White Matter Biomarkers Associated with Motor Change in Individuals with Stroke: A Continuous Theta Burst Stimulation Study.

Continuous theta burst stimulation (cTBS) is a form of noninvasive repetitive brain stimulation that, when delivered over the contralesional hemisphere, can influence the excitability of the ipsilesional hemisphere in individuals with stroke. cTBS applied prior to skilled motor practice interventions may augment motor learning; however, there is a high degree of variability in individual response to this intervention. The main objective of the present study was to assess white matter biomarkers of response to cTBS paired with skilled motor practice in individuals with chronic stroke. We tested the effects of stimulation of the contralesional hemisphere at the site of the primary motor cortex (M1c) or primary somatosensory cortex (S1c) and a third group who received sham stimulation. Within each stimulation group, individuals were categorized into responders or nonresponders based on their capacity for motor skill change. Baseline diffusion tensor imaging (DTI) indexed the underlying white matter microstructure of a previously known motor learning network, named the constrained motor connectome (CMC), as well as the corticospinal tract (CST) of lesioned and nonlesioned hemispheres. Across practice, there were no differential group effects. However, when categorized as responders vs. nonresponders using change in motor behaviour, we demonstrated a significant difference in CMC microstructural properties (as measured by fractional anisotropy (FA)) for individuals in M1c and S1c groups. There were no significant differences between responders and nonresponders in clinical baseline measures or microstructural properties (FA) in the CST. The present study identifies a white matter biomarker, which extends beyond the CST, advancing our understanding of the importance of white matter networks for motor after stroke.

Erythroderma with circulating atypical T-cells, likely Sézary syndrome.

The erythrodermic patient is often challenging and requires careful evaluation. Work-up should include an extensive and careful medication history, histological and laboratory testing, and if necessary, molecular studies for the evaluation of underlying malignancy. Herein, we present an erythrodermic patient with repeated biopsies demonstrating a spongiotic process who was found to have circulating atypical T-cells concerning for an underlying erythrodermic T-cell leukemia, most closely related to Sézary syndrome.

A case of porphyria cutanea tarda in the setting of hepatitis C infection and tobacco usage.

Porphyria cutanea tarda (PCT) is the most common type of porphyria, presenting in middle-aged patients with a photodistributed vesiculobullous eruption, milia, and scars. Porphyria cutanea tarda occurs in relation to inhibition of uroporphyrinogen decarboxylase, a key enzyme in the heme biosynthesis pathway. A number of genetic and acquired factors increase susceptibility to PCT by reducing uroporphyrinogen decarboxylase activity. A handful of other vesiculobullous conditions may mimic PCT both clinically and histologically; therefore, both skin biopsy and laboratory evaluation are helpful in confirming the diagnosis. We report a case of PCT in the setting of cigarette usage and untreated hepatitis C infection.

The impact of fluphenazine withdrawal: a mirror-image study.

BACKGROUND: Fluphenazine decanoate licenced as a long-acting injectable (LAI) first-generation antipsychotic (FGA) was withdrawn from sale in 2018. This study evaluates if its withdrawal resulted in increased relapse rates of psychosis in an Irish patient cohort and examines which prescribed alternative antipsychotic medications were associated with more optimal outcomes. METHODS: Fifteen participants diagnosed with a psychotic disorder were included. A mirror-image study over 24-months' pre-and post-withdrawal of fluphenazine was conducted. Kaplan-Meier survival and proportional hazards analyses were conducted. The impact of alternate antipsychotic agents (LAI flupenthixol compared to other antipsychotic medications) was evaluated. Semi-structured interviews with participants examined subjective opinions regarding the change in their treatment. RESULTS: Seven participants (46.7%) relapsed in the 24-month period subsequent to fluphenazine discontinuation compared to one individual (6.7%) in the previous identical time-period (p = 0.035). Flupenthixol treatment was associated with reduced relapse rates compared to other antipsychotics (χ2 = 5.402, p = 0.02). Thematic analysis revealed that participants believed that the discontinuation of fluphenazine deleteriously impacted the stability of their mental disorder. CONCLUSION: The withdrawal of fluphenazine was associated with increased relapse rate in individuals previously demonstrating stability of their psychotic disorder. While acknowledging the limitation of small sample size, preliminary evidence from this study suggests that treatment with the first-generation antipsychotic (FGA) flupenthixol was associated with a lower risk of relapse compared to SGAs. Reasons for this lower risk of relapse are not fully clear but could be related to dopamine hypersensitivity with this treatment change.

