Decisional role of the dorsolateral prefrontal cortex in ocular motor behaviour

Three patients with a unilateral cortical lesion affecting the dorsolateral prefrontal cortex (DLPFC), i.e. Brodmann area 46, were tested using different paradigms of reflexive saccades (gap and overlap tasks), intentional saccades (antisaccades, memory‐guided and predictive saccades) and smooth pursuit movements. Visually guided saccades with gap and overlap, latency of correct antisaccades and memory‐guided saccades and the gain of smooth pursuit were normal, compared with controls. These results confirm our anatomical data showing that the adjacent frontal eye field (FEF) was unimpaired in these patients. The specific pattern of abnormalities after a unilateral DLPFC lesion, compared with that of the FEF lesions previously reported, consists mainly of: (i) a bilateral increase in the percentage of errors in the antisaccade task (misdirected reflexive saccades); (ii) a bilateral increase in the variable error in amplitude, without significant decrease in the gain, in the memory‐guided saccade task; and (iii) a bilateral decrease in the percentage of anticipatory saccades in the predictive task. Taken together, these results suggest that the DLPFC plays a crucial role in the decisional processes, preparing saccades by inhibiting unwanted reflexive saccades (inhibition), maintaining memorized information for ongoing intentional saccades (short‐term spatial memory) or facilitating anticipatory saccades (prediction), depending upon current external environmental and internal circumstance

The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine

The antisaccade task provides a laboratory analogue of situations in which execution of the correct behavioural response requires the suppression of a more prepotent or habitual response. Errors (failures to inhibit a reflexive prosaccade towards a sudden onset target) are significantly increased in patients with damage to the dorsolateral prefrontal cortex and patients with schizophrenia. Recent models of antisaccade performance suggest that errors are more likely to occur when the intention to initiate an antisaccade is insufficiently activated within working memory. Nicotine has been shown to enhance specific working memory processes in healthy adults. MATERIALS AND METHODS: We explored the effect of nicotine on antisaccade performance in a large sample (N = 44) of young adult smokers. Minimally abstinent participants attended two test sessions and were asked to smoke one of their own cigarettes between baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine reduced antisaccade errors and correct antisaccade latencies if delivered before optimum performance levels are achieved, suggesting that nicotine supports the activation of intentions in working memory during task performance. The implications of this research for current theoretical accounts of antisaccade performance, and for interpreting the increased rate of antisaccade errors found in some psychiatric patient groups are discussed

Structural neural networks subserving oculomotor function in first-episode schizophrenia

BACKGROUND: Smooth pursuit and antisaccade abnormalities are well documented in schizophrenia, but their neuropathological correlates remain unclear. METHODS: In this study, we used statistical parametric mapping to investigate the relationship between oculomotor abnormalities and brain structure in a sample of first-episode schizophrenia patients (n = 27). In addition to conventional volumetric magnetic resonance imaging, we also used magnetization transfer ratio, a technique that allows more precise tissue characterization. RESULTS: We found that smooth pursuit abnormalities were associated with reduced magnetization transfer ratio in several regions, predominantly in the right prefrontal cortex. Antisaccade errors correlated with gray matter volume in the right medial superior frontal cortex as measured by conventional magnetic resonance imaging but not with magnetization transfer ratio. CONCLUSIONS: These preliminary results demonstrate that specific structural abnormalities are associated with abnormal eye movements in schizophrenia

Spatial working memory and Inhibition of Return

Recently we showed that maintaining a location in spatial working memory affects saccadic eye movement trajectories, in that the eyes deviate away from the remembered location (Theeuwes, Olivers, & Chizk, 2005). Such saccade deviations are assumed to be the result of inhibitory processes within the oculomotor system. The present study investigated whether this inhibition is related to the phenomenon of inhibition of return (IOR), the relatively slow selection of previously attended locations as compared with new locations. The results show that the size of IOR to a location was not affected by whether or not the location was kept in working memory, but the size of the saccade trajectory deviation was affected. We conclude that inhibiting working memory–related eye movement activity is not the same as inhibiting a previously attended location in space. Working memory is a system that allows for the temporary storage of information until a task is completed (see, e.g., Baddeley, 1986). Awh and colleagues (Awh & Jonides, 2001; Awh, Jonides, & Reuter-Lorenz, 1998) provided evidence for a strong link between working memory and attention. For example, they showed that when a locatio

