Multimodal mapping and monitoring is beneficial during awake craniotomy for intra-cranial tumours: results of a dual centre retrospective study.

BACKGROUND: The combination of awake craniotomy with multimodal neurophysiological mapping and monitoring in intra-axial tumour resection is not well described, but may have theoretical benefits which we sought to investigate. METHODS: All patients undergoing awake craniotomy for tumour resection with cortical and/or subcortical stimulation together with one or more of electrocorticography (ECoG/EEG), motor or somatosensory evoked potentials were identified from the operative records of two surgeons at two centres over a 5 year period. Patient, operative and outcome data were collated. Statistical analysis was performed to evaluate factors predictive of intra-operative seizures and surgical outcomes. RESULTS: 83 patients with a median age 50 years (18-80 years) were included. 80% had gliomas (37% low grade) and 13% metastases. Cortical mapping was negative in 35% (language areas) and 24% (motor areas). Complete or near total resection was achieved in 80% with 5% severe long-term neurological deficits. Negative cortical mapping was combined with positive subcortical mapping in 42% with no significant difference in extent of resection rates to patients undergoing positive cortical mapping (p = 0.95). Awake mapping could not be completed in 14%, but with no compromise to extent of resection (p = 0.55) or complication rates (p = 0.09). Intraoperative seizures occurred in 11% and were significantly associated with intra-operative EEG spikes (p = 0.003). CONCLUSIONS: Awake multi-modal monitoring is a safe and well tolerated technique. It provides preservation of extent of resection and clinical outcomes in cases of aborted awake craniotomy. Negative cortical mapping in combination with positive subcortical mapping was also shown to be safe, although not hitherto well described. Electrocorticography further enables the differentiation of seizure activity from true positive mapping, and the successful treatment of spikes prior to full clinical seizures occurring.

Awake brain surgery for autistic patients: Is it possible?

Background: Awake neurosurgery is currently the mainstay for eloquent brain lesions. Opting for an awake operation is affected by a number of patient-related factors. We present a case of a patient with autistic spectrum disorder (ASD) that was successfully operated for a brain tumor through awake craniotomy. To the best of our knowledge, this is the first reported case in the literature. Case Description: A 42-year-old patient, with known ASD since his childhood, underwent awake craniotomy for a left supplementary motor area tumor. Detailed preoperative preparation of the patient was done to identify special requirements and establish a good patient-team relationship. Intraoperatively, continuous language and motor testing were performed. Conversation and music were the main distractors used. Throughout the operation, the patient remained calm and cooperative, even during a focal seizure. Mapping allowed for >80% resection of the tumor. Postoperatively, the patient recovered without any deficits. Conclusion: This case shows that with growing experience and meticulous preparation, the limits of awake craniotomy can be expanded to include more patients that were previously considered unfit.

Awake craniotomy in the COVID-19 era - technical tips and feasibility.

There has been a growing anxiety in carrying out awake craniotomy surgeries during the SARS-CoV-2 pandemic, not only due to airway management but also close proximity to the team in theatre. We set out to safely perform the first documented awake craniotomy in the UK since the beginning of lockdown. We performed a thorough workup of the patient with minimal hospital visits, using remote communication wherever possible. We modified our existing awake craniotomy protocol/technique guided by local/national policies. An asleep-awake-asleep craniotomy for tumour resection was performed successfully without compromising patient and staff safety with excellent post-operative outcome. With appropriate pre- and peri-operative modifications to established protocols, awake craniotomies with functional mapping can be safely carried out. By incorporating novel aspects to our technique, we believe that this service can safely resume in carefully selected patients.

Semantic memory is impaired in patients with unilateral anterior temporal lobe resection for temporal lobe epilepsy.

Contemporary clinical and basic neuroscience studies have increasingly implicated the anterior temporal lobe regions, bilaterally, in the formation of coherent concepts. Mounting convergent evidence for the importance of the anterior temporal lobe in semantic memory is found in patients with bilateral anterior temporal lobe damage (e.g. semantic dementia), functional neuroimaging and repetitive transcranial magnetic stimulation studies. If this proposal is correct, then one might expect patients with anterior temporal lobe resection for long-standing temporal lobe epilepsy to be semantically impaired. Such patients, however, do not present clinically with striking comprehension deficits but with amnesia and variable anomia, leading some to conclude that semantic memory is intact in resection for temporal lobe epilepsy and thus casting doubt over the conclusions drawn from semantic dementia and linked basic neuroscience studies. Whilst there is a considerable neuropsychological literature on temporal lobe epilepsy, few studies have probed semantic memory directly, with mixed results, and none have undertaken the same type of systematic investigation of semantic processing that has been conducted with other patient groups. In this study, therefore, we investigated the semantic performance of 20 patients with resection for chronic temporal lobe epilepsy with a full battery of semantic assessments, including more sensitive measures of semantic processing. The results provide a bridge between the current clinical observations about resection for temporal lobe epilepsy and the expectations from semantic dementia and other neuroscience findings. Specifically, we found that on simple semantic tasks, the patients' accuracy fell in the normal range, with the exception that some patients with left resection for temporal lobe epilepsy had measurable anomia. Once the semantic assessments were made more challenging, by probing specific-level concepts, lower frequency/more abstract items or measuring reaction times on semantic tasks versus those on difficulty-matched non-semantic assessments, evidence of a semantic impairment was found in all individuals. We conclude by describing a unified, computationally inspired framework for capturing the variable degrees of semantic impairment found across different patient groups (semantic dementia, temporal lobe epilepsy, glioma and stroke) as well as semantic processing in neurologically intact participants.

