Consensus Paper: Language and the Cerebellum: an Ongoing Enigma

In less than three decades, the concept “cerebellar neurocognition” has evolved from a mere afterthought to an entirely new and multifaceted area of neuroscientific research. A close interplay between three main strands of contemporary neuroscience induced a substantial modification of the traditional view of the cerebellum as a mere coordinator of autonomic and somatic motor functions. Indeed, the wealth of current evidence derived from detailed neuroanatomical investigations, functional neuroimaging studies with healthy subjects and patients and in-depth neuropsychological assessment of patients with cerebellar disorders shows that the cerebellum has a cardinal role to play in affective regulation, cognitive processing, and linguistic function. Although considerable progress has been made in models of cerebellar function, controversy remains regarding the exact role of the “linguistic cerebellum” in a broad variety of nonmotor language processes. This consensus paper brings together a range of different viewpoints and opinions regarding the contribution of the cerebellum to language function. Recent developments and insights in the nonmotor modulatory role of the cerebellum in language and some related disorders will be discussed. The role of the cerebellum in speech and language perception, in motor speech planning including apraxia of speech, in verbal working memory, in phonological and semantic verbal fluency, in syntax processing, in the dynamics of language production, in reading and in writing will be addressed. In addition, the functional topography of the linguistic cerebellum and the contribution of the deep nuclei to linguistic function will be briefly discussed. As such, a framework for debate and discussion will be offered in this consensus paper.     

Developing the “120 by 20” Goal for the Global FP2020 Initiative

This report describes the purpose for developing a quantitative goal for the London Summit on Family Planning held in July 2012, the methodology behind its formulation, and the lessons learned in the process. The London Summit has evolved into the global initiative known as FP2020, and the goal has become “120 by 20,” or reaching 120 million additional users of modern contraceptive methods by 2020 in the world's poorest countries. The success of FP2020 will first be evaluated on the basis of quantitative verification to determine that the “120 by 20” goal was reached. More important, however, is the extent to which the goal today serves as a global rallying cry to mobilize resources and leadership around current family planning programs, with a focus on voluntary family planning and quality of care, and with an emphasis on meeting girls' and women's unmet needs and their right to practice contraception. We hope this article provides greater transparency and understanding of the FP2020 goal, and that the global goal spurs annual monitoring of progress toward national goals in the world's poorest countries.     

Has Omicron Changed the Evolution of the Pandemic?

BackgroundVariants of the SARS-CoV-2 virus carry differential risks to public health. The Omicron (B.1.1.529) variant, first identified in Botswana on November 11, 2021, has spread globally faster than any previous variant of concern. Understanding the transmissibility of Omicron is vital in the development of public health policy.ObjectiveThe aim of this study is to compare SARS-CoV-2 outbreaks driven by Omicron to those driven by prior variants of concern in terms of both the speed and magnitude of an outbreak.MethodsWe analyzed trends in outbreaks by variant of concern with validated surveillance metrics in several southern African countries. The region offers an ideal setting for a natural experiment given that most outbreaks thus far have been driven primarily by a single variant at a time. With a daily longitudinal data set of new infections, total vaccinations, and cumulative infections in countries in sub-Saharan Africa, we estimated how the emergence of Omicron has altered the trajectory of SARS-CoV-2 outbreaks. We used the Arellano-Bond method to estimate regression coefficients from a dynamic panel model, in which new infections are a function of infections yesterday and last week. We controlled for vaccinations and prior infections in the population. To test whether Omicron has changed the average trajectory of a SARS-CoV-2 outbreak, we included an interaction between an indicator variable for the emergence of Omicron and lagged infections.ResultsThe observed Omicron outbreaks in this study reach the outbreak threshold within 5-10 days after first detection, whereas other variants of concern have taken at least 14 days and up to as many as 35 days. The Omicron outbreaks also reach peak rates of new cases that are roughly 1.5-2 times those of prior variants of concern. Dynamic panel regression estimates confirm Omicron has created a statistically significant shift in viral spread.ConclusionsThe transmissibility of Omicron is markedly higher than prior variants of concern. At the population level, the Omicron outbreaks occurred more quickly and with larger magnitude, despite substantial increases in vaccinations and prior infections, which should have otherwise reduced susceptibility to new infections. Unless public health policies are substantially altered, Omicron outbreaks in other countries are likely to occur with little warning.     

