Two spatially distinct posterior alpha sources fulfill different functional roles in attention

Directing attention helps extracting relevant information and suppressing distracters. Alpha brain oscillations (8-12Hz) are crucial for this process, with power decreases facilitating processing of important information and power increases inhibiting brain regions processing irrelevant information. Evidence for this phenomenon arises from visual attention studies (Worden et al., 2000b), however, the effect also exists in other modalities, including the somatosensory system (Haegens et al., 2011) and inter-sensory attention tasks (Foxe and Snyder, 2011). We investigated in human participants (10 females, 10 males) the role of alpha oscillations in focused (0/100%) vs. divided (40/60%) attention, both across modalities (visual/somatosensory; Experiment 1) and within the same modality (visual domain: across hemifields; Experiment 2) while recording EEG over 128 scalp electrodes. In Experiment 1 participants divided their attention between visual and somatosensory modality to determine the temporal/spatial frequency of a target stimulus (vibrotactile stimulus/Gabor grating). In Experiment 2, participants divided attention between two visual hemifields to identify the orientation of a Gabor grating. In both experiments, pre-stimulus alpha power in visual areas decreased linearly with increasing attention to visual stimuli. In contrast, pre-stimulus alpha power in parietal areas was lower when attention was divided between modalities/hemifields, compared to focused attention. These results suggest there are two alpha sources, where one reflects the ‘visual spotlight of attention’ and the other reflects attentional effort. To our knowledge, this is the first study to show that attention recruits two spatially distinct alpha sources in occipital and parietal brain regions, acting simultaneously but serving different functions in attention

Evidence that the negative BOLD response is neuronal in origin: a simultaneous EEG–BOLD–CBF study in humans

Unambiguous interpretation of changes in the BOLD signal is challenging because of the complex neurovascular coupling that translates changes in neuronal activity into the subsequent haemodynamic response. In particular, the neurophysiological origin of the negative BOLD response (NBR) remains incompletely understood. Here, we simultaneously recorded BOLD, EEG and cerebral blood flow (CBF) responses to 10 s blocks of unilateral median nerve stimulation (MNS) in order to interrogate the NBR. Both negative BOLD and negative CBF responses to MNS were observed in the same region of the ipsilateral primary sensorimotor cortex (S1/M1) and calculations showed that MNS induced a decrease in the cerebral metabolic rate of oxygen consumption (CMRO2) in this NBR region. The ∆CMRO2/∆CBF coupling ratio (n) was found to be significantly larger in this ipsilateral S1/M1 region (n = 0.91 ± 0.04, M = 10.45%) than in the contralateral S1/M1 (n = 0.65 ± 0.03, M = 10.45%) region that exhibited a positive BOLD response (PBR) and positive CBF response, and a consequent increase in CMRO2 during MNS. The fMRI response amplitude in ipsilateral S1/M1 was negatively correlated with both the power of the 8–13 Hz EEG mu oscillation and somatosensory evoked potential amplitude. Blocks in which the largest magnitude of negative BOLD and CBF responses occurred therefore showed greatest mu power, an electrophysiological index of cortical inhibition, and largest somatosensory evoked potentials. Taken together, our results suggest that a neuronal mechanism underlies the NBR, but that the NBR may originate from a different neurovascular coupling mechanism to the PBR, suggesting that caution should be taken in assuming the NBR simply represents the neurophysiological inverse of the PBR

Global signal modulation of single-trial fMRI response variability: effect on positive vs negative BOLD response relationship

