Plant regeneration in eggplant (Solanum melongena L.): A review

Eggplant is highly responsive to various tissue culture techniques. Somatic embryogenesis and direct organogenesis are widely studied protocols in this crop, but potential of regeneration varies with genotype, explant and culture media supplemented with different combination and concentration of growth hormones. The genotype is the most important factor affecting somatic embryogenesis and organogenesis. Embryogenic competence  occurs even within explant segments. Among growth regulators, auxins and cytokinins are of more significance as their ratio determines callogenesis,rhizogenesis, embryogenesis and regeneration in eggplant. Organogenesis and somatic embryogenesis related gene expression has been studied and transcripts have been analyzed through molecular studies. Efficient plant regeneration protocols would make a platform for exploitation of usefulsomaclonal variations, mutation breeding, induction of di-haploids, and genetic transformation with economically important genes for the improvement of eggplant.Key words: Callus, somatic embryogenesis, organogenesis, hypocotyl, cotyledon, leaf

A Guide to Designing a Memory fMRI Paradigm for Pre-surgical Evaluation in Temporal Lobe Epilepsy

There has been increasing interest in the clinical and experimental use of memory functional Magnetic Resonance Imaging (fMRI). The 2017 American Academy of Neurology practice guidelines on the use of pre-surgical cognitive fMRI suggests that verbal memory fMRI could be used to lateralize memory functions in people with Temporal Lobe Epilepsy (TLE) and should be used to predict post-operative verbal memory outcome. There are however technical and methodological considerations, to optimize both the sensitivity and specificity of this imaging modality. Below we discuss these constraints and suggest recommendations to consider when designing a memory fMRI paradigm

Neuroimaging in epilepsy

PURPOSE OF REVIEW: Epilepsy neuroimaging is important for detecting the seizure onset zone, predicting and preventing deficits from surgery and illuminating mechanisms of epileptogenesis. An aspiration is to integrate imaging and genetic biomarkers to enable personalized epilepsy treatments. RECENT FINDINGS: The ability to detect lesions, particularly focal cortical dysplasia and hippocampal sclerosis, is increased using ultra high-field imaging and postprocessing techniques such as automated volumetry, T2 relaxometry, voxel-based morphometry and surface-based techniques. Statistical analysis of PET and single photon emission computer tomography (STATISCOM) are superior to qualitative analysis alone in identifying focal abnormalities in MRI-negative patients. These methods have also been used to study mechanisms of epileptogenesis and pharmacoresistance. Recent language fMRI studies aim to localize, and also lateralize language functions. Memory fMRI has been recommended to lateralize mnemonic function and predict outcome after surgery in temporal lobe epilepsy. SUMMARY: Combinations of structural, functional and post-processing methods have been used in multimodal and machine learning models to improve the identification of the seizure onset zone and increase understanding of mechanisms underlying structural and functional aberrations in epilepsy

Episodic Memory in Temporal Lobe Epilepsy

Individuals with temporal lobe epilepsy (TLE) have significant material specific episodic memory impairments with greater verbal and visual memory deficits accompanying left and right TLE respectively. More recently, however, widespread cognitive deficits have been described in patients with TLE in keeping with morphological and functional abnormalities that extend beyond the temporal lobes. Functional magnetic resonance imaging (fMRI) has demonstrated reorganisation of memory encoding networks within the temporal lobe in TLE, but little is known of the extra-temporal networks in these patients. Memory fMRI as a tool for predicting memory decline after anterior temporal lobe resection has been explored but a clinically applicable algorithm has yet to be defined. Fewer studies have described the changes in the memory encoding networks after temporal lobe surgery. This thesis presents methodological developments and novel applications to describe the pre-operative and post-operative verbal and visual memory networks in those with unilateral TLE. Pre-operatively, I investigated extra-temporal areas of memory reorganisation in left and right TLE patients, quantitatively compared to healthy controls. Novel findings include the ‘efficiency’ of extra-temporal reorganisation to successful memory formation. Next, using clinical parameters such as age at onset of epilepsy, epilepsy duration and seizure frequency as continuous regressors, I described the factors affecting verbal and visual memory reorganisation in TLE. In a separate pre-operative study, I used an alternative fMRI analysis method, multi-voxel pattern analysis (MVPA) that focuses on the patterns of activity across voxels 4 in specific brain regions that are associated with individual memory traces. I used MVPA-fMRI to assess the functional integrity of the hippocampi and other medial temporal lobe structures in patients with unilateral TLE. Next, I explored the predictive ability of temporal and extra-temporal activations in predicting post-operative verbal memory decline in left and right TLE patients and described a method of using memory fMRI as a clinically applicable tool in patients who had anterior temporal lobe resection. Finally, I explored memory encoding network plasticity four and 12 months after anterior temporal lobe resection. In this study, controls were also scanned at similar time intervals to patients. I report for the first time, dynamic changes in the memory encoding network four and 12 months after surgery, relative to changes in controls. Novel findings also include the efficiency of these post-operative networks. In this thesis, I also discuss methodological constraints, clinical applications and future directions

