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Article ; Online: Fluency test generation and errors in focal frontal and posterior lesions.

Robinson, Gail A / Tjokrowijoto, Priscilla / Ceslis, Amelia / Biggs, Vivien / Bozzali, Marco / Walker, David G

2021 Volume 163, Page(s) 108085

Abstract: The number produced on fluency tasks is widely used to measure voluntary response generation. To further evaluate the relationship between generation, errors, and the area of anatomical damage we administered eight fluency tasks (word, design, gesture, ... ...

Abstract	The number produced on fluency tasks is widely used to measure voluntary response generation. To further evaluate the relationship between generation, errors, and the area of anatomical damage we administered eight fluency tasks (word, design, gesture, ideational) to a large group of focal frontal (n = 69) and posterior (n = 43) patients and controls (n = 150). Lesions were analysed by a finer-grained frontal localisation method, and traditional subdivisions (anterior/posterior, left/right frontal). Thus, we compared patients with Lateral lesions to patients with Medial lesions. Our results show that all fluency tasks are sensitive to frontal lobe damage for the number of correct responses and, for the first time, we provide evidence that seven fluency tasks show frontal sensitivity in terms of errors (perseverations, rule-breaks). Lateral (not Medial) patients produced the highest error rates, indicative of task-setting or monitoring difficulties. There was a right frontal effect for perseverative errors when retrieving known or stored items and rule-break errors when creating novel responses. Left lateral effects were specific to phonemic word fluency rule-breaks and perseverations for meaningless gesture fluency. In addition, our generation output and error findings support a frontal role in novelty processes. Finally, we confirm our previous generation findings suggesting critical roles of the superior medial region in energization and the left inferior frontal region in selection (Robinson et al., 2012). Overall, these results support the notion that frontal functions comprise a set of highly specialised cognitive processes, supported by distinct frontal regions.
MeSH term(s)	Frontal Lobe/diagnostic imaging ; Frontal Lobe/physiology ; Humans ; Mental Processes ; Neuropsychological Tests ; Prefrontal Cortex/pathology ; Verbal Behavior/physiology
Language	English
Publishing date	2021-11-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207151-4
ISSN	1873-3514 ; 0028-3932
ISSN (online)	1873-3514
ISSN	0028-3932
DOI	10.1016/j.neuropsychologia.2021.108085
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Article: Cognitive screening in brain tumors: short but sensitive enough?

Robinson, Gail A / Biggs, Vivien / Walker, David G

Frontiers in oncology

2015 Volume 5, Page(s) 60

Abstract: Cognitive deficits in brain tumors are generally thought to be relatively mild and non-specific, although recent evidence challenges this notion. One possibility is that cognitive screening tools are being used to assess cognitive functions but their ... ...

Abstract	Cognitive deficits in brain tumors are generally thought to be relatively mild and non-specific, although recent evidence challenges this notion. One possibility is that cognitive screening tools are being used to assess cognitive functions but their sensitivity to detect cognitive impairment may be limited. For improved sensitivity to recognize mild and/or focal cognitive deficits in brain tumors, neuropsychological evaluation tailored to detect specific impairments has been thought crucial. This study investigates the sensitivity of a cognitive screening tool, the Montreal Cognitive Assessment (MoCA), compared to a brief but tailored cognitive assessment (CA) for identifying cognitive deficits in an unselected primary brain tumor sample (i.e., low/high-grade gliomas, meningiomas). Performance is compared on broad measures of impairment: (a) number of patients impaired on the global screening measure or in any cognitive domain; and (b) number of cognitive domains impaired and specific analyses of MoCA-Intact and MoCA-Impaired patients on specific cognitive tests. The MoCA-Impaired group obtained lower naming and word fluency scores than the MoCA-Intact group, but otherwise performed comparably on cognitive tests. Overall, based on our results from patients with brain tumor, the MoCA has extremely poor sensitivity for detecting cognitive impairments and a brief but tailored CA is necessary. These findings will be discussed in relation to broader issues for clinical management and planning, as well as specific considerations for neuropsychological assessment of brain tumor patients.
Language	English
Publishing date	2015-03-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2015.00060
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Article ; Online: When does a strategy intervention overcome a failure of inhibition? Evidence from two left frontal brain tumour cases.

