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Article ; Online: Social affective outcomes and brain injury in children and adolescents treated for brain tumours.

Igoshina, Elizaveta / Wu, Liliana C / Moxon-Emre, Iska / Mabbott, Donald J

The Lancet. Child & adolescent health

2023 Volume 7, Issue 8, Page(s) 577–587

Abstract: In this Review we critically evaluate the empirical literature investigating the effect of paediatric brain tumours and their treatment on social affective function. We focus specifically on relations between social affective function and compromised ... ...

Abstract	In this Review we critically evaluate the empirical literature investigating the effect of paediatric brain tumours and their treatment on social affective function. We focus specifically on relations between social affective function and compromised brain structure and function associated with treatment for a paediatric brain tumour. We concentrate on emotion recognition and regulation, because these are core components of social affective function. First, we provide an overview of the literature in typically developing children and discuss the underlying brain networks thought to subserve emotion (ie, limbic system and supporting white matter microstructure). We then focus on how damage to brain structure and function after treatment for a paediatric brain tumour might be related to compromised emotion recognition and regulation-as well as broader social affective outcomes. On the basis of our review of the literature across typically developing children and those with a paediatric brain tumour, we suggest that structural changes to fronto-limbic tracts might interrupt social network neural communication in children and adolescents treated for brain tumours. A critical analysis of the reviewed literature suggests a relationship between social affective dysfunction and childhood-acquired injury to white matter microstructure. We argue that the knowledge synthesised regarding paediatric brain tumours could extend to other neurological disorders. Finally, we identify considerations for future investigation and recommend research practices to be adopted in forthcoming studies to establish causal links between brain structure and function to social affective processes.
MeSH term(s)	Humans ; Child ; Adolescent ; Brain ; Brain Neoplasms/therapy ; Brain Neoplasms/pathology ; Emotions/physiology ; White Matter/pathology ; Brain Injuries/pathology
Language	English
Publishing date	2023-05-29
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ISSN	2352-4650
ISSN (online)	2352-4650
DOI	10.1016/S2352-4642(23)00079-2
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Article ; Online: Sleep Differentially and Profoundly Impairs Recall Memory in a Patient with Fornix Damage.

Matorina, Nelly / Tseng, Julie / Ladyka-Wojcik, Natalia / Olsen, Rosanna / Mabbott, Donald J / Barense, Morgan D

Journal of cognitive neuroscience

2023 Volume 35, Issue 10, Page(s) 1635–1655

Abstract: In March 2020, C.T., a kind, bright, and friendly young woman underwent surgery for a midline tumor involving her septum pellucidum and extending down into her fornices bilaterally. Following tumor diagnosis and surgery, C.T. experienced significant ... ...

Abstract	In March 2020, C.T., a kind, bright, and friendly young woman underwent surgery for a midline tumor involving her septum pellucidum and extending down into her fornices bilaterally. Following tumor diagnosis and surgery, C.T. experienced significant memory deficits: C.T.'s family reported that she could remember things throughout the day, but when she woke up in the morning or following a nap, she would expect to be in the hospital, forgetting all the information that she had learned before sleep. The current study aimed to empirically validate C.T.'s pattern of memory loss and explore its neurological underpinnings. On two successive days, C.T. and age-matched controls watched an episode of a TV show and took a nap or stayed awake before completing a memory test. Although C.T. performed numerically worse than controls in both conditions, sleep profoundly exacerbated her memory impairment, such that she could not recall any details following a nap. This effect was replicated in a second testing session. High-resolution MRI scans showed evidence of the trans-callosal surgical approach's impact on the mid-anterior corpus callosum, indicated that C.T. had perturbed white matter particularly in the right fornix column, and demonstrated that C.T.'s hippocampal volumes did not differ from controls. These findings suggest that the fornix is important for processing episodic memories during sleep. As a key output pathway of the hippocampus, the fornix may ensure that specific memories are replayed during sleep, maintain the balance of sleep stages, or allow for the retrieval of memories following sleep.
MeSH term(s)	Humans ; Female ; Sleep ; Mental Recall ; Fornix, Brain/diagnostic imaging ; Learning ; Hippocampus/diagnostic imaging ; Memory Disorders/etiology
Language	English
Publishing date	2023-08-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1007410-7
ISSN	1530-8898 ; 0898-929X ; 1096-8857
ISSN (online)	1530-8898
ISSN	0898-929X ; 1096-8857
DOI	10.1162/jocn_a_02038
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Zs.A 2623: Show issues

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Article ; Online: Homeostatic coordination and up-regulation of neural activity by activity-dependent myelination.

