New approaches to the study of human brain networks underlying spatial attention and related processes

Cognitive processes, such as spatial attention, are thought to rely on extended networks in the human brain. Both clinical data from lesioned patients and fMRI data acquired when healthy subjects perform particular cognitive tasks typically implicate a wide expanse of potentially contributing areas, rather than just a single brain area. Conversely, evidence from more targeted interventions, such as transcranial magnetic stimulation (TMS) or invasive microstimulation of the brain, or selective study of patients with highly focal brain damage, can sometimes indicate that a single brain area may make a key contribution to a particular cognitive process. But this in turn raises questions about how such a brain area may interface with other interconnected areas within a more extended network to support cognitive processes. Here, we provide a brief overview of new approaches that seek to characterise the causal role of particular brain areas within networks of several interacting areas, by measuring the effects of manipulations for a targeted area on function in remote interconnected areas. In human participants, these approaches include concurrent TMS-fMRI and TMS-EEG, as well as combination of the focal lesion method in selected patients with fMRI and/or EEG measures of the functional impact from the lesion on interconnected intact brain areas. Such approaches shed new light on how frontal cortex and parietal cortex modulate sensory areas in the service of attention and cognition, for the normal and damaged human brai

Distinct causal influences of parietal versus frontal areas on human visual cortex: evidence from concurrent TMS-fMRI

It has often been proposed that regions of the human parietal and/or frontal lobe may modulate activity in visual cortex, for example, during selective attention or saccade preparation. However, direct evidence for such causal claims is largely missing in human studies, and it remains unclear to what degree the putative roles of parietal and frontal regions in modulating visual cortex may differ. Here we used transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) concurrently, to show that stimulating right human intraparietal sulcus (IPS, at a site previously implicated in attention) elicits a pattern of activity changes in visual cortex that strongly depends on current visual context. Increased intensity of IPS TMS affected the blood oxygen level–dependent (BOLD) signal in V5/MT+ only when moving stimuli were present to drive this visual region, whereas TMS-elicited BOLD signal changes were observed in areas V1–V4 only during the absence of visual input. These influences of IPS TMS upon remote visual cortex differed significantly from corresponding effects of frontal (eye field) TMS, in terms of how they related to current visual input and their spatial topography for retinotopic areas V1–V4. Our results show directly that parietal and frontal regions can indeed have distinct patterns of causal influence upon functional activity in human visual cortex. Key words: attention, frontal cortex, functional magnetic resonance imaging, parietal cortex, top--down, transcranial magnetic stimulatio

Studying the Role of Human Parietal Cortex in Visuospatial Attention with Concurrent TMS-fMRI

Combining transcranial magnetic stimulation (TMS) with concurrent functional magnetic resonance imaging (fMRI) allows study of how local brain stimulation may causally affect activity in remote brain regions. Here, we applied bursts of high- or low-intensity TMS over right posterior parietal cortex, during a task requiring sustained covert visuospatial attention to either the left or right hemifield, or in a neutral control condition, while recording blood oxygenation-level-dependent signal with a posterior MR surface coil. As expected, the active attention conditions activated components of the well-described "attention network,” as compared with the neutral baseline. Also as expected, when comparing left minus right attention, or vice versa, contralateral occipital visual cortex was activated. The critical new finding was that the impact of high- minus low-intensity parietal TMS upon these visual regions depended on the currently attended side. High- minus low-intensity parietal TMS increased the difference between contralateral versus ipsilateral attention in right extrastriate visual cortex. A related albeit less pronounced pattern was found for left extrastriate visual cortex. Our results confirm that right human parietal cortex can exert attention-dependent influences on occipital visual cortex and provide a proof of concept for the use of concurrent TMS-fMRI in studying how remote influences can vary in a purely top-down manner with attentional demand

Long-term small-fiber neuropathy and pain sensitization in survivors of pediatric acute lymphoblastic leukemia after stem cell transplantation