One hertz repetitive transcranial magnetic stimulation over dorsal premotor cortex enhances offline motor memory consolidation for sequence-specific implicit learning.

Consolidation of motor memories associated with skilled practice can occur both online, concurrent with practice, and offline, after practice has ended. The current study investigated the role of dorsal premotor cortex (PMd) in early offline motor memory consolidation of implicit sequence-specific learning. Thirty-three participants were assigned to one of three groups of repetitive transcranial magnetic stimulation (rTMS) over left PMd (5 Hz, 1 Hz or control) immediately following practice of a novel continuous tracking task. There was no additional practice following rTMS. This procedure was repeated for 4 days. The continuous tracking task contained a repeated sequence that could be learned implicitly and random sequences that could not. On a separate fifth day, a retention test was performed to assess implicit sequence-specific motor learning of the task. Tracking error was decreased for the group who received 1 Hz rTMS over the PMd during the early consolidation period immediately following practice compared with control or 5 Hz rTMS. Enhanced sequence-specific learning with 1 Hz rTMS following practice was due to greater offline consolidation, not differences in online learning between the groups within practice days. A follow-up experiment revealed that stimulation of PMd following practice did not differentially change motor cortical excitability, suggesting that changes in offline consolidation can be largely attributed to stimulation-induced changes in PMd. These findings support a differential role for the PMd in support of online and offline sequence-specific learning of a visuomotor task and offer converging evidence for competing memory systems.

TB programme stakeholder views on lessons from the COVID-19 response in South Africa.

BACKGROUND: The global COVID-19 pandemic has reversed many of the hard-won gains made in TB programmes and the associated reduction in the number of TB deaths, case notifications and incidence over the last three decades. Modelling estimates show that the impact will be lasting. There are global calls to recover the shortfalls along the TB care cascade that have resulted from COVID-19, with the recognition that the COVID-19 response holds lessons to inform more robust and comprehensive TB programmes and services. OBJECTIVE: To explore lessons from response measures to the COVID-19 pandemic in two high TB burden South African provinces. DESIGN: This was an exploratory qualitative study. We conducted interviews with TB programme stakeholders (managers and facility-level staff: n = 35) between February and June 2022. RESULTS: We identified eight facilitators of the COVID-19 response, including political will, rapid policy development, multi-sectoral collaboration, patient-centred models of care delivery, community engagement, mHealth and telehealth technologies, rigorous contact tracing and widespread mask wearing. Political will was singled out as a critical driver of the response. CONCLUSION: Leveraging COVID-19 inspired collaborations, technologies and avenues for health service delivery is an opportunity to maximise benefits for the TB programme. Reinvestment in national TB programmes and political prioritisation of TB are critical.

