Human Sensorimotor Beta Event Characteristics and Aperiodic Signal Are Highly Heritable.

Individuals' phenotypes, including the brain's structure and function, are largely determined by genes and their interplay. The resting brain generates salient rhythmic patterns that can be characterized noninvasively using functional neuroimaging such as magnetoencephalography (MEG). One of these rhythms, the somatomotor (rolandic) beta rhythm, shows intermittent high amplitude "events" that predict behavior across tasks and species. Beta rhythm is altered in neurological disease. The aperiodic (1/f) signal present in electrophysiological recordings is also modulated by some neurological conditions and aging. Both sensorimotor beta and aperiodic signal could thus serve as biomarkers of sensorimotor function. Knowledge about the extent to which these brain functional measures are heritable could shed light on the mechanisms underlying their generation. We investigated the heritability and variability of human spontaneous sensorimotor beta rhythm events and aperiodic activity in 210 healthy male and female adult siblings' spontaneous MEG activity. The most heritable trait was the aperiodic 1/f signal, with a heritability of 0.87 in the right hemisphere. Time-resolved beta event amplitude parameters were also highly heritable, whereas the heritabilities for overall beta power, peak frequency, and measures of event duration remained nonsignificant. Human sensorimotor neural activity can thus be dissected into different components with variable heritability. We postulate that these differences partially reflect different underlying signal-generating mechanisms. The 1/f signal and beta event amplitude measures may depend more on fixed, anatomical parameters, whereas beta event duration and its modulation reflect dynamic characteristics, guiding their use as potential disease biomarkers.

Clinical and Brain Morphometry Predictors of Deep Brain Stimulation Outcome in Parkinson's Disease.

Subthalamic deep brain stimulation (STN-DBS) is known to improve motor function in advanced Parkinson's disease (PD) and to enable a reduction of anti-parkinsonian medication. While the levodopa challenge test and disease duration are considered good predictors of STN-DBS outcome, other clinical and neuroanatomical predictors are less established. This study aimed to evaluate, in addition to clinical predictors, the effect of patients' individual brain topography on DBS outcome. The medical records of 35 PD patients were used to analyze DBS outcomes measured with the following scales: Part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III) off medication at baseline, and at 6-months during medication off and stimulation on, use of anti-parkinsonian medication (LED), Abnormal Involuntary Movement Scale (AIMS) and Non-Motor Symptoms Questionnaire (NMS-Quest). Furthermore, preoperative brain MRI images were utilized to analyze the brain morphology in relation to STN-DBS outcome. With STN-DBS, a 44% reduction in the UPDRS-III score and a 43% decrease in the LED were observed (p<0.001). Dyskinesia and non-motor symptoms decreased significantly [median reductions of 78,6% (IQR 45,5%) and 18,4% (IQR 32,2%) respectively, p=0.001 - 0.047]. Along with the levodopa challenge test, patients' age correlated with the observed DBS outcome measured as UPDRS-III improvement (ρ= -0.466 - -0.521, p<0.005). Patients with greater LED decline had lower grey matter volumes in left superior medial frontal gyrus, in supplementary motor area and cingulum bilaterally. Additionally, patients with greater UPDRS-III score improvement had lower grey matter volume in similar grey matter areas. These findings remained significant when adjusted for sex, age, baseline LED and UPDRS scores respectively and for total intracranial volume (p=0.0041- 0.001). However, only the LED decrease finding remained significant when the analyses were further controlled for stimulation amplitude. It appears that along with the clinical predictors of STN-DBS outcome, individual patient topographic differences may influence DBS outcome. Clinical Trial Registration Number: NCT06095245, registration date October 23, 2023, retrospectively registered.

Cortical beta burst dynamics are altered in Parkinson's disease but normalized by deep brain stimulation.