Robinson, Gail A / Walker, David G / Biggs, Vivien / Shallice, Tim

Cortex; a journal devoted to the study of the nervous system and behavior

2016 Volume 79, Page(s) 123–129

Abstract: Introduction: Initiation and inhibition of responses are crucial for appropriate behaviour across different settings. Initiation and inhibition difficulties are well documented following frontal damage, although task differences have limited our ... ...

Abstract	Introduction: Initiation and inhibition of responses are crucial for appropriate behaviour across different settings. Initiation and inhibition difficulties are well documented following frontal damage, although task differences have limited our understanding. The Hayling Sentence Completion Test was designed to assess verbal initiation and inhibition within the same task. This study investigates the ability of two patients with left frontal tumours (KI: high grade glioma; PM: meningioma) to use a strategy to overcome profound suppression failures on the Hayling Test. Method: KI and PM completed the Hayling Test and two experimental tasks. The Selection Investigation assessed verbal initiation on a sentence completion task that varied selection demands (high/low). The Suppression and Strategy Investigation assessed ability to implement four strategies aimed to override a suppression failure and facilitate production of an unconnected word. Results: On the Hayling Test, KI and PM initiated responses to complete high constraint sentences, in contrast to impaired suppression. KI benefitted minimally from strategies to overcome suppression failure although one strategy (object naming) was partially successful. KI's errors revealed fast suppression errors, in contrast to slow no responses, and selection ability was also impaired for verbal initiation. PM, however, implemented each strategy 100% to overcome a suppression failure and had no difficulty completing sentences meaningfully, regardless of selection demands. Conclusion: This first investigation of strategy implementation to overcome profound suppression impairments provides insights into verbal initiation, inhibition, selection and strategy mechanisms, which has implications for neurorehabilitation. Specifically, both patients had profound inhibition deficits but KI also presented with a selection deficit and was unable to implement a strategy. By contrast, PM's selection ability was intact but she was unable to generate, rather than implement, a strategy. We suggest that KI has both fast, uncontrolled semantic output and response inhibition difficulty, whereas PM's difficulty is underpinned by motivational factors.
MeSH term(s)	Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/pathology ; Brain Neoplasms/psychology ; Cognition/physiology ; Female ; Frontal Lobe/diagnostic imaging ; Frontal Lobe/pathology ; Humans ; Inhibition (Psychology) ; Language ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuropsychological Tests ; Reaction Time/physiology
Language	English
Publishing date	2016-06
Publishing country	Italy
Document type	Journal Article
ZDB-ID	280622-8
ISSN	1973-8102 ; 0010-9452
ISSN (online)	1973-8102
ISSN	0010-9452
DOI	10.1016/j.cortex.2016.03.011
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Article: Cytomegalovirus as a novel target for immunotherapy of glioblastoma multiforme.

Schuessler, Andrea / Walker, David G / Khanna, Rajiv

Frontiers in oncology

2014 Volume 4, Page(s) 275

Abstract: Progress in the treatment of glioblastoma multiforme (GBM) over the last few decades has remained marginal and GBM is still universally fatal with short survival times after initial diagnosis. Much research is focused on finding new therapeutics for GBM ... ...

Abstract	Progress in the treatment of glioblastoma multiforme (GBM) over the last few decades has remained marginal and GBM is still universally fatal with short survival times after initial diagnosis. Much research is focused on finding new therapeutics for GBM and immune-based approaches have shown great promise. The detection of cytomegalovirus (CMV) antigens in malignant cells has suggested that treatment strategies based on immunological intervention, such as adoptive transfer of antiviral T cells or vaccination with viral epitopes, could be exploited as cancer therapy. Here, we review the rationale for using CMV as a therapeutic target and discuss the first clinical evidence for safety and efficacy of CMV-specific cellular immunotherapy for GBM.
Language	English
Publishing date	2014-10-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2014.00275
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Article: Cellular immunotherapy directed against human cytomegalovirus as a novel approach for glioblastoma treatment.

