Neurophysiology of the BOLD fMRI signal in awake monkeys

BACKGROUND: Simultaneous intracortical recordings of neural activity and blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in primary visual cortex of anesthetized monkeys demonstrated varying degrees of correlation between fMRI signals and the different types of neural activity, such as local field potentials (LFPs), multiple-unit activity (MUA), and single-unit activity (SUA). One important question raised by the aforementioned investigation is whether the reported correlations also apply to alert subjects. RESULTS: Monkeys were trained to perform a fixation task while stimuli within the receptive field of each recording site were used to elicit neural responses followed by a BOLD response. We show -- also in alert behaving monkeys -- that although both LFP and MUA make significant contributions to the BOLD response, LFPs are better and more reliable predictors of the BOLD signal. Moreover, when MUA responses adapt but LFP remains unaffected, the BOLD signal remains unaltered. CONCLUSIONS: The persistent coupling of the BOLD signal to the field potential when LFP and MUA have different time evolutions suggests that BOLD is primarily determined by the local processing of inputs in a given cortical area. In the alert animal the largest portion of the BOLD signal's variance is explained by an LFP range (20-60 Hz) that is most likely related to neuromodulation. Finally, the similarity of the results in alert and anesthetized subjects indicates that at least in V1 anesthesia is not a confounding factor. This enables the comparison of human fMRI results with a plethora of electrophysiological results obtained in alert or anesthetized animals.     

Time-dependent spatial specificity of high-resolution fMRI: insights into mesoscopic neurovascular coupling

High-resolution functional magnetic resonance imaging (fMRI) is becoming increasingly popular because of the growing availability of ultra-high magnetic fields which are capable of improving sensitivity and spatial resolution. However, it is debatable whether increased spatial resolutions for haemodynamic-based techniques, like fMRI, can accurately detect the true location of neuronal activity. We have addressed this issue in functional columns and layers of animals with haemoglobin-based optical imaging and different fMRI contrasts, such as blood oxygenation level-dependent, cerebral blood flow and cerebral blood volume fMRI. In this review, we describe empirical evidence primarily from our own studies on how well these fMRI signals are spatially specific to the neuronally active site and discuss insights into neurovascular coupling at the mesoscale.This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.     

Visual motion processing investigated using contrast agent-enhanced fMRI in awake behaving monkeys.

To reduce the information gap between human neuroimaging and macaque physiology and anatomy, we mapped fMRI signals produced by moving and stationary stimuli (random dots or lines) in fixating monkeys. Functional sensitivity was increased by a factor of approximately 5 relative to the BOLD technique by injecting a contrast agent (monocrystalline iron oxide nanoparticle [MION]). Areas identified as motion sensitive included V2, V3, MT/V5, vMST, FST, VIP, and FEF (with moving dots), as well as V4, TE, LIP, and PIP (with random lines). These regions sensitive for moving dots are largely in agreement with monkey single unit data and (except for V3A) with human fMRI results. Moving lines activate some regions that have not been previously implicated in motion processing. Overall, the results clarify the relationship between the motion pathway and the dorsal stream in primates.     

Dynamic statistical parametric mapping: combining fMRI and MEG for high-resolution imaging of cortical activity

Functional magnetic resonance imaging (fMRI) can provide maps of brain activation with millimeter spatial resolution but is limited in its temporal resolution to the order of seconds. Here, we describe a technique that combines structural and functional MRI with magnetoencephalography (MEG) to obtain spatiotemporal maps of human brain activity with millisecond temporal resolution. This new technique was used to obtain dynamic statistical parametric maps of cortical activity during semantic processing of visually presented words. An initial wave of activity was found to spread rapidly from occipital visual cortex to temporal, parietal, and frontal areas within 185 ms, with a high degree of temporal overlap between different areas. Repetition effects were observed in many of the same areas following this initial wave of activation, providing evidence for the involvement of feedback mechanisms in repetition priming.     

Imaging function in the working brain with fMRI

The intrinsic flexibility of functional magnetic resonance imaging has allowed ever more innovative neuroscience applications. New acquisition and analysis techniques have contributed to improvements in detection sensitivity, as well as spatial and temporal resolution. Furthermore, by considering the dynamic evolution of the active brain areas in a network, computational models are making the first steps towards linking brain and mind.     

Deep Brain Stimulation with Simultaneous fMRI in Rodents

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to image rodents with simultaneous DBS. DBS fMRI presents a number of technical challenges, including accuracy of electrode implantation, MR artifacts created by the electrode, choice of anesthesia and paralytic to minimize any neuronal effects while simultaneously eliminating animal motion, and maintenance of physiological parameters, deviation from which can confound the BOLD signal. Our laboratory has developed a set of procedures that are capable of overcoming most of these possible issues. For electrical stimulation, a homemade tungsten bipolar microelectrode is used, inserted stereotactically at the stimulation site in the anesthetized subject. In preparation for imaging, rodents are fixed on a plastic headpiece and transferred to the magnet bore. For sedation and paralysis during scanning, a cocktail of dexmedetomidine and pancuronium is continuously infused, along with a minimal dose of isoflurane; this preparation minimizes the BOLD ceiling effect of volatile anesthetics. In this example experiment, stimulation of the subthalamic nucleus (STN) produces BOLD responses which are observed primarily in ipsilateral cortical regions, centered in motor cortex. Simultaneous DBS and fMRI allows the unambiguous modulation of neural circuits dependent on stimulation location and stimulation parameters, and permits observation of neuronal modulations free of regional bias. This technique may be used to explore the downstream effects of modulating neural circuitry at nearly any brain region, with implications for both experimental and clinical DBS.     

