Spatio-temporal coupling of the electric and hemodynamic brain responses in humans

Our comprehension of human brain functions and their dynamics has been dramatically improved by recent developments in non-invasive imaging techniques. These methods can be divided into two different categories, according to the nature of the measured signal: hemodynamic techniques, such as functional magnetic resonance imaging (fMRI) and positiron emission tomography (PET), and electromagnetic techniques, such as electroencephalography (EEG) and magnetoencephalography (MEG). These two categories are have complementary characteristics: hemodynamic techniques have a good spatial resolution (on a millimeter spatial scale) but have a poor temporal resolution, which is inherently limited by the rate changes in blood flow and oxygenation. Electromagnetic techniques have sub-millisecond temporal resolution but have a poor spatial resolution, since the analysis of intracranial generators requires the solution of an underdetermined inverse problem (i.e. there are infinite solutions that can explain equally well the same scalp-recorded distribution). The complementarity of the characteristics of these two families of methods allowed researchers to suppose that the understanding of spatio-temporal brain dynamics can be drastically improved by their combination (so-called multimodal imaging). Unfortunately some caveats hinder such combination. First, the nature of neurovascular coupling is still poorly understood. Second, analytical methods for multimodal imaging are largely in their infancy. The first part of this thesis focuses on the analysis of the temporal characteristics of the blood oxygenation level dependent (BOLD) signal and on how they are modulated by stimulus conditions. To analyze the BOLD dynamics, a novel method for synchronizing stimulus delivery and volume acquisition was developed. This method allows for estimating the BOLD signal with a high temporal resolution (in this thesis up to 125 ms) and for studying how the temporal characteristics (in this thesis mainly the BOLD peak latency and slope) are modulated by stimulus conditions (with an approach similar to that used in the analysis of the EEG evoked potentials). We applied this novel technique to a simple reaction time task to lateralized visual stimuli (the so-called Poffenberger paradigm) as well as to a multisensory auditory-visual reaction time task. In the first study (the Poffenberger paradigm) the analysis of BOLD dynamics supported the theory of a bilateral visuo-motor pathway even in the case of a visual stimulus ipsilateral to the responding hand. In the second study, (the auditory-visual multisensory reaction-time task), the analysis showed auditory-visual interactions within both primary auditory and visual cortices that could not be otherwise revealed by traditional fMRI analysis methods since it does not involve changes in signal amplitude. The second part of this thesis focuses on the comparison of the statistical results obtained by the analyses of fMRI and of the intracranial local field potentials (LFPs), estimated by the ELECTRA inverse solution. We first developed a new method for the analysis of EEG data. This method is based on the statistical comparison of the spectral characteristics of the estimated intracranial LFPs of the pre- and post- stimulus onset periods. Each single trial is analyzed independently, without including an averaging step, so that the information carried by high frequencies is preserved. We also propose a new metric, called resemblance, to investigate the relationship between fMRI and the estimated intracranial LFPs. Single-trial analysis and the resemblance metric were applied in an experiment involving separate EEG and fMRI acquisitions during the same passive visual stimulation protocol. This experiment revealed that only a limited set of LFP frequencies shows a spatial correlation with fMRI. This set of frequencies changes across brain areas, such that progression from lower to higher cortical levels of visual processing incorporates at each step new frequencies. In conclusion, in this thesis we show that the estimation and the analysis of the BOLD time course can give an important contribution to better understanding brain functions and brain organization. To fully understand the meaning of changes in BOLD dynamics, we need a better knowledge of the neuro-vascular coupling. To do that, we introduced a new method for evaluating the relationship between EEG and fMRI across frequencies and anatomical regions

Object Representations for Multiple Visual Categories Overlap in Lateral Occipital and Medial Fusiform Cortex

How representations of visual objects are maintained across changes in viewpoint is a central issue in visual perception. Whether neural processes underlying view-invariant recognition involve distinct subregions within extrastriate visual cortex for distinct categories of visual objects remains unresolved. We used event-related functional magnetic resonance imaging in 16 healthy volunteers to map visual cortical areas responding to a large set (156) of exemplars from 3 object categories (faces, houses, and chairs), each repeated once after a variable time lag (3-7 intervening stimuli). Exemplars were repeated with the same viewpoint (but different retinal size) or with different viewpoint and size. The task was kept constant across object categories (judging items as "young” vs. "old”). We identified object-selective adaptation effects by comparing neural responses to the first presentation versus repetition of each individual exemplar. We found that exemplar-specific adaptation effects partly overlapped with regions showing category-selective responses (as identified using a separate localizer scan). These included the lateral fusiform gyrus (FG) for faces, parahippocampal gyrus for houses, and lateral occipital complex (LOC) for chairs. In face-selective fusiform gyrus (FG), adaptation effects occurred only for faces repeated with the same viewpoint, but not with a different viewpoint, confirming previous studies using faces only. By contrast, a region in right medial FG, adjacent to but nonoverlapping with the more lateral and face-selective FG, showed repetition effects for faces and to a lesser extent for other objects, regardless of changes in viewpoint or in retinal image-size. Category- and viewpoint-independent repetition effects were also found in bilateral LOC. Our results reveal a common neural substrate in bilateral LOC and right medial FG underlying view-invariant and category-independent recognition for multiple object identities, with only a relative preference for faces in medial FG but no selectivity in LO