The differential contributions of pFC and temporo-parietal cortex to multimodal semantic control: exploring refractory effects in semantic aphasia.

Aphasic patients with multimodal semantic impairment following pFC or temporo-parietal (TP) cortex damage (semantic aphasia [SA]) have deficits characterized by poor control of semantic activation/retrieval, as opposed to loss of semantic knowledge per se. In line with this, SA patients show "refractory effects"; that is, declining accuracy in cyclical word-picture matching tasks when semantically related sets are presented rapidly and repeatedly. This is argued to follow a build-up of competition between targets and distractors. However, the link between poor semantic control and refractory effects is still controversial for two reasons. (1) Some theories propose that refractory effects are specific to verbal or auditory tasks, yet SA patients show poor control over semantic processing in both word and picture semantic tasks. (2) SA can result from lesions to either the left pFC or TP cortex, yet previous work suggests that refractory effects are specifically linked to the left inferior frontal cortex. For the first time, verbal, visual, and nonverbal auditory refractory effects were explored in nine SA patients who had pFC (pFC+) or TP cortex (TP-only) lesions. In all modalities, patient accuracy declined significantly over repetitions. This refractory effect at the group level was driven by pFC+ patients and was not shown by individuals with TP-only lesions. These findings support the theory that SA patients have reduced control over multimodal semantic retrieval and, additionally, suggest there may be functional specialization within the posterior versus pFC elements of the semantic control network.

Relearning in semantic dementia reflects contributions from both medial temporal lobe episodic and degraded neocortical semantic systems: evidence in support of the complementary learning systems theory.

When relearning words, patients with semantic dementia (SD) exhibit a characteristic rigidity, including a failure to generalise names to untrained exemplars of trained concepts. This has been attributed to an over-reliance on the medial temporal region which captures information in sparse, non-overlapping and therefore rigid representations. The current study extends previous investigations of SD relearning by re-examining the additional contribution made by the degraded cortical semantic system. The standard relearning protocol was modified by careful selection of foils to show that people with semantic dementia were sometimes able to extend their learning appropriately but that this correct generalisation was minimal (i.e. the patients under-generalised their learning). The revised assessment procedure highlighted the fact that, after relearning, the participants also incorrectly over-generalised the learned label to closely related concepts. It is unlikely that these behaviours would occur if the participants had only formed sparse hippocampal representations. These novel data build on the notion that people with semantic dementia engage both the degraded cortical semantic (neocortex) and the episodic (medial temporal) systems to learn. Because of neocortical damage to the anterior temporal lobes, relearning is disordered with a characteristic pattern of under- and over-generalisation.

Phonological learning in semantic dementia.

Patients with semantic dementia (SD) have anterior temporal lobe (ATL) atrophy that gives rise to a highly selective deterioration of semantic knowledge. Despite pronounced anomia and poor comprehension of words and pictures, SD patients have well-formed, fluent speech and normal digit span. Given the intimate connection between phonological STM and word learning revealed by both neuropsychological and developmental studies, SD patients might be expected to show good acquisition of new phonological forms, even though their ability to map these onto meanings is impaired. In contradiction of these predictions, a limited amount of previous research has found poor learning of new phonological forms in SD. In a series of experiments, we examined whether SD patient, GE, could learn novel phonological sequences and, if so, under which circumstances. GE showed normal benefits of phonological knowledge in STM (i.e., normal phonotactic frequency and phonological similarity effects) but reduced support from semantic memory (i.e., poor immediate serial recall for semantically degraded words, characterised by frequent item errors). Next, we demonstrated normal learning of serial order information for repeated lists of single-digit number words using the Hebb paradigm: these items were well-understood allowing them to be repeated without frequent item errors. In contrast, patient GE showed little learning of nonsense syllable sequences using the same Hebb paradigm. Detailed analysis revealed that both GE and the controls showed a tendency to learn their own errors as opposed to the target items. Finally, we showed normal learning of phonological sequences for GE when he was prevented from repeating his errors. These findings confirm that the ATL atrophy in SD disrupts phonological processing for semantically degraded words but leaves the phonological architecture intact. Consequently, when item errors are minimised, phonological STM can support the acquisition of new phoneme sequences in patients with SD.