Crossmodal processing of object features in human anterior intraparietal cortex: an fMRI study implies equivalencies between humans and monkeys

The organization of macaque posterior parietal cortex (PPC) reflects its functional specialization in integrating polymodal sensory information for object recognition and manipulation. Neuropsychological and recent human imaging studies imply equivalencies between human and macaque PPC, and in particular, the cortex buried in the intraparietal sulcus (IPS). Using functional MRI, we tested the hypothesis that an area in human anterior intraparietal cortex is activated when healthy subjects perform a crossmodal visuo-tactile delayed matching-to-sample task with objects. Tactile or visual object presentation (encoding and recognition) both significantly activated anterior intraparietal cortex. As hypothesized, neural activity in this area was further enhanced when subjects transferred object information between modalities (crossmodal matching). Based on both the observed functional properties and the anatomical location, we suggest that this area in anterior IPS is the human equivalent of macaque area AIP.     

Polymodal motion processing in posterior parietal and premotor cortex: a human fMRI study strongly implies equivalencies between humans and monkeys

In monkeys, posterior parietal and premotor cortex play an important integrative role in polymodal motion processing. In contrast, our understanding of the convergence of senses in humans is only at its beginning. To test for equivalencies between macaque and human polymodal motion processing, we used functional MRI in normals while presenting moving visual, tactile, or auditory stimuli. Increased neural activity evoked by all three stimulus modalities was found in the depth of the intraparietal sulcus (IPS), ventral premotor, and lateral inferior postcentral cortex. The observed activations strongly suggest that polymodal motion processing in humans and monkeys is supported by equivalent areas. The activations in the depth of IPS imply that this area constitutes the human equivalent of macaque area VIP.     

Food-exchange with humans in brown capuchin monkeys

To assess how brown capuchin monkeys (Cebus apella) delay gratification and maximize payoff, we carried out four experiments in which six subjects could exchange food pieces with a human experimenter. The pieces differed either in quality or quantity. In qualitative exchanges, all subjects gave a piece of food to receive another of higher value. When the difference of value between the rewards to be returned and those expected was higher, subjects performed better. Only two subjects refrained from nibbling the piece of food before returning it. All subjects performed two or three qualitative exchanges in succession to obtain a given reward. In quantitative exchanges, three subjects returned a food item to obtain a bigger one, but two of them nibbled the item before returning it. Individual differences were marked. Subjects had some difficulties when the food to be returned was similar or equal in quality to that expected.     

Correlating ribosome function with high-resolution structures

Ribosome research has undergone astonishing progress in recent years. Crystal structures have shed light on the functional properties of the translation machinery and revealed how the striking architecture of the ribosome is ingeniously designed as the framework for its unique capabilities: precise decoding, substrate-mediated peptide-bond formation and efficient polymerase activity. New findings include the two concerted elements of tRNA translocation: sideways shift and a ribosomal-navigated rotatory motion; the dynamics of the nascent-chain exit tunnel and the shelter formed by the ribosome-bound trigger-factor, which acts as a chaperone to prevent nascent-chain aggregation and misfolding. The availability of these structures has also illuminated the action, selectivity, resistance and synergism of antibiotics that target ribosomes.     

Perspectives with cryogenic RF probes in biomedical MRI

Since discovery of high-temperature superconductive (HTS) ceramics by Bednorz and Muller in 1986, there has been an accelerated development of cold technologies in industry, including the domain of NMR detection. The purpose of this paper is to fix ideas about the stage that cryogenic radio frequency (RF) probe techniques have reached in biomedical magnetic resonance imaging (MRI). Readers confronted to the literature about this emerging topic have to understand a large range of motivations with somewhat unclearly defined technical limitations and actual outlets. An overview of sensitivity issues in the general context of biomedical MRI is provided here and the contribution of RF coil techniques to recent advances is identified. The domains where cooled coil materials such as copper, low- or high-temperature superconductors, could actually increase the RF coil sensitivity are delimited by a quantitative analysis of noise mechanisms. Technical keys, cryogenic means and cold RF coil technologies are considered, and first achievements in different fields of biomedical MRI are reviewed. This survey provides a basis for discussing about the future impact of cryogenic probes for MRI investigations.     

Degradation of oxalate in rats implanted with immobilized oxalate oxidase

Accumulation of oxalate leads to hyperoxaluria and calcium oxalate nephrolithiasis in man. Since oxalate is a metabolic end product in mammals, the feasibility of its enzymic degradation has been tested in vivo in rats by administering exogenous oxalate oxidase. Oxalate oxidase, isolated from banana fruit peels, in its native form was found to be non-active at the physiological pH of the recipient animal. However, its functional viability in the recipient animal was ensured by its prior binding with ethylenemaleic anhydride, thus shifting its pH activity curve towards the alkaline range. Rats implanted with dialysis membrane capsules containing such immobilized oxalate oxidase in their peritoneal cavities effectively metabolized intraperitoneally injected [14C]oxalate as well as its precursor [14C]glyoxalate. The implantation of capsules containing coentrapped multienzyme preparations of oxalate oxidase, catalase and peroxidase led to a further degradation of administered [14C]oxalate in rats.