Exaggerated subthalamic beta oscillatory activity and increased beta range cortico-subthalamic synchrony have crystallized as the electrophysiological hallmarks of Parkinson's disease. Beta oscillatory activity is not tonic but occurs in 'bursts' of transient amplitude increases. In Parkinson's disease, the characteristics of these bursts are altered especially in the basal ganglia. However, beta oscillatory dynamics at the cortical level and how they compare with healthy brain activity is less well studied. We used magnetoencephalography (MEG) to study sensorimotor cortical beta bursting and its modulation by subthalamic deep brain stimulation in Parkinson's disease patients and age-matched healthy controls. We show that the changes in beta bursting amplitude and duration typical of Parkinson's disease can also be observed in the sensorimotor cortex, and that they are modulated by chronic subthalamic deep brain stimulation, which, in turn, is reflected in improved motor function at the behavioural level. In addition to the changes in individual beta bursts, their timing relative to each other was altered in patients compared to controls: bursts were more clustered in untreated Parkinson's disease, occurring in 'bursts of bursts', and re-burst probability was higher for longer compared to shorter bursts. During active deep brain stimulation, the beta bursting in patients resembled healthy controls' data. In summary, both individual bursts' characteristics and burst patterning are affected in Parkinson's disease, and subthalamic deep brain stimulation normalizes some of these changes to resemble healthy controls' beta bursting activity, suggesting a non-invasive biomarker for patient and treatment follow-up.

Pallidal Deep Brain Stimulation Reduces Sensorimotor Cortex Activation in Focal/Segmental Dystonia.

BACKGROUND: Although deep brain stimulation of the globus pallidus internus (GPi-DBS) is an established treatment for many forms of dystonia, including generalized as well as focal forms, its effects on brain (dys-)function remain to be elucidated, particularly for focal and segmental dystonia. Clinical response to GPi-DBS typically comes with some delay and lasts up to several days, sometimes even weeks, once stimulation is discontinued. OBJECTIVE: This study investigated how neural activity during rest and motor activation is affected by GPi-DBS while excluding the potential confound of altered feedback as a result of therapy-induced differences in dystonic muscle contractions. METHODS: Two groups of patients with focal or segmental dystonia were included in the study: 6 patients with GPi-DBS and 8 without DBS (control group). All 14 patients had cervical dystonia. Using H215 O PET, regional cerebral blood flow was measured at rest and during a motor task performed with a nondystonic hand. RESULTS: In patients with GPi-DBS (stimulation ON and OFF), activity at rest was reduced in a prefrontal network, and during the motor task, sensorimotor cortex activity was lower than in patients without DBS. Within-group contrasts (tapping > rest) showed less extensive task-induced motor network activation in GPi-DBS patients than in non-DBS controls. Reduced sensorimotor activation amounted to a significant group-by-task interaction only in the stimulation ON state. CONCLUSIONS: These findings support previous observations in generalized dystonia that suggested that GPi-DBS normalizes dystonia-associated sensorimotor and prefrontal hyperactivity, indicating similar mechanisms in generalized and focal or segmental dystonia. Evidence is provided that these effects extend into the OFF state, which was not previously demonstrated by neuroimaging. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

A R2R3-MYB gene-based marker for the non-darkening seed coat trait in pinto and cranberry beans (Phaseolus vulgaris L.) derived from 'Wit-rood boontje'.

KEY MESSAGE: The gene Phvul.010G130600 which codes for a MYB was shown to be tightly associated with seed coat darkening in Phaseolus vulgaris and a single nucleotide deletion in the allele in Wit-rood disrupts a transcription activation region that likely prevents its functioning in this non-darkening genotype. The beige and white background colors of the seed coats of conventional pinto and cranberry beans turn brown through a process known as postharvest darkening (PHD). Seed coat PHD is attributed to proanthocyanidin accumulation and its subsequent oxidation in the seed coat. The J gene is an uncharacterized classical genetic locus known to be responsible for PHD in common bean (P. vulgaris) and individuals that are homozygous for its recessive allele have a non-darkening (ND) seed coat phenotype. A previous study identified a major colorimetrically determined QTL for seed coat color on chromosome 10 that was associated with the ND trait. The objectives of this study were to identify a gene associated with seed coat postharvest darkening in common bean and understand its function in promoting seed coat darkening. Amplicon sequencing of 21 candidate genes underlying the QTL associated with the ND trait revealed a single nucleotide deletion (c.703delG) in the candidate gene Phvul.010G130600 in non-darkening recombinant inbred lines derived from crosses between ND 'Wit-rood boontje' and a regular darkening pinto genotype. In silico analysis indicated that Phvul.010G130600 encodes a protein with strong amino acid sequence identity (70%) with a R2R3-MYB-type transcription factor MtPAR, which has been shown to regulate proanthocyanidin biosynthesis in Medicago truncatula seed coat tissue. The deletion in the 'Wit-rood boontje' allele of Phvul.010G130600 likely causes a translational frame shift that disrupts the function of a transcriptional activation domain contained in the C-terminus of the R2R3-MYB. A gene-based dominant marker was developed for the dominant allele of Phvul.010G130600 which can be used for marker-assisted selection of ND beans.

