Brain-computer interfaces (BCIs) provide communication that does not depend on neuromuscular activity. Several studies have demonstrated that those with advanced ALS can use noninvasive BCIs (e.g.,1,2,3). In able-bodied users, Townsend et al2 showed that a pseudorandom -or checkerboard paradigm (CBP) significantly improves P300-BCI performance compared to the standard or row/column paradigm (RCP). The CBP flashes stimuli in quasi-random groups that do not contain adjacent items, and it ensures at least six flashes between flashes of a given item. The combination of these two factors improves accuracy and bitrate. Townsend et al [2] also reported anecdotal improvements with the CBP in people with ALS who had extensive experience with the RCP. The present study seeks to verify these results in a larger group of people with ALS.

Severe motor disabilities such as amyotrophic lateral sclerosis (ALS) reduce or eliminate neuromuscular control and deprive affected patients of vital communication and control. Recent advances in noninvasive EEG-based BCIs have given patients new hope for communication and environmental control not provided by other assistive devices[1]. General lapses of attention, mind wandering, and lack of focus may all undermine BCI performance[2]. In a P300-BCI, non-target flashes are exogenous cues that could attract attention away from the endogenous task of attending to target item flashes. Thus, inducing a heightened state of attentional awareness and reducing distractibility may improve BCI performance. Mindfulness meditation and induction (MMI) offers such a possibility[3,4]. We expect MMI to have several important consequences for P300-based BCI use: one, it will focus attention to the target item; two, it will reduce distraction from non-target flashes; three, it will reduce P300 target latencies; four it will produce higher amplitude ERPs

Since the introduction of the P300 BCI speller by Farwell and Donchin1 speed and accuracy of the system has been significantly improved. Larger electrode montages and various signal processing techniques are responsible for most of the improvement in performance. The present study takes advantage of a new presentation paradigm to improve performance, the “checkerboard?(CB) paradigm2. The CB presents quasi-random groups of six items instead of using the typical row/column presentation. To determine if reducing distraction from neighbouring items could improve subsequent performance on a copy-spelling task, the CB paradigm was used and compared to a condition that suppressed (i.e., did not flash) items during the calibration phase of the experiment.

Since its inception, the P300-based BCI has typically flashed in rows and columns [1]. Recently, the “checkerboard?(CB) paradigm was introduced in which targets are grouped in rows and columns on two “virtual matrices?taken from the white and black squares of a checkerboard overlaid on the physical matrix [2]. Disassociating the physical rows and columns of the matrix from how they are grouped to flash brings advantages by: 1) avoiding the problematic effects of double target flashes [3], and 2) not allowing adjacent targets to flash together. In this study, this disassociation of the “flash groups?from the physical matrix is taken further. The flash groups become purely “abstract?bearing no relationship to rows or columns either physical or virtual. This study compares performance of this new paradigm named ?-Flash?(5F) to the CB.