The multisensory function of the human primary visual cortex

It has been nearly 10 years since Ghazanfar and Schroeder (2006) proposed that the neocortex is essentially multisensory in nature. However, it is only recently that sufficient and hard evidence that supports this proposal has accrued. We review evidence that activity within the human primary visual cortex plays an active role in multisensory processes and directly impacts behavioural outcome. This evidence emerges from a full pallet of human brain imaging and brain mapping methods with which multisensory processes are quantitatively assessed by taking advantage of particular strengths of each technique as well as advances in signal analyses. Several general conclusions about multisensory processes in primary visual cortex of humans are supported relatively solidly. First, haemodynamic methods (fMRI/PET) show that there is both convergence and integration occurring within primary visual cortex. Second, primary visual cortex is involved in multisensory processes during early post-stimulus stages (as revealed by EEG/ERP/ERFs as well as TMS). Third, multisensory effects in primary visual cortex directly impact behaviour and perception, as revealed by correlational (EEG/ERPs/ERFs) as well as more causal measures (TMS/tACS). While the provocative claim of Ghazanfar and Schroeder (2006) that the whole of neocortex is multisensory in function has yet to be demonstrated, this can now be considered established in the case of the human primary visual cortex

Distinct contributions of Brodmann areas 1 and 2 to body ownership

Although body ownership—i.e. the feeling that our bodies belong to us—modulates activity within the primary somatosensory cortex (S1), it is still unknown whether this modulation occurs within a somatotopically defined portion of S1. We induced an illusory feeling of ownership for another person's finger by asking participants to hold their palm against another person's palm and to stroke the two joined index fingers with the index and thumb of their other hand. This illusion (numbness illusion) does not occur if the stroking is performed asynchronously or by the other person. We combined this somatosensory paradigm with ultra-high field functional magnetic resonance imaging finger mapping to study whether illusory body ownership modulates activity within different finger-specific areas of S1. The results revealed that the numbness illusion is associated with activity in Brodmann area (BA) 1 within the representation of the finger stroking the other person's finger and in BA 2 contralateral to the stroked finger. These results show that changes in bodily experience modulate the activity within certain subregions of S1, with a different finger-topographical selectivity between the representations of the stroking and of the stroked hand, and reveal that the high degree of somatosensory specialization in S1 extends to bodily self-consciousnes

Perceptual and Semantic Contributions to Repetition Priming of Environmental Sounds

Repetition of environmental sounds, like their visual counterparts, can facilitate behavior and modulate neural responses, exemplifying plasticity in how auditory objects are represented or accessed. It remains controversial whether such repetition priming/suppression involves solely plasticity based on acoustic features and/or also access to semantic features. To evaluate contributions of physical and semantic features in eliciting repetition-induced plasticity, the present functional magnetic resonance imaging (fMRI) study repeated either identical or different exemplars of the initially presented object; reasoning that identical exemplars share both physical and semantic features, whereas different exemplars share only semantic features. Participants performed a living/man-made categorization task while being scanned at 3T. Repeated stimuli of both types significantly facilitated reaction times versus initial presentations, demonstrating perceptual and semantic repetition priming. There was also repetition suppression of fMRI activity within overlapping temporal, premotor, and prefrontal regions of the auditory "what” pathway. Importantly, the magnitude of suppression effects was equivalent for both physically identical and semantically related exemplars. That the degree of repetition suppression was irrespective of whether or not both perceptual and semantic information was repeated is suggestive of a degree of acoustically independent semantic analysis in how object representations are maintained and retrieve

Visuo-motor pathways in humans revealed by event-related fMRI

Whether different brain networks are involved in generating unimanual responses to a simple visual stimulus presented in the ipsilateral versus contralateral hemifield remains a controversial issue. Visuo-motor routing was investigated with event-related functional magnetic resonance imaging (fMRI) using the Poffenberger reaction time task. A 2 hemifield×2 response hand design generated the "crossed” and "uncrossed” conditions, describing the spatial relation between these factors. Both conditions, with responses executed by the left or right hand, showed a similar spatial pattern of activated areas, including striate and extrastriate areas bilaterally, SMA, and M1 contralateral to the responding hand. These results demonstrated that visual information is processed bilaterally in striate and extrastriate visual areas, even in the "uncrossed” condition. Additional analyses based on sorting data according to subjects' reaction times revealed differential crossed versus uncrossed activity only for the slowest trials, with response strength in infero-temporal cortices significantly correlating with crossed-uncrossed differences (CUD) in reaction times. Collectively, the data favor a parallel, distributed model of brain activation. The presence of interhemispheric interactions and its consequent bilateral activity is not determined by the crossed anatomic projections of the primary visual and motor pathways. Distinct visuo-motor networks need not be engaged to mediate behavioral responses for the crossed visual field/response hand condition. While anatomical connectivity heavily influences the spatial pattern of activated visuo-motor pathways, behavioral and functional parameters appear to also affect the strength and dynamics of responses within these pathway