Memory fMRI predicts verbal memory decline after anterior temporal lobe resection.

To develop a clinically applicable memory functional MRI (fMRI) method of predicting postsurgical memory outcome in individual patients

Structural correlates of impaired working memory in hippocampal sclerosis

PURPOSE: Temporal lobe epilepsy (TLE) has been considered to impair long-term memory, whilst not affecting working memory, but recent evidence suggests that working memory is compromised. Functional MRI (fMRI) studies demonstrate that working memory involves a bilateral frontoparietal network the activation of which is disrupted in hippocampal sclerosis (HS). A specific role of the hippocampus to deactivate during working memory has been proposed with this mechanism faulty in patients with HS. Structural correlates of disrupted working memory in HS have not been explored. METHODS: We studied 54 individuals with medically refractory TLE and unilateral HS (29 left) and 28 healthy controls. Subjects underwent 3T structural MRI, a visuospatial n-back fMRI paradigm and diffusion tensor imaging (DTI). Working memory capacity assessed by three span tasks (digit span backwards, gesture span, motor sequences) was combined with performance in the visuospatial paradigm to give a global working memory measure. Gray and white matter changes were investigated using voxel-based morphometry and voxel-based analysis of DTI, respectively. KEY FINDINGS: Individuals with left or right HS performed less well than healthy controls on all measures of working memory. fMRI demonstrated a bilateral frontoparietal network during the working memory task with reduced activation of the right parietal lobe in both patient groups. In left HS, gray matter loss was seen in the ipsilateral hippocampus and parietal lobe, with maintenance of the gray matter volume of the contralateral parietal lobe associated with better performance. White matter integrity within the frontoparietal network, in particular the superior longitudinal fasciculus and cingulum, and the contralateral temporal lobe, was associated with working memory performance. In right HS, gray matter loss was also seen in the ipsilateral hippocampus and parietal lobe. Working memory performance correlated with the gray matter volume of both frontal lobes and white matter integrity within the frontoparietal network and contralateral temporal lobe. SIGNIFICANCE: Our data provide further evidence that working memory is disrupted in HS and impaired integrity of both gray and white matter is seen in functionally relevant areas. We suggest this forms the structural basis of the impairment of working memory, indicating widespread and functionally significant structural changes in patients with apparently isolated HS

Progressive myoclonic epilepsy due to rare mitochondrial ND6 mutation, m.14487T>C

INTRODUCTION: Mitochondrial diseases exhibit wide phenotypic heterogeneity, and can present as progressive myoclonic epilepsy. SUMMARY: We report a case of adult-onset drug-resistant epilepsy, cortical myoclonus and bilateral optic neuropathies due to m.14487T>C, a rare mitochondrial gene mutation identified on whole-genome sequencing. This mutation, which affects the NADH dehydrogenase 6 (ND6) subunit of the mitochondrial respiratory chain, is most commonly implicated in cases of infantile-onset Leigh syndrome, although a broader phenotypic spectrum including migraine with aura and progressive myoclonic epilepsy have been described. Serial MRI scans over a 2-year period demonstrated the interval development of bihemispheric stroke-like lesions. Giant somatosensory evoked potentials and short-duration myoclonic jerks with craniocaudal spread on surface electromyography were consistent with cortical myoclonus. Optical coherence tomography showed bilateral symmetric thinning of the nerve fibre layer in the papillomacular bundles. CONCLUSION: Whole-genome sequencing can help to provide a definitive diagnosis for mitochondrial disease and should be considered in situations where clinical suspicion remains high despite normal genetic panels or muscle histopathology. Mitochondrial disease can present as adult-onset progressive myoclonic epilepsy, and bilateral optic neuropathies can be a striking feature of ND6 mitochondrial gene mutations. In our case, severe cortical myoclonus affecting speech and swallowing remained highly drug-resistant, however, symptomatic benefit was derived from targeted onabotulinum toxin A injections