In functional magnetic resonance imaging (fMRI), the relationship between positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to stimulation is potentially informative about the balance of excitatory and inhibitory brain responses in sensory cortex. In this study, we performed three separate experiments delivering visual, motor or somatosensory stimulation unilaterally, to one side of the sensory field, to induce PBR and NBR in opposite brain hemispheres. We then assessed the relationship between the evoked amplitudes of contralateral PBR and ipsilateral NBR at the level of both single-trial and average responses. We measure single-trial PBR and NBR peak amplitudes from individual time-courses, and show that they were positively correlated in all experiments. In contrast, in the average response across trials the absolute magnitudes of both PBR and NBR increased with increasing stimulus intensity, resulting in a negative correlation between mean response amplitudes. Subsequent analysis showed that the amplitude of single-trial PBR was positively correlated with the BOLD response across all grey-matter voxels and was not specifically related to the ipsilateral sensory cortical response. We demonstrate that the global component of this single-trial response modulation could be fully explained by voxel-wise vascular reactivity, the BOLD signal standard deviation measured in a separate resting-state scan (resting state fluctuation amplitude, RSFA). However, bilateral positive correlation between PBR and NBR regions remained. We further report that modulations in the global brain fMRI signal cannot fully account for this positive PBR-NBR coupling and conclude that the local sensory network response reflects a combination of superimposed vascular and neuronal signals. More detailed quantification of physiological and noise contributions to the BOLD signal is required to fully understand the trial-by-trial PBR and NBR relationship compared with that of average responses

Post-stimulus fMRI and EEG responses: evidence for a neuronal origin hypothesised to be inhibitory

Post-stimulus undershoots, negative responses following cessation of stimulation, are widely observed in functional magnetic resonance (fMRI) blood oxygenation level dependent (BOLD) data. However, the debate surrounding whether the origin of this response phase is neuronal or vascular, and whether it provides functionally relevant information, that is additional to what is contained in primary response, means that undershoots are widely overlooked. We simultaneously recorded electroencephalography (EEG), BOLD and cerebral blood-flow (CBF) [obtained from arterial spin labelled (ASL) fMRI] fMRI responses to hemifield checkerboard stimulation to test the potential neural origin of the fMRI post-stimulus undershoot. The post-stimulus BOLD and CBF signal amplitudes in both contralateral and ipsilateral visual cortex depended on the post-stimulus power of the 8-13 Hz (alpha) EEG neuronal activity, such that trials with highest EEG power showed largest fMRI undershoots in contralateral visual cortex. This correlation in post-stimulus EEG-fMRI responses was not predicted by the primary response amplitude. In the contralateral visual cortex we observed a decrease in both cerebral rate of oxygen metabolism (CMRO2) and CBF during the post-stimulus phase. In addition, the coupling ratio (n) between CMRO2 and CBF was significantly lower during the positive contralateral primary response phase compared with the post-stimulus phase and we propose that this reflects an altered balance of excitatory and inhibitory neuronal activity. Together our data provide strong evidence that the post-stimulus phase of the BOLD response has a neural origin which reflects, at least partially, an uncoupling of the neuronal responses driving the primary and post-stimulus responses, explaining the uncoupling of the signals measured in the two response phases. We suggest our results are consistent with inhibitory processes driving the post-stimulus EEG and fMRI responses. We therefore propose that new methods are required to model the post-stimulus and primary responses independently, enabling separate investigation of response phases in cognitive function and neurological disease

Intrinsic variability in the human response to pain is assembled from multiple, dynamic brain processes

The stimulus-evoked response is the principle measure used to elucidate the timing and spatial location of human brain activity. Brain and behavioural responses to pain are influenced by multiple intrinsic and extrinsic factors and display considerable, natural trial-by-trial variability. However, because the neuronal sources of this variability are poorly understood the functional information it contains is under-exploited for understanding the relationship between brain function and behaviour. We recorded simultaneous EEG-fMRI during rest and noxious thermal stimulation to characterise the relationship between natural fluctuations in behavioural pain-ratings, the spatiotemporal dynamics of brain network responses and intrinsic connectivity. We demonstrate that fMRI response variability in the pain network is: dependent upon its resting-state functional connectivity; modulated by behaviour; and correlated with EEG evoked-potential amplitude. The pre-stimulus default-mode network (DMN) fMRI signal predicts the subsequent magnitude of pain ratings, evoked-potentials and pain network BOLD responses. Additionally, the power of the ongoing EEG alpha oscillation, an index of cortical excitability, modulates the DMN fMRI response to pain. The complex interaction between alpha-power, DMN activity and both the behavioural report of pain and the brain's response to pain demonstrates the neurobiological significance of trial-by-trial variability. Furthermore, we show that multiple, interconnected factors contribute to both the brain's response to stimulation and the psychophysiological emergence of the subjective experience of pain. © 2013 Elsevier Inc

