OBJECTIVE The modern management of patients with Koos grade IV vestibular schwannomas (VSs) aims at functional preservation and long-term tumor control. Gross-total resection (GTR) leads to optimal tumor control but frequently also results in permanent facial nerve (FN) palsy. Subtotal resection (STR) or near-total resection (NTR) followed by a waitand-scan protocol and second-line radiation therapy (RT) in case of progressive residuals yields excellent tumor control rates with less permanent morbidity. METHODS The authors present the results of their prospective cohort of Koos grade IV VS patients who underwent less-than-total resection followed by a wait-and-scan protocol between January 2009 and December 2019 and discuss the latest evidence on this controversial subject. The cohort was followed up with annual clinical and volumetric outcome analyses after standardized MRI. RESULTS Forty-eight patients were included in the analysis. The mean extent of resection was 87% (median 91%, range 45%-100%), best fitting into the definition of STR rather than NTR. In 2 cases, the proximal portion of the FN at the brainstem could not be reliably identified and monitored during the initial operation, and a second-stage resection was necessary. At 4.4 years after surgery, 81% (39/48) of the tumor residuals regressed or were stable in size. The percentage of regressive tumor residuals increased over time. Nineteen percent (9/48) of the tumor residuals displayed volumetric progression within a mean time of 35 months (median 36 months, range 14-72 months), resulting in a Kaplan-Meier estimate for progression-free survival of 79% after 4 years; higher postoperative volume showed a linear correlation with higher volumetric progression (factor 1.96, 95% CI 1.67-2.30; p < 0.001). Thirty-four of the 48 (71%) patients continue to undergo a wait-and-scan protocol. Second-line RT was performed in 14 patients (29%) within a mean time of 25 months (median 23 months, range 5-54 months), 12 (86%) of whom responded with post-RT pseudoprogression, resulting in an overall tumor control rate of 96%. At the 4.4-year follow-up from the initial resection, 92% of the patients had a good facial outcome (House-Brackmann [HB] grade I or II), 6% had a fair facial outcome (HB grade III), and 2% had a poor facial outcome (HB grades IV-VI). So far, there has been no need for salvage surgery after RT. CONCLUSIONS STR followed by observation and second-line RT in cases of progression leads to good facial outcome and an excellent tumor control rate in the longer term.

BACKGROUND The etiologies of parkinsonism are diverse. A possible and rare cause of hemiparkinsonism is mechanical compression of the basal ganglia and its connecting white matter tracts. The authors present a case of hemiparkinsonism caused by a lateral sphenoid wing meningioma, discuss the underlying pathophysiology based on tractography, and systematically review the existing literature. OBSERVATIONS A 59-year-old female was referred for a left-sided tremor of the hand, accompanied by a cogwheel rigidity of the left arm. Symptomatology appeared 1 year earlier and worsened in the previous 6 months, finally also showing involvement of the left leg. Magnetic resonance imaging (MRI) showed a space-occupying suspected meningioma originating from the right lateral sphenoid wing and compressing the ipsilateral striatum. Tractography studies contributed to elucidate the underlying pathophysiology. Resection of the meningioma could be performed without complications. At the 4-month follow-up, the patient’s hemiparkinsonism had completely recovered. LESSONS An intracranial space-occupying lesion may be a rare cause of hemiparkinsonism. In new-onset parkinsonism, especially if a secondary form is suspected, brain MRI should be performed promptly to avoid misdiagnosis and treatment. Tractography studies help understand the underlying pathophysiology. After surgical decompression of the affected structures, symptoms can recover completely.