Mapping the non-darkening trait from 'Wit-rood boontje' in bean (Phaseolus vulgaris).

KEY MESSAGE: A QTL for non-darkening seed coat from 'Wit-rood boontje' was mapped in pinto bean population on chromosome Pv10, comprising 40 candidate genes. The seed coat colour darkens with age in some market classes of dry beans (Phaseolus vulgaris), including pinto bean. Beans with darkened seed coats are discounted in the market place, since they are believed to be associated with lower nutritional quality, increased cooking time, and decreased palatability. The objective of this research was to map a non-darkening gene from a cranberry-like bean 'Wit-rood boontje' using a recombinant inbred line population, derived from a cross between 'Wit-rood boontje' and a slow-darkening pinto bean (1533-15). The population was characterized for seed phenotype and genotyped with an Illumina BeadChip. A genetic linkage map was constructed with 1327 informative SNP markers plus an STS marker (OL4S500) and an SSR marker (Pvsd-0028), previously associated with the J gene and Sd gene, respectively, as well as non-darkening and slow-darkening phenotypes. The linkage map spanned 1253.2 cM over 11 chromosomes. A major QTL for the non-darkening trait was flanked by SNP 715646341 and SNP 715646348 on chromosome Pv10. The region, which spanned 13.2 cM, explained 48% of the phenotypic variation for seed coat darkening. Forty candidate genes were identified in the QTL interval. This information can be used to develop a gene-based marker to facilitate breeding non-darkening pinto beans and may lead to a better understanding of the molecular mechanism for the postharvest darkening phenomenon in pinto bean.

Microbial detoxification of eleven food and feed contaminating trichothecene mycotoxins.

BACKGROUND: Contamination of agricultural commodities with multiple trichothecene mycotoxins, produced by toxigenic Fusarium species, is a food safety issue, which greatly affects grain production and marketing worldwide. Importantly, exposure to multiple trichothecenes may increase toxicity in animals due to their synergistic and/or additive effects. To address the problem this study aimed to achieve a novel biological trait capable of detoxifying various food and feed contaminating trichothecenes under aerobic and anaerobic conditions and wide range of temperatures. RESULTS: A highly enriched microbial consortium (called DX100) capable of transforming eleven trichothecenes to significantly less toxic de-epoxy forms was achieved after prolonged incubation of soil microbial culture with 200 µg/mL deoxynivalenol (DON). DX100 demonstrated de-epoxidation activity under aerobic and anaerobic conditions, a greater range of temperatures and around neutral pH. The consortium contains 70% known and 30% unknown bacterial species, dominated by Stenotrophomonas species. Probably novel bacteria including strains of Stenotrophomonas and Alkaliphilus-Blautia species complex could be involved in aerobic and anaerobic de-epoxidation of trichothecenes, respectively. DX100 showed rapid and stable activity by de-epoxidizing 100% of 50 µg/mL deoxynivalenol at 48 h of incubation and retaining de-epoxidation ability after 100 subcultures in mineral salts broth (MSB). It was able to de-epoxidize high concentration of DON (500 µg/mL), and transformed ten more food contaminating trichothecenes into de-epoxy forms and/or other known/unknown compounds. Microbial de-epoxidation rate increased with increasing trichothecene concentrations in the broth media, suggesting that DX100 maintains a robust trichothecene detoxifying mechanism. Furthermore, the nature of microbial de-epoxidation reaction and inhibition of the reaction by sodium azide and the finding that bacterial cell culture lysate retained activity suggests that certain cytoplasmic reductases may be responsible for the de-epoxidation activity. CONCLUSIONS: This study reports the enrichment procedure for obtaining an effective and stable microbial consortium DX100 capable of de-epoxidizing several food contaminating trichothecene mycotoxins. DX100, which has de-epoxidation ability under wide range of conditions, represents a unique enzymatic source which has great industrial potential for reducing contamination of foods/feeds with multiple trichothecenes, and minimizing their synergistic/additive cytotoxic effects on consumer health.