CONTEXTE: La pandémie mondiale de COVID-19 a réduit à néant une grande partie des gains durement acquis dans les programmes de lutte contre la TB et la réduction associée du nombre de décès dus à la TB, de notifications de cas et d'incidence au cours des trois dernières décennies. Les estimations de la modélisation montrent que l'impact sera durable. Des appels ont été lancés au niveau mondial pour combler les lacunes dans la chaîne de soins de la TB qui ont résulté de la pandémie de COVID-19, en reconnaissant que la réponse à cette pandémie est porteuse d'enseignements qui permettront d'élaborer des programmes et des services de lutte contre la TB plus solides et plus complets. OBJECTIF: Etudier les enseignements tirés des mesures prises en réponse à la pandémie de COVID-19 dans deux provinces sud-africaines à forte charge de morbidité TB. MÉTHODE: Il s'agit d'une étude qualitative exploratoire. Nous avons mené des entretiens avec les parties prenantes des programmes de lutte contre la TB (responsables et personnel au niveau des établissements : n = 35) entre février et juin 2022. RÉSULTATS: Nous avons identifié huit facilitateurs de la riposte au COVID-19, notamment la volonté politique, l'élaboration rapide de directives, la collaboration multisectorielle, les modèles de prestation de soins centrés sur le patient, l'engagement communautaire, les technologies de mHealth et de télésanté, la recherche rigoureuse des contacts et le port généralisé de masques. La volonté politique a été désignée comme un moteur essentiel de la riposte. CONCLUSION: L'exploitation des collaborations, des technologies et des moyens inspirés du COVID-19 pour la prestation de services de santé est une occasion de maximiser les avantages pour le programme de lutte contre la TB. Il est essentiel de réinvestir dans les programmes nationaux de lutte contre la TB et d'en faire une priorité politique.

Lessons for TB from the COVID-19 response: qualitative data from Brazil, India and South Africa.

BACKGROUND: Brazil, India and South Africa are among the top 30 high TB burden countries globally and experienced high rates of SARS-CoV-2 infection and mortality. The COVID-19 response in each country was unprecedented and complex, informed by distinct political, economic, social and health systems contexts. While COVID-19 responses have set back TB control efforts, they also hold lessons to inform future TB programming and services. METHODS: This was a qualitative exploratory study involving interviews with TB stakeholders (n = 76) in Brazil, India and South Africa 2 years into the COVID-19 pandemic. Interview transcripts were analysed using an inductive coding strategy. RESULTS: Political will - whether national or subnational - enabled implementation of widespread prevention measures during the COVID-19 response in each country and stimulated mobile and telehealth service delivery innovations. Participants in all three countries emphasised the importance of mobilising and engaging communities in public health responses and noted limited health education and information as barriers to implementing TB control efforts at the community level. CONCLUSIONS: Building political will and social mobilisation must become more central to TB programming. COVID-19 has shown this is possible. A similar level of investment and collaborative effort, if not greater, as that seen during the COVID-19 pandemic is needed for TB through multi-sectoral partnerships.

CONTEXTE: Le Brésil, l'Inde et l'Afrique du Sud figurent parmi les 30 pays les plus touchés par la TB dans le monde et ont connu des taux élevés d'infection et de mortalité dus au SARS-CoV-2. La réponse au COVID-19 dans chacun de ces pays a été sans précédent et complexe, en raison de contextes politiques, économiques, sociaux et de systèmes de santé distincts. Si les réponses au COVID-19 ont fait reculer les efforts de lutte contre la TB, elles permettent également de tirer des enseignements pour les futurs programmes et services de lutte contre la TB. MÉTHODES: Il s'agit d'une étude exploratoire qualitative comprenant des entretiens avec des acteurs de la lutte contre la TB (n = 76) au Brésil, en Inde et en Afrique du Sud, 2 ans après le début de la pandémie de COVID-19. Les transcriptions des entretiens ont été analysées à l'aide d'une stratégie de codage inductive. RÉSULTATS: La volonté politique ­ qu'elle soit nationale ou infranationale ­ a permis la mise en œuvre de mesures de prévention généralisées au cours de la riposte au COVID-19 dans chaque pays et a stimulé les innovations en matière de prestation de services mobiles et de télésanté. Les participants des trois pays ont souligné l'importance de la mobilisation et de l'engagement des communautés dans les réponses de santé publique et ont noté que l'éducation et l'information sanitaires limitées constituaient des obstacles à la mise en œuvre des efforts de lutte contre la TB au niveau communautaire. CONCLUSIONS: La volonté politique et la mobilisation sociale doivent occuper une place plus centrale dans les programmes de lutte contre la TB. La conférence COVID-19 a montré que c'était possible. Un niveau d'investissement et de collaboration similaire, voire supérieur, à celui observé lors de la pandémie de COVID-19 est nécessaire pour lutter contre la TB par le biais de partenariats multisectoriels.