Who has not experienced that sensation of losing the power of speech owing to an involuntary bout of laughter? An investigation of this phenomenon affords an insight into the neuronal processes that underlie laughter. In our functional magnetic resonance imaging study, participants were made to laugh by tickling in a first condition; in a second one they were requested to produce vocal utterances under the provocation of laughter by tickling. This investigation reveals increased neuronal activity in the sensorimotor cortex, the anterior cingulate gyrus, the insula, the nucleus accumbens, the hypothalamus and the periaqueductal grey for both conditions, thereby replicating the results of previous studies on ticklish laughter. However, further analysis indicates the activity in the emotion-associated regions to be lower when tickling is accompanied by voluntary vocalization. Here, a typical pattern of activation is identified, including the primary sensory cortex, a ventral area of the anterior insula and the ventral tegmental field, to which belongs to the nucleus ambiguus, namely, the common effector organ for voluntary and involuntary vocalizations. During the conflictual voluntary-vocalization versus laughter experience, the laughter-triggering network appears to rely heavily on a sensory and a deep interoceptive analysis, as well as on motor effectors in the brainstem. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.

-BACKGROUND: Several intraoperative imaging methods exist in cerebrovascular surgery to visualize and analyze the vascular anatomy flow. A new method based on mul-tispectral fluorescence (MFL) imaging of indocyanine green (ICG) video angiography (VA) allows real-time, augmented reality (AR) visualization of blood flow super-imposed on white-light microscopic images. We describe our single-center experience using MFL AR in cerebro-vascular surgery. -METHODS: Case descriptions are provided of cerebro-vascular surgery with intraoperative use of MFL AR images performed at our institution from June 2018 to April 2020. MFL superimposes the blood flow in real time on white -light microscopic images. We used MFL AR imaging as well as standard ICG-VA visualization and intraoperative digital subtraction angiography (DSA) as a control. -RESULTS: A total of 39 cases (33 aneurysm clippings, 4 arteriovenous malformations, and 2 external carotid-internal carotid bypass surgeries), were per-formed using MFL technology-based AR visualization of ICG. MFL AR imaging and DSA showed a high correlation concerning aneurysm occlusion and vessel patency. In arteriovenous malformation resection surgery, MFL AR imaging facilitated early identification of the feeding arteries and draining veins. Because of increased sensi-tivity of MFL AR, a reduced dose of ICG could be used, allowing repeated intraoperative imaging. There were no postoperative complications, side effects, or technical problems related to the use of MFL AR imaging. -CONCLUSIONS: MFL AR is an easy-to-use adjunct in cerebrovascular surgery and shows a high correlation with intraoperative DSA. No interruption of the surgery is necessary because MFL AR images of the blood flow are superimposed in real time on white-light microscopic images.

In analogy to the appreciation of humor, that of tickling is based upon the re-interpretation of an anticipated emotional situation. Hence, the anticipation of tickling contributes to the final outburst of ticklish laughter. To localize the neuronal substrates of this process, functional magnetic resonance imaging (fMRI) was conducted on 31 healthy volunteers. The state of anticipation was simulated by generating an uncertainty respecting the onset of manual foot tickling. Anticipation was characterized by an augmented fMRI signal in the anterior insula, the hypothalamus, the nucleus accumbens and the ventral tegmental area, as well as by an attenuated one in the internal globus pallidus. Furthermore, anticipatory activity in the anterior insula correlated positively with the degree of laughter that was produced during tickling. These findings are consistent with an encoding of the expected emotional consequences of tickling and suggest that early regulatory mechanisms influence, automatically, the laughter circuitry at the level of affective and sensory processing. Tickling activated not only those regions of the brain that were involved during anticipation, but also the posterior insula, the anterior cingulate cortex and the periaqueductal gray matter. Sequential or combined anticipatory and tickling-related neuronal activities may adjust emotional and sensorimotor pathways in preparation for the impending laughter response.

