Multimodal Imaging Evidence for Axonal and Myelin Deterioration in Amnestic Mild Cognitive Impairment

White matter (WM) microstructural declines have been demonstrated in Alzheimer\u27s disease and amnestic mild cognitive impairment (aMCI). However, the pattern of WM microstructural changes in aMCI after controlling for WM atrophy is unknown. Here, we address this issue through joint consideration of aMCI alterations in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, as well as macrostructural volume in WM and gray matter compartments. Participants were 18 individuals with aMCI and 24 healthy seniors. Voxelwise analyses of diffusion tensor imaging data was carried out using tract-based spatial statistics (TBSS) and voxelwise analyses of high-resolution structural data was conducted using voxel based morphometry. After controlling for WM atrophy, the main pattern of TBSS findings indicated reduced fractional anisotropy with only small alterations in mean diffusivity/radial diffusivity/axial diffusivity. These WM microstructural declines bordered and/or were connected to gray matter structures showing volumetric declines. However, none of the potential relationships between WM integrity and volume in connected gray matter structures was significant, and adding fractional anisotropy information improved the classificatory accuracy of aMCI compared to the use of hippocampal atrophy alone. These results suggest that WM microstructural declines provide unique information not captured by atrophy measures that may aid the magnetic resonance imaging contribution to aMCI detection

Exchanging Equations: Anthropology as/beyond Symmetry

Peer reviewe

Radiological and surgical aspects of polymorphous low-grade neuroepithelial tumor of the young (PLNTY)

Background: Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a low-grade epilepsy-associated tumor recently introduced in WHO 2021 classification. Since it has been recognized as an independent nosological entity, PLNTY has been mainly studied from a genetic and molecular perspective, not recognizing unique characteristic clinical and radiological features. Methods: A systematic literature research has been conducted aiming to identify all relevant studies about the radiological, clinical and surgical features of PLNTY. We described a representative case of a 45-year-old man treated with awake-surgery with confirmed diagnosis of PLNTY, reporting the radiological and surgical characteristics through imaging and intra-operative video. We performed a statistical meta-analysis attempting to assess the presence of relationships between surgical and radiologic tumor characteristics and clinical outcome and type of surgery. Results: A total of 16 studies were included in the systematic review. The final cohort was composed of 51 patients. Extent of resection (EOR) and outcome are not significantly associated with the different genetic profiling (p = 1), the presence of cystic intralesional component, calcification (p = 0.85), contrast-enhancing and lesion boundaries (p = 0.82). No significant correlation there is between EOR and remission or better control of epilepsy-related symptoms (p = 0.38). The contrast enhancement in the tumor is significantly associated with recurrence or poor control of epileptic symptoms (p = 0.07). Conclusions: In PLNTYs, contrast enhancement seems to impact prognosis, recurrence, and seizure control much more than radiological features, genetic features and type of resection of the tumor

