent role in this context, as it has been shown to affect fear learning. However, investigations have focused on cue conditioning, and fear extinction. Its differential role for cue and context fear acquisition is still not known. In a randomized, double-blind, placebo (PLC)-controlled design, we administered an intranasal dose of OXT or PLC before the acquisition of cue and context fear conditioning in healthy individuals (n = 52), and assessed brain responses, skin conductance responses and self-reports (valence/arousal/contingency). OXT compared with PLC significantly induced decreased responses in the nucleus accumbens during early cue and context acquisition, and decreased responses of the anterior cingulate cortex and insula during early as well as increased hippocampal response during late context, but not cue acquisition. The OXT group additionally showed significantly higher arousal in late cue and context acquisition. OXT modulates various aspects of cue and context conditioning, which is relevant from a mechanism-based perspective and might have implications for the treatment of fear and anxiety.
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http://dx.doi.org/10.1093/scan/nsx028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472122PMC
June 2017