BACKGROUND:The goals of treating Koos grade IV vestibular schwannomas are to relieve brainstem compression, preserve or restore neurological function, and achieve long-term tumor control while minimizing tumor- and treatment-related morbidity. OBJECTIVE:To propose a treatment paradigm involving the intentional near-total removal of Koos grade IV vestibular schwannomas, in which a small amount of residual tumor is not dissected off the cisternal portion of the facial nerve. Patients are then followed by a wait-and-scan approach. Any subsequent volumetric progression of the residual tumor is treated with radiosurgery. METHODS:This is a case series of 44 consecutive unselected patients who underwent intended near-total resection of a Koos grade IV vestibular schwannoma through a retrosigmoid approach from January 2009 to December 2015. Pre- and postoperative volumetric analyses were performed on routine magnetic resonance imaging sequences (constructive interference in steady state and gadolinium-enhanced T1-weighted sequence). RESULTS:The mean preoperative tumor volume was 10.9 cm3. The mean extent of resection was 89%. At the last clinical follow-up, facial nerve function was good [House and Brackmann (HB) I-II] in 89%, fair (HB III) in 9%, and poor (HB IV-VI) in 2% of the patients. At the last radiological follow-up, the residual tumor had become smaller or remained the same size in 84% of patients. Volumetric progression was negatively correlated with the original extent of resection and positively correlated with postoperative residual tumor volume (P = .01, P < .001, respectively). CONCLUSION:Intended near-total removal results in excellent preservation of facial nerve function and has a low recurrence rate. Any progressive residual tumor may be treated by radiosurgery.

Objectives: To date the temporal resolution of the detection of almost simultaneously applied intranasal trigeminal stimuli is unknown. The aim of our study was to examine this temporal resolution in an/hyposmic subjects, who are known to have reduced trigeminal sensitivity and compare it with healthy controls. Methods: Participants were 20 posttraumatic an/hyposmic patients, and 23 healthy controls (matched with regard to sex and age). Olfactory function was tested psychophysically using the Sniffin' Sticks test battery. Bilateral trigeminal stimulation was carried out using a birhinal high-precision olfactometer. The trigeminal stimulus used was CO2 60% v/v, the interstimulus interval ranged from 28 to 32 s, stimulus duration was 200 ms. Time-lags tested between right and left side of stimulation were at 40, 80, 120, 160 and 200 ms. Subjects raised their left or right hand to indicate the side on which the stimulus had been perceived first. Results: In both groups the accuracy in the trigeminal lateralization task increased with the time-lag but normosmic subjects significantly outperformed an/hyposmics in the 200 ms time-lag condition. Normosmics significantly exceeded 50% chance level at the time-lag of 80 ms, whereas an/hyposmics were only able to score above chance starting from 120 ms time-lag. Lateralization scores significantly decreased with age. Conclusions: At a time lag of 200 ms intranasal trigeminal stimuli can be lateralized. The reduced trigeminal sensitivity in patients with anosmia or hyposmia leads to an increased time lag required for correct perception of intranasal, almost simultaneously, applied stimuli.

The insular cortex is fundamentally involved in the processing of interoceptive information. It has been postulated that the integrative monitoring of the bodily responses to environmental stimuli is crucial for the recognition and experience of emotions. Because emotional arousal is known to be closely coupled to functions of the anterior insula, we suspected laughter to be associated primarily with neuronal activity in this region. An anatomically constrained re-analysis of our imaging data pertaining to ticklish laughter, to inhibited ticklish laughter, and to voluntary laughter revealed regional differences in the levels of neuronal activity in the posterior and mid-/anterior portions of the insula. Ticklish laughter was associated specifically with right ventral anterior insular activity, which was not detected under the other two conditions. Hence, apparently, only laughter that is evoked as an emotional response bears the signature of autonomic arousal in the insular cortex.

OBJECTIVE: This study aims to examine humans ́ abilities to localize odorants within the open field. METHODOLOGY: Young participants were tested on a localization task using a relatively selective olfactory stimulus (2-phenylethyl-alcohol, PEA) and cineol, an odorant with a strong trigeminal component. Participants were blindfolded and had to localize an odorant source at 2 m distance (far-field condition) and a 0.4 m distance (near-field condition) with either two nostrils open or only one open nostril. RESULTS: For the odorant with trigeminal properties, the number of correct trials did not differ when one or both nostrils were used, while more PEA localization trials were correctly completed with both rather than one nostril. In the near-field condition, correct localization was possible in 72-80% of the trials, irrespective of the odorant and the number of nostrils used. Localization accuracy, measured as spatial deviation from the olfactory source, was significantly higher in the near-field compared to the far-field condition, but independent of the odorant being localized. CONCLUSION: Odorant localization within the open field is difficult, but possible. In contrast to the general view, humans seem to be able to exploit the two-nostril advantage with increasing task difficulty.