Talidou, Afroditi / Frankland, Paul W / Mabbott, Donald / Lefebvre, Jérémie

Nature computational science

2022 Volume 2, Issue 10, Page(s) 665–676

Abstract: Activity-dependent myelination (ADM) is a fundamental dimension of brain plasticity through which myelin changes as a function of neural activity. Mediated by structural changes in glia, ADM notably regulates axonal conduction velocity. Yet, it remains ... ...

Abstract	Activity-dependent myelination (ADM) is a fundamental dimension of brain plasticity through which myelin changes as a function of neural activity. Mediated by structural changes in glia, ADM notably regulates axonal conduction velocity. Yet, it remains unclear how neural activity impacts myelination to orchestrate the timing of neural signalling, and how ADM shapes neural activity. We developed a model of spiking neurons enhanced with neuron-oligodendrocyte feedback and examined the relationship between ADM and neural activity. We found that ADM implements a homeostatic gain control mechanism that enhances neural firing rates and correlations through the temporal coordination of action potentials as axon lengths increase. Stimuli engage ADM plasticity to trigger bidirectional and reversible changes in conduction delays, as may occur during learning. Furthermore, ADM was found to enhance information transmission under various types of time-varying stimuli. These results highlight the role of ADM in shaping neural activity and communication.
MeSH term(s)	Up-Regulation ; Myelin Sheath/physiology ; Neurons ; Axons/physiology ; Neuroglia
Language	English
Publishing date	2022-10-03
Publishing country	United States
Document type	Journal Article
ISSN	2662-8457
ISSN (online)	2662-8457
DOI	10.1038/s43588-022-00315-z
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Article: Multimodal imaging with magnetization transfer and diffusion tensor imaging reveals evidence of myelin damage in children and youth treated for a brain tumor.

Skocic, Jovanka / Richard, Logan / Ferkul, Ashley / Cox, Elizabeth / Tseng, Julie / Laughlin, Suzanne / Bouffet, Eric / Mabbott, Donald James

Neuro-oncology practice

2024 Volume 11, Issue 3, Page(s) 307–318

Abstract: Background: The microstructural damage underlying compromise of white matter following treatment for pediatric brain tumors is unclear. We use multimodal imaging employing advanced diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) ... ...

Abstract	Background: The microstructural damage underlying compromise of white matter following treatment for pediatric brain tumors is unclear. We use multimodal imaging employing advanced diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) MRI methods to examine chronic microstructural damage to white matter in children and adolescents treated for pediatric brain tumor. Notably, MTI may be more sensitive to macromolecular content, including myelin, than DTI. Methods: Fifty patients treated for brain tumors (18 treated with surgery ± chemotherapy and 32 treated with surgery followed by cranial-spinal radiation; time from diagnosis to scan ~6 years) and 45 matched healthy children completed both MTI and DTI scans. Voxelwise and region-of-interest approaches were employed to compare white matter microstructure metrics (magnetization transfer ratio (MTR); DTI- fractional anisotropy [FA], radial diffusivity [RD], axial diffusivity [AD], mean diffusivity [MD]) between patients and healthy controls. Results: MTR was decreased across multiple white matter tracts in patients when compared to healthy children, Conclusions: Our findings provide evidence that the white matter damage observed in patients years after treatment of pediatric posterior fossa tumors, likely reflects myelin disruption.
Language	English
Publishing date	2024-01-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2768945-1
ISSN	2054-2585 ; 2054-2577
ISSN (online)	2054-2585
ISSN	2054-2577
DOI	10.1093/nop/npae003
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Article ; Online: Cross-translational models of late-onset cognitive sequelae and their treatment in pediatric brain tumor survivors.

Al Dahhan, Noor Z / Cox, Elizabeth / Nieman, Brian J / Mabbott, Donald J

Neuron

2022 Volume 110, Issue 14, Page(s) 2215–2241

Abstract: Pediatric brain tumor treatments have a high success rate, but survivors are at risk of cognitive sequelae that impact long-term quality of life. We summarize recent clinical and animal model research addressing pathogenesis or evaluating candidate ... ...

