SNC'21 | LIVE

In this section please find answers to the questions exceeding the available discussion time.

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SARS-CoV-2 and Brain Symposium

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For Prof. Raimund Helbok (Neuro-COVID: what it is and what it is not)

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Q: Do any broadly accepted treatment options exist for persistent post-COVID olfactory dysfunction that does not resolve on its own?

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A: No randomised controlled trial data available. Based on previous experience (viral diseases with hyposmia) smelling training can be tried, some observational studies show benefit. I would not recommend corticoid treatment althoug some countries/ENR doctors do so...

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Q: Could be depression and anxiety associated with obligatory social isolation during acute phase of disease?

 

A: Sure, especially in patients with preexisting preclinical/clinical disorders.

 

Q: Are there gender differences in neurological consequences of Covid-19? 

A: Interesting question: in general, women do better, however, it seems that this is more true in hospitalized patients. We have seen that being a women is strongly associated with long term effects in non-hospitalized patients. 

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Q: Have you spotted any differences in long term effects between those who were vaccinated before having been infected with Covid - and those who weren't? 

 

A: There are currently insufficient data to seriously answer this question, sorry. We are studying the variants now. 

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Q: How can Slovenian neurologists join the EANcore?

 

A: Please, contact either me or the EAN using this Email: covidregistry@ean.org 

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For Prof. Jennifer Frontera (Neurological Associations of COVID-19 Vaccines)

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Q: Would you recommend classical protein vaccines more than novel ones (mRNA, DNA, ...)?

 

A: At this point the data on efficacy and safety of mRNA vaccines is very robust.  The nanoparticle vaccine Novavax also has promising data but there is much less real world experience with it at this point.  The mRNA vaccines appear to perform better than the adenovirus vaccines, though any vaccination is better than no vaccination.

 

Q: What pathologies are included in the »movement disorder« in your data? 

A: Movement disorder included primarily tremor, but also blepharospasm and dystonia were reported.  

  

For Prof. Zsuzsa Blaskó (Learning during the pandemic: mapping potential education inequalities across Europe)

 

Q: In your opinion, is it ok that during the pandemic, an education took place online for a very long time?

 

A: Yes and no. If the school closure was indeed very well justified from the perspective of stopping the spread of the virus – then, BUT only then! -  I do not see a better alternative, distance teaching had to be provided. It could still offer a sense of regularity, some limited form of social interactions and – especially for the older students – it could still promote learning. The mode of provision matters a lot as does the age of the child. Different modes and intensity would be desirable for the young and for the older students and ideally, other individual factors should also be taken into account. All in all, from an educational and social perspective, school closures should be very the last options in our fight against a pandemic.

 

Q: Will "pandemic" generations develop different social skills as previous generations?

 

A: It depends on the length of time children spent away from school, but also on how much time in the end they spend wearing masks and being among people wearing masks. Also different age groups are likely to be affected differently with those in critical age-groups (e.g. very young ones, but also teenagers) can be particularly badly affected. We will have to wait some more years for having good research evidence on this. And even when, it will be a challenge to disentangle the generational Covid effect for example from the cohort effect of growing up with screens that is also likely to massively influence young people's social skills.

 

Q: In your opinion, is it better to learn in school or online from home?

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A: For me there is no doubt here, I see big advantages of learning in school – it is so much better for the improvement of social and emotional skills, which are as needed as cognitive ones. Exceptions might be some academic learning in higher secondary school, but even that needs to be combined with regular school attendance.

 

Q: Are there any standards on how the hybrid system shall be performed? Will lessons learned be applied in the future for those that for some reasons can not be involved to the F2F educational system (temporary) and reduce inequalities of these groups?

 

A: I am not aware of such standards being developed at the European level, but they might be in the Member States. Certainly a topic that requires lots of attention in the future.

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For Prof. Adrian Owen (Cognitive and Neurological Consequences of COVID-19)

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Q: Who may use the Cambridge Brain Sciences platform (both as a participant and for research purposes)? It sounds like a great resource!

 

A: Anyone may use the platform. You can visit cambridgebrainsciences.com to try the tests and to see what is available. To use them for academic studies, 'CBS Research' is the fully configured tool to set up trials, run them and store data. For clinical studies 'CBS Health' offers more functionality in terms of automatic data interpretation and output. To discuss possibilities the best contact is Mike (mike.battista@cambridgebrainsciences.com)

 

Q: The data is from the whole world or from a specific region? 