Schuessler, Andrea / Walker, David G / Khanna, Rajiv

Oncoimmunology

2014 Volume 3, Page(s) e29381

Abstract: Glioblastoma multiforme (GBM) has a very poor prognosis, despite multimodal therapy including surgery, radiation and chemotherapy. A novel adoptive immunotherapy that exploits the presence of cytomegalovirus antigens in malignant brain cancer cells has ... ...

Abstract	Glioblastoma multiforme (GBM) has a very poor prognosis, despite multimodal therapy including surgery, radiation and chemotherapy. A novel adoptive immunotherapy that exploits the presence of cytomegalovirus antigens in malignant brain cancer cells has been shown to be safe and elicit potential clinical benefit for the treatment of recurrent GBM.
Language	English
Publishing date	2014-06-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-4011
ISSN (online)	2162-402X
ISSN	2162-4011
DOI	10.4161/onci.29381
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Article: Impact of pre-therapy glioblastoma multiforme microenvironment on clinical response to autologous CMV-specific T-cell therapy.

Walker, David G / Shakya, Reshma / Morrison, Beth / Neller, Michelle A / Matthews, Katherine K / Nicholls, John / Smith, Corey / Khanna, Rajiv

Clinical & translational immunology

2019 Volume 8, Issue 11, Page(s) e01088

Abstract: Objectives: Clinical response to antibody-based immunotherapies targeting checkpoint inhibitors is critically dependent on the tumor immune microenvironment (TIME). However, the precise impact of the TIME on adoptive cellular immunotherapy remains ... ...

Abstract	Objectives: Clinical response to antibody-based immunotherapies targeting checkpoint inhibitors is critically dependent on the tumor immune microenvironment (TIME). However, the precise impact of the TIME on adoptive cellular immunotherapy remains unexplored. Here we have conducted a long-term follow-up analysis of patients with recurrent glioblastoma multiforme (GBM) who were treated with autologous CMV-specific T-cell therapy to delineate the potential impact of the TIME on their clinical response. Methods: Multiplexed immunohistochemical analysis of CD3, PD-L1 and Sox-2 in GBM tissue biopsies obtained before autologous T-cell therapy was carried out and correlated with long-term survival of GBM patients adoptively treated with T-cell therapy. Results: Tumor microenvironment analyses revealed that the pre-treatment cellular composition of the tumor tissue may influence the subsequent response to adoptive T-cell therapy. GBM patients who showed prolonged overall survival following T-cell therapy had a significantly lower number of tumor-infiltrating CD3 Conclusion: We hypothesise that lack of PD-L1-mediated immunosuppression in the TIME may allow efficient immune control following adoptive T-cell therapy. Future studies combining anti-PD-L1 or genetically modified T cells with PD-1 receptor knockdown could be considered to improve clinical responses in patients who have high PD-L1 expression in their tumors.
Language	English
Publishing date	2019-11-05
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2694482-0
ISSN	2050-0068
ISSN	2050-0068
DOI	10.1002/cti2.1088
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Article ; Online: Progressive dysembryoplastic neuroepithelial tumour.

Alexander, Hamish / Tannenburg, Anthony / Walker, David G / Coyne, Terry

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia

2015 Volume 22, Issue 1, Page(s) 221–224

Abstract: Dysembryoplastic neuroepithelial tumour (DNET) is a benign tumour characterised by cortical location and presentation with drug resistant partial seizures in children. Recently the potential for malignant transformation has been reported, however ... ...