Proanthocyanidin accumulation and transcriptional responses in the seed coat of cranberry beans (Phaseolus vulgaris L.) with different susceptibility to postharvest darkening.

BACKGROUND: Edible dry beans (Phaseolus vulgaris L.) that darken during postharvest storage are graded lower and are less marketable than their non-darkened counterparts. Seed coat darkening in susceptible genotypes is dependent upon the availability of proanthocyanidins, and their subsequent oxidation to reactive quinones. Mature cranberry beans lacking this postharvest darkening trait tend to be proanthocyanidin-deficient, although the underlying molecular and biochemical determinants for this metabolic phenomenon are unknown. RESULTS: Seed coat proanthocyanidin levels increased with plant maturation in a darkening-susceptible cranberry bean recombinant inbred line (RIL), whereas these metabolites were absent in seeds of the non-darkening RIL plants. RNA sequencing (RNA-seq) analysis was used to monitor changes in the seed coat transcriptome as a function of bean development, where transcript levels were measured as fragments per kilobase of exon per million fragments mapped. A total of 1336 genes were differentially expressed between darkening and non-darkening cranberry bean RILs. Structural and regulatory genes of the proanthocyanidin biosynthesis pathway were upregulated in seed coats of the darkening RIL. A principal component analysis determined that changes in transcript levels for two genes of unknown function and three proanthocyanidin biosynthesis genes, FLAVANONE 3-HYDROXYLASE 1, DIHYDROFLAVONOL 4-REDUCTASE 1 and ANTHOCYANIDIN REDUCTASE 1 (PvANR1) were highly correlated with proanthocyanidin accumulation in seed coats of the darkening-susceptible cranberry bean RIL. HPLC-DAD analysis revealed that in vitro activity of a recombinant PvANR1 was NADPH-dependent and assays containing cyanidin yielded epicatechin and catechin; high cyanidin substrate levels inhibited the formation of both of these products. CONCLUSION: Proanthocyanidin oxidation is a pre-requisite for postharvest-related seed coat darkening in dicotyledonous seeds. In model plant species, the accumulation of proanthocyanidins is dependent upon upregulation of biosynthetic genes. In this study, proanthocyanidin production in cranberry bean seed coats was strongly associated with an increase in PvANR1 transcripts during seed maturation. In the presence of NADPH, PvANR1 converted the physiologically relevant substrate cyanidin to epicatechin and catechin.

Molecular characterization of dihydroneopterin aldolase and aminodeoxychorismate synthase in common bean-genes coding for enzymes in the folate synthesis pathway.

Common beans (Phaseolus vulgaris) are excellent sources of dietary folates, but different varieties contain different amounts of these compounds. Genes coding for dihydroneopterin aldolase (DHNA) and aminodeoxychorismate synthase (ADCS) of the folate synthesis pathway were characterized by PCR amplification, BAC clone sequencing, and whole genome sequencing. All DHNA and ADCS genes in the Mesoamerican cultivar OAC Rex were isolated and compared with those genes in the genome of Andean genotype G19833. Both genotypes have two functional DHNA genes and one pseudo gene. PvDHNA1 and PvDHNA2 proteins have similar secondary structures and conserved residues as DHNA homologs in Staphylococcus aureus and Arabidopsis. Sequence analysis and synteny mapping indicated that PvDHNA1 might be a duplicated and transposed copy of PvDHNA2. There is only one ADCS gene (PvADCS) identified in the bean genome and it is identical in OAC Rex and G19833. PvADCS has the conserved motifs required for catalytic activity similar to other plant ADCS homologs. DHNA and ADCS gene-specific markers were developed, mapped, and compared to their physical locations on chromosomes 1 and 7, respectively. The gene-specific markers developed in this study should be useful for detection and selection of varieties with enhanced folate contents in bean breeding programs.

Thalamomuscular coherence in essential tremor: hen or egg in the emergence of tremor?