Apoptosis of the fibrocytes type 1 in the spiral ligament and blood labyrinth barrier disturbance cause hearing impairment in murine cerebral malaria

<p>Abstract</p> <p>Background</p> <p>Experimental murine malaria has been shown to result in significant hearing impairment. Microscopic evaluation of the temporal bones of these animals has revealed regular morphology of the cochlea duct. Furthermore, the known vascular pathologic changes being associated with malaria could not be found. Immunohistochemistry for ICAM1 showed a strong marking in the <it>stria vascularis</it>, indicating a disturbance of the endocochlear potential. The aim of this study was to evaluate the role of apoptosis and the disturbance of the blood labyrinth barrier in the murine malaria associated hearing impairment.</p> <p>Methods</p> <p>The temporal bones of seven mice with cerebral malaria-four with hearing impairment, three without hearing impairment-were evaluated with immunohistochemistry for cleaved caspase 3 to detect apoptosis and connexin 26, a gap junction protein being a cornerstone in the endocochlear potassium recirculation. Furthermore five animals with cerebral malaria were treated with Evans blue prior to sacrification to detect disturbances of the blood labyrinth barrier.</p> <p>Results</p> <p>Cleaved caspase 3 could clearly be detected by immunohistochemistry in the fibrocytes of the spiral ligament, more intensively in animals with hearing impairment, less intensively in those without. Apoptosis signal was equally distributed in the spiral ligament as was the connexin 26 gap junction protein. The Evans blue testing revealed a strong signal in the malaria animals and no signal in the healthy control animals.</p> <p>Conclusion</p> <p>Malfunction of the fibrocytes type 1 in the spiral ligament and disruption of the blood labyrinth barrier, resulting in a breakdown of the endocochlear potential, are major causes for hearing impairment in murine cerebral malaria.</p

Distributed representations of the "preparatory set" in the frontal oculomotor system: a TMS study

<p>Abstract</p> <p>Background</p> <p>The generation of saccades is influenced by the level of "preparatory set activity" in cortical oculomotor areas. This preparatory activity can be examined using the gap-paradigm in which a temporal gap is introduced between the disappearance of a central fixation target and the appearance of an eccentric target.</p> <p>Methods</p> <p>Ten healthy subjects made horizontal pro- or antisaccades in response to lateralized cues after a gap period of 200 ms. Single-pulse transcranial magnetic stimulation (TMS) was applied to the dorsolateral prefrontal cortex (DLPFC), frontal eye field (FEF), or supplementary eye field (SEF) of the right hemisphere 100 or 200 ms after the disappearance of the fixation point. Saccade latencies were measured to probe the disruptive effect of TMS on saccade preparation. In six individuals, we gave realistic sham TMS during the gap period to mimic auditory and somatosensory stimulation without stimulating the cortex.</p> <p>Results</p> <p>TMS to DLPFC, FEF, or SEF increased the latencies of contraversive pro- and antisaccades. This TMS-induced delay of saccade initiation was particularly evident in conditions with a relatively high level of preparatory set activity: The increase in saccade latency was more pronounced at the end of the gap period and when participants prepared for prosaccades rather than antisaccades. Although the "lesion effect" of TMS was stronger with prefrontal TMS, TMS to FEF or SEF also interfered with the initiation of saccades. The delay in saccade onset induced by real TMS was not caused by non-specific effects because sham stimulation shortened the latencies of contra- and ipsiversive anti-saccades, presumably due to intersensory facilitation.</p> <p>Conclusion</p> <p>Our results are compatible with the view that the "preparatory set" for contraversive saccades is represented in a distributed cortical network, including the contralateral DLPFC, FEF and SEF.</p