Abstract	Dysembryoplastic neuroepithelial tumour (DNET) is a benign tumour characterised by cortical location and presentation with drug resistant partial seizures in children. Recently the potential for malignant transformation has been reported, however progression without malignant transformation remains rare. We report a case of clinical and radiologic progression of a DNET in a girl 10 years after initial biopsy.
MeSH term(s)	Adolescent ; Biopsy ; Brain Neoplasms/pathology ; Brain Neoplasms/surgery ; Disease Progression ; Female ; Humans ; Magnetic Resonance Imaging ; Neoplasms, Neuroepithelial/pathology ; Neoplasms, Neuroepithelial/surgery ; Neurosurgical Procedures/methods ; Seizures/drug therapy ; Seizures/etiology
Language	English
Publishing date	2015-01
Publishing country	Scotland
Document type	Case Reports ; Journal Article
ZDB-ID	1193674-5
ISSN	1532-2653 ; 0967-5868
ISSN (online)	1532-2653
ISSN	0967-5868
DOI	10.1016/j.jocn.2014.07.022
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Article: CONDYLAR RESORPTION IN PATIENTS WITH TMD.

Cevidanes, Lucia H / Walker, David G / Styner, Martin / Lim, Pei Feng

Craniofacial growth series

2014 Volume 46, Page(s) 147–157

Abstract: The objective of this study is to determine the nature of the difference between condyle morphology of osteoarthritic temporomandibular joint (TMJ) and non-osteoarthritic TMJ, using 3D surface models constructed from cone-beam CT (CBCT) images. Three- ... ...

Abstract	The objective of this study is to determine the nature of the difference between condyle morphology of osteoarthritic temporomandibular joint (TMJ) and non-osteoarthritic TMJ, using 3D surface models constructed from cone-beam CT (CBCT) images. Three-dimensional Shape Correspondence was used to localize and quantify condylar morphological differences of 20 patients with RDC/TMD group III (arthralgia, arthritis, arthrosis) compared to 40 asymptomatic subjects. Three-dimensional models of right and left condyles for each subject were constructed from CBCT images and shape analysis performed using the publicly available SPHARM-PDM software. The right and left condyles were normalized using rigid Procrustes alignment to an overall mean condylar surface per group. The mean differences between groups were compared using the Hotelling T2 analysis with permutation-test derived p-values, corrected for False Discovery Rate. The differences between the group mean surfaces were visualized with color-coded magnitude and difference vectors. The condylar morphology of the TMD group was statistically significantly different from the asymptomatic group (p = 0.05, average surface distance differences of 1.9 mm for the right condyles and 2.3 mm for the left condyles). The average condylar morphology in the TMD patients showed resorption of the anterior surface of the lateral pole and flattening of the articular surface compared to the mean morphology in asymptomatic subjects. The condylar morphology and condylar dimensions of the TMD patients were different, on average, from those of the asymptomatic subjects. The preliminary findings in this cross-sectional study will lead to future investigations to elucidate osteoarthritic changes in TMD and their role in the pathophysiology of TMD. Supported by NIDCR DE017727.
Language	English
Publishing date	2014-11-20
Publishing country	United States
Document type	Journal Article
ISSN	0162-7279
ISSN	0162-7279
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Article ; Online: Selective preservation of the beat in apperceptive music agnosia: a case study.

Baird, Amee D / Walker, David G / Biggs, Vivien / Robinson, Gail A

Cortex; a journal devoted to the study of the nervous system and behavior

2014 Volume 53, Page(s) 27–33

Abstract: Introduction: Music perception involves processing of melodic, temporal and emotional dimensions that have been found to dissociate in healthy individuals and after brain injury. Two components of the temporal dimension have been distinguished, namely ... ...

