Negative Blood Oxygenation Level-dependent Research Articles

Reproducibility of swallow-induced cortical BOLD positive and negative fMRI activity

Functional MRI (fMRI) studies have demonstrated that a number of brain regions (cingulate, insula, prefrontal, and sensory/motor cortices) display blood oxygen level-dependent (BOLD) positive activity during swallow. Negative BOLD activations and reproducibility of these activations have not been systematically studied. The aim of our study was to investigate the reproducibility of swallow-related cortical positive and negative BOLD activity across different fMRI sessions. We studied 16 healthy volunteers utilizing an fMRI event-related analysis. Individual analysis using a general linear model was used to remove undesirable signal changes correlated with motion, white matter, and cerebrospinal fluid. The group analysis used a mixed-effects multilevel model to identify active cortical regions. The volume and magnitude of a BOLD signal within each cluster was compared between the two study sessions. All subjects showed significant clustered BOLD activity within the known areas of cortical swallowing network across both sessions. The cross-correlation coefficient of percent fMRI signal change and the number of activated voxels across both positive and negative BOLD networks were similar between the two studies (r ≥ 0.87, P < 0.0001). Swallow-associated negative BOLD activity was comparable to the well-defined "default-mode" network, and positive BOLD activity had noticeable overlap with the previously described "task-positive" network. Swallow activates two parallel cortical networks. These include a positive and a negative BOLD network, respectively, correlated and anticorrelated with swallow stimulus. Group cortical activity maps, as well as extent and amplitude of activity induced by volitional swallowing in the cortical swallowing network, are reproducible between study sessions.

A temporal analysis of the central neural processing of itch

Pruritus, or itch, is the most prevalent symptom of allergic and inflammatory skin disease. Although it is known that itch induces activation of a neural network in the brain, the temporal dynamics of the network as well as the pathophysiology and neurobiology are not well understood. The study aimed to elucidate (i) the temporal dynamics of the itch response identified in earlier studies and (ii) the relationship between central and subjective responses to itch. Using a novel time-series analysis, we performed a double-blind, placebo-controlled, randomized, within-subject functional magnetic resonance imaging (fMRI) study of the cerebral processing of histamine-induced itch in healthy volunteers (n = 16) by tracking the 8-min period following a single skin prick. Histamine-induced itch compared with saline resulted in significant area under the curve blood oxygen level dependent (BOLD) signal changes in the middle/superior temporal gyrus and right inferior frontal gyrus/insula. We observed negative itch-induced BOLD signal changes compared with saline in (i) the pregenual anterior cingulate cortex (ACC)/medial frontal gyrus, (ii) subgenual ACC/ventral striatum, (iii) bilateral temporal pole/parahippocampal gyrus and (iv) several regions within the cerebellum. We noted a trend significance in the left precentral gyrus part of the motor cortex. The BOLD signal change in several of these regions correlated with perception of itch intensity. In contrast to other fMRI studies we observed a multifocal negative signal. An improved understanding of both activated and deactivated brain regions during the itch response may in the long term facilitate development of more effective management strategies.

Is optical imaging spectroscopy a viable measurement technique for the investigation of the negative BOLD phenomenon? A concurrent optical imaging spectroscopy and fMRI study at high field (7T)

Traditionally functional magnetic resonance imaging (fMRI) has been used to map activity in the human brain by measuring increases in the Blood Oxygenation Level Dependent (BOLD) signal. Often accompanying positive BOLD fMRI signal changes are sustained negative signal changes. Previous studies investigating the neurovascular coupling mechanisms of the negative BOLD phenomenon have used concurrent 2D-optical imaging spectroscopy (2D-OIS) and electrophysiology (Boorman et al., 2010). These experiments suggested that the negative BOLD signal in response to whisker stimulation was a result of an increase in deoxy-haemoglobin and reduced multi-unit activity in the deep cortical layers. However, Boorman et al. (2010) did not measure the BOLD and haemodynamic response concurrently and so could not quantitatively compare either the spatial maps or the 2D-OIS and fMRI time series directly. Furthermore their study utilised a homogeneous tissue model in which is predominantly sensitive to haemodynamic changes in more superficial layers.Here we test whether the 2D-OIS technique is appropriate for studies of negative BOLD. We used concurrent fMRI with 2D-OIS techniques for the investigation of the haemodynamics underlying the negative BOLD at 7 Tesla. We investigated whether optical methods could be used to accurately map and measure the negative BOLD phenomenon by using 2D-OIS haemodynamic data to derive predictions from a biophysical model of BOLD signal changes. We showed that despite the deep cortical origin of the negative BOLD response, if an appropriate heterogeneous tissue model is used in the spectroscopic analysis then 2D-OIS can be used to investigate the negative BOLD phenomenon.

