Combining Stochastic Tendency and Distribution Overlap Towards Improved Nonparametric Effect Measures and Inference

A fundamental functional in nonparametric statistics is the Mann-Whitney functional ${\theta} = P (X < Y )$ , which constitutes the basis for the most popular nonparametric procedures. The functional ${\theta}$ measures a location or stochastic tendency effect between two distributions. A limitation of ${\theta}$ is its inability to capture scale differences. If differences of this nature are to be detected, specific tests for scale or omnibus tests need to be employed. However, the latter often suffer from low power, and they do not yield interpretable effect measures. In this manuscript, we extend ${\theta}$ by additionally incorporating the recently introduced distribution overlap index (nonparametric dispersion measure) $I_2$ that can be expressed in terms of the quantile process. We derive the joint asymptotic distribution of the respective estimators of ${\theta}$ and $I_2$ and construct confidence regions. Extending the Wilcoxon- Mann-Whitney test, we introduce a new test based on the joint use of these functionals. It results in much larger consistency regions while maintaining competitive power to the rank sum test for situations in which {\theta} alone would suffice. Compared with classical omnibus tests, the simulated power is much improved. Additionally, the newly proposed inference method yields effect measures whose interpretation is surprisingly straightforward.Comment: Submitted to Electronic Journal of Statistic

Prevalence and Characteristics of Metabolic Hyperferritinemia in a Population-Based Central-European Cohort

Background: Hyperferritinemia (HF) is a common finding and can be considered as metabolic HF (MHF) in combination with metabolic diseases. The definition of MHF was heterogenous until a consensus statement was published recently. Our aim was to apply the definition of MHF to provide data on the prevalence and characteristics of MHF in a Central-European cohort. Methods: This study was a retrospective analysis of the Paracelsus 10,000 study, a population-based cohort study from the region of Salzburg, Austria. We included 8408 participants, aged 40-77. Participants with HF were divided into three categories according to their level of HF and evaluated for metabolic co-morbidities defined by the proposed criteria for MHF. Results: HF was present in 13% (n = 1111) with a clear male preponderance (n = 771, 69% of HF). Within the HF group, 81% (n = 901) of subjects fulfilled the metabolic criteria and were defined as MHF, of which 75% (n = 674) were characterized by a major criterion. In the remaining HF cohort, 52% (n = 227 of 437) of subjects were classified as MHF after application of the minor criteria. Conclusion: HF is a common finding in the general middle-aged population and the majority of cases are classified as MHF. The new classification provides useful criteria for defining MHF

Ipsilateral motor evoked potentials in a patient with unihemispheric cortical atrophy due to Rasmussen encephalitis

The role of the ipsilaterally descending motor pathways in the recovery mechanisms after unilateral hemispheric damage is still poorly understood. Motor output reorganization was investigated in a 56-year-old male patient with acquired unilateral hemispheric atrophy due to Rasmussen encephalitis. In particular, the ipsilateral corticospinal pathways were explored using focal transcranial magnetic stimulation. In the first dorsal interosseous and wrist extensors muscles, the median amplitudes of the ipsilateral motor evoked potentials induced by transcranial magnetic stimulation in the patient were higher than those of 10 age-matched healthy control subjects. In the biceps brachii muscle, the median amplitudes of the ipsilateral motor evoked potentials were the second largest in the patient compared to the controls. This study demonstrated a reinforcement of ipsilateral motor projections from the unaffected motor cortex to the hemiparetic hand in a subject with acquired unihemispheric cortical damage

Functional data analysis : an overview of methods for the comparison of multiple indepent samples of curve data

eingereicht von Patrick Benjamin LangthalerLiteraturverzeichnis: Blatt 114-117Abstract in deutscher und englischer SpracheParis-Lodron-Universität Salzburg, Masterarbeit, 2018(VLID)500310

Imagine There Is No Plegia. Mental Motor Imagery Difficulties in Patients with Traumatic Spinal Cord Injury