Abstract	Introduction: Music perception involves processing of melodic, temporal and emotional dimensions that have been found to dissociate in healthy individuals and after brain injury. Two components of the temporal dimension have been distinguished, namely rhythm and metre. We describe an 18 year old male musician 'JM' who showed apperceptive music agnosia with selectively preserved metre perception, and impaired recognition of sad and peaceful music relative to age and music experience matched controls after resection of a right temporoparietal tumour. Method: Two months post-surgery JM underwent a comprehensive neuropsychological evaluation including assessment of his music perception abilities using the Montreal Battery for Evaluation of Amusia (MBEA, Peretz, Champod, & Hyde, 2003). He also completed several experimental tasks to explore his ability to recognise famous songs and melodies, emotions portrayed by music and a broader range of environmental sounds. Five age-, gender-, education- and musical experienced-matched controls were administered the same experimental tasks. Results: JM showed selective preservation of metre perception, with impaired performances compared to controls and scoring below the 5% cut-off on all MBEA subtests, except for the metric condition. He could identify his favourite songs and environmental sounds. He showed impaired recognition of sad and peaceful emotions portrayed in music relative to controls but intact ability to identify happy and scary music. Conclusion: This case study contributes to the scarce literature documenting a dissociation between rhythmic and metric processing, and the rare observation of selectively preserved metric interpretation in the context of apperceptive music agnosia. It supports the notion that the anterior portion of the superior temporal gyrus (STG) plays a role in metric processing and provides the novel observation that selectively preserved metre is sufficient to identify happy and scary, but not sad or peaceful emotions portrayed in music.
MeSH term(s)	Adolescent ; Agnosia/psychology ; Auditory Perception/physiology ; Brain Neoplasms/complications ; Brain Neoplasms/psychology ; Brain Neoplasms/surgery ; Cognition/physiology ; Craniotomy/adverse effects ; Humans ; Male ; Music/psychology ; Neurologic Examination ; Neuropsychological Tests ; Oligodendroglioma/complications ; Oligodendroglioma/psychology ; Oligodendroglioma/surgery ; Postoperative Complications/psychology ; Recognition (Psychology)/physiology
Language	English
Publishing date	2014-04
Publishing country	Italy
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	280622-8
ISSN	1973-8102 ; 0010-9452
ISSN (online)	1973-8102
ISSN	0010-9452
DOI	10.1016/j.cortex.2014.01.005
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Article: Neuropsychological assessment of individuals with brain tumor: comparison of approaches used in the classification of impairment.

Dwan, Toni Maree / Ownsworth, Tamara / Chambers, Suzanne / Walker, David G / Shum, David H K

Frontiers in oncology

2015 Volume 5, Page(s) 56

Abstract: Approaches to classifying neuropsychological impairment after brain tumor vary according to testing level (individual tests, domains, or global index) and source of reference (i.e., norms, controls, and pre-morbid functioning). This study aimed to ... ...

Abstract	Approaches to classifying neuropsychological impairment after brain tumor vary according to testing level (individual tests, domains, or global index) and source of reference (i.e., norms, controls, and pre-morbid functioning). This study aimed to compare rates of impairment according to different classification approaches. Participants were 44 individuals (57% female) with a primary brain tumor diagnosis (mean age = 45.6 years) and 44 matched control participants (59% female, mean age = 44.5 years). All participants completed a test battery that assesses pre-morbid IQ (Wechsler adult reading test), attention/processing speed (digit span, trail making test A), memory (Hopkins verbal learning test-revised, Rey-Osterrieth complex figure-recall), and executive function (trail making test B, Rey-Osterrieth complex figure copy, controlled oral word association test). Results indicated that across the different sources of reference, 86-93% of participants were classified as impaired at a test-specific level, 61-73% were classified as impaired at a domain-specific level, and 32-50% were classified as impaired at a global level. Rates of impairment did not significantly differ according to source of reference (p > 0.05); however, at the individual participant level, classification based on estimated pre-morbid IQ was often inconsistent with classification based on the norms or controls. Participants with brain tumor performed significantly poorer than matched controls on tests of neuropsychological functioning, including executive function (p = 0.001) and memory (p < 0.001), but not attention/processing speed (p > 0.05). These results highlight the need to examine individuals' performance across a multi-faceted neuropsychological test battery to avoid over- or under-estimation of impairment.
Language	English
Publishing date	2015-03-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2015.00056
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