Deciphering the Neuronal Circuitry Controlling Local Blood Flow in the Cerebral Cortex with Optogenetics in PV::Cre Transgenic Mice

Although it is know since more than a century that neuronal activity is coupled to blood supply regulation, the underlying pathways remains to be identified. In the brain, neuronal activation triggers a local increase of cerebral blood flow (CBF) that is controlled by the neurogliovascular unit composed of terminals of neurons, astrocytes, and blood vessel muscles. It is generally accepted that the regulation of the neurogliovascular unit is adjusted to local metabolic demand by local circuits. Today experimental data led us to realize that the regulatory mechanisms are more complex and that a neuronal system within the brain is devoted to the control of local brain-blood flow. Recent optogenetic experiments combined with functional magnetic resonance imaging have revealed that light stimulation of neurons expressing the calcium binding protein parvalbumin (PV) is associated with positive blood oxygen level-dependent (BOLD) signal in the corresponding barrel field but also with negative BOLD in the surrounding deeper area. Here, we demonstrate that in acute brain slices, channelrhodopsin-2 (ChR2) based photostimulation of PV containing neurons gives rise to an effective contraction of penetrating arterioles. These results support the neurogenic hypothesis of a complex distributed nervous system controlling the CBF.

Negative BOLD signal changes in ipsilateral primary somatosensory cortex are associated with perfusion decreases and behavioral evidence for functional inhibition

We used functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) to study the negative blood oxygenation level dependent (BOLD) signal and its underlying blood flow changes in healthy human subjects. This was combined with psychophysiological measurements to test that the negative BOLD signal is associated with functional inhibition. Electrical stimulation of the median nerve at 7 Hz evoked robust negative BOLD signals in the primary somatosensory cortex (SI) ipsilateral to stimulation, and positive BOLD signals in contralateral SI. The negative BOLD signal in ipsilateral SI was accompanied by commensurate decreases in relative regional cerebral blood flow (rCBF). Conjunction analysis of the fMRI and PET data revealed a region in the ipsilateral postcentral gyrus showing overlap of negative BOLD signals and relative rCBF decreases. The current perception threshold (CPT) at the ipsilateral finger during concomitant stimulation of the contralateral median nerve increased significantly, suggesting augmented functional inhibition. Since the CPT in the ipsilateral hallux did not significantly change in response to median nerve stimulation, it is more likely that the CPT-increase for the finger is due to functional inhibition (Kastrup et al., 2008) than to changes in selective attention. In conclusion, our data provide evidence that stimulus-induced reductions in relative rCBF may underlie the negative BOLD signal, which in turn may reflect increments in functional inhibition.

Sustained Negative BOLD Response in Human fMRI Finger Tapping Task

In this work, we investigated the sustained negative blood oxygen level-dependent (BOLD) response (sNBR) using functional magnetic resonance imaging during a finger tapping task. We observed that the sNBR for this task was more extensive than has previously been reported. The cortical regions involved in sNBR are divided into the following three groups: frontal, somatosensory and occipital. By investigating the spatial structure, area, amplitude, and dynamics of the sNBR in comparison with those of its positive BOLD response (PBR) counterpart, we made the following observations. First, among the three groups, the somatosensory group contained the greatest number of activated voxels and the fewest deactivated voxels. In addition, the amplitude of the sNBR in this group was the smallest among the three groups. Second, the onset and peak time of the sNBR are both larger than those of the PBR, whereas the falling edge time of the sNBR is less than that of the PBR. Third, the long distance between most sNBR foci and their corresponding PBR foci makes it unlikely that they share the same blood supply artery. Fourth, the couplings between the sNBR and its PBR counterpart are distinct among different regions and thus should be investigated separately. These findings imply that the origin of most sNBR foci in the finger-tapping task is much more likely to be neuronal activity suppression rather than “blood steal.”