Abstract	Pediatric brain tumor treatments have a high success rate, but survivors are at risk of cognitive sequelae that impact long-term quality of life. We summarize recent clinical and animal model research addressing pathogenesis or evaluating candidate interventions for treatment-induced cognitive sequelae. Assayed interventions encompass a broad range of approaches, including modifications to radiotherapy, modulation of immune response, prevention of treatment-induced cell loss or promotion of cell renewal, manipulation of neuronal signaling, and lifestyle/environmental adjustments. We further emphasize the potential of neuroimaging as a key component of cross-translation to contextualize laboratory research within broader clinical findings. This cross-translational approach has the potential to accelerate discovery to improve pediatric cancer survivors' long-term quality of life.
MeSH term(s)	Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/therapy ; Cognition ; Disease Progression ; Humans ; Neuroimaging ; Quality of Life/psychology ; Survivors/psychology
Language	English
Publishing date	2022-05-05
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2022.04.009
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Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

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Article ; Online: Insult to Short-Range White Matter Connectivity in Childhood Brain Tumor Survivors.

Oyefiade, Adeoye / Parthab, Nadeem / Skocic, Jovanka / Moxon-Emre, Iska / Tabori, Uri / Bouffet, Eric / Ramaswamy, Vijay / Laughlin, Susanne / Mabbott, Donald J

International journal of radiation oncology, biology, physics

2023 Volume 116, Issue 4, Page(s) 878–888

Abstract: Purpose: Children treated for brain tumors are at an increased risk for cognitive impairments due to the effect of radiation therapy on developing white matter (WM). Although damage to long-range WM is well documented in pediatric brain tumor survivors, ...

Abstract	Purpose: Children treated for brain tumors are at an increased risk for cognitive impairments due to the effect of radiation therapy on developing white matter (WM). Although damage to long-range WM is well documented in pediatric brain tumor survivors, the effect of radiation therapy on short-range WM remains unelucidated. We sought to clarify whether radiation treatment affects short-range WM by completing a virtual dissection of these connections and comparing their microstructural properties between brain tumor survivors and typically developing children. Methods and materials: T1-weighted and diffusion-weighted magnetic resonance images were acquired for 26 brain tumor survivors and 26 typically developing children. Short-range WM was delineated using a novel, whole-brain approach. A random forest classifier was used to identify short-range connections with the largest differences in microstructure between patients and typically developing children. Results: The random forest classifier identified differences in short-range WM microstructure across the brain with an accuracy of 87.5%. Nine connections showed the largest differences in short-range WM between patients and typically developing children. For these connections, fractional anisotropy and axial diffusivity were significantly lower in patients. Short-range connections in the posterior fossa were disproportionately affected, suggesting that greater radiation exposure to the posterior fossa was more injurious to short-range WM. Lower craniospinal radiation dose did not predict reduced toxicity to short-range WM. Conclusions: Our findings indicate that treatment for medulloblastoma resulted in changes in short-range WM in patients. Lower fractional anisotropy and axial diffusivity may reflect altered microstructural organization and coherence of these connections, especially in the posterior fossa. Short-range WM may be especially sensitive to the effect of craniospinal radiation therapy, resulting in compromise to these connections regardless of dose.
MeSH term(s)	Child ; Humans ; White Matter/radiation effects ; Brain/diagnostic imaging ; Brain/pathology ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/radiotherapy ; Brain Neoplasms/pathology ; Cerebellar Neoplasms/radiotherapy ; Survivors ; Anisotropy
Language	English
Publishing date	2023-01-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2023.01.024
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Zs.A 1218: Show issues

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Article ; Online: Neurocognitive outcomes in pediatric brain tumors after treatment with proton versus photon radiation: a systematic review and meta-analysis.

Lassaletta, Álvaro / Morales, Javier S / Valenzuela, Pedro L / Esteso, Borja / Kahalley, Lisa S / Mabbott, Donald J / Unnikrishnan, Soumya / Panizo, Elena / Calvo, Felipe

World journal of pediatrics : WJP

2023 Volume 19, Issue 8, Page(s) 727–740

Abstract: Background: Advances in cancer treatments, particularly the development of radiation therapy, have led to improvements in survival outcomes in children with brain tumors. However, radiation therapy is associated with significant long-term neurocognitive ...