Between Intent and Achievement in Sector-Wide Approaches: Staking a Claim for Reproductive Health

Since 1995, sector-wide approaches (SWAps) to health development have significantly influenced health aid to developing countries. SWAps offer guidelines for new partnerships with international donors led by government, new relationships between donors and shared financing, development and implementation of agreed packages of health sector reforms. These structural and funding changes have significant implications for reproductive health. The early experience of SWAps suggests that the extent of donor commitment is constrained for administrative, philosophical and political reasons, with vertical programmes (including those relevant to reproductive health) protecting their 'core' business, and reproductive health, as an integrative concept, lacking strong advocates. Defining the sector in terms of government health systems focuses resources on building effective district health systems, but with uncertain outcomes for elements of reproductive health that depend on multi-sectoral strategies, e.g. safe motherhood. The context of the reforms remains a determining factor in their success, but despite savings available through increased efficiencies and coordinated services, the total per capita expenditure on health to ensure minimum clinical and public health services often remains beyond the budget available to least developed nations. Despite this, many of the elements of SWAps--government leadership, new donor relationships, better coordination, sectoral reform and service integration--offer the potential for more effective and efficient health services, including those for reproductive health

Intoxicações natural e experimental por amitraz em eqüídeos: aspectos clínicos Natural and experimental poisoning by amitraz in horses and donkey: clinical aspects

