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We aimed to quantitatively characterize progressive brain network disruption in Amyotrophic Lateral Sclerosis (ALS) during cognition using the mismatch negativity (MMN), an electrophysiological index of attention switching. We measured the MMN using 128-channel EEG longitudinally (2-5 timepoints) in 60 ALS patients and cross-sectionally in 62 healthy controls. Using dipole fitting and linearly constrained minimum variance beamforming we investigated cortical source activity changes over time. In ALS, the inferior frontal gyri (IFG) show significantly lower baseline activity compared to controls. The right IFG and both superior temporal gyri (STG) become progressively hyperactive longitudinally. By contrast, the left motor and dorsolateral prefrontal cortices are initially hyperactive, declining progressively. Baseline motor hyperactivity correlates with cognitive disinhibition, and lower baseline IFG activities correlate with motor decline rate, while left dorsolateral prefrontal activity predicted cognitive and behavioural impairment. Shorter survival correlates with reduced baseline IFG and STG activity and later STG hyperactivation. Source-resolved EEG facilitates quantitative characterization of symptom-associated and symptom-preceding motor and cognitive-behavioral cortical network decline in ALS., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Temporal lobe studies in motor neuron disease overwhelmingly focus on white matter alterations and cortical grey matter atrophy. Reports on amygdala involvement are conflicting and the amygdala is typically evaluated as single structure despite consisting of several functionally and cytologically distinct nuclei. A prospective, single-centre, neuroimaging study was undertaken to comprehensively characterise amygdala pathology in 100 genetically-stratified ALS patients, 33 patients with PLS and 117 healthy controls. The amygdala was segmented into groups of nuclei using a Bayesian parcellation algorithm based on a probabilistic atlas and shape deformations were additionally assessed by vertex analyses. The accessory basal nucleus (p = .021) and the cortical nucleus (p = .022) showed significant volume reductions in C9orf72 negative ALS patients compared to controls. The lateral nucleus (p = .043) and the cortico-amygdaloid transition (p = .024) were preferentially affected in C9orf72 hexanucleotide carriers. A trend of total volume reduction was identified in C9orf72 positive ALS patients (p = .055) which was also captured in inferior-medial shape deformations on vertex analyses. Our findings highlight that the amygdala is affected in ALS and our study demonstrates the selective involvement of specific nuclei as opposed to global atrophy. The genotype-specific patterns of amygdala involvement identified by this study are consistent with the growing literature of extra-motor clinical features. Mesial temporal lobe pathology in ALS is not limited to hippocampal pathology but, as a key hub of the limbic system, the amygdala is also affected in ALS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The thalamus is a key cerebral hub relaying a multitude of corticoefferent and corticoafferent connections and mediating distinct extrapyramidal, sensory, cognitive and behavioural functions. While the thalamus consists of dozens of anatomically well-defined nuclei with distinctive physiological roles, existing imaging studies in motor neuron diseases typically evaluate the thalamus as a single structure. Based on the unique cortical signatures observed in ALS and PLS, we hypothesised that similarly focal thalamic involvement may be observed if the nuclei are individually evaluated. A prospective imaging study was undertaken with 100 patients with ALS, 33 patients with PLS and 117 healthy controls to characterise the integrity of thalamic nuclei. ALS patients were further stratified for the presence of GGGGCC hexanucleotide repeat expansions in C9orf72. The thalamus was segmented into individual nuclei to examine their volumetric profile. Additionally, thalamic shape deformations were evaluated by vertex analyses and focal density alterations were examined by region-of-interest morphometry. Our data indicate that C9orf72 negative ALS patients and PLS patients exhibit ventral lateral and ventral anterior involvement, consistent with the 'motor' thalamus. Degeneration of the sensory nuclei was also detected in C9orf72 negative ALS and PLS. Both ALS groups and the PLS cohort showed focal changes in the mediodorsal-paratenial-reuniens nuclei, which mediate memory and executive functions. PLS patients exhibited distinctive thalamic changes with marked pulvinar and lateral geniculate atrophy compared to both controls and C9orf72 negative ALS. The considerable ventral lateral and ventral anterior pathology detected in both ALS and PLS support the emerging literature of extrapyramidal dysfunction in MND. The involvement of