Two-center experience of cannabidiol use in adults with Dravet syndrome

We describe real-world experience with cannabidiol (CBD) in adults with Dravet Syndrome (DS) via GW Pharma early access programme at two UK neurology centres. Adults with genetically-confirmed DS had CBD added to existing therapy, titrated up to 20 mg/kg, as tolerated. The primary outcome measure was percentage reduction in convulsive seizures. Secondary outcome measures included changes in myoclonic seizures, and in cognition and quality of life as assessed by the Caregiver Global Impression of Change (CGIC), and incidence of adverse events (AEs). 18 adults (7 female; median age 27.5 years; range 20–51) were included. Median follow-up was 176 days. In one, another antiseizure drug, clobazam, was introduced during the programme. 3/17 (17.6%) had >30% reduction in convulsive seizures (range: 87.5–100%). AEs occurred in all, the most common being transaminitis (52.9%). Behavioural AEs led to discontinuation in 3/18 (16.7%), including a seizure-free responder. In 7/18, CBD was stopped due to lack of effect. 8/18 continue on treatment. Improvements in CGIC were reported in 41.2% and 47.1% by physicians and families, respectively. 17.6% achieved sufficient reduction in convulsive seizure frequency to qualify for NHS funding. AEs led to withdrawal in only 16.7%. Close monitoring and dose adjustments of other antiseizure drugs were necessary

Memory network plasticity after temporal lobe resection: a longitudinal functional imaging study

Anterior temporal lobe resection can control seizures in up to 80% of patients with temporal lobe epilepsy. Memory decrements are the main neurocognitive complication. Preoperative functional reorganization has been described in memory networks, but less is known of postoperative reorganization. We investigated reorganization of memory-encoding networks preoperatively and 3 and 12 months after surgery. We studied 36 patients with unilateral medial temporal lobe epilepsy (19 right) before and 3 and 12 months after anterior temporal lobe resection. Fifteen healthy control subjects were studied at three equivalent time points. All subjects had neuropsychological testing at each of the three time points. A functional magnetic resonance imaging memory-encoding paradigm of words and faces was performed with subsequent out-of-scanner recognition assessments. Changes in activations across the time points in each patient group were compared to changes in the control group in a single flexible factorial analysis. Postoperative change in memory across the time points was correlated with postoperative activations to investigate the efficiency of reorganized networks. Left temporal lobe epilepsy patients showed increased right anterior hippocampal and frontal activation at both 3 and 12 months after surgery relative to preoperatively, for word and face encoding, with a concomitant reduction in left frontal activation 12 months postoperatively. Right anterior hippocampal activation 12 months postoperatively correlated significantly with improved verbal learning in patients with left temporal lobe epilepsy from preoperatively to 12 months postoperatively. Preoperatively, there was significant left posterior hippocampal activation that was sustained 3 months postoperatively at word encoding, and increased at face encoding. For both word and face encoding this was significantly reduced from 3 to 12 months postoperatively. Patients with right temporal lobe epilepsy showed increased left anterior hippocampal activation on word encoding from 3 to 12 months postoperatively compared to preoperatively. On face encoding, left anterior hippocampal activations were present preoperatively and 12 months postoperatively. Left anterior hippocampal and orbitofrontal cortex activations correlated with improvements in both design and verbal learning 12 months postoperatively. On face encoding, there were significantly increased left posterior hippocampal activations that reduced significantly from 3 to 12 months postoperatively. Postoperative changes occur in the memory-encoding network in both left and right temporal lobe epilepsy patients across both verbal and visual domains. Three months after surgery, compensatory posterior hippocampal reorganization that occurs is transient and inefficient. Engagement of the contralateral hippocampus 12 months after surgery represented efficient reorganization in both patient groups, suggesting that the contralateral hippocampus contributes to memory outcome 12 months after surgery