Music and musicality in brain surgery:The effect on delirium and language

Delirium is a neuropsychiatric clinical syndrome with overlapping symptoms withthe neurologic primary disease. This is why delirium is such a difficult and underexposedtopic in neurosurgical literature. Delirium is a complication which mightaffect recovery after brain surgery, hence we describe in Chapter 2 a systematicreview which focuses on how delirium is defined in the neurosurgical literature.We included twenty-four studies (5589 patients) and found no validation studiesof screening instruments in neurosurgical papers. Delirium screening instruments,validated in other cohorts, were used in 70% of the studies, consisting of theConfusion Assessment Method (- Intensive Care Unit) (45%), Delirium ObservationScreening Scale (5%), Intensive Care Delirium Screening Checklist (10%), Neelonand Champagne Confusion Scale (5%), and Nursing Delirium Screening Scale (5%).Incidence of post-operative delirium after intracranial surgery was 19%, ranging from12 – 26% caused by variation in clinical features and delirium assessment methods.Our review highlighted the need of future research on delirium in neurosurgery,which should focus on optimizing diagnosis, and assessing prognostic significanceand management.It is unclear what the impact of delirium is on the recovery after brain surgery,as delirium is often a self-limiting and temporary complication. In Chapter 3 wetherefore investigated the impact of delirium, by means of incidence and healthoutcomes, and identified independent risk factors by including 2901 intracranialsurgical procedures. We found that delirium was present in 19.4% with an averageonset (mean/SD) within 2.62/1.22 days and associated with more Intensive CareUnit (ICU) admissions and more discharge towards residential care. These numbersconfirm the impact of delirium with its incidence rates, which were in line with ourprevious systematic review, and significant health-related outcomes. We identifiedseveral independent non-modifiable risk factors such as age, pre-existing memoryproblems, emergency operations, and modifiable risk factors such as low preoperativepotassium and opioid and dexamethasone administration, which shed lighton the pathophysiologic mechanisms of POD in this cohort and could be targetedfor future intervention studies.10As listening to recorded music has been proven to lower delirium-eliciting factors inthe surgical population, such as pain, we were interested in the size of analgesic effectand its underlying mechanism before applying this into our clinical setting. In Chapter4 we describe the results of a two-armed experimental randomized controlled trial inwhich 70 participants received increasing electric stimuli through their non-dominantindex finger. This study was conducted within a unique pain model as participantswere blinded for the outcome. Participants in the music group received a 20-minutemusic intervention and participants in the control group a 20-minute resting period.Although the effect of the music intervention on pain endurance was not statisticallysignificant in our intention-to-treat analysis (p = 0.482, CI -0.85; 1.79), the subgroupanalyses revealed an increase in pain endurance in the music group after correcting fortechnical uncertainties (p = 0.013, CI 0.35; 2.85). This effect on pain endurance couldbe attributed to increased parasympathetic activation, as an increased Heart RateVariability (HRV) was observed in the music vs. the control group (p=0.008;0.032).As our prior chapters increased our knowledge on the significance of delirium on thepost-operative recovery after brain surgery and the possible beneficial effects of music,we decided to design a randomized controlled trial. In Chapter 5 we describe theprotocol and in Chapter 6 we describe the results of this single-centered randomizedcontrolled trial. In this trial we included 189 patients undergoing craniotomy andcompared the effects of music administered before, during and after craniotomy withstandard of clinical care. The primary endpoint delirium was assessed by the deliriumobservation screening scale (DOSS) and confirmed by a psychiatrist accordingto DSM-5 criteria. A variety of secondary outcomes were assessed to substantiatethe effects of music on delirium and its clinical implications. Our results supportthe efficacy of music in preventing delirium after craniotomy, as found with DOSS(OR:0.49, p=0.048) but not after DSM-5 confirmation (OR:0.47, p=0.342). Thispossible beneficial effect is substantiated by the effect of music on pre-operativeautonomic tone, measured with HRV (p=0.021;0.025), and depth of anesthesia(p=&lt;0.001;0.022). Our results fit well within the current literature and support theimplementation of music for the prevention of delirium within the neurosurgicalpopulation. However, delirium screening tools should be validated and the long-termimplications should be evaluated after craniotomy to assess the true impact of musicafter brain surgery.Musicality and language in awake brain surgeryIn the second part of this thesis, the focus swifts towards maintaining musicality andlanguage functions around awake craniotomy. Intra-operative mapping of languagedoes not ensure complete maintenance which mostly deteriorates after tumor resection.Most patients recover to their baseline whereas other remain to suffer from aphasiaaffecting their quality of life. The level of musical training might affect the speed andextend of postoperative language recovery, as increased white matter connectivity inthe corpus callosum is described in musicians compared to non-musicians. Hence,in Chapter 7 we evaluate the effect of musicality on language recovery after awakeglioma surgery in a cohort study of forty-six patients. We divided the patients intothree groups based on the musicality and compared the language scores between thesegroups. With the first study on this topic, we support that musicality protects againstlanguage decline after awake glioma surgery, as a trend towards less deterioration oflanguage was observed within the first three months on the phonological domain (p= 0.04). This seemed plausible as phonology shares a common hierarchical structurebetween language and singing. Moreover, our results support the hypothesis ofmusicality induced contralateral compensation in the (sub-) acute phase through thecorpus callosum as the largest difference of size was found in the anterior corpuscallosum in non- musicians compared to trained musicians (p = 0.02).In Chapter 8 we addressed musicality as a sole brain function and whether it canbe protected during awake craniotomy in a systematic review consisting of tenstudies and fourteen patients. Isolated music disruption, defined as disruption duringmusic tasks with intact language/speech and/or motor functions, was identified intwo patients in the right superior temporal gyrus, one patient in the right and onepatient in the left middle frontal gyrus and one patient in the left medial temporalgyrus. Pre-operative functional MRI confirmed these localizations in three patients.Assessment of post-operative musical function, only conducted in seven patients bymeans of standardized (57%) and non-standardized (43%) tools, report no loss ofmusical function. With these results we concluded that mapping music is feasibleduring awake craniotomy. Moreover, we identified certain brain regions relevant formusic production and detected no decline during follow-up, suggesting an addedvalue of mapping musicality during awake craniotomy. A systematic approach to mapmusicality should be implemented, to improve current knowledge on the added valueof mapping musicality during awake craniotomy.<br/

