Cortical thinning and altered functional brain coherence in survivors of childhood sarcoma.

High-dose chemotherapy is increasingly evidenced to be neurotoxic and result in long-term neurocognitive sequelae. However, research investigating grey matter alterations in childhood cancer patients remains limited. As childhood sarcoma patients receive high-dose chemotherapy, we aimed to investigate cortical brain alterations in adult survivors. We analyzed high-resolution structural (T1-weighted) MRI and resting-state functional MRI (rsfMRI), to derive structural and functional cortical information in survivors of childhood sarcoma, treated with high-dose intravenous chemotherapy (n = 33). These scans were compared to age- and gender- matched controls (n = 34). Cortical volume and thickness were investigated using voxel-based morphometry and vertex-wise surface-based morphometry. Brain regions showing significant group differences in volume or thickness were implemented as seeds of interest to estimate their resting state co-activity with other areas (i.e. functional coherence). We explored whether structural measures were associated with potential risk factors, such as age at diagnosis, and cumulative doses of chemotherapeutic agents (methotrexate, ifosfamide). Finally, we investigated the link between functional regional strength, neurocognitive assessments and daily life complaints. In patients relative to controls we observed lower grey matter volumes in cerebellar and frontal areas, as well as frontal cortical thinning. Cerebellar volume and orbitofrontal thickness appeared dose- and age-related, respectively. Cortical thickness of the parahippocampal area appeared lower, only if the group comparison was not adjusted for depression. This region specifically showed lower functional coherence, which was associated with lower processing speed. This study suggests cortical thinning as well as decreased functional coherence in survivors of childhood sarcoma, which could be important for both long-term attentional functioning and emotional distress in daily life. Frontal areas might be specifically vulnerable during adolescence.

Network level characteristics in the emotion recognition network after unilateral temporal lobe surgery.

The human amygdala is considered a key region for successful emotion recognition. We recently reported that temporal lobe surgery (TLS), including resection of the amygdala, does not affect emotion recognition performance (Journal of Neuroscience, 2018, 38, 9263). In the present study, we investigate the neural basis of this preserved function at the network level. We use generalized psychophysiological interaction and graph theory indices to investigate network level characteristics of the emotion recognition network in TLS patients and healthy controls. Based on conflicting emotion processing theories, we anticipated two possible outcomes: a substantial increase of the non-amygdalar connections of the emotion recognition network to compensate functionally for the loss of the amygdala, in line with basic emotion theory versus only minor changes in network level properties as predicted by psychological construction theory. We defined the emotion recognition network in the total sample and investigated group differences on five network level indices (i.e. characteristic path length, global efficiency, clustering coefficient, local efficiency and small-worldness). The results did not reveal a significant increase in the left or right temporal lobectomy group (compared to the control group) in any of the graph measures, indicating that preserved behavioural emotion recognition in TLS is not associated with a massive connectivity increase between non-amygdalar nodes at network level. We conclude that the emotion recognition network is robust and functionally able to compensate for structural damage without substantial global reorganization, in line with a psychological construction theory.

Age-dependent brain volume and neuropsychological changes after chemotherapy in breast cancer patients.

This study investigated volumetric brain changes and cognitive performance in premenopausal and postmenopausal patients treated for early-stage breast cancer. Participants underwent elaborate neurocognitive assessments (neuropsychological testing, cognitive failure questionnaire, and high-resolution T1-weighted structural MRI) before and after chemotherapy. Volumetric brain changes were estimated, using longitudinal deformation-based morphometry, and correlated with cognitive changes. In total, 180 women participated in this study, of whom 72 patients with breast cancer had received adjuvant chemotherapy (C+), 49 patients did not receive chemotherapy (C-), and 59 healthy controls (HC). The population was categorized into two age groups: A young group who were premenopausal and younger than 52 years at baseline (n = 55C+/32C-/41HC), and an older group who were postmenopausal and older than 60 years (n = 17C+/17C-/18HC). Cognitive impairment occurred after chemotherapy in both young and older patients, although older patients showed more decline in processing speed (Trail making test b). White matter volume expansion was observed after chemotherapy, only significantly present in the younger subgroup of patients. In patients not treated with chemotherapy, diffuse gray and white matter volume reduction was observed. Less white matter expansion concurred with more cognitive decline (r > .349, p < .05). In conclusion, we found age-dependent cognitive decline and white matter volume changes in patients with breast cancer after chemotherapy, which could possibly be linked to neuroinflammatory processes. White matter expansion after chemotherapy, more pronounced in premenopausal patients, correlated with less cognitive decline. This suggests such expansion to be age-dependent, possibly caused by a protective response in the younger brain to chemotherapy-induced neurotoxicity.