sensory nuclei is consistent with sporadic reports of sensory impairment in MND. The unique thalamic signature of PLS is in line with the distinctive clinical features of the phenotype. Our data confirm phenotype-specific patterns of thalamus involvement in motor neuron diseases with the preferential involvement of nuclei mediating motor and cognitive functions. Given the selective involvement of thalamic nuclei in ALS and PLS, future biomarker and natural history studies in MND should evaluate individual thalamic regions instead overall thalamic changes., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Primary lateral sclerosis (PLS) is a low incidence motor neuron disease which carries a markedly better prognosis than amyotrophic lateral sclerosis (ALS). Despite sporadic reports of extra-motor symptoms, PLS is widely regarded as a pure upper motor neuron disorder. The post mortem literature of PLS is strikingly sparse and very little is known of subcortical grey matter pathology in this condition., Methods: A prospective imaging study was undertaken with 33 PLS patients, 117 healthy controls and 100 ALS patients to specifically assess the integrity of subcortical grey matter structures and determine whether PLS and ALS have divergent thalamic, hippocampal and basal ganglia signatures. Volumetric, morphometric, segmentation and vertex-wise analyses were carried out in the three study groups to evaluate the integrity of thalamus, hippocampus, caudate, amygdala, pallidum, putamen and accumbens nucleus in each hemisphere. The hippocampus was further parcellated to characterise the involvement of specific subfields., Results: Considerable thalamic, caudate, and hippocampal atrophy was detected in PLS based on both volumetric and vertex analyses. Significant volume reductions were also detected in the accumbens nuclei. Hippocampal atrophy in PLS was dominated by dentate gyrus, hippocampal tail and CA4 subfield volume reductions. The morphometric comparison of ALS and PLS cohorts revealed preferential medial bi-thalamic pathology in PLS compared to the predominant putaminal degeneration detected in ALS. Another distinguishing feature between ALS and PLS was the preferential atrophy of the amygdala in ALS., Conclusions: PLS is associated with considerable subcortical grey matter degeneration and due to the extensive extra-motor involvement, it should no longer be regarded a pure upper motor neuron disorder. Given its unique pathological features and a clinical course which differs considerably from ALS, dedicated research studies and disease-specific therapeutic strategies are urgently required in PLS., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To localise and characterise changes in cognitive networks in Amyotrophic Lateral Sclerosis (ALS) using source analysis of mismatch negativity (MMN) waveforms., Rationale: The MMN waveform has an increased average delay in ALS. MMN has been attributed to change detection and involuntary attention switching. This therefore indicates pathological impairment of the neural network components which generate these functions. Source localisation can mitigate the poor spatial resolution of sensor-level EEG analysis by associating the sensor-level signals to the contributing brain sources. The functional activity in each generating source can therefore be individually measured and investigated as a quantitative biomarker of impairment in ALS or its sub-phenotypes., Methods: MMN responses from 128-channel electroencephalography (EEG) recordings in 58 ALS patients and 39 healthy controls were localised to source by three separate localisation methods, including beamforming, dipole fitting and exact low resolution brain electromagnetic tomography., Results: Compared with controls, ALS patients showed significant increase in power of the left posterior parietal, central and dorsolateral prefrontal cortices (false discovery rate = 0.1). This change correlated with impaired cognitive flexibility (rho = 0.45, 0.45, 0.47, p = .042, .055, .031 respectively). ALS patients also exhibited a decrease in the power of dipoles representing activity in the inferior frontal (left: p = 5.16 × 10 -6 , right: p = 1.07 × 10 -5 ) and left superior temporal gyri (p = 9.30 × 10 -6 ). These patterns were detected across three source localisation methods. Decrease in right inferior frontal gyrus activity was a good discriminator of ALS patients from controls (AUROC = 0.77) and an excellent discriminator of C9ORF72 expansion-positive patients from controls (AUROC = 0.95)., Interpretation: Source localization of evoked potentials can reliably discriminate patterns of functional network impairment in ALS and ALS subgroups during involuntary attention switching. The discriminative ability of the detected cognitive changes in specific brain regions are comparable to those of functional magnetic resonance imaging (fMRI). Source analysis of high-density EEG patterns has excellent potential to provide non-invasive, data-driven quantitative biomarkers of network disruption that could be harnessed as novel neurophysiology-based outcome measures in clinical trials., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