Music and musicality in brain surgery:The effect on delirium and language

Delirium is a neuropsychiatric clinical syndrome with overlapping symptoms withthe neurologic primary disease. This is why delirium is such a difficult and underexposedtopic in neurosurgical literature. Delirium is a complication which mightaffect recovery after brain surgery, hence we describe in Chapter 2 a systematicreview which focuses on how delirium is defined in the neurosurgical literature.We included twenty-four studies (5589 patients) and found no validation studiesof screening instruments in neurosurgical papers. Delirium screening instruments,validated in other cohorts, were used in 70% of the studies, consisting of theConfusion Assessment Method (- Intensive Care Unit) (45%), Delirium ObservationScreening Scale (5%), Intensive Care Delirium Screening Checklist (10%), Neelonand Champagne Confusion Scale (5%), and Nursing Delirium Screening Scale (5%).Incidence of post-operative delirium after intracranial surgery was 19%, ranging from12 – 26% caused by variation in clinical features and delirium assessment methods.Our review highlighted the need of future research on delirium in neurosurgery,which should focus on optimizing diagnosis, and assessing prognostic significanceand management.It is unclear what the impact of delirium is on the recovery after brain surgery,as delirium is often a self-limiting and temporary complication. In Chapter 3 wetherefore investigated the impact of delirium, by means of incidence and healthoutcomes, and identified independent risk factors by including 2901 intracranialsurgical procedures. We found that delirium was present in 19.4% with an averageonset (mean/SD) within 2.62/1.22 days and associated with more Intensive CareUnit (ICU) admissions and more discharge towards residential care. These numbersconfirm the impact of delirium with its incidence rates, which were in line with ourprevious systematic review, and significant health-related outcomes. We identifiedseveral independent non-modifiable risk factors such as age, pre-existing memoryproblems, emergency operations, and modifiable risk factors such as low preoperativepotassium and opioid and dexamethasone administration, which shed lighton the pathophysiologic mechanisms of POD in this cohort and could be targetedfor future intervention studies.10As listening to recorded music has been proven to lower delirium-eliciting factors inthe surgical population, such as pain, we were interested in the size of analgesic effectand its underlying mechanism before applying this into our clinical setting. In Chapter4 we describe the results of a two-armed experimental randomized controlled trial inwhich 70 participants received increasing electric stimuli through their non-dominantindex finger. This study was conducted within a unique pain model as participantswere blinded for the outcome. Participants in the music group received a 20-minutemusic intervention and participants in the control group a 20-minute resting period.Although the effect of the music intervention on pain endurance was not statisticallysignificant in our intention-to-treat analysis (p = 0.482, CI -0.85; 1.79), the subgroupanalyses revealed an increase in pain endurance in the music group after correcting fortechnical uncertainties (p = 0.013, CI 0.35; 2.85). This effect on pain endurance couldbe attributed to increased parasympathetic activation, as an increased Heart RateVariability (HRV) was observed in the music vs. the control group (p=0.008;0.032).As our prior chapters increased our knowledge on the significance of delirium on thepost-operative recovery after brain surgery and the possible beneficial effects of music,we decided to design a randomized controlled trial. In Chapter 5 we describe theprotocol and in Chapter 6 we describe the results of this single-centered randomizedcontrolled trial. In this trial we included 