Exploring available options in characterising the health impact of industrially contaminated sites

Industrially contaminated sites (ICS) are of high concern from an environmental public health perspective, since industrial plants may produce a widespread contamination that can result in several health impacts on the populations living in their neighbourhood. The objective of this contribution is to briefly explore available options in studying the health impact of ICS, mainly referring to information provided by documents and activities developed by the WHO and the WHO Collaborating Center for Environmental Health in Contaminated Sites. In current practice the health impact of ICS is evaluated using studies and assessments falling in two broad types of strategies: one based on epidemiology and the other on risk assessment methods. In recent years, traditional approaches to assess relationships between environmental risks and health has been evolved considering the intricate nature between them and other factors. New developments should be explored in the context of ICS to find common strategies and tools to assess their impacts and to guide public health interventions

Object representations for multiple visual categories overlap in lateral occipital and medial fusiform cortex

How representations of visual objects are maintained across changes in viewpoint is a central issue in visual perception. Whether neural processes underlying view-invariant recognition involve distinct subregions within extrastriate visual cortex for distinct categories of visual objects remains unresolved. We used event-related functional magnetic resonance imaging in 16 healthy volunteers to map visual cortical areas responding to a large set (156) of exemplars from 3 object categories (faces, houses, and chairs), each repeated once after a variable time lag (3-7 intervening stimuli). Exemplars were repeated with the same viewpoint (but different retinal size) or with different viewpoint and size. The task was kept constant across object categories (judging items as "young" vs. "old"). We identified object-selective adaptation effects by comparing neural responses to the first presentation versus repetition of each individual exemplar. We found that exemplar-specific adaptation effects partly overlapped with regions showing category-selective responses (as identified using a separate localizer scan). These included the lateral fusiform gyrus (FG) for faces, parahippocampal gyrus for houses, and lateral occipital complex (LOC) for chairs. In face-selective fusiform gyrus (FG), adaptation effects occurred only for faces repeated with the same viewpoint, but not with a different viewpoint, confirming previous studies using faces only. By contrast, a region in right medial FG, adjacent to but nonoverlapping with the more lateral and face-selective FG, showed repetition effects for faces and to a lesser extent for other objects, regardless of changes in viewpoint or in retinal image-size. Category- and viewpoint-independent repetition effects were also found in bilateral LOC. Our results reveal a common neural substrate in bilateral LOC and right medial FG underlying view-invariant and category-independent recognition for multiple object identities, with only a relative preference for faces in medial FG but no selectivity in LOC

Multisensory Interactions within Human Primary Cortices Revealed by BOLD Dynamics

Whether signals from different sensory modalities converge and interact within primary cortices in humans is unresolved, despite emerging evidence in animals. This is partially because of debates concerning the appropriate analyses of functional magnetic resonance imaging (fMRI) data in response to multisensory phenomena. Using event-related fMRI, we observed that simple auditory stimuli (noise bursts) activated primary visual cortices and that simple visual stimuli (checkerboards) activated primary auditory cortices, indicative of multisensory convergence. Moreover, analyses of blood oxygen level-dependent response dynamics revealed facilitation of hemodynamic response peak latencies and slopes for multisensory auditory-visual stimuli versus either unisensory condition, indicative of multisensory interactions within primary sensory cortices. Neural processing at the lowest cortical levels can be modulated by interactions between the senses. Temporal information in fMRI data can reveal these modulations and overcome analytic and interpretational challenges of more traditional procedures. In addition to providing an essential translational link with animal models, these results suggest that longstanding notions of cortical organization need to be revised to include multisensory interactions as an inherent component of functional brain organizatio

Functional connectivity and alterations in baseline brain state in humans

This work examines the influence of changes in baseline activity on the intrinsic functional connectivity fMRI (fc-fMRI) in humans. Baseline brain activity was altered by inducing anesthesia (sevoflurane end-tidal concentration 1%) in human volunteers and fc-fMRI maps between the pre-anesthetized and anesthetized conditions were compared across different brain networks. We particularly focused on low-level sensory areas (primary somatosensory, visual, and auditory cortices), the thalamus, and pain (insula), memory (hippocampus) circuits, and the default mode network (DMN), the latter three to examine higher-order brain regions. The results indicate that, while fc-fMRI patterns did not significantly differ (p<0.005; 20-voxel cluster threshold) in sensory cortex and in the DMN between the pre- and anesthetized conditions, fc-fMRI in high-order cognitive regions (i.e. memory and pain circuits) was significantly altered by anesthesia. These findings provide further evidence that fc-fMRI reflects intrinsic brain properties, while also demonstrating that 0.5 MAC sevoflurane anesthesia preferentially modulates higher-order connections