There is strong clinical, imaging and pathological evidence that neurodegeneration is associated with altered brain connectivity. While functional imaging (fMRI) can detect resting and activated states of metabolic activity, its use is limited by poor temporal resolution, cost and confounding vascular parameters. By contrast, electrophysiological (e.g. EEG/MEG) recordings provide direct measures of neural activity with excellent temporal resolution, and source localization methodologies can address problems of spatial resolution, permitting measurement of functional activity of brain networks with a spatial resolution similar to that of fMRI. This opens an exciting therapeutic approach focussed on pharmacological and physiological modulation of brain network activity. This review describes current neurophysiological approaches towards evaluating cortical network dysfunction in common neurodegenerative disorders. It explores how modern neurophysiologic tools can provide markers for diagnosis, prognosis, subcategorization and clinical trial outcome measures, and how modulation of brain networks can contribute to new therapeutic approaches., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Early detection of white spot lesions (WSLs) around brackets during orthodontic treatment is important for treatment and prevention. But it is unclear whether red fluorescent plaque (RFP) bacteria Porphyromonas gingivalis and its co-existence with Streptococcus mutans and Streptococcus gordonii has any significant influence on this. Therefore the role of this bacterial co existence and WSLs formation during one year of fixed orthodontic therapy was evaluated., Methods: Fourteen 12 to 22 year old (mean 15 ± 3 years) consecutive patients attending the University of Liverpool dental hospital were recruited for this study. Quantitative Light-induced Fluorescence (QLF) was used to identify RFP and enamel demineralisation, respectively, on anterior labial surfaces before and after placement of fixed orthodontic appliances. Bacterial composition was determined by denaturing gradient gel electrophoresis (DGGE) following nested PCR amplification of the 16S rRNA V2-V3 hypervariable region., Results: WSLs were recorded on 4.2% of tooth surfaces and WSL development was not associated with RFP bacteria P. gingivalis presence. Differences in RFP bacteria P. gingivalis presence with S. mutans and S. gordonii, were observed before and after appliance placement. Intra subject changes in plaque flora between visits were not significantly associated with WSL development (p > 0.05). However, DGGE profiles indicated that apart from S. mutans, S. gordonii might also have a role in human enamel demineralisation., Conclusions: Fixed orthodontic brackets in adolescents may play a role in altering bacterial composition around brackets during orthodontic treatment and it is plausible that S. gordonii also have a role in human enamel demineralisation. Combinatorial approach of QLF technology and DGGE may be useful in determining bacterial composition during orthodontic therapy which could inform clinical interventions., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Shapiro syndrome is a rare entity, comprising a triad of recurrent hypothermia, hyperhidrosis and congenital agenesis of the corpus callosum. Fewer than 50 cases have been described, almost invariably in patients presenting in childhood or early adulthood. We present a case of an 80 year old woman presenting with recurrent bouts of shivering, sweating and profound malaise, who sought medical attention because the frequency and severity of attacks worsened in her later years. MRI Brain demonstrated agenesis of the corpus callosum; a rigorous work-up excluded other causes for her symptomatology. The intricate interplay of neuronal networks involved in thermoregulation remains to be fully elucidated and as such, little is known about the pathophysiological mechanisms underlying the clinical manifestations of Shapiro syndrome. We present novel data from FDG-PET imaging of our patient, demonstrating hypermetabolism in a number of brainstem and cerebellar regions during the symptomatic phase. These findings imply that aberrant thermoregulation in Shapiro syndrome involves a number of structures remote from the callosal region. We also present neuropsychometric findings in our patient, of which there have been no reports to date. We postulate that the ageing brain may be more susceptible to the paroxysmal neurochemical fluxes implicated in the syndrome., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: Our aim was to determine predictors for the presence and degree of demineralization during orthodontic treatment. This study was a post-hoc analysis of recruits for a