Abstract	Background: Advances in cancer treatments, particularly the development of radiation therapy, have led to improvements in survival outcomes in children with brain tumors. However, radiation therapy is associated with significant long-term neurocognitive morbidity. The present systematic review and meta-analysis aimed to compare the neurocognitive outcomes of children and adolescents with brain tumors treated with photon radiation (XRT) or proton therapy (PBRT). Methods: A systematic search was conducted (PubMed, Embase, Cochrane, and Web of Science from inception until 02/01/2022) for studies comparing the neurocognitive outcomes of children and adolescents with brain tumors treated with XRT vs. PBRT. The pooled mean differences (expressed as Z scores) were calculated using a random effects method for those endpoints analyzed by a minimum of three studies. Results: Totally 10 studies (n = 630 patients, average age range: 1-20 years) met the inclusion criteria. Patients who had received PBRT achieved significantly higher scores (difference in Z scores ranging from 0.29-0.75, all P < 0.05 and significant in sensitivity analyses) after treatment than those who had received XRT for most analyzed neurocognitive outcomes (i.e., intelligence quotient, verbal comprehension and perceptual reasoning indices, visual motor integration, and verbal memory). No robust significant differences (P > 0.05 in main analyses or sensitivity analyses) were found for nonverbal memory, verbal working memory and working memory index, processing speed index, or focused attention. Conclusions: Pediatric brain tumor patients who receive PBRT achieve significantly higher scores on most neurocognitive outcomes than those who receive XRT. Larger studies with long-term follow-ups are needed to confirm these results.
MeSH term(s)	Child ; Adolescent ; Humans ; Infant ; Child, Preschool ; Young Adult ; Adult ; Protons ; Brain Neoplasms/radiotherapy ; Brain Neoplasms/pathology ; Proton Therapy/adverse effects ; Proton Therapy/methods
Chemical Substances	Protons
Language	English
Publishing date	2023-05-08
Publishing country	Switzerland
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	2236681-7
ISSN	1867-0687 ; 1708-8569
ISSN (online)	1867-0687
ISSN	1708-8569
DOI	10.1007/s12519-023-00726-6
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Zs.A 6309: Show issues

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Article: Long-term neurocognitive and psychological outcomes in meningioma survivors: Individual changes over time and radiation dosimetry.

Sekely, Angela / Zakzanis, Konstantine K / Mabbott, Donald / Tsang, Derek S / Kongkham, Paul / Zadeh, Gelareh / Edelstein, Kim

Neuro-oncology practice

2023 Volume 11, Issue 2, Page(s) 157–170

Abstract: Background: This study investigates long-term changes in neurocognitive performance and psychological symptoms in meningioma survivors and associations with radiation dose to circumscribed brain regions.: Methods: We undertook a retrospective study ... ...

Abstract	Background: This study investigates long-term changes in neurocognitive performance and psychological symptoms in meningioma survivors and associations with radiation dose to circumscribed brain regions. Methods: We undertook a retrospective study of meningioma survivors who underwent longitudinal clinical neurocognitive assessments. Change in neurocognitive performance or psychological symptoms was assessed using reliable change indices. Radiation dosimetry, if prescribed, was evaluated based on treatment-planning computerized tomography co-registered with contrast-enhanced 3D T1-weighted magnetic resonance imaging. Mixed effects analyses were used to explore whether incidental radiation to brain regions outside the tumor influences neurocognitive and psychological outcomes. Results: Most (range = 41%-93%) survivors demonstrated stable-albeit often below average-neurocognitive and psychological trajectories, although some also exhibited improvements (range = 0%-31%) or declines (range = 0%-36%) over time. Higher radiation dose to the parietal-occipital region (partial Conclusions: Meningioma survivors experience neurocognitive deficits and psychological symptoms many years after diagnosis, and a proportion of them decline over time. This study offers proof of concept that incidental radiation to brain regions beyond the tumor site may contribute to these sequelae. Future investigations should include radiation dosimetry when examining risk factors that contribute to the quality of survivorship in this growing population.
Language	English
Publishing date	2023-11-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2768945-1
ISSN	2054-2585 ; 2054-2577
ISSN (online)	2054-2585
ISSN	2054-2577
DOI	10.1093/nop/npad072
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Article ; Online: Delayed oculomotor response associates with optic neuritis in youth with demyelinating disorders.