A administração oral e a aspersão com amitraz reproduziram experimentalmente em 17eqüinos e um asinino um quadro de intoxicação muito similar a outro que vinha ocorrendo em cavalos no Estado do Rio de Janeiro. O início dos sintomas após a administração oral variou entre 15min. e 2h05min., na aplicação por aspersão variou entre 6h28min. e 8h38min. A evolução nos casos de administração oral foi de 4 a 9 dias, nos de aspersão de 5 a 6 dias. Somente morreram animais que receberam a administração oral. Um animal aspergido com o amitraz foi sacrificado. Por via oral foram usadas dosagens de 5,5 mg/kg (uma administração), 5,8 mg/kg (duas administrações) e num terceiro animal, doses que variaram entre 7,2 e 36,4 mg/kg (cinco administrações). Nas aplicações por aspersão, a intoxicação foi reproduzida com soluções nas concentrações de 0,1 e 0,2%. Com relação ao sistema nervoso, os principais sinais observados foram apatia, sonolência, ptoses palpebral e auricular, dificuldade de apreensão, mastigação e deglutição do alimento, arrastar das pinças dos cascos no solo, exposição do pênis, sensibilidade cutânea diminuída/ausente, instabilidade em estação, abdução dos membros, cabeça baixa, incoordenação, bocejos, flacidez labial, exposição da língua, cruzamento dos membros ao caminhar, resposta postural diminuída após cruzar e abduzir os membros, reflexos do lábio superior, palatal, lingual, de deglutição e flexor diminuídos/ausentes, reflexos auricular, palpebral e de ameaça diminuídos e resposta ambulatória diminuída ao teste de girar em círculo de pequeno raio. No que se refere ao sistema digestivo, foram evidenciados, principalmente, hipomotilidade/atonia intestinal, edema dos lábios, distensão abdominal, deitar e levantar com freqüência, rolar no solo, olhar para o flanco, gemer e impactação do intestino grosso. Observaram-se ainda taquicardia, aumento do tempo de preenchimento capilar e mucosas congestas, estridor, taquipnéia, dispnéia, secreção nasal, bradipnéia e respiração abdominal. Todos os três casos naturais ocorreram após aspersão do amitraz. Os primeiros sintomas foram observados 2 e 3 dias após o banho. A evolução foi de 6, 7 e 17 dias. Um animal manifestou a maioria dos sinais referentes ao sistema nervoso observados nos experimentos, com exceção dos sinais de cruzamento dos membros ao caminhar, bocejos, lábios flácidos e exposição do pênis. Outro animal, intoxicado espontaneamente, manifestou somente sintomas digestivos como rolar, ''patear'', hipomotilidade/atonia intestinal e impactação do intestino grosso. Um terceiro animal, inicialmente manifestou sintomas digestivos caracterizados por patear, rolar, atonia intestinal e impactação do intestino grosso, com conseqüente desenvolvimento de laminite; na fase final exibiu acentuada sintomatologia nervosa mostrando compressão da cabeça contra obstáculos, incoordenação motora com cruzamento dos membros ao caminhar e relutância em se movimentar. Baseados no quadro clínico observado, são sugeridos possíveis locais de lesão no sistema nervoso.<br>Poisoning by amitraz was experimentally reproduced in 17 horses and a donkey. First symptoms were observed between 15 min. and 2 h 5 min. after oral administration, and between 6 h 28 min. and 8 h 38 min. after spraying with amitraz. The course of poisoning after oral administration was 4 to 9 days, and after spraying 5 to 6 days. Death of experimental animals occurred only after oral administration. One animal was euthanized after spraying. Doses of 5.5 mg/kg (1 administration), 5.8 mg/kg (2 administrations) and doses which varied between 7.2 and 36.4 mg/kg (5 administrations) were used when amitraz was given by mouth, all causing symptoms of poisoning. When the administration of amitraz was by spraying, poisoning was reproduced with solutions of 0.1 and 0.2 % . Regarding the nervous system, the main signs observed were recumbency, somnolence, palpebral and auricular ptosis, difficulties in apprehension, chewing and swallowing of food, dragging of the hooves, exposure of the penis, diminished or absent cutaneous sensibility, instability, abduction of the legs, lowering of the head, incoordination, jawning, labial flacity, exposure of the tongue, crossing of the legs when walking, diminished postural response after crossing or abducting the legs, diminished/absent reflex of the upper lip, palatal, tongue, flexor and swallowing reflex, diminished auricular, palpebral and menace reflex. The ambulatory response was diminished when tested by walking in circles of small radius. Regarding the digestive system, the signs were mainly intestinal hypomotility/atony, edema of the lips, abdominal distention, frequent lying down and standing up, rolling on the ground, looking at the flancs, groaning and impaction of the large bowel. Regarding the circulatory system, the main clinical signs were tachycardia, increase of the refilling time of capillaries, congested mucosa and splitting of the cardiac sounds. Regarding the respiratory system, stridor, tachypnoea, dyspnoea, nasal discharge, bradypnoea and abdominal respiration was observed. Beside these signs, there were alterations of the general condition, as apathy and hypothermia. All natural cases occurred after spraying with amitraz. First symptoms were seen 2 to 3 days after the application of amitraz. The course was 6, 7 and 17 days. One animal showed mainly the nervous signs as seen in the experiments, with exception of the signs of crossing the legs when walking, yawning and exposure of the penis. Another animal had only digestive symptoms as rolling, pawing, intestinal hypomotility/atony and impaction of the large bowel. A third animal initially showed digestive symptoms characterized by pawing, rolling, intestinal atony and impaction of the large bowel, followed by laminitis; in the final stage this animal showed severe nervous signs as pressing the head against obstacles, incoordination with crossing the legs when walking and reluctance to move. Possible location of lesions in the nervous system according to the clinical signs are suggested