A: Yes, the data were acquired from the whole world so it includes people from many different countries. That said, because of where the study was run and my nationality, most participants came from the UK, the US or Canada.

 

Q: What triggers neurological impairments after infection with Sars-Cov-2?

 

A: That we really do not completely understand yet. But as I outlined in my talk (and Prof Helbok gave more details) there are likely both direct and indirect influences. 'Direct' refers to direct infection of brain tissue. 'Indirect' refers to things like blood clots, low oxygen levels and the effects of sedatives.   

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Q: What were the effect sizes for the cognitive effects?

 

A: The effects sizes were small (0.2 SDs). The whole preprint is available to reade here: https://www.researchsquare.com/article/rs-373663/v1  

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Q: Will there be follow-up research determining what makes patients more likely to develop either a physical or a mental health outcome? Are there any existing hypotheses regarding this already?

 

A: Once we have the 12 month data fully analysed then we will be able to answer this question more clearly. At present we know that age is important (the younger you are the less likely to are to have severe physical symptoms but the more likely you are to have mental heath issues). Sex/gender does not seem to be very important (in our sample at least), but a reasonable hypothesis is that premorbid conditions will play an important role.

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Metabolic brain imaging in neurodegenerative disorders

 

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For Matej Perovnik (Specific Metabolic Brain Patterns in Alzheimer’s dementia and dementia with Lewy bodies)

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Q: Have you a separate DLBRP from those patient AB+ and other from those AB-? Are they different?

 

A: Unfortunately, our sample of DLB-AB+ patients was too small to derive two different DLBRPs. It would be a very interesting hypothesis to be tested.

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For Tomaž Rus (Correlations between brain metabolism and neuropathology in sporadic Creutzfeldt-Jakob disease)

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Q: Maybe I missed this - what was the disease duration of the CJD patients ? Given the fast progression in those patients it might be an important factor?

 

A: Median disease duration was 4.7 ± 5.2 months. We were not interested only in absolute disease duration but also relative disease duration (i.e. percentage of time between disease onset and death). On average relative disease duration at FDG-PET was 64.1% ± 16.3%. What was interesting, patients that underwent imaging relatively early have somewhat different metabolic pattern (as expected), so probably the imaging pattern would be even firmer including only patients that underwent imaging in late disease.

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Q: Have you taken into account the disease duration (time from PET to death)? It could explain part of the lack of correlation.

 

A: For now we did not study the effect of absolute disease duration on pathological changes. We plan to do it in the future.

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Educational workshop on CNS protein misfolding

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For Professor Rogelj (TDP-43 proteinopathies) 

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Q: I read that soccer players may be at higher risk for ALS. If concussive head injury is to blame, why ALS and not CTE?

 

A: This is a hotly debated topic, where intesive activity may be detremental. On the other hand moderate cativity may be benfitial.  However, it needs more studies and greater numbers for more confidence.

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Q: How soon before the appearance of symptoms in ALS can we already see TDP-43 accumulation?

 

A: TDP-43 pathology can only be seen postmortem. As there is a lot of redundancy in the system (ie. Adjacent motorneurons take over the innervation of musculature of the dying motorneuron) the symptoms are observed when more than 50% of motorneurons are already gone.  However, studies of presymtomatic mutation carriers have shown that there are phyiological differences when compared to controls. These changes can be observed even 20 years before the predicted disease onset.

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For Professor Brundin (Now it is time for research to crack Parkinson’s disease)  

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Q: Do you believe that one target approach (i.e. a-syn) will be enough to treat PD, or do you expect than an approach targeting different pathways, such as inflammation, etc., would be needed? 

 

A: This is a difficult question, especially since there currently are no treatments that slow progression of PD. If I have to guess, I can imagine that there would be benefit from targeting more than one process and that possibly different aspects of the disease progression (e.g. motor, cognitive, depression/anxiety, fatigue, constipation, etc) will respond differently to the different treatments. That said, it will be a challenge, both from a scientific and regulatory standpoint, to prove that treatment combinations are more efficacious than individual treatments.

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Q: You were very involved in the neurotransplantation approach to treating Parkinson disease. It seemed promising. Is it still a viable option or may it become relevant again with the development of stem cell research?

 

A: Yes it is still a viable option. There are now several initiatives sponsored by biotech companies or big Pharma (or both in joint ventures) trying to move human ES cell or induced pluripotent stem (iPS) cell derived dopamine neurons into clinical transplantation trials. Some of the first trials actually started not so long ago, and there are more to come. The different programs use slightly different approaches when it comes to how the donor cells are prepared and the surgery is performed. There is a good, short summary in this review article, published a few months ago:

https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28628.

