Gabriella Bottini

Bio: Gabriella Bottini is an academic researcher from University of Pavia. The author has contributed to research in topics: Vestibular system & Population. The author has an hindex of 27, co-authored 112 publications receiving 1675 citations. Previous affiliations of Gabriella Bottini include University of Milano-Bicocca.

Vestibular modulation of somatosensory perception.

Abstract: Functional imaging studies show that vestibular and somatosensory projections overlap in the human brain. However, it remains unclear whether and how vestibular inputs affect somatosensory function. To address this issue, we studied the effects of left caloric vestibular stimulation (CVS) on detection of near-threshold somatosensory stimuli delivered to the left and right hands of healthy volunteers. To investigate whether these effects were somatosensory specific, or supramodal, we also tested CVS modulation of visual contrast detection. Signal detection analyses showed increased somatosensory perceptual sensitivity immediately after CVS, both ipsilaterally and contralaterally. No statistically reliable effects on visual contrast sensitivity were found. These findings suggest that vestibular stimulation has a specific facilitatory effect on somatosensory detection, distinct from non-specific arousal and spatial attentional effects of CVS. Thus, the overlap in brain activations for vestibular and somatosensory inputs is not simply an anatomical curiosity, but may reflect a functional cross-modal perceptual interaction.

Mental images across the adult lifespan: a behavioural and fMRI investigation of motor execution and motor imagery

Abstract: Motor imagery (M.I.) is a mental state in which real movements are evoked without overt actions. There is some behavioural evidence that M.I. declines with ageing. The neurofunctional correlates of these changes have been investigated only in two studies, but none of the these studies has measured explicit correlations between behavioural variables and the brain response, nor the correlation of M.I. and motor execution (M.E.) of the same acts in ageing. In this paper, we report a behavioural and functional magnetic resonance imaging (fMRI) experiment that aimed to address this issue. Twenty-four young subjects (27 ± 5.6 years) and twenty-four elderly subjects (60 ± 4.6 years) performed two block-design fMRI tasks requiring actual movement (M.E.) or the mental rehearsal (M.I.) of finger movements. Participants also underwent a behavioural mental chronometry test in which the temporal correlations between M.I. and M.E. were measured. We found significant neurofunctional and behavioural differences between the elderly subjects and the young subjects during the M.E. and the M.I. tasks: for the M.E. task, the elderly subjects showed increased activation in frontal and prefrontal (pre-SMA) cortices as if M.E. had become more cognitively demanding; during the M.I. task, the elderly over-recruited occipito-temporo-parietal areas, suggesting that they may also use a visual imagery strategy. We also found between-group behavioural differences in the mental chronometry task: M.I. and M.E. were highly correlated in the young participants but not in the elderly participants. The temporal discrepancy between M.I. and M.E. in the elderly subjects correlated with the brain regions that showed increased activation in the occipital lobe in the fMRI. The same index was correlated with the premotor regions in the younger subjects. These observations show that healthy elderly individuals have decreased or qualitatively different M.I. compared to younger subjects.

CHF5074 reduces biomarkers of neuroinflammation in patients with mild cognitive impairment: a 12-week, double-blind, placebo-controlled study.

Abstract: As neuroinflammation is an early event in the pathogenesis of Alzheimer' s disease, new selective antiinflammatory drugs could lead to promising preventive strategies. We evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of CHF5074, a new microglial modulator, in a 12-week, double-blind, placebo-controlled, parallel groups, ascending dose study involving 96 MCI patients. Subjects were allocated into three successive study cohorts to receive ascending, titrated doses of CHF5074 (200, 400 or 600 mg/day) or placebo. Vital signs, cardiac safety, neuropsychological performance and safety clinical laboratory parameters were assessed on all subjects. Plasma samples were collected throughout the study for measuring drug concentrations, soluble CD40 ligand (sCD40L) and TNF-α. At the end of treatment, cerebrospinal fluid (CSF) samples were optionally collected after the last dose to measure drug levels, β- amyloid1-42 (Aβ42), tau, phospho-tau181, sCD40L and TNF-α. Ten patients did not complete the study: one in the placebo group (consent withdrawn), two in the 200-mg/day treatment group (consent withdrawn and unable to comply) and seven in the 400-mg/day treatment group (five AEs, one consent withdrawn and one unable to comply). The most frequent treatment-emergent adverse events were diarrhea, dizziness and back pain. There were no clinically significant treatmentrelated clinical laboratory, vital sign or ECG abnormalities. CHF5074 total body clearance depended by gender, age and glomerular filtration rate. CHF5074 CSF concentrations increased in a dose-dependent manner. At the end of treatment, mean sCD40L and TNF-α levels in CSF were found to be inversely related to the CHF5074 dose (p=0.037 and p=0.001, respectively). Plasma levels of sCD40L in the 600-mg/day group were significantly lower than those measured in the placebo group (p=0.010). No significant differences between treatment groups were found in neuropsychological tests but a positive dose-response trend was found on executive function in APOE4 carriers. This study shows that CHF5074 is well tolerated in MCI patients after a 12-week titrated treatment up to 600 mg/day and dose-dependently affects central nervous system biomarkers of neuroinflammation.

Management of psychogenic non-epileptic seizures: a multidisciplinary approach.

Abstract: The International League against Epilepsy (ILAE) proposed a diagnostic scheme for psychogenic non-epileptic seizure (PNES). The debate on ethical aspects of the diagnostic procedures is ongoing, the treatment is not standardized and management might differ according to age group. The objective was to reach an expert and stakeholder consensus on PNES management. A board comprising adult and child neurologists, neuropsychologists, psychiatrists, pharmacologists, experts in forensic medicine and bioethics as well as patients' representatives was formed. The board chose five main topics regarding PNES: diagnosis; ethical issues; psychiatric comorbidities; psychological treatment; and pharmacological treatment. After a systematic review of the literature, the board met in a consensus conference in Catanzaro (Italy). Further consultations using a model of Delphi panel were held. The global level of evidence for all topics was low. Even though most questions were formulated separately for children/adolescents and adults, no major age-related differences emerged. The board established that the approach to PNES diagnosis should comply with ILAE recommendations. Seizure induction was considered ethical, preferring the least invasive techniques. The board recommended looking carefully for mood disturbances, personality disorders and psychic trauma in persons with PNES and considering cognitive-behavioural therapy as a first-line psychological approach and pharmacological treatment to manage comorbid conditions, namely anxiety and depression. Psychogenic non-epileptic seizure management should be multidisciplinary. High-quality long-term studies are needed to standardize PNES management.

Vestibular inputs modulate somatosensory cortical processing

Abstract: The vestibular system is unique among the senses because of the entirely multisensory nature of its cortical projections. Neuroanatomical and neuroimaging studies show that vestibular stimulation activates somatosensory areas, and particularly the so-called parieto-insular vestibular cortex (PIVC) in the monkey, while deactivating visual areas. Further, recent psychophysical studies showed that vestibular stimulation facilitates detection of electrocutaneous stimuli, suggesting a vestibular-somatosensory perceptual interaction. However, the functional mechanism underlying this perceptual facilitation remains unclear. We therefore recorded somatosensory potentials evoked by left median nerve stimulation, before and immediately after left cold caloric vestibular stimulation (CVS), in a small-scale study of eight healthy volunteers. CVS selectively enhanced the N80 component recorded over both ipsilateral and contralateral somatosensory areas, without significantly affecting earlier or later components. Interestingly, the N80 component has been localised to the parietal operculum, which includes the human homologue of the monkey PIVC, and is thus a prime neuroanatomical candidate for vestibular-somatosensory convergence. As a control, we measured visual evoked potentials to reversing checkerboard patterns and found no effects of vestibular stimulation. This rules out explanations based on indirect effects of vestibular modulations, such as general arousal or supramodal spatial attention. We believe our results provide the first clue linking brain structure to function for the interaction between vestibular and somatosensory systems.

Immune attack: the role of inflammation in Alzheimer disease

Abstract: The past two decades of research into the pathogenesis of Alzheimer disease (AD) have been driven largely by the amyloid hypothesis; the neuroinflammation that is associated with AD has been assumed to be merely a response to pathophysiological events. However, new data from preclinical and clinical studies have established that immune system-mediated actions in fact contribute to and drive AD pathogenesis. These insights have suggested both novel and well-defined potential therapeutic targets for AD, including microglia and several cytokines. In addition, as inflammation in AD primarily concerns the innate immune system - unlike in 'typical' neuroinflammatory diseases such as multiple sclerosis and encephalitides - the concept of neuroinflammation in AD may need refinement.

Machine learning with Python

Abstract: This presentation is a case study taken from the travel and holiday industry. Paxport/Multicom, based in UK and Sweden, have recently adopted a recommendation system for holiday accommodation bookings. Machine learning techniques such as Collaborative Filtering have been applied using Python (3.5.1), with Jupyter (4.0.6) as the main framework. Data scale and sparsity present significant challenges in the case study, and so the effectiveness of various techniques are described as well as the performance of Python-based libraries such as Python Data Analysis Library (Pandas), and Scikit-learn (built on NumPy, SciPy and matplotlib). The presentation is suitable for all levels of programmers.

Contributions to Neuropsychological Assessment

Abstract: on to develop full blown Parkinson's disease with rigidity and bradykinesia in the next few years. For those interested in the mechanisms of tremor, there are the customary authoritative reviews by Llinas, De Long, Lamarre, Rothwell and Deuschl, but uncertainty remains with respect to the relative importance of central autonomous generators and instability of peripheral reflex loops. Well written chapters are also included on primary orthostatic tremor and its relationship to essential tremor, writing tremor, neuropathic tremor, midbrain tremor and the increasingly acknowledged psychogenic tremors. Complex interrelationship between dystonia and postural tremor is also covered in depth. This cornucopia will be coveted and dipped into by those neurologists with a special interest in abnormal movement disorders, but who would not consider themselves to have a research interest in tremor. However, for the majority of clinicians involved in the hurly burly of clinical practice, I suspect that regrettably time and cost factors will conspire together to keep this excellent book out of reach. ANDREW LEES