Thalamomuscular coherence in essential tremor (ET) has consistently been detected in numerous neurophysiological studies. Thereby, spatial properties of coherence indicate a differentiated, somatotopic organization; so far, however, little attention has been paid to temporal aspects of this interdependency. Further insight into the relationship between tremor onset and the onset of coherence could pave the way to more efficient deep brain stimulation (DBS) algorithms for tremor. We studied 10 severely affected ET patients (six females, four males) during surgery for DBS-electrode implantation and simultaneously recorded local field potentials (LFPs) and surface electromyographic signals (EMGs) from the extensor and flexor muscles of the contralateral forearm during its elevation. The temporal relationship between the onset of significant wavelet cross spectrum (WCS) and tremor onset was determined. Moreover, we examined the influence of electrode location within one recording depth on this latency and the coincidence of coherence and tremor for depths with strong overall coherence ("tremor clusters") and those without. Data analysis revealed tremor onset occurring 220 ± 460 ms before the start of significant LFP-EMG coherence. Furthermore, we could detect an anterolateral gradient of WCS onset within one recording depth. Finally, the coincidence of tremor and coherence was significantly higher in tremor clusters. We conclude that tremor onset precedes the beginning of coherence. Besides, within one recording depth there is a spread of the tremor signal. This reflects the importance of somatosensory feedback for ET and questions the suitability of thalamomuscular coherence as a biomarker for "closed-loop" DBS systems to prevent tremor emergence.

Deep brain stimulation in the ventrolateral thalamus/subthalamic area in dystonia with head tremor.

BACKGROUND: Pallidal deep brain stimulation (GPi-DBS) effectively ameliorates idiopathic dystonia, although approximately 15% of patients respond insufficiently. Although various thalamic and subthalamic targets have been suggested for dystonic tremor, no systematic studies have been published on thalamic DBS in dystonic tremor. We assessed the effect of thalamic/subthalamic area DBS (Th-DBS) on dystonic head tremor and dystonia in a single-blind design. METHODS: Dystonic head tremor and dystonia before and 3 months after surgery were quantified via blinded video-ratings using the Fahn-Tolosa-Marin-Tremor-Scale and the Burke-Fahn-Marsden-Dystonia-Rating-Scale in seven patients with idiopathic cervical or segmental dystonia, dystonic head tremor, and bilateral Th-DBS. Pain, side effects, adverse events, and stimulation parameters were assessed. RESULTS: Th-DBS improved dystonic tremor and dystonia (P < 0.05; 57.1% and 70.4%, respectively). Head tremor amplitude and pain were also improved (P < 0.05; 77.5% and 90.0%, respectively). Side effects included dysarthria, gait disturbance, slowness of movement, and weight gain. CONCLUSION: Dystonic head tremor and dystonia can be improved with Th-DBS.

Cooked navy and black bean diets improve biomarkers of colon health and reduce inflammation during colitis.

Common beans contain non-digestible fermentable components (SCFA precursors) and phenolic compounds (phenolic acids, flavonoids and anthocyanins) with demonstrated antioxidant and anti-inflammatory potential. The objective of the present study was to assess the in vivo effect of cooked whole-bean flours, with differing phenolic compound levels and profiles, in a mouse model of acute colitis. C57BL/6 mice were fed a 20 % navy bean or black bean flour-containing diet or an isoenergetic basal diet (BD) for 2 weeks before the induction of experimental colitis via 7 d dextran sodium sulphate (DSS, 2 % (w/v) in the drinking-water) exposure. Compared with the BD, both bean diets increased caecal SCFA and faecal phenolic compound concentrations (P< 0·05), which coincided with both beneficial and adverse effects on colonic and systemic inflammation. On the one hand, bean diets reduced mRNA expression of colonic inflammatory cytokines (IL-6, IL-9, IFN-γ and IL-17A) and increased anti-inflammatory IL-10 (P< 0·05), while systemically reduced circulating cytokines (IL-1ß, TNFα, IFNγ, and IL-17A, P< 0·05) and DSS-induced oxidative stress. On the other hand, bean diets enhanced DSS-induced colonic damage as indicated by an increased histological injury score and apoptosis (cleaved caspase-3 and FasL mRNA expression) (P< 0·05). In conclusion, bean-containing diets exerted both beneficial and adverse effects during experimental colitis by reducing inflammatory biomarkers both locally and systemically while aggravating colonic mucosal damage. Further research is required to understand the mechanisms through which beans exert their effects on colonic inflammation and the impact on colitis severity in human subjects.