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For Professor Aguzzi (Transmissible Spongiform Encephalopathies)   

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Q: Should real-time quaking-induced conversion (RT-QuIC) that had "revolutionised" diagnosing prion diseases perhaps be considered worthy of Nobel prize? 

 

A: Absolutely NOT. The technical invention that is at the basis of this is PMCA, which was created by Claudio Soto. RT-QuiC is a further refinement, but it would have never happened if Soto would not have invented PMCA and shown that it amplifies prions. When celebrating scientists, we must be careful of assigning credit to the people who deserve it. In this case, it’s not Caughey. It’s Soto.

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For Professor Wille (A structural biologist’s view of neuroscience)  

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Q: Do vaccine antibodies reach and neutralize intracellular prion proteins as well? 

 

A: Since the prion protein is an extracellular protein, which sits on the cell surface, it should be much more accessible than intracellular proteins. However, some antibodies have been shown to cross the cell membrane, but it would be much more difficult to therapeutically target an intracellular protein with antibodies. Given the extracellular location of the prion protein, the vaccine approach doesn't have to deal with that obstacle.

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Systems all the way down: studying mental health problems as biopsychosocial systems

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For Eiko Fried 

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Q: Some people can suffer from depression for years and influence their every day life. Is there an approach that can help this people to recover faster?

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A: The best evidence we have points to cognitive behavioral therapy, potentially combined with antidepressants.

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Q: One mental state can be realized in multiple neural states (multiple realization argument). Given this, is it actually (in principle) possible to find true correlates/substrates of psychiatric symptoms?

 

A: Multiple realizability is indeed a really big problem for hardcore biological reductionism of mental states: the core idea here is that there of course is a relation between mind and brain states, but that relating them to each other statistically, at the group level, may remain challenging (or, for some aspects, fundamentally impossible, perhaps, if they are massively multiply realized).

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Q: Could we build an app or some kind of programe that could ''see'' the early warning signs and direct people to get preventive help/therapy before they develop a disorder?

 

A: That's the idea of our research program — the data come into our computer (all sorts of data), we calculate early warning signs, and communicate them (e.g. via a smartphone app) in time. 

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Q: Reductionism in psychiatry is usually mentioned in the context of biology. Can psychological approaches to treat and understand mental disorders also be reductionist? For example, cognitive-behavioral therapy tries to reduce mental disorders to thought patterns and symptoms.

 

A: I personally see the biggest claims, and the biggest funding infrastructure, on the level of biology. But yes, I would assume you could call Foucault or Szazs  who argued that mental disorders are socially made up "social reducionists", and if a clinical psychologist would maintain the *only* cognitions and emotions matter, that would be a psychological reductionism. My criticism was directed against the most common form of reductionism in my area, biological reductionism, but that was merely an example.

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Q: There is an old joke: how does psychiatrist know that you are depressed? You tell him. - Given this, is it valid for patients to self-diagnose and self-treat their symptoms, especially for non-psychotic disorders?

 

A: Difficult question. As a psychologist, I see very strong value in self-reported symptoms, especially in people (and you make that distinction correctly of course) who have insight into their own ill-ness. Self-diagnosing and self-treating ... for mental disorders (not just stress or problems of living), nearly everybody should look for professional help—similar to medical disorders.

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Music and brain: evidence-based music interventions in medicine

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For Daniele Schoen (Neurology of Music and Brain) 

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Q: Are there methods developped to assess these mood and emotional states, evoked by music?

 

A: One interesting and simple way to assess these may be the Barcelona Music Reward Questionnair, particularly interesting to see if the participant/patient is music anhedonic.

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Q: Could musical training have effect on epilepsy patients through neural synchrony?

 

A: This could be possible in theory, and some research exist on the link between listening to music and seizures, although finings are not clear cut and the underlying mechanisms are noy yet established. Music could act via increased or modified synchronization in the fronto-temporal network but also in terms of reducing anxiety in patients. 

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Q: Brassens always a bit out of tune, prediction error ear cannot change, so careful to the text. When sung perfectly, hardly any change needed from the priors, so the brain goes into indulging in beauty hardly interested in the text. Does this mean diffeent brain mechanisms involved?

 

A: Not sure I completely understand the question, but it may be relevant here to clarify that predictions and priors are not always accessible at a conscious level. Actually, most predictions are automatic. As such, if you here a "surprising" event in a Mozart symphony, the brain will be "surprised" every time one will listen to the musical piece. This is because in this case, priors will concern the rules of harmony and not the specific musical piece. (sorry if I misunderstood the questions).