189 patients undergoing craniotomy andcompared the effects of music administered before, during and after craniotomy withstandard of clinical care. The primary endpoint delirium was assessed by the deliriumobservation screening scale (DOSS) and confirmed by a psychiatrist accordingto DSM-5 criteria. A variety of secondary outcomes were assessed to substantiatethe effects of music on delirium and its clinical implications. Our results supportthe efficacy of music in preventing delirium after craniotomy, as found with DOSS(OR:0.49, p=0.048) but not after DSM-5 confirmation (OR:0.47, p=0.342). Thispossible beneficial effect is substantiated by the effect of music on pre-operativeautonomic tone, measured with HRV (p=0.021;0.025), and depth of anesthesia(p=&lt;0.001;0.022). Our results fit well within the current literature and support theimplementation of music for the prevention of delirium within the neurosurgicalpopulation. However, delirium screening tools should be validated and the long-termimplications should be evaluated after craniotomy to assess the true impact of musicafter brain surgery.Musicality and language in awake brain surgeryIn the second part of this thesis, the focus swifts towards maintaining musicality andlanguage functions around awake craniotomy. Intra-operative mapping of languagedoes not ensure complete maintenance which mostly deteriorates after tumor resection.Most patients recover to their baseline whereas other remain to suffer from aphasiaaffecting their quality of life. The level of musical training might affect the speed andextend of postoperative language recovery, as increased white matter connectivity inthe corpus callosum is described in musicians compared to non-musicians. Hence,in Chapter 7 we evaluate the effect of musicality on language recovery after awakeglioma surgery in a cohort study of forty-six patients. We divided the patients intothree groups based on the musicality and compared the language scores between thesegroups. With the first study on this topic, we support that musicality protects againstlanguage decline after awake glioma surgery, as a trend towards less deterioration oflanguage was observed within the first three months on the phonological domain (p= 0.04). This seemed plausible as phonology shares a common hierarchical structurebetween language and singing. Moreover, our results support the hypothesis ofmusicality induced contralateral compensation in the (sub-) acute phase through thecorpus callosum as the largest difference of size was found in the anterior corpuscallosum in non- musicians compared to trained musicians (p = 0.02).In Chapter 8 we addressed musicality as a sole brain function and whether it canbe protected during awake craniotomy in a systematic review consisting of tenstudies and fourteen patients. Isolated music disruption, defined as disruption duringmusic tasks with intact language/speech and/or motor functions, was identified intwo patients in the right superior temporal gyrus, one patient in the right and onepatient in the left middle frontal gyrus and one patient in the left medial temporalgyrus. Pre-operative functional MRI confirmed these localizations in three patients.Assessment of post-operative musical function, only conducted in seven patients bymeans of standardized (57%) and non-standardized (43%) tools, report no loss ofmusical function. With these results we concluded that mapping music is feasibleduring awake craniotomy. Moreover, we identified certain brain regions relevant formusic production and detected no decline during follow-up, suggesting an addedvalue of mapping musicality during awake craniotomy. A systematic approach to mapmusicality should be implemented, to improve current knowledge on the added valueof mapping musicality during awake craniotomy.<br/

Rule(s) over regulation: the making of water reforms and regulatory cultures in Maharashtra, India.