Differential Electrophysiological Coupling for Positive and Negative BOLD Responses during Unilateral Hand Movements

The coupling between neural cellular activity and blood oxygen level-dependent (BOLD) signal is of critical importance to the interpretation of fMRI. Largely unknown, however, is the degree to which different neuronal events (i.e., excitation and inhibition) maintain or disrupt the neural-hemodynamic relationship, especially in humans. In the present study, we compared local electroencephalographic (EEG) oscillations and the positive/negative BOLD responses of simultaneously recorded data from healthy human volunteers performing unilateral finger tapping at graded rates. By quantifying the single-trial modulations of EEG using source imaging, we tested for their correlation with positive BOLD response (PBR) and negative BOLD response (NBR) after coregistering their spatial locations. PBR was found to be overlapped with and correlated to the decrease of alpha (8-13 Hz) and beta (13-30 Hz) band EEG in the contralateral sensorimotor cortex. Regional EEG modulations at the sensorimotor cortex further predicted a spatially distributed and interconnected network of motor-related cortical areas. Alternatively, no significant correlation was found at the ipsilateral sensorimotor cortex between the NBR and EEG despite their spatial overlapping. This differential electrophysiological coupling of the positive and negative BOLD responses suggests that the underlying neuronal events may not only influence the direction of the signal change but also the neural-hemodynamic relationship.

Modeling of the Neurovascular Coupling in Epileptic Discharges

Despite the interest in simultaneous EEG-fMRI studies of epileptic spikes, the link between epileptic discharges and their corresponding hemodynamic responses is poorly understood. In this context, biophysical models are promising tools for investigating the mechanisms underlying observed signals. Here, we apply a metabolic-hemodynamic model to simulated epileptic discharges, in part generated by a neural mass model. We analyze the effect of features specific to epileptic neuronal activity on the blood oxygen level dependent (BOLD) response, focusing on the issues of linearity in neurovascular coupling and on the origin of negative BOLD signals. We found both sub- and supra-linearity in simulated BOLD signals, depending on whether one observes the early or the late part of the BOLD response. The size of these non-linear effects is determined by the spike frequency, as well as by the amplitude of the excitatory activity. Our results additionally indicate a minor deviation from linearity at the neuronal level. According to a phase space analysis, the possibility to obtain a negative BOLD response to an epileptic spike depends on the existence of a long and strong excitatory undershoot. Moreover, we strongly suggest that a combined EEG-fMRI modeling approach should include spatial assumptions. The present study is a step towards an increased understanding of the link between epileptic spikes and their BOLD responses, aiming to improve the interpretation of simultaneous EEG-fMRI recordings in epilepsy.

Cerebral Regulation of Facial Expressions of Pain

Facial expression of affective states plays a key role in social interactions. Interestingly, however, individuals differ substantially in their level of expressiveness, ranging from high expressive to stoic individuals. Here, we investigate which brain mechanisms underlie the regulation of facial expressiveness to acute pain. Facial responses, pain ratings, and brain activity (BOLD-fMRI) evoked by noxious heat and warm (control) stimuli were recorded in 34 human volunteers with different degrees of facial expressiveness. Within-subject and between-subject variations in blood oxygenation level-dependent (BOLD) responses were examined specifically in relation to facial responses. Pain expression was inversely related to frontostriatal activity, consistent with a role in downregulating facial displays. More detailed analyses of the peak activity in medial prefrontal cortex revealed negative BOLD responses to thermal stimuli, an effect generally associated with the default mode network. Given that this negative BOLD response was weaker in low expressive individuals during pain, it could reflect stronger engagement in, or reduced disengagement from, self-reflective processes in stoic individuals. The occurrence of facial expressions during pain was coupled with stronger primary motor activity in the face area and-interestingly-in areas involved in pain processing. In conclusion, these results indicate that spontaneous pain expression reflects activity within nociceptive pathways while stoicism involves the active suppression of expression, a manifestation of learned display rules governing emotional communication and possibly related to an increased self-reflective or introspective focus.

Functional deactivations: Multiple ipsilateral brain areas engaged in the processing of somatosensory information

Somatosensory signals modulate activity throughout a widespread network in both of the brain hemispheres: the contralateral as well as the ipsilateral side of the brain relative to the stimulated limb. To analyze the ipsilateral somatosensory brain areas that are engaged during limb stimulation, we performed functional magnetic resonance imaging (fMRI) in 12 healthy subjects during electrical median nerve stimulation using both a block- and an event-related fMRI design. Data were analyzed through the use of model-dependent (SPM) and model-independent (ICA) approaches. Beyond the well-known positive blood oxygenation level-dependent (BOLD) responses, negative deflections of the BOLD response were found consistently in several ipsilateral brain areas, including the primary somatosensory cortex, the supplementary motor area, the insula, the dorsal part of the posterior cingulate cortex, and the contralateral cerebellum. Compared to their positive counterparts, the negative hemodynamic responses showed a different time course, with an onset time delay of 2.4 s and a peak delay of 0.7 s. This characteristic delay was observed in all investigated areas and verified by a second (purely tactile) event-related paradigm, suggesting a systematic difference for brain areas involved in the processing of somatosensory information. These findings may indicate that the physiological basis of these deactivations differs from that of the positive BOLD responses. Therefore, an altered model for the negative BOLD response may be beneficial to further model-dependent fMRI analyses.