Early interactions with newly diagnosed TB patients in hospital can support linkage to care.

BACKGROUND: In South Africa, failure to link individuals diagnosed with TB to care remains an important gap in the TB care cascade. Compared to people diagnosed at primary healthcare (PHC) facilities, people diagnosed in hospitals are more likely to require additional support to be linked with PHC TB treatment services. We describe a patient interaction process to support linkage to TB care. METHODS: We implemented a step-by-step early patient interaction process with 84 adults newly diagnosed with TB in one district hospital in Khayelitsha, Cape Town, South Africa (August 2020-March 2021). We confirmed patient contact details, provided TB and health information, shared information on accessing care at PHC facilities and answered patients' questions in their home language. RESULTS: Most patients (54/84, 64%) provided updated telephone numbers, and 19/84 (23%) reported changes in their physical address. Patients welcomed practical and health information in their home language. The majority (74/84, 88%) were linked to care after hospital discharge. CONCLUSIONS: A simple early patient interaction process implemented as part of routine care is a feasible strategy to facilitate early TB treatment initiation and registration.

CONTEXTE: En Afrique du Sud, l'incapacité à relier les personnes dont la TB a été diagnostiquée aux soins reste une lacune importante dans la cascade des soins antituberculeux. Comparativement aux personnes diagnostiquées dans les établissements de soins de santé primaires (PHC), les personnes diagnostiquées dans les hôpitaux sont plus susceptibles d'avoir besoin d'un soutien supplémentaire pour être reliées aux services de traitement de la TB des PHC. Nous décrivons un processus d'interaction avec le patient pour favoriser le lien avec les soins antituberculeux. MÉTHODES: Nous avons mis en œuvre un processus d'interaction précoce, étape par étape, avec 84 adultes chez qui la TB a été récemment diagnostiquée dans un hôpital de district de Khayelitsha, au Cap, en Afrique du Sud (août 2020­mars 2021). Nous avons confirmé les coordonnées des patients, fourni des informations sur la TB et la santé, partagé des informations sur l'accès aux soins dans les établissements de PHC et répondu aux questions des patients dans leur langue maternelle. RÉSULTATS: La plupart des patients (54/84 ; 64%) ont fourni des numéros de téléphone actualisés, et 19/84 (23%) ont signalé des changements dans leur adresse physique. Les patients ont apprécié les informations pratiques et ceux ayant trait à la santé dans leur langue maternelle. La majorité d'entre eux (74/84 ; 88%) ont été reliés aux soins après leur sortie de l'hôpital. CONCLUSIONS: Un processus simple d'interaction précoce avec le patient, mis en œuvre dans le cadre des soins de routine, est une stratégie réalisable pour faciliter l'initiation et l'enregistrement précoce du traitement de la TB.

The COVID-19 and TB syndemic: the way forward.

Together, SARS-CoV-2 and M. tuberculosis have killed approximately 5.7 million people worldwide over the past 2 years. The COVID-19 pandemic, and the non-pharmaceutical interventions to mitigate COVID-19 transmission (including social distancing regulations, partial lockdowns and quarantines), have disrupted healthcare services and led to a reallocation of resources to COVID-19 care. There has also been a tragic loss of healthcare workers who succumbed to the disease. This has had consequences for TB services, and the fear of contracting COVID-19 may also have contributed to reduced access to TB services. Altogether, this is projected to have resulted in a 5-year setback in terms of mortality from TB and a 9-year setback in terms of TB detection. In addition, past and present TB disease has been reported to increase both COVID-19 fatality and incidence. Similarly, COVID-19 may adversely affect TB outcomes. From a more positive perspective, the pandemic has also created opportunities to improve TB care. In this review, we highlight similarities and differences between these two infectious diseases, describe gaps in our knowledge and discuss solutions and priorities for future research.