This research focuses on how water sector reforms are unfolding in the state of Maharashtra, India. In 2005, Maharashtra launched an ambitious reform programme with support from the World Bank to establish an independent water regulator and make water user associations mandatory for water delivery in the state. The establishment of the regulator, the first of its kind in the Indian water sector, invited much attention from policy makers and civil society organisations after which several Indian states followed Maharashtra’s footsteps. Celebrated for its ‘independent’ and ‘apolitical’ virtues, this model of regulation was designed to provide answers to inefficiency and political opportunism in the water sector. What gained immense traction in the regulatory discourse was the concept of entitlements and the possibility of introducing water markets for ‘efficient’ pricing and distribution of water. To date, however, this reform project has faced reversals, limitations and subversions which have been described as ‘evolution’ by pro-reformers and ‘failures’ by the resisting groups. This thesis shows how a seemingly ‘apolitical' initiative aimed to dilute the authority of the State in the water sector is subverted to shape and reinforce its control. Though the idea of independent water regulator is increasingly getting mainstreamed into water policy discourses in India, divergent framings and rationales have made regulation a deeply contested political process. In Maharashtra, the turf war between politicians, the water resources department and the water regulator coupled with cases of corporate water grab lie at the heart of rule-making for regulation. This has made the authority of the water regulator and the meaning of regulation ambiguous and blurred. This ambiguity in turn shapes the distribution of water entitlements. In the sugarcane belt of Western Maharashtra where farmers access water from different sources, entitlements are shaped by persistent inequities in water distribution. They take on different meanings as they are subsumed into struggles over water control between the irrigation officials and the farmers on one hand, and amongst different groups of the farmers on the other. This struggle over meanings and practices across the reform process constitutes what I call “regulatory cultures” in this thesis. Using anthropological methods to study policy processes, this work shows how water regulation is discursively shaped and becomes a deeply political practice embedded in networks of power. These networks are formed at the intersection of donors, different layers of irrigation bureaucracy, water user associations and prosperous sugarcane farmers. I argue that the architecture of the Indian State, embedded in these very networks, is central to understanding the politics and practice of water regulation in Maharashtra

CEREBRAL ACTIVATION DURING THERMAL STIMULATION OF BURNING MOUTH DISORDER PATIENTS: AN fMRI STUDY

Functional magnetic resonance imaging (fMRI) has been widely used to study cortical and subcortical mechanisms related to pain. The pathophysiology of burning mouth disorder (BMD) is not clearly understood. Central neuropathic mechanisms are thought to be main players in BMD. This study aimed to compare the location and extension of brain activation following thermal stimulation of the trigeminal nerve with fMRI blood oxygenation level dependent (BOLD) signal. This study included 8 female patients with BMD and 8 matched pain-free volunteers. Qualitative and quantitative differences in brain activation patterns between the two study groups were demonstrated. There were differences in the activation maps regarding the location of activation, with patients displaying greater BOLD signal changes in the right anterior cingulate cortex (ACC BA 32/24) and bilateral precuneus (pandlt;0.005). The control group showed larger BOLD signal changes in the bilateral thalamus, right middle frontal gyrus, right pre-central gyrus, left lingual gyrus and cerebellum (pandlt;0.005). It was also demonstrated that patients had far less volumetric activation throughout the entire brain compared to the control group. These data are discussed in light of recent findings suggesting brain hypofunction as a key player in chronic neuropathic pain conditions

Risk Assessment by Pre-surgical Tractography in Left Hemisphere Low-Grade Gliomas

Background: Tracking the white matter principal tracts is routinely typically included during the pre-surgery planning examinations and has revealed to limit functional resection of low-grade gliomas (LGGs) in eloquent areas. Objective: We examined the integrity of the Superior Longitudinal Fasciculus (SLF) and Inferior Fronto-Occipital Fasciculus (IFOF), both known to be part of the language-related network in patients with LGGs involving the temporo-insular cortex. In a comparative approach, we contrasted the main quantitative fiber tracking values in the tumoral (T) and healthy (H) hemispheres to test whether or not this ratio could discriminate amongst patients with different post-operative outcomes. Methods: Twenty-six patients with LGGs were included. We obtained quantitative fiber tracking values in the tumoral and healthy hemispheres and calculated the ratio (HIFOF\u2013TIFOF)/HIFOF and the ratio (HSLF\u2013TSLF)/HSLF on the number of streamlines. We analyzed how these values varied between patients with and without post-operative neurological outcomes and between patients with different post-operative Engel classes. Results: The ratio for both IFOF and SLF significantly differed between patient with and without post-operative neurological language deficits. No associations were found between white matter structural changes and post-operative seizure outcomes. Conclusions: Calculating the ratio on the number of streamlines and fractional anisotropy between the tumoral and the healthy hemispheres resulted to be a useful approach, which can prove to be useful during the pre-operative planning examination, as it gives a glimpse on the potential clinical outcomes in patients with LGGs involving the left temporo-insular cortex