randomized controlled trial. Two hundred thirty patients were included in this study and assessed for demineralization at debond by using quantitative light-induced fluorescence to determine their eligibility for a randomized controlled trial assessing the effectiveness of various toothpastes at reducing demineralization during retention., Methods: Data about patients' demographics, treatments, oral hygiene, and pretreatment status of the first permanent molars were extracted from case notes. Data on the presence and severity of white spot lesions (WSLs) were obtained from the trial's data base. Univariate analyses and multiple regression were undertaken to assess for associations between the factors and the presence and severity of WSLs., Results: Sixty-five patients (28.3%) had no WSLs, and 165 (71.7%) had 1 to 12. The mean number of WSLs per patient with demineralization was 2.9 (95% CI, 2.5 and 3.3). Patients with WSLs were significantly (P = 0.002) younger and more likely to have diseased first molars (P = 0.04). Participants with inadequate pretreatment oral hygiene developed more WSLs (P = 0.03). Boys (P = 0.001) and participants with diseased first molars (P = 0.06) had significantly greater demineralization., Conclusions: Sex, pretreatment age, oral hygiene, and clinical status of the first molars can be used as predictors for the development and severity of WSLs during orthodontic treatment., (Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.)

Aim: To assess the long-term seizure outcome of Irish patients who underwent resective surgery for refractory epilepsy since 1975. We also wished to determine the impact of pathology and surgical technique (with particular reference to neocorticectomy) on seizure outcome., Methods: A retrospective review of medical notes, radiological and histopathological records, was undertaken between 1975 and 2005. Missing data was supplemented by telephone calls to patients. One hundred and ninety-nine patients suited the criteria for inclusion and had at least 1-year follow-up (1-24 years, mean 7.0 years). Engel's criteria were used to classify seizure outcome at 1, 2, 5, 10, 15 and >15 years follow-up., Results: The percentage of patients seizure free at 2, 5, 10, 15 and >15 years were, 56.6%, 41.4%, 44%, 25% and 31.3%, respectively. Of patients with a pathologically confirmed diagnosis of mesial temporal sclerosis, 55.6% were seizure free at 10 years. Equivalent figures for tumour were 62.5%, for cortical dysplasia, 34.8%, for those without any demonstrable pathologic abnormality, 50%, for dual pathology, 50% and for all others, 33.3%. Of those with 10 years or greater follow-up only 20% of neocorticectomy patients were in Engel class 1, compared with an average of 58.5% for the other surgical techniques., Conclusion: Seizure freedom rates for Irish Patients were comparable to other large retrospective studies. Patients who underwent selective procedures tended to do better than those undergoing lobar resections, in keeping with international trends. The surgical technique unique to the Irish cohort, temporal necocorticectomy, had the worst long-term outcome., (Copyright 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: Many tools are available to quantify dental erosion, but each technique has its own inherent disadvantages. This study aims to validate the use of quantitative light-induced fluorescence (QLF) and non-contacting surface profilometry compared to the gold standard transverse microradiography (TMR) for the quantification of enamel erosion in vitro., Methods: This was an in vitro laboratory based study. 60 bovine incisors were divided into 6 groups of 10. Each tooth's labial surface was completely varnished except for a window of enamel approximately 3mmx5mm. Each was baseline imaged with QLF and non-contacting surface profilometry before being subjected to an erosive solution (pH 3.4) for up to 36h. The lesions were imaged using non-contacting surface profilometry and QLF, sectioned and analysed with TMR. Correlation coefficients were calculated to assess the validity of the methods of measurement as compared to TMR., Results: A range of lesion severities resulted. Mineral loss measured as DeltaQ (QLF) and step height (profilometry), was recorded and confirmed by TMR. A correlation was found between DeltaZ (TMR) and profilometry lesion depth of r=0.648 (p<0.001). A poorer correlation was found between DeltaZ and DeltaQ: r=0.217 (p=0.096)., Conclusions: Profilometry lesion depth and DeltaZ correlated significantly. Both methods allow for quantification of erosive crater depth. QLF correlated poorly with DeltaZ, but is useful for measuring subsurface loss of mineralisation. TMR is valuable but is destructive and can only be used in vitro. Currently only QLF can be used in vivo. Advances in these technologies may allow the development of non-destructive in vivo measurements of mineral loss, combining the positive features of each measurement method.