Use of interactive messaging to reduce pre-diagnosis loss to follow-up for TB care.

OBJECTIVE: To investigate the uptake and usage of a WhatsApp-based interactive communication strategy to avert pre-diagnosis loss to follow-up (LTFU) from TB care in a high-incidence setting.METHODS: We enrolled adults (≥18 years) who underwent routine sputum TB testing in two primary healthcare clinics in Khayelitsha, Cape Town, South Africa. The intervention consisted of structured WhatsApp-based reminders (prompts) sent prior to a routine clinic appointment scheduled 2-3 days after the diagnostic visit. Pre-diagnosis LTFU was defined as failure to return for the scheduled appointment and within 10 days.RESULTS: We approached 332 adults with presumptive TB, of whom 103 (31%) were successfully enrolled; 213 (64%) did not own a WhatsApp-compatible phone. Of 103 participants, 74 (72%) actively responded to WhatsApp prompts; 69 (67%) opted to include a close contact in group communication to co-receive reminders. Pre-diagnosis LTFU was low overall (n = 7, 6.8%) and was not associated with failure to respond to WhatsApp prompts.CONCLUSION: In this high-incidence setting, enrolment in a WhatsApp-based communication intervention among adults with presumptive TB was low, mainly due to low availability of WhatsApp-compatible phones. Among participants, we observed high message response rates and low LTFU, suggesting potential for interactive messaging services to support pre-diagnosis TB care.

Survival after short- or long-term ventilation after acute spinal cord injury: a single-centre 25-year retrospective study.

STUDY DESIGN: A retrospective review of acute spinal cord injury patients having assisted ventilation on or after admission between 1981 and 2005. OBJECTIVE: To assess survival after acute ventilatory support. SETTING: Northwest Regional Spinal Injuries Centre, Southport, England. METHODS: Causes of death were ascertained from the Office of National Statistics. Kaplan-Meier analysis of survival was calculated according to ventilator-wean status at discharge. Risk factors were obtained by Cox regression analysis. RESULTS: Over 50% of deaths in weaned and ventilated patients were respiratory in origin. The mean survival of weaned patients in the age group 31-45 was 19.3 compared with 10.5 years for ventilated patients (P=0.047). Those under 30 survived a further 22.1 and 18.4 years (P=0.31), while those over 45 lived for 11.0 and 8.3 years (P=0.50), values for weaned and ventilated patients, respectively. The survival advantage for weaned patients in the middle age group was less evident when the 1-year survivors were compared. The mean survival time of younger patients with diaphragm pacing was 1.8 years longer than those on mechanical ventilation (P=0.142). The variables with significant hazard ratios were any comorbidity (3.07); mechanical ventilation on discharge (2.26); and older age at injury, (3.1). CONCLUSIONS: The survival time for patients with high tetraplegia on long-term ventilation compares with other datasets and older patients have a proportionately greater loss in life expectancy. Self-ventilating patients with tetraplegia remain at considerable risk from respiratory death and consideration needs to be given to more effective preventative measures.

Changes in cortical hemodynamics with the emergence of skilled motor ability in infants: An fNIRS study.