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Q: Can it be said that those who have received musical training during their earlier years, when they suffer from a neurological damage such as stroke, head Injury or dementia, have chances of improved prognosis in terms of language recovery?

 

A: I am not sure that we can say so because we do not have enough data. However, music listening seems to positively impact stroke recovery and music making may reduce brain ageing via dopaminergic effects and perhaps neural genesis in the dentate gyrus (cf talk of Dr Koelsch). Overall, music making may have a compensatory effect with respect to aging and dementia, but more research is needed to assess this hypothesis.

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For Prof. Stefan Koelsch (Research towards evidence-based music interventions) 

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Q: In a place where only a few research steps have been made towards music interventions, what interventions would you advise to start with, to persuade decison makers about its usefulness?

 

A: I think more research on depression would go a long way. And related to this, as well as to Q2: Also more research on therapeutic effects of music in PTSD and anxiety is needed.

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Q: Is music, via it's emotional memory role, then useful for pathologies related to maladaptive emotional memories such as PTSD or anxiety? 

 

A: Yes, both PTSD and anxiety; there is relative little high-quality research on this, and especially research on PTSD should be done together with an experienced music therapy person (in my opinion), because music can also have negative side-effects in individuals with PTSD (thus, music has to be chosen carefully).

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For Prof. Manuela Flippa (The mother's voice, singing and speaking, as a special tool for early interventions in the NICU) 

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Q: Can you tell us how you collect the subtle observations about babies' interactions in a busy NICU? Cameras and monitors cannot detect all the fine effects that you are studying. Do you have an appointed research nurse or an assistant researcher when you are not there?

 

A: Thank you for this question. Our observations were limited to the period of the vocal intervention. During this period a trained nurse in the "Pain study", a trained nurse evaluated the initial infant's state and we collected physiological data by the monitor recording, behavioural data by the video recording and hormonal data from saliva samples. The video recordings were then coded by two independent researchers on muted videotracks, so they could be blinded to the conditions. The research nurse presence and expertise was essential for the recruitment also.

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Q: How do you follow the autonomic and pain changes? 

 

A: In the study titled "Maternal speech decreases pain scores and increases oxytocin levels in preterm infants during painful procedures" the autonomic changes were tracked thanks to the physiological parameters: heart rate, respiration rate, oxygen saturation as well as critical events (such apnoeas, bradycardia etc) were collected and analysed for assessing the PIPPS (Preterm Infant's Pain Profile score). According to the PIPPs guidelines, pain was assessed during the 30 seconds following the painful procedure through a cluster of physiological and behavioural parameters. The PIPPs was assessed by a trained nurse online (during the painful procedure) and offline. Offline the video recordings were then coded by two independent researchers on muted videotracks, so they could be blinded to the conditions.

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For Prof. dr. Uroš Kovačič (Heart rate variability in relation to self-selected music or music genres preselected by the researchers) 

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Q: Would your results suggest that cardiological wards should have a repertoire of musical offer available for patients?  Or that people should prepare a playlist of music as a standard measure in case an adverse event should occur in their heart (or also in the brain) to use it for stabilisation of autonomic function and promote better recovery and rehabilittaion?

 

A: Yes &... yes. Repeated activation and brain engagement while listening to music (especially one's own favorite music) that begins in the early (subacute) phase of the disease could strengthen the autonomic nervous system and eventually even improve the clinical outcome.

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Q: How the music changes sympathetic nervous system? 

 

A: Increase in heart rate and LF parameter of HRV frequency domain during music listening indicates that the sympathetic branch of ANS is activated.

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Brain Health Accross the Lifespan - Findings from the Lifebrain Project

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For Prof. dr. Klaus Ebmeier (Ageing and brain imaging in Lifebrain) 

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Q: Do you think that "cognitive reserve" which is a preventive factor in developing cognitive decline in Alzheimer disease ppatients is related to the education itself (i.e., a direct effect on the brain function), or rather a consequence of healthier life style that more educated people lead?

 

A: Interesting question! We had a stab at that in https://onlinelibrary.wiley.com/doi/10.1002/hbm.25316 If you look at Table 5, you find that cognitive reserve, here defined as 'cognitive age gap' controlled for 'brain age gap' is associated with premorbid IQ and less with education, while the brain age gap was weakly predicted by lifestyle. As I said, a first stab, but one could think of trying to answer the question with studies of this kind.