Purpose: We aimed at describing for the first time peripheral small-fiber neurotoxicity and pain sensitization in survivors of pediatric acute lymphoblastic leukemia after stem cell transplantation (SCT). Methods: In a cross-sectional, retrospective, single-center study, we assessed 25 relapse-free long-term survivors (median age at SCT: 11 ± 4.9 years; median time between SCT and testing: 8.25 years, 19 males) using a reduced version of the pediatric-modified total neuropathy score for clinical assessment and Quantitative Sensory Testing (QST). Inclusion criteria: ≥ 6 years old at testing, ≤ 18 years old at time of SCT, ≥ 1 year between SCT and testing. Results: Nine patients (36%) had peripheral neuropathy as defined by the clinical red-pmTNS (≥ 4). The QST parameters mechanical pain sensitivity, mechanical detection threshold, thermal sensory limen, vibration detection threshold and pressure pain threshold were significantly abnormal in the survivor cohort (p < 0.0038). Except for one, all survivors showed at least one abnormal QST parameter. When using QST, signs of small and large fiber dysfunction were present in 22 (88%) and 17 (68%) survivors, respectively. More than half of all survivors were found to experience pathologic sensitization to pain. Conclusions and implications for cancer survivors: Survivors of pediatric acute lymphoblastic leukemia after SCT are at high risk for long-term peripheral neuropathy with a dominating small-fiber and pain sensitization pattern

The perception of touch and the ventral somatosensory pathway

Preusser et al. use MRI-based lesion-symptom mapping to confirm the causal role of a ventral pathway in the perception of touch. This pathway originates downstream of the postcentral gyrus in the parietal operculum, passes the insula and the putamen, before terminating in white matter projections extending to inferior lateral prefrontal corte

Hemispheric differences in frontal and parietal influences on human occipital cortex: direct confirmation with concurrent TMS-fMRI

We used concurrent TMS-fMRI to test directly for hemispheric differences in causal influences of the right or left fronto-parietal cortex on activity (BOLD signal) in the human occipital cortex. Clinical data and some behavioral TMS studies have been taken to suggest right-hemisphere specialization for top-down modulation of vision in humans, based on deficits such as spatial neglect or extinction in lesioned patients, or findings that TMS to right (vs. left) fronto-parietal structures can elicit stronger effects on visual performance. But prior to the recent advent of concurrent TMS and neuroimaging, it was not possible to directly examine the causal impact of one (stimulated) brain region upon others in humans. Here we stimulated the frontal or intraparietal cortex in the left or right hemisphere with TMS, inside an MR scanner, while measuring with fMRI any resulting BOLD signal changes in visual areas V1-V4 and V5/MT+. For both frontal and parietal stimulation, we found clear differences between effects of right- versus left-hemisphere TMS on activity in the visual cortex, with all differences significant in direct statistical comparisons. Frontal TMS over either hemisphere elicited similar BOLD decreases for central visual field representations in V1-V4, but only right frontal TMS led to BOLD increases for peripheral field representations in these regions. Hemispheric differences for effects of parietal TMS were even more marked: Right parietal TMS led to strong BOLD changes in V1-V4 and V5/MT+, but left parietal TMS did not. These data directly confirm that the human frontal and parietal cortex show right-hemisphere specialization for causal influences on the visual cortex

New approaches to the study of human brain networks underlying spatial attention and related processes

Cognitive processes, such as spatial attention, are thought to rely on extended networks in the human brain. Both clinical data from lesioned patients and fMRI data acquired when healthy subjects perform particular cognitive tasks typically implicate a wide expanse of potentially contributing areas, rather than just a single brain area. Conversely, evidence from more targeted interventions, such as transcranial magnetic stimulation (TMS) or invasive microstimulation of the brain, or selective study of patients with highly focal brain damage, can sometimes indicate that a single brain area may make a key contribution to a particular cognitive process. But this in turn raises questions about how such a brain area may interface with other interconnected areas within a more extended network to support cognitive processes. Here, we provide a brief overview of new approaches that seek to characterise the causal role of particular brain areas within networks of several interacting areas, by measuring the effects of manipulations for a targeted area on function in remote interconnected areas. In human participants, these approaches include concurrent TMS-fMRI and TMS-EEG, as well as combination of the focal lesion method in selected patients with fMRI and/or EEG measures of the functional impact from the lesion on interconnected intact brain areas. Such approaches shed new light on how frontal cortex and parietal cortex modulate sensory areas in the service of attention and cognition, for the normal and damaged human brain

DASMI: exchanging, annotating and assessing molecular interaction data

Motivation: Ever increasing amounts of biological interaction data are being accumulated worldwide, but they are currently not readily accessible to the biologist at a single site. New techniques are required for retrieving, sharing and presenting data spread over the Internet

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead