• Morphological alterations and microstructural changes are related to fatigue in multiple sclerosis • Thalamic alterations in particular were related to fatigue in early MS • Fatigued patients exhibited subjective but not measurable cognitive impairment • Compensatory processes help preserve or maintain cognitive performance but also contribute to fatigue.

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We previously reported speaking-related activity changes associated with assisted recovery induced by a fluency shaping therapy program and unassisted recovery from developmental stuttering (Kell et al., Brain 2009). While assisted recovery re-lateralized activity to the left hemisphere, unassisted recovery was specifically associated with the activation of the left BA 47/12 in the lateral orbitofrontal cortex. These findings suggested plastic changes in speakingrelated functional connectivity between left hemispheric speech network nodes. We reanalyzed these data involving 13 stuttering men before and after fluency shaping, 13 men who recovered spontaneously from their stuttering, and 13 male control participants, and examined functional connectivity during overt vs. covert reading by means of psychophysiological interactions computed across left cortical regions involved in articulation control. Persistent stuttering was associated with reduced auditory-motor coupling and enhanced integration of somatosensory feedback between the supramarginal gyrus and the prefrontal cortex. Assisted recovery reduced this hyper-connectivity and increased functional connectivity between the articulatory motor cortex and the auditory feedback processing anterior superior temporal gyrus. In spontaneous recovery, both auditory-motor coupling and integration of somatosensory feedback were normalized. In addition, activity in the left orbitofrontal cortex and superior cerebellum appeared uncoupled from the rest of the speech production network. These data suggest that therapy and spontaneous recovery normalizes the left hemispheric speaking-related activity via an improvement of auditory-motor mapping. By contrast, long-lasting unassisted recovery from stuttering is additionally supported by a functional isolation of the superior cerebellum from the rest of the speech production network, through the pivotal left BA 47/12. KeywordsPsychophysiological interactions; speech production; overt reading; auditorymotor interactions, left inferior frontal gyrus Corresponding AuthorChristian Kell To view all the submission files, including those not included in the PDF, click on the manuscript title on your EVISE Homepage, then click 'Download zip file'. We dealt with all their remarks, hopefully convincingly, and we hope that this version is now acceptable for publication. Order of Authors GOETHE UNIVERSITY FRANKFURT MEDICAL FACULTYYours faithfully, Christian Kell Response to ReviewersWe thank both reviewers for their careful evaluation of the manuscript. We have reanalyzed the data, updated all results, and re-written parts of the Introduction and Discussion based on their suggestions. Please find our answers below. Reviewer #1 INTRODUCTIONComment: The authors claim that "relapses are frequent" and "rarely adults who stutter recover spontaneously", "fluency induction due to scanner noise", and statements about subjects not entering a consistent "default mode". Can they provide citations for each of these statements? I have heard t...

CT improved functional deficits after visual field loss compared with standard OT and may be the intervention of choice during inpatient rehabilitation. A larger trial that includes lesion location in the analysis is recommended.

Human deep sleep is characterized by reduced sensory activity, responsiveness to stimuli, and conscious awareness. Given its ubiquity and reversible nature, it represents an attractive paradigm to study the neural changes which accompany the loss of consciousness in humans. In particular, the deepest stages of sleep can serve as an empirical test for the predictions of theoretical models relating the phenomenology of consciousness with underlying neural activity. A relatively recent shift of attention from the analysis of evoked responses toward spontaneous (or “resting state”) activity has taken place in the neuroimaging community, together with the development of tools suitable to study distributed functional interactions. In this review we focus on recent functional Magnetic Resonance Imaging (fMRI) studies of spontaneous activity during sleep and their relationship with theoretical models for human consciousness generation, considering the global workspace theory, the information integration theory, and the dynamical core hypothesis. We discuss the venues of research opened by these results, emphasizing the need to extend the analytic methodology in order to obtain a dynamical picture of how functional interactions change over time and how their evolution is modulated during different conscious states. Finally, we discuss the need to experimentally establish absent or reduced conscious content, even when studying the deepest sleep stages.