In rehabilitation of patients with spinal cord injury (SCI), imagination of movement is a candidate tool to promote long-term recovery or to control futuristic neuroprostheses. However, little is known about the ability of patients with spinal cord injury to perform this task. It is likely that without the ability to effectively perform the movement, the imagination of movement is also problematic. We therefore examined, whether patients with SCI experience increased difficulties in motor imagery (MI) compared to healthy controls. We examined 7 male patients with traumatic spinal cord injury (aged 23–70 years, median 53) and 20 healthy controls (aged 21–54 years, median 30). All patients had incomplete SCI, with AIS (ASIA Impairment Scale) grades of C or D. All had cervical lesions, except one who had a thoracic injury level. Duration after injury ranged from 3 to 314 months. We performed the Movement Imagery Questionnaire Revised as well as the Beck Depression Inventory in all participants. The self-assessed ability of patients to visually imagine movements ranged from 7 to 36 (Md = 30) and tended to be decreased in comparison to healthy controls (ranged 16–49, Md = 42.5; W = 326.5, p = 0.055). Also, the self-assessed ability of patients to kinesthetically imagine movements (range = 7–35, Md = 31) differed significantly from the control group (range = 23–49, Md = 41; W = 337.5, p = 0.0047). Two patients yielded tendencies for depressive mood and they also reported most problems with movement imagination. Statistical analysis however did not confirm a general relationship between depressive mood and increased difficulty in MI across both groups. Patients with spinal cord injury seem to experience difficulties in imagining movements compared to healthy controls. This result might not only have implications for training and rehabilitation programs, but also for applications like brain-computer interfaces used to control neuroprostheses, which are often based on the brain signals exhibited during the imagination of movements

Cholinergic neurotransmission and olfactory function in obstructive sleep apnea syndrome: a TMS study

PURPOSE: The purpose of our study was to describe ultra-widefield (UWF) imaging and optical coherence tomography angiography (OCT-A) findings in affected and fellow eyes of patients with Coats' disease. METHODS: Consecutive patients affected by Coats' disease were prospectively recruited at the Department of Ophthalmology, San Raffaele Hospital, Milan, Italy in this cross-sectional, observational study. Patients underwent UWF color fundus photographs, UWF green autofluorescence, UWF fluorescein angiography (FA), optical coherence tomography (OCT), with 3 × 3 mm and 6 × 6 mm OCT-A scans of the macula. Images were qualitatively evaluated by two independent operators for the presence of pathology. RESULTS: Eleven patients affected by Coats' disease (eight males, mean age 17.1 ± 6.7 years). Nine and two patients had a clinical diagnosis of unilateral and bilateral disease, respectively. Five eyes had macular fibrosis. All clinically affected eyes exhibited retinal pathology at UWF imaging with the temporal sector most involved followed by the inferior, nasal, superior and macula. In all eyes with macular fibrosis, OCT-A revealed replacement of the foveal avascular zone with coarse vessels suggestive of vascularized fibrosis and flow void area in the choriocapillaris due to a masking effect; type 3 neovascularization was seen in 75% of cases. Seven out of nine clinically unaffected fellow eyes showed retinal pathology at UWF FA with the temporal quadrant most involved. CONCLUSION: We demonstrated that Coats' disease is a highly asymmetric bilateral disease and that UWF imaging is able to identify more retinal pathology than standard fundus imaging, thus guiding proper retinal photocoagulation. OCT-A allowed easy identification of type 3 neovascularization in a proportion of patients with macular fibrosis

Connectivity Analysis during Rubber Hand Illusion—A Pilot TMS-EEG Study in a Patient with SCI

Background. Bodily self-perception is an important concept for several neurological disorders, including spinal cord injury (SCI). Changing one’s bodily self-perception, e.g., via rubber hand illusion (RHI), induces alterations of bottom-up and top-down pathways and with this the connectivity between involved brain areas. We aim to examine whether (1) this process can be manipulated by changing cortical excitability, (2) connectivity between relevant brain areas differ when the RHI cannot be evoked, and (3) how this projection differs in a patient with SCI. Method. We applied RHI and facilitatory theta burst stimulation (TBS) on the right primary somatosensory cortex (S1) of 18 healthy participants and one patient with incomplete, cervical SCI. During RHI, we recorded high-density electroencephalography (HD-EEG) and extracted directed and nondirected connectivity measures. Results. There is no difference in connectivity between sham and real TBS or in the effectivity of RHI. We observed a higher laterality in the patient, i.e., higher connectivity of the right and lower of the left hemisphere. Besides this, connectivity patterns do not differ between healthy participants and the patient. Conclusion. This connectivity pattern might represent a neuroplastic response in the attempt to overcome the functional impairment of the patient resulting in a similar overall connectivity pattern to the healthy participants, yet with a higher sensitivity towards RHI and a higher laterality. The cortico-cortical communication was not altered depending on whether the illusion was provoked or not; hence, the perceptory illusion could not be observed in the EEG analysis