Bakgrund: Amyotrofisk lateralskleros (ALS) är en obotlig sjukdom som bryter ned de perifera och centrala motoriska nervcellerna i nervsystemet och har ett dödligt utfall. Närstående får ofta ta rollen som primärvårdgivare och sjukdomen innebär en stor livsomställning för såväl den sjuke som närstående. Som sjuksköterska är det viktigt att ha kunskap om närståendes upplevelser för att kunna bidra med rätt stöttning samt att ge god omvårdnad. Syfte: Syftet med litteraturstudien var att beskriva upplevelser av att vara närstående till en person med amyotrofisk lateralskleros. Metod: En litteraturstudie baserad på nio kvalitativa studier. Fribergs femstegsmodell användes för att analysera, hitta likheter och skillnader i artiklarna för att kunna framställa ett resultat. Resultat: Ur analysen framkom tre huvudkategorier: Känslor som följer med sjukdomen, Tankar under sjukdomsprogressionen och Förändrad situation för de närstående, med medföljande underkategorier. Konklusion: Närstående till personer med ALS upplever en rad känslor, begränsningar och förändringar i relationer och vardagen under sjukdomsförloppet. Vårdpersonal och sjuksköterska kan arbeta hälsofrämjande genom hälsostödjande familjesamtal, då ges möjlighet till närstående och drabbad att lyfta känslor och tankar. / Background: Amyotrophic lateral sclerosis is a disease that breaks down the peripheral and central motor neurons of the nervous system and has a fatal outcome. Relatives often have to take on the role of primary care provider, and the disease means a major life adjustment for both the sick person and the relatives. As a nurse, it is important to have knowledge of the experiences of relatives in order to be able to give the right support and to provide good care. Aim: The aim of the study was to describe experiences of being a relative to a person with amyotrophic lateral sclerosis. Methods: A literature study based on nine qualitative studies. Friberg's five-step model was used to analyze, find similarities and differences in the articles. Results: Three main categories emerged from the analysis: Feelings that accompany the illness, Thoughts during the progression of the illness and Changed situation for the relatives, with accompanying subcategories. Conclusion: Relatives experience a range of emotions, limitations and changes in relationships and everyday life during the course of the disease. Nurses can work to promote health through health-supporting family conversations, then relatives and those affected are given the opportunity to raise feelings and thoughts.

Bakgrund: ALS är en fortskridande neurodegenerativ sjukdom som leder till förlust av frivillig muskelfunktion vilket slutligen leder till döden. Det finns ännu inget botemedel för sjukdomen, behandlingsåtgärderna inriktas istället på att lindra symtomen. Det är inte bara individen som drabbas av ALS som påverkas utan även de anhöriga. Att sjuksköterskan är lyhörd och bemöter hela familjens behov är därför viktigt. Syfte: Syftet med studien var att beskriva anhörigas upplevelse av att leva med en närstående som drabbats av ALS. Metod: Allmän litteraturstudie som baserades på åtta vetenskapliga resultatartiklar. Resultat: Anhörigas välbefinnande påverkades i samband med sjukdomen. Egentiden åsidosattes i samband med den ökade belastningen vilket genererade i emotionell påverkan. Anhöriga upplevde behov av stöd från vårdpersonalen. Sjukvårdspersonalen i hemdistriktet upplevdes dock inte vara tillräckligt kompetenta vilket resulterade i att anhöriga tog över ansvaret som omsorgsgivare. Bristande utbildning i omvårdnadsåtgärder beskrevs även bidra till ökad osäkerhet och rädsla. Konklusion: Anhörigas livssituation påverkades negativt och de önskade ett större stöd från vårdpersonalen än vad som erbjöds. Vården bör samordnas bättre så att vårdpersonalen kan möta hela familjens behov och erbjuda det stöd som familjen behöver i omvårdnadsprocessen. / Background: ALS is a progressive neurodegenerative disease leading to deterioration and loss of voluntary muscle function, ultimately leading to fatality. There is yet no medical interventions for the disease, the focus lays on mitigating the symptoms. It´s not only the individual that are suffering, but also their relatives. Therefore, it´s important that the nurses are attentive and responsive to the needs of the family as whole. Aim: The aim was to describe the relatives’ experiences of living with a next of kin with ALS. Method: A general litterature study, which generated in eight research articles. Result: Relatives' well-being was affected in correlation with the illness. The heightened stressors affected the individual’s time spent on themselves, which in turn had a negative emotional effect. The relatives expressed increased needs from health professionals. The local health-care workers were reportedly not meeting their needs in terms of competence, resulting in relatives taking over the responsibility as caregiver. Lack of education regarding nursing measures were described as a factor of the heightened uncertainty and fear. Conclusion: Relatives’ life situation was negatively affected and they wished for more support from the caregivers than what they were offered. The care should be better coordinated so the caregivers can meet the needs of the entire family and offer the support that the family needs in the nursing process.