The brain activity changes during infancy that underpin the emergence of functional motor skills, such as reaching and stepping, are not well understood. The current study used functional near-infrared spectroscopy (fNIRS) to examine the hemodynamic response across the frontal, mid-coronal plane (sensorimotor cortex) and external occipital protuberance (cerebellar cortex) regions of typically developing infants (5 to 13 months) during reach-to-grasp or supported treadmill stepping behaviour. Motor ability was assessed using the third edition of the Motor Subscale of the Bayley Scales of Infant Development (BSID-III). Infants with enhanced motor ability demonstrated greater oxy-hemoglobin (HbO) concentration in the contralateral anterior mid-coronal and frontal-dorsal areas during right-handed reach-to-grasp. During bilateral reaching behavior, infants with enhanced motor ability showed greater HbO increases in right frontal-dorsal regions and lower HbO increases in left anterior mid-coronal areas. In contrast, infants' motor ability was associated with changes in de-oxyhemoglobin (HbR) concentration in the ipsilateral anterior mid-coronal, contralateral frontal and left external occipital protuberance regions during left-handed reaching behavior. These relationships between upper limb hemodynamics and infant motor ability are consistent with increased lateralization and cognitive-motor coupling as motor skills emerge. During stepping behavior, infants with enhanced motor ability demonstrated smaller increases in HbR concentration in the bilateral external occipital protuberance region consistent with an emerging efficiency as cruising and independent stepping behavior is still nascent. Together, the current results identify several distinct neural markers of functional motor ability during infancy that may be relevant to diagnostic testing and rehabilitation of developmental movement disorders.

Role of the thymus in transplantation tolerance in miniature swine. I. Requirement of the thymus for rapid and stable induction of tolerance to class I-mismatched renal allografts.

The almost uniform failure in transplant patients of tolerance-inducing regimens that have been found to be effective in rodents, has made it necessary to examine large animal models before testing of new approaches clinically. Miniature swine have been shown to share many relevant immunologic parameters with humans, and because of their reproducible genetics, have proved extremely useful in providing such a large animal model. We have previously shown that indefinite systemic tolerance to renal allografts in miniature swine is induced in 100% of cases across a two-haplotype class I plus minor histocompatibility antigen disparity by a 12-d course of Cyclosporine A (CyA), in contrast to irreversible rejection observed uniformly without CyA treatment. In the present study, we have examined the role of the thymus during the induction of tolerance by performing a complete thymectomy 21 d before renal transplantation. This analysis demonstrated a striking difference between thymectomized and nonthymectomized animals. Thymectomized swine developed acute cellular rejection characterized by a T cell (CD25(+)) infiltrate, tubulitis, endothelialitis and glomerulitis, and anti-donor CTL reactivity in vitro. Nonthymectomized and sham thymectomized animals had a mild T cell infiltrate with few CD25(+) cells and no anti-donor CTL response in vitro. These results indicate that the thymus is required for rapid and stable induction of tolerance.

Role of the primary somatosensory cortex in motor learning: An rTMS study.

Somatosensation is thought to play an important role in skilled motor learning. The present study investigated how healthy adults learn a continuous implicit motor task when somatosensation is altered by 1 Hz repetitive transcranial magnetic stimulation (rTMS) delivered over the primary somatosensory cortex (S1). Twenty-seven right-handed participants enrolled in a two-part experiment. In Experiment 1, we verified that 20 min of 1 Hz rTMS over S1 disrupted cutaneous somatosensation (indexed by two-point discrimination) in the wrist/hand; the impact of 1 Hz rTMS on wrist proprioception (tested by limb-position matching) was variable. Sham rTMS had no effect on either measure. We exploited these effects in Experiment 2 by pairing either 1 Hz or sham rTMS with practice of a continuous tracking task over two separate sessions on different days. Implicit motor learning was indexed on a third, separate retention test day when no rTMS was delivered. Across practice in Experiment 2, both the 1 Hz and sham rTMS groups showed improved tracking performance; however, 1 Hz rTMS was associated with less accurate tracking and smaller improvements in performance. Importantly, at the no rTMS retention test the effects of altering sensation with stimulation over S1 were still evident in the persistently less accurate tracking behavior of the 1 Hz rTMS group. The current study shows that disruption of somatosensation during task practice impairs the magnitude of change associated with motor learning, perhaps through the development of an inaccurate internal model.