Objectives: To report the use of Quantitative Light-induced Fluorescence (QLF) to determine if there was a tendency for bleached enamel to take up extrinsic stains more than unbleached enamel., Methods: Bovine teeth devoid of stains were selected, the roots removed and enamel gently pumiced. Each tooth was sectioned into two and each half randomly assigned to two groups (bleached or unbleached). Windows were created on each half using clear acid resistant varnish. 38% Hydrogen peroxide gel was applied to the exposed windows of the bleached group for 1 hour. The teeth were rinsed and dried. Bleached and unbleached halves of the same teeth were then mounted on glass rods attached to pot lids using green stick. QLF images were taken. The teeth were subjected to a cycle of artificial saliva, chlorhexidine and tea (2 minutes in each solution). This was repeated 5 times. QLF images were taken at the end of each cycle., Results: The uptake and progression of stain was detected in all the sections by QLF. Using paired t- test (SPSS) there was no significant difference between the two groups for the change from baseline to the final stain cycle (p > 0.05), however there was variability in stain uptake within the groups as the cycles progressed., Conclusion: Bleaching of enamel in vitro does not appear to increase the susceptibility of enamel to extrinsic staining.

Objectives: This study compares the use of QLF with digital imaging in the detection and quantification of the development and removal of stain on teeth., Methods: Two experimental phases, tooth staining and tooth whitening, conducted in vitro on labial 12 mm(2) enamel windows made on ten extracted bovine teeth, developed stains in 6-min cycles (2 min in each solution) using artificial saliva, chlorhexidine and tea solutions and removed them using sodium perborate monohydrate in 2-min cycle monitored at the end of each cycle with QLF (Inspektor Research Systems, NL) and digital photography (Fuji, Japan). The stain values were quantified as DeltaQ derived from QLF and DeltaE from digital imaging. This was observed by the two methods correlated with Pearson correlation coefficient (r). Regression equations (R(2)) were also obtained., Results: For both staining and stain removal there was a statistically significant (p<0.01) reverse correlation between DeltaQ values for QLF (r=-0.924, R(2)=85.4%) and DeltaE values for digital imaging (r=-0.994, R(2)=98.8%), respectively., Conclusion: QLF showed a high correlation with digital imaging as a technique for detecting and monitoring tooth stains and tooth whitening in vitro. The potential for QLF with further development as a tool for monitoring staining and whitening of teeth may be possible in vivo in addition to the diagnostic ability for caries detection.

Objectives: To investigate the use of computerised image analysis to measure the area of demineralisation on the buccal surface of a tooth and to analyse the effect on that measurement of varying the angle at which a photographic image of the buccal surface of a tooth is taken., Methods: Twenty-two teeth with areas of incremental demineralisation on the buccal surface were photographed perpendicular to the buccal surface and at angles of 20 and 40 degrees, above (Cuspal) and below (Gingival) the perpendicular. The images were captured and analysed using computerised image analysis., Results: The Gingival views showed lower limits of agreement than the Cuspal views, probably due to the positioning of the masking on the lower part of the flash, to reduce reflection. There was a significant difference between the areas of demineralisation measured for the three angles from the Gingival views (p<0.001). The mean differences in areas measured were not linear, but there was a significantly greater reduction in area measured for the 40 degrees views., Conclusions: Computerised image analysis to measure areas of demineralisation from a captured 35mm slide is reproducible. The position of the masking on the camera flash and the angle of the camera makes a difference to the area measured and the grey scales recorded. Images taken at a larger angle than 20 degrees to the perpendicular will record a significantly reduced area of demineralisation. Standardisation of photographs with the use of calibration markers and manipulation of images is discussed.