Different impairments of semantic cognition in semantic dementia and semantic aphasia: evidence from the non-verbal domain.

Disorders of semantic cognition in different neuropsychological conditions result from diverse areas of brain damage and may have different underlying causes. This study used a comparative case-series design to examine the hypothesis that relatively circumscribed bilateral atrophy of the anterior temporal lobe in semantic dementia (SD) produces a gradual degradation of core semantic representations, whilst a deficit of cognitive control produces multi-modal semantic impairment in a subset of patients with stroke aphasia following damage involving the left prefrontal cortex or regions in and around the temporoparietal area; this condition, which transcends traditional aphasia classifications, is referred to as 'semantic aphasia' (SA). There have been very few direct comparisons of these patient groups to date and these previous studies have focussed on verbal comprehension. This study used a battery of object-use tasks to extend this line of enquiry into the non-verbal domain for the first time. A group of seven SA patients were identified who failed both word and picture versions of a semantic association task. These patients were compared with eight SD cases. Both groups showed significant deficits in object use but these impairments were qualitatively different. Item familiarity correlated with performance on object-use tasks for the SD group, consistent with the view that core semantic representations are degrading in this condition. In contrast, the SA participants were insensitive to the familiarity of the objects. Further, while the SD patients performed consistently across tasks that tapped different aspects of knowledge and object use for the same items, the performance of the SA participants reflected the control requirements of the tasks. Single object use was relatively preserved in SA but performance on complex mechanical puzzles was substantially impaired. Similarly, the SA patients were able to complete straightforward item matching tasks, such as word-picture matching, but performed more poorly on associative picture-matching tasks, even when the tests involved the same items. The two groups of patients also showed a different pattern of errors in object use. SA patients made substantial numbers of erroneous intrusions in their demonstrations, such as inappropriate object movements. In contrast, response omissions were more common in SD. This study provides converging evidence for qualitatively different impairments of semantic cognition in SD and SA, and uniquely demonstrates this pattern in a non-verbal expressive domain-object use.

Selective short-term memory deficits arise from impaired domain-general semantic control mechanisms.

Semantic short-term memory (STM) patients have a reduced ability to retain semantic information over brief delays but perform well on other semantic tasks; this pattern suggests damage to a dedicated buffer for semantic information. Alternatively, these difficulties may arise from mild disruption to domain-general semantic processes that have their greatest impact on demanding STM tasks. In this study, mild semantic processing impairments were demonstrated in 2 semantic STM patients. They performed well on untimed semantic tasks but were deficient in accuracy and reaction times on speeded tasks. Demanding semantic production tasks were also affected. These patients were compared with a case series of individuals with semantic aphasia whose multimodal semantic difficulties stemmed from poor cognitive control. STM and semantic performance were more impaired in this group, but there were qualitative similarities to the semantic STM patients. The difference between the 2 patient types may be a matter of degree. In semantic aphasia, severe disruption to semantic control leads to global semantic impairments, whereas in semantic STM milder disruption might impact mainly on STM tests because of the high control demands of these tasks.

Semantic memory is key to binding phonology: converging evidence from immediate serial recall in semantic dementia and healthy participants.

Patients with semantic dementia (SD) make numerous phoneme migration errors when recalling lists of words they no longer fully understand, suggesting that word meaning makes a critical contribution to phoneme binding in verbal short-term memory. Healthy individuals make errors that appear similar when recalling lists of nonwords, which also lack semantic support. Although previous studies have assumed that the errors in these two groups stem from the same underlying cause, they have never been directly compared. We tackled this issue by examining immediate serial recall for SD patients and controls on "pure" word lists and "mixed" lists that contained a mixture of words and nonwords. SD patients were equally poor at pure and mixed lists and made numerous phoneme migration errors in both conditions. In contrast, controls recalled pure lists better than mixed lists and only produced phoneme migrations for mixed lists. We also examined the claim that semantic activation is critical for words in the primacy portion of the list. In fact, the effect of mixed lists was greatest for later serial positions in the control group and in the SD group recall was poorest towards the ends of lists. These results suggest that mixing nonwords with words in healthy participants closely mimics the impact of semantic degradation in SD on word list recall. The study provides converging evidence for the idea that lexical/semantic knowledge is an important source of constraint on phonological coherence, ensuring that phonemes in familiar words are bound to each other and emerge together in recall.