Young adults with dyskinetic cerebral palsy improve subjectively on pallidal stimulation, but not in formal dystonia, gait, speech and swallowing testing.

BACKGROUND: Pharmacological treatment of dyskinetic cerebral palsy (CP) is often ineffective. Data about outcome of deep brain stimulation (DBS) in these patients remains scarce. METHODS: Eight patients with dyskinetic CP and DBS of the Globus Pallidus internus were investigated. Using pre- and postoperative videos the severity of dystonia and changes thereof during standardized settings ('on') and after the stimulator had been switched off ('off') were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Furthermore, subjective impression (SI) of the extent of postoperative change as well as gait (Leonardo Mechanograph® Gangway), speech (Frenchay Dysarthria) and swallowing performances (fiberoptic laryngoscopy) were assessed during 'on' and 'off'. RESULTS: When comparing pre- and postoperative as well as 'on' and 'off', the BFMDRS and most of the gait, speech, and swallowing parameters did not differ significantly. In contrast, patients reported significant improvement of their SI postoperatively (3.1 on a 10-point-scale). CONCLUSION: Data show that our CP-patients did not benefit from GPi-DBS when tested formally for dystonia, gait, speech and swallowing. In stark contrast, these patients reported significant subjective improvement. Taken together, and in light of current unsatisfactory medical treatment options, our data suggest that further assessment of the effects of GPi-DBS in dyskinetic CP is warranted.

Agrobacterium tumefaciens-mediated transformation of corn (Zea mays L.) multiple shoots.

An Agrobacterium tumefaciens-mediated corn transformation method based on multiple shoot tissue cultures was developed, which is effective with a variety of corn inbred lines and standard binary vectors. Six factors that affected the success of corn transformation were tested, including A. tumefaciens strain, corn genotype, tissue culture growth stage, medium composition, co-culture temperature and surfactant treatment. Agropine-type bacteria (EHA 101 and AGL 1) were eightfold more effective than octopine-type strain for corn multi-shoot tissues transformation. The average frequency of Glucuronidase (GUS)-positive explants obtained from 14 corn genotypes ranged from 36% to 76%. L-proline (0.7 g L-1) in the co-culture medium apparently improved the frequency of transformation. The newly initiated multi-shoot tissues were most responsive to Agrobacterium infection. A positive correlation was found between multi-shoot tissue susceptibility to Agrobacterium and the proportion of cells in G1 phase. Transformants were identified by reverse transcription Polymerase Chain Reaction (PCR) and by southern blot hybridization assays. The frequency of transformants was approximately 2% based on the number of multi-shoot explants co-cultivated with Agrobacterium.

Human sensorimotor resting state beta events and aperiodic activity show good test-retest reliability.

OBJECTIVE: Diseases affecting sensorimotor function impair physical independence. Reliable functional clinical biomarkers allowing early diagnosis or targeting treatment and rehabilitation could reduce this burden. Magnetoencephalography (MEG) non-invasively measures brain rhythms such as the somatomotor 'rolandic' rhythm which shows intermittent high-amplitude beta (14-30 Hz) 'events' that predict behavior across tasks and species and are altered by sensorimotor neurological diseases. METHODS: We assessed test-retest stability, a prerequisite for biomarkers, of spontaneous sensorimotor aperiodic (1/f) signal and beta events in 50 healthy human controls across two MEG sessions using the intraclass correlation coefficient (ICC). Beta events were determined using an amplitude-thresholding approach on a narrow-band filtered amplitude envelope obtained using Morlet wavelet decomposition. RESULTS: Resting sensorimotor characteristics showed good to excellent test-retest stability. Aperiodic component (ICC 0.77-0.88) and beta event amplitude (ICC 0.74-0.82) were very stable, whereas beta event duration was more variable (ICC 0.55-0.7). 2-3 minute recordings were sufficient to obtain stable results. Analysis automatization was successful in 86%. CONCLUSIONS: Sensorimotor beta phenotype is a stable feature of an individual's resting brain activity even for short recordings easily measured in patients. SIGNIFICANCE: Spontaneous sensorimotor beta phenotype has potential as a clinical biomarker of sensorimotor system integrity.