Attention focus modulates afferent input to motor cortex during skilled action.

Psychomotor studies have identified a key role for attention in skill performance and acquisition. However, the neural mechanisms that underpin attention's role in motor control are not well understood. The current study investigated the differential effects of focus of attention upon short-latency afferent inhibition (SAI). SAI was chosen as it is positively correlated with the amount of sensory afference reaching the cortex. SAI is also sensitive to cholinergic influence, the same neurotransmitter involved in regulating attention, and is known to interact with other intracortical networks in the motor cortex. SAI in the first dorsal interosseous muscle was assessed while two separate groups produced the same physical sequential skill represented as a series of response key colors (external focus) or response fingers (internal focus). SAI was assessed at rest, immediately preceding, one element before or two elements before an index finger response. Compared to rest, both attention focus groups demonstrated a reduction in first dorsal interosseous SAI across the three sequence elements. However, the relative magnitude of SAI was greater under an internal focus of attention as an index finger response approached. This pattern indicates an attentional enhancement of somatosensory afference when attention is directed to a bodily dimension that counters the typical movement-related suppression of SAI. The current results support contemporary theories of attention's role in motor control, where an external focus of attention promotes a cortical state that maximizes effector coordination to maximize motor outcome.

The effects of five sessions of continuous theta burst stimulation over contralesional sensorimotor cortex paired with paretic skilled motor practice in people with chronic stroke.

BACKGROUND: In individuals with chronic stroke, impairment of the paretic arm may be exacerbated by increased contralesional transcallosal inhibition (TCI). Continuous theta burst stimulation (cTBS) can decrease primary motor cortex (M1) excitability and TCI. However, contralesional cTBS shows inconsistent effects after stroke. Variable effects of cTBS could stem from failure to pair stimulation with skilled motor practice or a focus of applying cTBS over M1. OBJECTIVE: Here, we investigated the effects of pairing cTBS with skilled practice on motor learning and arm function. We considered the differential effects of stimulation over two different brain regions: contralesional M1 (M1c) or contralesional primary somatosensory cortex (S1c). METHODS: 37 individuals with chronic stroke participated in five sessions of cTBS and paretic arm skilled practice of a serial targeting task (STT); participants received either cTBS over M1c or S1c or sham before STT practice. Changes in STT performance and Wolf Motor Function Test (WMFT) were assessed as primary outcomes. Assessment of bilateral corticospinal, intracortical excitability and TCI were secondary outcomes. RESULTS: cTBS over sensorimotor cortex did not improve STT performance and paretic WMFT-rate beyond sham cTBS. TCI was reduced bi-directionally following the intervention, regardless of stimulation group. In addition, we observed an association between STT performance change and paretic WMFT-rate change in the M1c stimulation group only. CONCLUSIONS: Multiple sessions of STT practice can improve paretic arm function and decrease TCI bilaterally, with no additional benefit of prior cTBS. Our results suggest that improvement in STT practice following M1c cTBS scaled with change in paretic arm function in some individuals. Our results highlight the need for a better understanding of the mechanisms of cTBS to effectively identify who may benefit from this form of brain stimulation.

Paired-pulse transcranial magnetic stimulation of primary somatosensory cortex differentially modulates perception and sensorimotor transformations.