Medio-Frontal and Anterior Temporal abnormalities in children with attention deficit hyperactivity disorder (ADHD) during an acoustic antisaccade task as revealed by electro-cortical source reconstruction

<p>Abstract</p> <p>Background</p> <p>Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent disorders in children and adolescence. Impulsivity is one of three core symptoms and likely associated with inhibition difficulties. To date the neural correlate of the antisaccade task, a test of response inhibition, has not been studied in children with (or without) ADHD.</p> <p>Methods</p> <p>Antisaccade responses to visual and acoustic cues were examined in nine unmedicated boys with ADHD (mean age 122.44 ± 20.81 months) and 14 healthy control children (mean age 115.64 ± 22.87 months, three girls) while an electroencephalogram (EEG) was recorded. Brain activity before saccade onset was reconstructed using a 23-source-montage.</p> <p>Results</p> <p>When cues were acoustic, children with ADHD had a higher source activity than control children in Medio-Frontal Cortex (MFC) between -230 and -120 ms and in the left-hemispheric Temporal Anterior Cortex (TAC) between -112 and 0 ms before saccade onset, despite both groups performing similarly behaviourally (antisaccades errors and saccade latency). When visual cues were used EEG-activity preceding antisaccades did not differ between groups.</p> <p>Conclusion</p> <p>Children with ADHD exhibit altered functioning of the TAC and MFC during an antisaccade task elicited by acoustic cues. Children with ADHD need more source activation to reach the same behavioural level as control children.</p

Global Carbon Budget 2018

Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere – the “global carbon budget” – is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO2 emissions (EFF) are based on energy statistics and cement production data, while emissions from land use and land-use change (ELUC), mainly deforestation, are based on land use and land-use change data and bookkeeping models. Atmospheric CO2 concentration is measured directly and its growth rate (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) and terrestrial CO2 sink (SLAND) are estimated with global process models constrained by observations. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the last decade available (2008–2017), EFF was 9.4±0.5 GtC yr−1, ELUC 1.5±0.7 GtC yr−1, GATM 4.7±0.02 GtC yr−1, SOCEAN 2.4±0.5 GtC yr−1, and SLAND 3.2±0.8 GtC yr−1, with a budget imbalance BIM of 0.5 GtC yr−1 indicating overestimated emissions and/or underestimated sinks. For the year 2017 alone, the growth in EFF was about 1.6 % and emissions increased to 9.9±0.5 GtC yr−1. Also for 2017, ELUC was 1.4±0.7 GtC yr−1, GATM was 4.6±0.2 GtC yr−1, SOCEAN was 2.5±0.5 GtC yr−1, and SLAND was 3.8±0.8 GtC yr−1, with a BIM of 0.3 GtC. The global atmospheric CO2 concentration reached 405.0±0.1 ppm averaged over 2017. For 2018, preliminary data for the first 6–9 months indicate a renewed growth in EFF of +2.7 % (range of 1.8 % to 3.7 %) based on national emission projections for China, the US, the EU, and India and projections of gross domestic product corrected for recent changes in the carbon intensity of the economy for the rest of the world. The analysis presented here shows that the mean and trend in the five components of the global carbon budget are consistently estimated over the period of 1959–2017, but discrepancies of up to 1 GtC yr−1 persist for the representation of semi-decadal variability in CO2 fluxes. A detailed comparison among individual estimates and the introduction of a broad range of observations show (1) no consensus in the mean and trend in land-use change emissions, (2) a persistent low agreement among the different methods on the magnitude of the land CO2 flux in the northern extra-tropics, and (3) an apparent underestimation of the CO2 variability by ocean models, originating outside the tropics. This living data update documents changes in the methods and data sets used in this new global carbon budget and the progress in understanding the global carbon cycle compared with previous publications of this data set (Le Quéré et al., 2018, 2016, 2015a, b, 2014, 2013). All results presented here can be downloaded from https://doi.org/10.18160/GCP-2018