Levodopa-Entacapone-Carbidopa Intestinal Gel Treatment in Advanced Parkinson's Disease: A Single-Center Study of 30 Patients.

BACKGROUND: Levodopa-entacapone-carbidopa intestinal gel (LECIG) is a novel device assisted treatment option for advanced Parkinson's disease (PD). It has been available in Finland since 2020. There is paucity of scientific studies considering LECIG treatment in clinical practice. OBJECTIVES: Objectives of this study were to evaluate the changes in medication, adverse events and early discontinuations of LECIG treatment in real life clinical practice. METHODS: The records of 30 consecutive patients, who received LECIG between years 2020 and 2022 in Helsinki University Hospital, were retrospectively analyzed. Data considering changes in medication, discontinuations, and adverse events during the first six months of LECIG treatment was collected. RESULTS: Mean levodopa equivalent daily dose (LEDD) rose significantly between baseline before LECIG and six months with treatment (1230 mg vs. 1570 mg, P = 0.001). Three patients were discarded during nasojejunal tube test phase and seven discontinued the treatment during six-month follow-up. Most common reasons for discontinuation were difficulty in finding suitable infusion rate and neuropsychiatric problems. Safety issues encountered were similar to those reported with levodopa-carbidopa intestinal gel (LCIG) treatment. One case of rhabdomyolysis due to severe dyskinesia during LECIG treatment was observed. Patients were satisfied with the small size of the pump system. CONCLUSIONS: LEDD seems to increase during the first months of LECIG treatment. When compared to studies on LCIG, safety profile of LECIG appears similar, but early discontinuation rate is higher than expected. However, long-term studies are lacking. Only clear advantage to LCIG appears to be the smaller LECIG pump size.

Effects of deep brain stimulation in dyskinetic cerebral palsy: a meta-analysis.

Secondary dystonia encompasses a heterogeneous group with different etiologies. Cerebral palsy is the most common cause. Pharmacological treatment is often unsatisfactory. There are only limited data on the therapeutic outcomes of deep brain stimulation in dyskinetic cerebral palsy. The published literature regarding deep brain stimulation and secondary dystonia was reviewed in a meta-analysis to reevaluate the effect on cerebral palsy. The Burke-Fahn-Marsden Dystonia Rating Scale movement score was chosen as the primary outcome measure. Outcome over time was evaluated and summarized by mixed-model repeated-measures analysis, paired Student t test, and Pearson's correlation coefficient. Twenty articles comprising 68 patients with cerebral palsy undergoing deep brain stimulation assessed by the Burke-Fahn-Marsden Dystonia Rating Scale were identified. Most articles were case reports reflecting great variability in the score and duration of follow-up. The mean Burke-Fahn-Marsden Dystonia Rating Scale movement score was 64.94 ± 25.40 preoperatively and dropped to 50.5 ± 26.77 postoperatively, with a mean improvement of 23.6% (P < .001) at a median follow-up of 12 months. The mean Burke-Fahn-Marsden Dystonia Rating Scale disability score was 18.54 ± 6.15 preoperatively and 16.83 ± 6.42 postoperatively, with a mean improvement of 9.2% (P < .001). There was a significant negative correlation between severity of dystonia and clinical outcome (P < .05). Deep brain stimulation can be an effective treatment option for dyskinetic cerebral palsy. In view of the heterogeneous data, a prospective study with a large cohort of patients in a standardized setting with a multidisciplinary approach would be helpful in further evaluating the role of deep brain stimulation in cerebral palsy. © 2013 Movement Disorder Society.

A new rechargeable device for deep brain stimulation: a prospective patient satisfaction survey.