Amyotrofisk lateralskleros (ALS) är i nuläget en obotlig sjukdom och sjukdomsförloppet går ofta väldigt fort. Omvårdnaden måste därför vara specifik för dessa patienter. Syfte: Huvudsyftet med denna litteraturstudie var att belysa vårdpersonalens stöd och bemötande av patienter med en obotlig sjukdom som ALS och deras närstående. Syftet var även att belysa hur de närstående påverkas av att vara vårdgivande åt sin närstående med ALS. Metod: För att besvara våra frågeställningar har vi valt att göra en litteraturstudie som bygger på tio vetenskapliga artiklar. Artiklarna kvalitetsbedömdes utifrån Carlsson och Eimans bedömningsmall för kvalitativa och kvantitativa studier. Som teoretisk referensram har vi använt oss av en modell av Carnevali. Resultat: Att vara närstående till patienter med ALS påverkar de flesta negativt på något sätt i deras dagliga liv. Alla patienter och dess närstående måste bemötas utifrån sina behov och individuell information är en viktig del i omvårdnadsarbetet. Slutsats: De slutsatser vi drar utifrån vårt resultat är att alla patienter och deras närstående är individer och bör därför bemötas på ett individuellt sätt utifrån deras individuella behov. / In the present time amyotrophic lateral sclerosis (ALS) is an untreatable disease and the course of the disease is often very fast. Nursing of the patients has to be specific. Purpose: The purpose of this literature study was to elucidate caregivers encounter of patients with an untreatable disease like ALS and those who are close to the patients. Method: To answer our research questions we have chosen to do a literature study witch is based on ten scientific articles. The articles were quality rated using Carlsson and Eimans ratingscale for qualitative and quantitative studies. As a frame of reference we used a model by Carnevali. Result: To be one of those who are close to the patients with ALS can affect them in a negative way in their daily life. All patients and those who are close to them have to be encountered by their own needs and individual information is an important part of nursing. Conclusion: From our result we made the conclusions that all patients and those who are close to them are individuals and should be encountered by their personal needs.

Mitochondria play important roles in neuronal function and survival, including ATP production, Ca2+ buffering, and apoptosis. Mitochondrial dysfunction is a common event in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD); however, what causes the mitochondrial dysfunction remains unclear. Mitochondrial fission is mediated by dynamin-related protein 1 (DRP1) and fusion by mitofusin 1/2 (MFN1/2) and optic atrophy 1 (OPA1), which are essential for mitochondrial function. Mutations in the mitochondrial fission and fusion machinery lead to neurodegeneration. Thus, whether defective mitochondrial dynamics participates in ALS and HD requires further investigation. ALS is a fatal neurodegenerative disease characterized by upper and lower motor neuron loss. Mutations in Cu/Zn superoxide dismutase (SOD1) cause the most common familiar form of ALS by mechanisms not fully understood. Here, a new motor neuron-astrocyte coculture system was created and live-cell imaging was used to evaluate mitochondrial dynamics. Excessive mitochondrial fission was observed in mutant SOD1G93A motor neurons, correlating with impaired axonal transport and neuronal cell death. Inhibition of mitochondrial fission restored mitochondrial dynamics and protected neurons against SOD1G93A -induced mitochondrial fragmentation and neuronal cell death, implicating defects in mitochondrial dynamics in ALS pathogenesis. iv HD is an inherited neurodegenerative disorder caused by glutamine (Q) expansion in the polyQ region of the huntingtin (HTT) protein. In the current work, mutant HTT caused mitochondrial fragmentation in a polyQ-dependent manner in both primary cortical neurons and fibroblasts from human patients. An abnormal interaction between DRP1 and HTT was observed in mutant HTT mice and inhibition of mitochondrial fission or promotion of mitochondrial fusion restored mitochondrial dynamics and protected neurons against mutant HTT-induced cell death. Thus, mutant HTT may increase mitochondrial fission by elevating DRP1 GTPase activity, suggesting that mitochondrial dynamics plays a causal role in HD. In summary, rebalanced mitochondrial fission and fusion rescues neuronal cell death in ALS and HD, suggesting that mitochondrial dynamics could be the molecular mechanism underlying these diseases. Furthermore, DRP1 might be a therapeutic target to delay or prevent neurodegeneration.