Intermodal selective attention is generally associated with facilitation of relevant information. However, recent studies demonstrate reduced activation of primary somatosensory cortex (S1) with continuous vibrotactile tracking during bimodal stimulation. Reduced activation has been hypothesized to reflect an interaction between the sensorimotor and intermodal requirements of the tracking task. Recently, it has been shown that transcranial magnetic stimulation (TMS) involving a supra-threshold test stimulus (TS) preceded by a sub-threshold conditioning stimulus (CS) adversely affects tactile perception by altering excitability of local intracortical circuits. The purpose of the current paper was to use TMS to assess the effects of differential sensorimotor requirements in the right sensorimotor cortex upon local intracortical networks and sensory processing in the left primary somatosensory cortex during constant multimodal stimulation. Single and paired-pulse TMS was used to probe intracortical networks in S1 and sensory processing during a sensorimotor task where a vibrotactile stimulus to the right index finder guided either continuous or discrete sensorimotor responses of the left hand. It was hypothesized that paired-pulse TMS would alter local intracortical networks and reduce performance during the discrete sensorimotor task, but that these effects would be mitigated during the continuous sensorimotor task, possibly a reflection of reduced S1 activation observed previously during a similar continuous sensorimotor task. Regardless of sensorimotor requirements, single-pulse TMS delivered over S1 decreased sensorimotor performance. Paired-pulse TMS further decreased sensorimotor performance only when the vibrotactile stimulus guided a discrete motor response but not when it was required to continuously guide the motor response. This effect disappeared when the TS was replaced by a sub-threshold stimulus. These results suggest that the CS facilitates sensory output neurons during perceptual detection but that differential responsiveness of local cortical networks in S1 suppresses the CS effects during continuous sensory-guided movement. This study highlights the importance of sensorimotor requirements in determining the net result of task-related sensory processing in S1.

Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury.

Studies in the rat have pointed to a role for intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of acute tubular necrosis. These studies used antibodies, which may have nonspecific effects. We report that renal ICAM-1 mRNA levels and systemic levels of the cytokines IL-1 and TNF-alpha increase 1 h after ischemia/ reperfusion in the mouse. We sought direct proof for a critical role for ICAM-1 in the pathophysiology of ischemic renal failure using mutant mice genetically deficient in ICAM-1. ICAM-1 is undetectable in mutant mice in contrast with normal mice, in which ICAM-1 is prominent in the endothelium of the vasa recta. Mutant mice are protected from acute renal ischemic injury as judged by serum creatinine, renal histology, and animal survival . Renal leukocyte infiltration, quantitated morphologically and by measuring tissue myeloperoxidase, was markedly less in ICAM-1-deficient than control mice. To evaluate whether prevention of neutrophil infiltration could be responsible for the protection observed in the mutant mice, we treated normal mice with antineutrophil serum to reduce absolute neutrophil counts to < 100 cells/mm3. These neutrophil-depleted animals were protected against ischemic renal failure. Anti-1CAm-1 antibody protected normal mice against renal ischemic injury but did not provide additional protection to neutrophil-depleted animals. Thus, ICAM-1 is a key mediator of ischemic acute renal failure likely acting via potentiation of neutrophilendothelial interactions.

Attention modulates specific motor cortical circuits recruited by transcranial magnetic stimulation.

Skilled performance and acquisition is dependent upon afferent input to motor cortex. The present study used short-latency afferent inhibition (SAI) to probe how manipulation of sensory afference by attention affects different circuits projecting to pyramidal tract neurons in motor cortex. SAI was assessed in the first dorsal interosseous muscle while participants performed a low or high attention-demanding visual detection task. SAI was evoked by preceding a suprathreshold transcranial magnetic stimulus with electrical stimulation of the median nerve at the wrist. To isolate different afferent intracortical circuits in motor cortex SAI was evoked using either posterior-anterior (PA) or anterior-posterior (PA) monophasic current. In an independent sample, somatosensory processing during the same attention-demanding visual detection tasks was assessed using somatosensory-evoked potentials (SEP) elicited by median nerve stimulation. SAI elicited by AP TMS was reduced under high compared to low visual attention demands. SAI elicited by PA TMS was not affected by visual attention demands. SEPs revealed that the high visual attention load reduced the fronto-central P20-N30 but not the contralateral parietal N20-P25 SEP component. P20-N30 reduction confirmed that the visual attention task altered sensory afference. The current results offer further support that PA and AP TMS recruit different neuronal circuits. AP circuits may be one substrate by which cognitive strategies shape sensorimotor processing during skilled movement by altering sensory processing in premotor areas.