Objectives: To investigate the validity and reproducibility of a method of morphometric assessment of enamel demineralisation., Methods: An in vitro investigation was carried out on 22 human teeth. One investigator coated the crowns of the teeth with an acid-resistant varnish, leaving a small window on the buccal surface. This was incrementally occluded by varnish over a 14-day period, during which the teeth were placed in a demineralising gel at pH 4.5. After varnish removal, a second investigator blindly quantitated the demineralised area by three methods of examination; direct visual, microscopic and from photographs. The microscopic and photographic measurements were carried out using a morphometric assessment with a 121-dot array. Photographs and assessments were repeated after 1 week. The readings were analysed using the kappa statistic, the limits of agreement and the coefficient of repeatability., Results: Photographic assessments demonstrated excellent agreement for grid positioning (kappa > 0.81) and substantial agreement for reading reproducibility (kappa = 0.61-0.80). The coefficients of repeatability were found to be the same for repeat readings of the same slide and the repeated slides (5.0 mm2). They were higher for the microscopic technique (6.8 mm2) and for the direct visual technique (7.8 mm2). The limits of agreement are presented graphically., Conclusions: The photographic technique used was a reproducible method of measuring artificial enamel demineralisation. Measurement from photographs was more reproducible than direct measurement with the naked eye. Subjectiveness of the index leads to most variation and more objective means of assessing enamel demineralisation need to be found.

Purpose: This longitudinal study investigated gender-specific changes in physical activity beliefs and behaviors across the elementary to junior high school transition., Methods: Physical activity beliefs and behaviors were measured in a cohort of 132 racially diverse youth during the year prior to and following the transition. Questionnaires assessed variables hypothetically linked to activity. Physical activity was monitored with the Child/Adolescent Activity Log., Results: Gender differences in physical activity beliefs emerged. Across the transition, boys reported decreased efficacy, social support, and expectations (norms) to be physically active. Although girls also reported decreased social support for physical activity, they further reported exposure to fewer active role models and were less likely to perceive that the benefits of regular activity out-weighed the barriers following the transition. Gender differences in activity levels were apparent, with girls being less active than boys. Despite changes in physical activity beliefs across the school transition, no significant changes in actual level of activity occurred over this period. Although beliefs were significantly related to behaviors in the domain of physical activity, pretransition activity level was the best predictor of posttransition activity level., Conclusions: These data indicate that physical activity beliefs of adolescents change over the school transition. These changes are significantly, but not highly, related to level of physical activity. Future research should explore the influences of activity-related affect and social and physical contexts on physical activity across adolescence.

Three cohorts of patients, discharged within three, 12-month periods from a tertiary referral Neuropsychiatry/Epilepsy Unit, were asked whether they felt their condition had improved as a result of their admission, how they valued the admission and how easy they had found the admission to manage. They were also asked about their psychological and psychosocial state. For the first cohort a longer admission was more greatly valued and was associated with a better self-perceived outcome, and for the second cohort with the manageability of the admission. Replies to questionnaires sent to the referring doctors of two of the three cohorts of patients indicated that, in addition to their being satisfied with the service, there was a positive correlation between their ratings of patients' improvement and those ratings offered by the patients themselves. Issues relating to length and purpose of admissions, finances and the distribution of assessment and treatment of patients across different services are discussed in the light of the findings.

This study examines methods of improving the bond strengths of the light-activated composites, Heliosit-orthodontic, and Transbond. Begg brackets were bonded onto each of the four surfaces of 50 molar teeth that had been previously extracted. The bonding systems used were Right-on (R), Heliosit-orthodontic (H), Heliosit with a precured composite resin on the mesh (HPC), Heliosit with a precured intermediate bonding resin on the mesh (HPR), Transbond (T), and Transbond with a precured layer of resin on the mesh (TPC). The shear bond strengths were tested on a M5K tensile tester, crosshead speed 0.5 mm/min. After bracket removal, the enamel surface of the bonding site was examined and assessed with the adhesive remnant index (ARI). The shear bond strength in mean mPa +/- 1 SD was found to be significantly greater for HPC, HPR, and TPC than for H (P < 0.001). The ARI scores suggest that bond failure is associated more with the micromechanical bond with enamel for HPC and HPR. The results indicate that the chemical properties of the two light-activated adhesives were improved by precuring on the mesh base of the bracket before bonding.