OBJECTIVE Despite the rising number of women in higher education and leadership positions, the proportional rise of female neurosurgeons still lags behind these fields. This study evaluates the gender distribution in German neurosurgical departments across all career levels, and is aimed at heightening the awareness of gender disparity and the need for improving gender equality and its related opportunities. METHODS Data on gender distribution across all professional levels in German neurosurgical departments were obtained from departmental websites as well as by email and telephone request. Results were additionally analyzed in reference to hospital ownership type of the neurosurgical departments. RESULTS A total of 140 German neurosurgical departments employing 2324 neurosurgeons were evaluated. The analysis revealed a clear preponderance of men in leadership positions. Only 9 (6.3%) of 143 department heads were women, and there were only 1 (2.4%), 17 (14.5%), and 4 (12.5%) women among 42 vice-directors, 117 chief senior physicians, and 32 managing senior physicians, respectively. Senior physicians not holding a leadership position were female in 23.1%, whereas board-certified neurosurgeons not holding a senior physician position and residents were female in 33.6% and 35.0%, respectively. Of note, the highest proportion of female department heads (15.6%) was found in private hospitals. CONCLUSIONS The number of women in leadership positions in German neurosurgical departments is dramatically low, and with increasing leadership status gender disparity increases. Mentorship, recruitment, the perception of benefits offered by diversity and programs facilitating gender equality, job sharing, parental leave policies, and onsite childcare programs are needed to turn German neurosurgical departments into modern medical departments reflecting the gender profile of the general patient population.

Due to anticipated postoperative neuropsychological sequelae, patients with gliomas infiltrating the corpus callosum rarely undergo tumor resection and mostly present in a poor neurological state. We aimed at investigating the benefit of glioma resection in the corpus callosum, hypothesizing neuropsychological deficits were mainly caused by tumor presence. Between 01/2017 and 1/2020, 21 patients who underwent glioma resection in the corpus callosum were prospectively enrolled into this study. Neuropsychological function was assessed preoperatively, before discharge and after 6 months. Gross total tumor resection was possible in 15 patients, and in 6 patients subtotal tumor resection with a tumor reduction of 97.7% could be achieved. During a median observation time of 12.6 months 9 patients died from glioblastoma after a median of 17 months. Preoperatively, all cognitive domains were affected in up to two thirds of patients, who presented a median KPS of 100% (range 60–100%). After surgery, the proportion of impaired patients increased in all neurocognitive domains. Most interestingly, after 6 months, significantly fewer patients showed impairments in attention, executive functioning, memory and depression, which are domains considered crucial for everyday functionality. Thus, the results of our study strongly support our hypothesis that in patients with gliomas infiltrating the corpus callosum the benefit of tumor resection might outweigh morbidity.

Background With refinements in diagnosis and therapy of gliomas, the importance of survival time as the sole outcome parameter has decreased, and patient-centered outcome parameters have gained interest. Pursuing a profession is an indispensable component of human happiness. The aim of this study was to analyze the professional outcomes besides their neuro-oncological and functional evaluation after surgery for gliomas in eloquent areas. Methods We assessed neuro-oncological and functional outcomes of patients with gliomas WHO grades II and III undergoing surgery between 2012 and 2018. All patients underwent routine follow-up and adjuvant treatment. Treatment and survival parameters were collected prospectively. Repercussions of the disease on the patients’ professional status, socio-economic situation, and neurocognitive function were evaluated retrospectively with questionnaires. Results We analyzed data of 58 patients with gliomas (WHO II: 9; III: 49). Median patient age was 35.8 years (range 21–63 years). Awake surgery techniques were applied in 32 patients (55.2%). Gross total and subtotal tumor resections were achieved in 33 (56.9%) and 17 (29.3%) patients, respectively, whereas in 8 patients (13.8%) resection had to remain partial. Most patients (n = 46; 79.3%) received adjuvant treatment. Median follow up was 43.8 months (range 11–82 months). After treatment 41 patients (70.7%) were able to resume a working life. Median time until returning to work was 8.0 months (range 0.2–22.0 months). To be younger than 40 at the time of the surgery was associated with a higher probability to return to work (p < .001). Multivariable regression analysis showed that patient age < 40 years as well as occupational group and self-reported fatigue were factors independently associated with the ability to return to work. Conclusion The ability to resume professional activities following brain tumor surgery is an important patient-oriented outcome parameter. We found that the majority of patients with gliomas were able to return to work following surgical and adjuvant treatment. Preservation of neurological function is of utmost relevance for individual patients´ quality of life.