The 43 kDa TAR DNA binding protein (TDP-43) has been identified as one of the major proteins that accumulates in the cytoplasm of brain and spinal cord from the patients affected with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Under basal conditions, TDP-43 localizes in nucleus functioning as an RNA binding protein to regulate different aspects of RNA metabolism, such as alternative splicing of messenger RNA. In ALS/FTLD brains and spinal cords, TDP-43 forms well-defined cytoplasmic granules, the behavior very similar to stress granule (SG) proteins, but the mechanisms are poorly understood. To investigate the mechanism of TDP-43 granule formation and to identify potential therapeutic targets by inhibiting the granule formation, our laboratory screened a chemical library of 75,000 compounds using the inducible PC12 cells that express EGFP-tagged wild-type human TDP-43. We used the biological effect of cycloheximide on SGs as a basis for the screen, since it is known to prevent the formation of SGs and TDP-43 granules, pointing to a novel biological pathway that regulates TDP-43 granule formation. One of the candidate compounds, Compound 8 (C8) and its analog C8j dose- dependently decreased the arsenite-induced TDP-43 granules without cytotoxicity, and reduced the protein levels of full-length, truncated, high molecular weight and phosphorylated TDP-43. In addition, we found C8j reduced the phosphorylation at novel, previously unknown Thr103-Ser104 amino acid residues of human TDP-43 under arsenite stress. The phospho-mimetic mutations at these sites induced spontaneous intracellular TDP-43 granules, indicating their regulatory role in TDP-43 granule formation. We also performed a series of gene expression analysis combined with the systems biology algorithm, mode of action by network identification (MNI), to identify the mode of action of C8, and found C8 potentially targets protein metabolism and modification processes to reduce the TDP-43 granules. Our study identified a family of non-cytotoxic chemical compounds that reduces the formation of arsenite-induced TDP-43 granules and their potential mode of action. Furthermore, we identified previously unknown TDP-43 phosphorylation sites Thr103- Ser104 that are involved in the TDP-43 granule formation. We anticipate this study will elucidate the biological pathways regulating TDP-43 aggregation and potential therapeutics for ALS/FTLD-U.

The mechanisms by which mitochondria convert nutrients into cellular energy have been described in intricate detail, and yet, the regulation and compartmentalization of such metabolic pathways are poorly understood. As a result, the underlying causes of mitochondrial dysfunction and bioenergetic deficiency in diseases such as amyotrophic lateral sclerosis (ALS) remain elusive. To address this longstanding gap in the field, we first sought to understand how the metabolism of glucose and glucose-derived pyruvate are regulated in the cell. Previous research has suggested that this metabolic regulation is mediated by specialized lipid raft domains of the endoplasmic reticulum (ER) in close contact with mitochondria, referred to as mitochondria-associated ER membranes (MAM). Using density gradient ultracentrifugation and immunoblotting techniques, we found that MAM domains play a role in the compartmentalization of glycolysis by recruiting and promoting the interaction of specific glycolytic enzymes. We then performed a series of bioenergetic, proteomic, and lipidomic analyses to determine how the establishment of ER-mitochondria contact sites at MAM affects the biology of mitochondria attached at these domains. We observed a novel distinction between mitochondria in contact with ER-MAM domains (MER) and those that are free from the ER (FM), with MER displaying a higher capacity for pyruvate-driven respiration and FM being specialized for fatty acid-driven energy production. Finally, using cell and mouse models of ALS with mutations in superoxide dismutase 1 (SOD1), we found that the glycolytic deficiency in ALS is a direct consequence of the progressive disruption of MAM structure and function, which thereby hinders the use of glucose-derived pyruvate as a mitochondrial fuel. This triggers a shift in mitochondrial substrate from pyruvate to fatty acids that, when sustained over time, contributes to the death of motor neurons and the progression of this fatal disease. Overall, this work aims to advance our understanding of metabolic compartmentalization, mitochondrial substrate specificity, and the relevance of both to ALS etiology.