Huang, Jeff / Brien, Donald / Coe, Brian C / Longoni, Giulia / Mabbott, Donald J / Munoz, Douglas P / Yeh, E Ann

Multiple sclerosis and related disorders

2023 Volume 79, Page(s) 104969

Abstract: Introduction: Impairment in visual and cognitive functions occur in youth with demyelinating disorders such as multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease. Quantitative ... ...

Abstract	Introduction: Impairment in visual and cognitive functions occur in youth with demyelinating disorders such as multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease. Quantitative behavioral assessment using eye-tracking and pupillometry can provide functional metrics for important prognostic and clinically relevant information at the bedside. Methods: Children and adolescents diagnosed with demyelinating disorders and healthy, age-matched controls completed an interleaved pro- and anti-saccade task using video-based eye-tracking and underwent spectral-domain optical coherence tomography examination for evaluation of retinal nerve fiber layer and ganglion cell inner plexiform layer thickness. Low-contrast visual acuity and Symbol Digit Modalities Test were performed for visual and cognitive functional assessments. We assessed saccade and pupil parameters including saccade reaction time, direction error rate, pupil response latency, peak constriction time, and peak constriction and dilation velocities. Generalized Estimating Equations were used to examine the association of eye-tracking parameters with optic neuritis history, structural metrics, and visual and cognitive scores. Results: The study included 36 demyelinating disorders patients, aged 8-18 yrs. (75% F; median = 15.22 yrs., SD = 2.8) and 34 age-matched controls (65% F; median = 15.26 yrs., SD = 2.3). Surprisingly, pro- and anti-saccade performance was comparable between patients and controls, whereas pupil control was altered in patients. Oculomotor latency measures were strongly associated with the number of optic neuritis episodes, including saccade reaction time, pupil response latency, and peak constriction time. Peak constriction time was associated with both retinal nerve fiber layer and ganglion cell inner plexiform layer thickness. Pupil response latency and peak constriction time were associated with visual acuity. Pupil velocity for both constriction and dilation was associated with Symbol Digit Modalities Test scores. Conclusion: The strong associations between oculomotor measures with history of optic neuritis, structural, visual, and cognitive assessments in these cohorts demonstrates that quantitative eye-tracking can be useful for probing demyelinating injury of the brain and optic nerve. Future studies should evaluate their utility in discriminating between demyelinating disorders and tracking disease progression.
MeSH term(s)	Child ; Humans ; Adolescent ; Optic Neuritis/complications ; Optic Neuritis/diagnostic imaging ; Optic Nerve ; Neuromyelitis Optica/diagnosis ; Retina ; Nerve Fibers ; Multiple Sclerosis/complications ; Multiple Sclerosis/diagnostic imaging ; Tomography, Optical Coherence
Language	English
Publishing date	2023-08-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2023.104969
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Article ; Online: Children's family income is associated with cognitive function and volume of anterior not posterior hippocampus.

Decker, Alexandra L / Duncan, Katherine / Finn, Amy S / Mabbott, Donald J

Nature communications

2020 Volume 11, Issue 1, Page(s) 4040

Abstract: Children from lower income backgrounds tend to have poorer memory and language abilities than their wealthier peers. It has been proposed that these cognitive gaps reflect the effects of income-related stress on hippocampal structure, but the empirical ... ...

Abstract	Children from lower income backgrounds tend to have poorer memory and language abilities than their wealthier peers. It has been proposed that these cognitive gaps reflect the effects of income-related stress on hippocampal structure, but the empirical evidence for this relationship has not been clear. Here, we examine how family income gaps in cognition relate to the anterior hippocampus, given its high sensitivity to stress, versus the posterior hippocampus. We find that anterior (but not posterior) hippocampal volumes positively correlate with family income up to an annual income of ~$75,000. Income-related differences in the anterior (but not posterior) hippocampus also predicted the strength of the gaps in memory and language. These findings add anatomical specificity to current theories by suggesting a stronger relationship between family income and anterior than posterior hippocampal volumes and offer a potential mechanism through which children from different income homes differ cognitively.
MeSH term(s)	Adolescent ; Child ; Child, Preschool ; Cognition/physiology ; Family ; Female ; Hippocampus/anatomy & histology ; Humans ; Image Processing, Computer-Assisted ; Income ; Linear Models ; Male ; Memory/physiology ; Minority Groups ; Organ Size ; Task Performance and Analysis ; Vocabulary ; Young Adult
Language	English
Publishing date	2020-08-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-17854-6
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