Abnormal cortical synaptic plasticity in minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) represents the earliest stage of hepatic encephalopathy (HE). MHE is characterized by cognitive function impairment in the domains of attention, vigilance and integrative function, while obvious clinical manifestations are lacking. In the present study, we aimed at assessing whether subjects with MHE showed alterations in synaptic plasticity within the motor cortex. Previous findings suggest that learning in human motor cortex occurs through long-term potentiation (LTP)-like mechanisms. We employed therefore the paired associative stimulation (PAS) protocol by transcranial magnetic stimulation (TMS), which is able to induce LTP-like effects in the motor cortex of normal subjects. Fifteen patients with MHE and 15 age- and sex-matched cirrhotic patients without MHE were recruited. PAS consisted of 180 electrical stimuli of the right median nerve paired with a single TMS over the hotspot of right abductor pollicis brevis (APB) at an ISI of 25ms (PAS25). We measured motor evoked potentials (MEPs) before and after each intervention for up to 30min. In healthy subjects the PAS25 protocol was followed by a significant increase of the MEP amplitude. On the contrary, in patients with MHE the MEP amplitude was slightly reduced after PAS. These findings demonstrated that associative sensorimotor plasticity, an indirect probe for motor learning, is impaired in MHE patients

Modulation of non-painful phantom sensation in subjects with spinal cord injury by means of rTMS

We aimed in this study to investigate whether repetitive transcranial magnetic stimulation (rTMS), given as theta burst stimulation (TBS), can interfere with non-painful phantom sensations in subjects with spinal cord injury (SCI). In double-blind, sham-controlled experiments in five subjects with cervical or thoracic traumatic SCI, we evaluated the effects of a single session of inhibitory (continuous) TBS, excitatory (intermittent) TBS, or placebo TBS, on simplex and complex non-painful phantom sensations. The interventions targeted the contralateral primary motor cortex (M1), the primary sensory cortex (S1) and the posterior parietal cortex (PPC). Measurements were carried out at baseline (T0), 5min (T1) and 30min later (T2) after the intervention. Descriptive evaluation of results shows that non-painful phantom sensations were not affected by rTMS applied over M1. Continuous (inhibitory) TBS over S1 induced a short-lasting decrease of simple non-painful phantom sensations, while continuous TBS over PPC induced a short-lasting decrease of both simple and complex phantom sensations. Intermittent (excitatory) TBS over PPC induced a slight increase of non-painful phantom sensations. Tests for significance confirm these observations, but must be interpreted with caution because of the small sample size. In conclusion, non-painful phantom sensations may be associated to a hyperexcitability of PPC and to a lesser extent of S1, which can be normalized by inhibitory rTMS. Our preliminary provide further evidence that neuromodulatory techniques are able to reverse phantom sensations not only after limb amputation but also in other conditions characterized by deafferentation such as SCI

Impaired cholinergic transmission in patients with Parkinson's disease and olfactory dysfunction

Olfactory dysfunction represents a frequent and disturbing non-motor manifestation of Parkinson's disease (PD). The pathophysiology of olfactory dysfunction in PD is still poorly understood. Experimental evidence suggests that olfactory impairment could be related to central cholinergic dysfunction. Short latency afferent inhibition (SAI) technique gives the opportunity to test an inhibitory cholinergic circuit in the human cerebral motor cortex. The objective of the study was to assess the cholinergic function, as measured by SAI, in PD patients with different degrees of olfactory dysfunction. We applied SAI technique in 31 patients with PD. These patients also underwent Olfactory Event-Related Potentials (OERPs) studies to objectively evaluate the olfactory system and a battery of neuropsychological tests to assess the cognitive functions. Absent OERPs indicated a severe olfactory dysfunction in 13 subjects. The presence of OERPs with an alteration in latency and/or amplitude can be considered as a borderline condition of slight alteration of smell and was found in other 15 patients. Only 3 patients showed normal OERPs. SAI was significantly reduced in the PD patients with absent OERPs compared with those with present but abnormal OERPs. Neuropsychological examination showed a mild cognitive impairment in 12 out of 13 PD patients with severe olfactory dysfunction, and in 3 out of the 15 patients with borderline olfactory dysfunction. SAI abnormalities and presence of severe olfactory impairment strongly support the hypothesis of cholinergic dysfunction in some patients with PD, who will probably develop a dementia. Longitudinal studies are required to verify whether SAI abnormalities in PD patients with olfactory dysfunction can predict a future severe cognitive decline