Early acquisition of a second language influences the development of language abilities and cognitive functions. In the present study, we used functional Magnetic Resonance Imaging (fMRI) to investigate the impact of early bilingualism on the organization of the cortical language network during sentence production. Two groups of adult multilinguals, proficient in three languages, were tested on a narrative task; early multilinguals acquired the second language before the age of three years, late multilinguals after the age of nine. All participants learned a third language after nine years of age. Comparison of the two groups revealed substantial differences in language-related brain activity for early as well as late acquired languages. Most importantly, early multilinguals preferentially activated a fronto-striatal network in the left hemisphere, whereas the left posterior superior temporal gyrus (pSTG) was activated to a lesser degree than in late multilinguals. The same brain regions were highlighted in previous studies when a non-target language had to be controlled. Hence the engagement of language control in adult early multilinguals appears to be influenced by the specific learning and acquisition conditions during early childhood. Remarkably, our results reveal that the functional control of early and subsequently later acquired languages is similarly affected, suggesting that language experience has a pervasive influence into adulthood. As such, our findings extend the current understanding of control functions in multilinguals.

The burst of laughter that is evoked by tickling is a primitive form of vocalization. It evolves during an early phase of postnatal life and appears to be independent of higher cortical circuits. Clinicopathological observations have led to suspicions that the hypothalamus is directly involved in the production of laughter. In this functional magnetic resonance imaging investigation, healthy participants were 1) tickled on the sole of the right foot with permission to laugh, 2) tickled but asked to stifle laughter, and 3) requested to laugh voluntarily. Tickling that was accompanied by involuntary laughter activated regions in the lateral hypothalamus, parietal operculum, amygdala, and right cerebellum to a consistently greater degree than did the 2 other conditions. Activation of the periaqueductal gray matter was observed during voluntary and involuntary laughter but not when laughter was inhibited. The present findings indicate that hypothalamic activity plays a crucial role in evoking ticklish laughter in healthy individuals. The hypothalamus promotes innate behavioral reactions to stimuli and sends projections to the periaqueductal gray matter, which is itself an important integrative center for the control of vocalization. A comparison of our findings with published data relating to humorous laughter revealed the involvement of a common set of subcortical centers.

Objectives Patients Patients with Parkinson s disease (PD) commonly show olfactory deficits in the early stages of the disease These deficits can be verified psychophysically or electrophysiologically using olfactory event-related potentials (OERP) While psychophysical olfactory function in PD patients can improve over time the course of OERPs in PD has not yet been investigatedMethods Olfactory function was investigated twice in 19 patients at 5-year intervals Psychophysical tests Included the Sniffin Sticks test battery In addition OERPs were recorded in response to two odors on each side (phenyl-ethyl-alcohol 40% (v/v) H2S 6 ppm) OERPs were evaluated regarding existence (yes/no) Average disease duration at follow-up was 90 years and the average Hoehn and Yahr score (disease stage) was 2 2Results Psychophysically 1 patient was normosmic 14 were hyposmic and 4 were functionally anosmic at the initial visit Re-examination revealed 1 normosmic 9 hyposmic and 8 functionally anosmic patients Mean olfactory function decreased significantly in all patients OERPs were initially existent in 3 out of 19 patients At follow-up OERPs were no longer present in these patients but were detectable in 3 other patientsConclusions Overall mean olfactory function decreased although improvements were observed at the individual level We confirmed previous findings regarding psychophysical follow-up results Electrophysiological measures showed a pattern of fluctuation in olfactory function comparable to that of the psychophysical results These fluctuations do not seem to predict the course of the disease (C) 2010 Elsevier Ireland Ltd All rights reserved