Proof of concept study to develop a novel connectivity-based electric-field modelling approach for individualized targeting of transcranial magnetic stimulation treatment

Resting state functional connectivity (rsFC) offers promise for individualizing stimulation targets for transcranial magnetic stimulation (TMS) treatments. However, current targeting approaches do not account for non-focal TMS effects or large-scale connectivity patterns. To overcome these limitations, we propose a novel targeting optimization approach that combines whole-brain rsFC and electric-field (e-field) modelling to identify single-subject, symptom-specific TMS targets. In this proof of concept study, we recruited 91 anxious misery (AM) patients and 25 controls. We measured depression symptoms (MADRS/HAMD) and recorded rsFC. We used a PCA regression to predict symptoms from rsFC and estimate the parameter vector, for input into our e-field augmented model. We modeled 17 left dlPFC and 7 M1 sites using 24 equally spaced coil orientations. We computed single-subject predicted ΔMADRS/HAMD scores for each site/orientation using the e-field augmented model, which comprises a linear combination of the following elementwise products (1) the estimated connectivity/symptom coefficients, (2) a vectorized e-field model for site/orientation, (3) rsFC matrix, scaled by a proportionality constant. In AM patients, our connectivity-based model predicted a significant decrease depression for sites near BA9, but not M1 for coil orientations perpendicular to the cortical gyrus. In control subjects, no site/orientation combination showed a significant predicted change. These results corroborate previous work suggesting the efficacy of left dlPFC stimulation for depression treatment, and predict better outcomes with individualized targeting. They also suggest that our novel connectivity-based e-field modelling approach may effectively identify potential TMS treatment responders and individualize TMS targeting to maximize the therapeutic impact.Subject terms: Cognitive control, Depression     

Prospective cohort study of referred Malawian children and their survival by hypoxaemia and hypoglycaemia status

ObjectiveTo investigate survival in children referred from primary care in Malawi, with a focus on hypoglycaemia and hypoxaemia progression.MethodsThe study involved a prospective cohort of children aged 12 years or under referred from primary health-care facilities in Mchinji district, Malawi in 2019 and 2020. Peripheral blood oxygen saturation (SpO₂) and blood glucose were measured at recruitment and on arrival at a subsequent health-care facility (i.e. four hospitals and 14 primary health-care facilities). Children were followed up 2 weeks after discharge or their last clinical visit. The primary study outcome was the case fatality ratio at 2 weeks. Associations between SpO₂ and blood glucose levels and death were evaluated using Cox proportional hazards models and the treatment effect of hospitalization was assessed using propensity score matching.FindingsOf 826 children recruited, 784 (94.9%) completed follow-up. At presentation, hypoxaemia was moderate (SpO₂: 90–93%) in 13.1% (108/826) and severe (SpO₂: < 90%) in 8.6% (71/826) and hypoglycaemia was moderate (blood glucose: 2.5–4.0 mmol/L) in 9.0% (74/826) and severe (blood glucose: < 2.5 mmol/L) in 2.3% (19/826). The case fatality ratio was 3.7% (29/784) overall but 26.3% (5/19) in severely hypoglycaemic children and 12.7% (9/71) in severely hypoxaemic children. Neither moderate hypoglycaemia nor moderate hypoxaemia was associated with mortality.ConclusionPresumptive pre-referral glucose treatment and better management of hypoglycaemia could reduce the high case fatality ratio observed in children with severe hypoglycaemia. The morbidity and mortality burden of severe hypoxaemia was high; ways of improving hypoxaemia identification and management are needed.     

Tumour localisation with a metal coil before the administration of neo-adjuvant chemotherapy

Complete clinical response (CR) with tumour disappearance is not uncommon after neo-adjuvant chemotherapy (NAC) for locally advanced breast cancer, avoiding 25% mastectomies by facilitating breast-conserving procedures. We reviewed our series to understand the feasibility and utility of marking the cancer site before administering NAC. In total, 23 women (median age 47 years) with T2-4, N0-1, M0 tumours were considered unsuitable for breast conserving surgery between January 2002 and November 2003, thus received NAC following a coil placement at the core of tumour. All patients had the coil successfully inserted and no migration or infection was recorded. Eight patients (35%) had a radiological CR (rCR) including 3 (13%) with pathological CR (pCR). In total, 87% patients were managed conservatively. The insertion of a metal coil is a simple mean to provide a landmark for localisation and excision when the breast lump becomes impalpable and radiologically undetectable after the administration of NAC.