BACKGROUND: Deep brain stimulation (DBS) is highly successful in treating Parkinson's disease (PD), dystonia, and essential tremor (ET). Until recently implantable neurostimulators were nonrechargeable, battery-driven devices, with a lifetime of about 3-5 years. This relatively short duration causes problems for patients (e.g. programming and device-use limitations, unpredictable expiration, surgeries to replace depleted batteries). Additionally, these batteries (relatively large with considerable weight) may cause discomfort. To overcome these issues, the first rechargeable DBS device was introduced: smaller, lighter and intended to function for 9 years. METHODS: Of 35 patients implanted with the rechargeable device, 21 (including 8 PD, 10 dystonia, 2 ET) were followed before and 3 months after surgery and completed a systematic survey of satisfaction with the rechargeable device. RESULTS: Overall patient satisfaction was high (83.3 ± 18.3). Dystonia patients tended to have lower satisfaction values for fit and comfort of the system than PD patients. Age was significantly negatively correlated with satisfaction regarding process of battery recharging. CONCLUSIONS: Dystonia patients (generally high-energy consumption, severe problems at the DBS device end-of-life) are good, reliable candidates for a rechargeable DBS system. In PD, younger patients, without signs of dementia and good technical understanding, might have highest benefit.

Mapping yield and yield-related traits using diverse common bean germplasm.

Common bean (bean) is one of the most important legume crops, and mapping genes for yield and yield-related traits is essential for its improvement. However, yield is a complex trait that is typically controlled by many loci in crop genomes. The objective of this research was to identify regions in the bean genome associated with yield and a number of yield-related traits using a collection of 121 diverse bean genotypes with different yields. The beans were evaluated in replicated trials at two locations, over two years. Significant variation among genotypes was identified for all traits analyzed in the four environments. The collection was genotyped with the BARCBean6K_3 chip (5,398 SNPs), two yield/antiyield gene-based markers, and seven markers previously associated with resistance to common bacterial blight (CBB), including a Niemann-Pick polymorphism (NPP) gene-based marker. Over 90% of the single-nucleotide polymorphisms (SNPs) were polymorphic and separated the panel into two main groups of small-seeded and large-seeded beans, reflecting their Mesoamerican and Andean origins. Thirty-nine significant marker-trait associations (MTAs) were identified between 31 SNPs and 15 analyzed traits on all 11 bean chromosomes. Some of these MTAs confirmed genome regions previously associated with the yield and yield-related traits in bean, but a number of associations were not reported previously, especially those with derived traits. Over 600 candidate genes with different functional annotations were identified for the analyzed traits in the 200-Kb region centered on significant SNPs. Fourteen SNPs were identified within the gene model sequences, and five additional SNPs significantly associated with five different traits were located at less than 0.6 Kb from the candidate genes. The work confirmed associations between two yield/antiyield gene-based markers (AYD1m and AYD2m) on chromosome Pv09 with yield and identified their association with a number of yield-related traits, including seed weight. The results also confirmed the usefulness of the NPP marker in screening for CBB resistance. Since disease resistance and yield measurements are environmentally dependent and labor-intensive, the three gene-based markers (CBB- and two yield-related) and quantitative trait loci (QTL) that were validated in this work may be useful tools for simplifying and accelerating the selection of high-yielding and CBB-resistant bean cultivars.

Task-specific modulation of effective connectivity during two simple unimanual motor tasks: a 122-channel EEG study.

Neural oscillations are thought to underlie coupling of spatially remote neurons and gating of information within the human sensorimotor system. Here we tested the hypothesis that different unimanual motor tasks are specifically associated with distinct patterns of oscillatory coupling in human sensorimotor cortical areas. In 13 healthy, right-handed subjects, we recorded task-induced neural activity with 122-channel electroencephalography (EEG) while subjects performed fast self-paced extension-flexion movements with the right index finger and an isometric contraction of the right forearm. Task-related modulations of inter-regional coupling within a core motor network comprising the left primary motor cortex (M1), lateral premotor cortex (lPM) and supplementary motor area (SMA) were then modeled using dynamic causal modeling (DCM). A network model postulating coupling both within and across frequencies best captured observed spectral responses according to Bayesian model selection. DCM revealed dominant coupling within the ß-band (13-30 Hz) between M1 and SMA during isometric contraction of the forearm, whereas fast repetitive finger movements were characterized by strong coupling within the γ-band (31-48 Hz) and between the θ- (4-7 Hz) and the γ-band. This coupling pattern was mainly expressed in connections from lPM to SMA and from lPM to M1. We infer that human manual motor control involves task-specific modulation of inter-regional oscillatory coupling both within and across distinct frequency bands. The results highlight the potential of DCM to characterize context-specific changes in coupling within functional brain networks.