Olfactory dysfunction is a frequent nonmotor symptom in idiopathic Parkinson's disease (PD) and may be considered as an early clinical feature of the disease preceding motor symptoms by years. According to recent neuropathological staging concepts, impaired olfaction is assumed to indicate an early pathological process and might be associated with structural changes in the brain. A morphometric analysis of magnetic resonance images [voxel-based morphometry (VBM)] was used to investigate gray matter atrophy related to psychophysically measured scores of olfactory function in early PD patients ( n = 15, median Hoehn and Yahr stage 1.5), moderately advanced PD patients ( n = 12, median Hoehn and Yahr stage 2.5), and age-matched healthy controls ( n = 17). In PD patients, but not in controls, cortical atrophy in olfactory-related brain regions correlated specifically with olfactory dysfunction. Positive correlations between olfactory performance and gray matter volume were observed in the right piriform cortex in early PD patients and in the right amygdala in moderately advanced patients. The results provided first evidence that olfactory dysfunction in PD is related to atrophy in olfactory-eloquent regions of the limbic and paralimbic cortex. In addition, olfactory-correlated atrophy in these brain regions is consistent with the assumption that olfactory impairment as an early symptom of PD is likely to be associated with extranigral pathology.

Olfactory disorders are common in patients with idiopathic Parkinson's disease (IPD). In IPD patients with hyposmia olfactory event-related potentials (ERPs) are typically found to be delayed or absent. Altered ERPs in IPD patients may also be consistent with reduced neuronal activity in the medial temporal lobe following olfactory stimulation, as demonstrated by functional magnetic resonance imaging (fMRI). We analyzed ERPs and fMRI scans of hyposmic IPD patients (n=18) to gain further insight about the brain regions involved in generation of olfactory ERPs. Patients were separated into two groups (n=9 per group), based on the detectability (+) or non-detectability (−) of ERPs. Central activation during olfactory stimulation was examined using fMRI. Both ERP+ and ERP− patients showed activity in brain areas relevant to olfactory processing, such as the amygdala, parahippocampal regions, and temporal regions (BA 37, 21/22). Comparison of both groups revealed higher activation in ERP+ patients, especially in the amygdala, parahippocampal cortex, inferior frontal gyrus (BA 47), insula, cingulate gyrus, striatum, and inferior temporal gyrus. The relationship between the expression of olfactory ERPs and cortical activation patterns seen during olfactory stimulation in fMRI in IPD patients supports the idea that ERPs are a sensitive marker of neurodegeneration in olfactory regions. In accordance with current neuropathological staging concepts, olfactory ERPs may be reflecting pathological changes in olfactory regions, independent of the typically observed nigro-striatal degeneration in IPD. Reduced activation of primary olfactory areas in the ERP-group may reflect a severe disruption of olfactory processing in these patients.

Background: Olfactory dysfunction is a frequent non-motor symptom in Parkinson's disease (PD) and is considered to be an early manifestation of the disease. Objective: To establish the cortical basis of olfactory function in patients with PD. Method: Functional magnetic resonance imaging (fMRI) was used to investigate brain activity related to olfactory processing in patients with hyposmic PD at mild to moderate stages of the disease (n = 12, median Hoehn and Yahr stage 2.0) and in healthy, age-matched controls (n = 16) while passively perceiving a positively valenced (rose-like) odorant. Results: In both patients with PD and healthy controls, olfactory stimulation activated brain regions relevant for olfactory processing (ie the amygdaloid complex, lateral orbitofrontal cortex, striatum, thalamus, midbrain and the hippocampal formation). In controls, a bilateral activation of the amygdala and hippocampus was observed, whereas patients with PD involved these structures in the left hemisphere only. Group comparison showed that regions of higher activation in patients with PD were located bilaterally in the inferior frontal gyrus (BA 44/45) and anterior cingulate gyrus (BA 24/32), and the left dorsal and right ventral striatum. Conclusions: In patients with PD, results obtained under the specific conditions used suggest that neuronal activity in the amygdala and hippocampus is reduced. Assuming an impact on olfactory-related regions early in PD, our findings support the idea that selective impairment of these brain regions contributes to olfactory dysfunction. Furthermore, neuronal activity in components of the dopaminergic, cortico-striatal loops appears to be upregulated, indicating that compensatory processes are involved. This mechanism has not yet been demonstrated during olfactory processing in PD.