BOLD signal changes preceding negative responses in EEG‐fMRI in patients with focal epilepsy

In simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), increased neuronal activity from epileptiform spikes commonly elicits positive blood oxygenation level-dependent (BOLD) responses. Negative responses are also occasionally seen and have not been explained. Recent studies describe BOLD signal changes before focal EEG spikes. We aimed to systematically study if the undershoot of a preceding positive response might explain the negative BOLD seen in the focus. Eighty-two patients with focal epilepsy who underwent EEG-fMRI at 3T were retrospectively studied. Studies with a focal negative BOLD response in the region of the spike field were reanalyzed using models with hemodynamic response functions (HRFs) peaking from -9 to +9 s around the spike. Eight patients met the inclusion criteria, showing negative BOLD responses in the spike field on standard analysis. None had positive BOLD responses immediately adjacent to the areas of deactivation. Regions of deactivation were found to have congruent preceding positive responses in two cases. These early activations were seen at the combined maps of -5 to -9 s. This study indicates that in a small proportion of patients with focal epilepsy in whom the standard analysis reveals focal negative responses, an earlier positive BOLD response is probably the cause. The origin of negative BOLD signal changes in the focus as a result of an epileptic event remains, however, unexplained in most of the patients in whom it occurs.

The Effect of Opioid Receptor Blockade on the Neural Processing of Thermal Stimuli

The endogenous opioid system represents one of the principal systems in the modulation of pain. This has been demonstrated in studies of placebo analgesia and stress-induced analgesia, where anti-nociceptive activity triggered by pain itself or by cognitive states is blocked by opioid antagonists. The aim of this study was to characterize the effect of opioid receptor blockade on the physiological processing of painful thermal stimulation in the absence of cognitive manipulation. We therefore measured BOLD (blood oxygen level dependent) signal responses and intensity ratings to non-painful and painful thermal stimuli in a double-blind, cross-over design using the opioid receptor antagonist naloxone. On the behavioral level, we observed an increase in intensity ratings under naloxone due mainly to a difference in the non-painful stimuli. On the neural level, painful thermal stimulation was associated with a negative BOLD signal within the pregenual anterior cingulate cortex, and this deactivation was abolished by naloxone.

Poststroke Aphasia Recovery Assessed With Functional Magnetic Resonance Imaging and a Picture Identification Task

Stroke patients often display deficits in language function, such as correctly naming objects. Our aim was to evaluate the reliability and the patterns of poststroke language recovery using a picture identification task during functional magnetic resonance imaging (fMRI) at 4 T. Four healthy subjects and 4 subjects with left middle cerebral artery stroke with chronic (>1 year) aphasia were enrolled in the study. In each subject, 10 fMRI scans were performed over a 10-week period using a picture-identification task. The active condition involved presenting subject with a panel of 4 figures (eg, drawings of 4 animals) every 6 seconds and asking the subject to indicate which figure matched the written name in the center. The control condition was a same/different judgment task with pairs of geometric figures (squares, octagons, or combination) presented every 6 seconds. Thirty-second active/control blocks were repeated 5 times each, and responses were recorded. The stoke subjects and controls had similar demographic characteristics, including age (46 vs 53 years), personal handedness (Edinburg Handedness Inventory, 89 vs 95), familial handedness (93 vs 95), and years of education (14.3 vs 14.8). For the active condition, the controls performed better than the stroke subjects (97.7% vs 89.1%; P < .001); the 2 groups performed similarly for the control condition (99.5% vs 98.8%; P = .23). On fMRI, the controls exhibited bilateral,L> R positive blood oxygenation level-dependent (BOLD) activations in frontal andtemporal language areas and symmetric retrosplenial and posterior cingulate areas and symmetric negative BOLD activations in bilateral frontotemporal language networks. In contrast, the stroke subjects exhibited positive BOLD activations predominantly in peristroke areas and negative BOLD activations in the unaffected (right) hemisphere. Both groups displayed high activation reliability (asmeasured by the intraclass correlation coefficient [ICC]) in the left frontal and temporal language areas, although in the stroke subjects the ICC in the frontal regions was spread over a much larger peristroke area. This study documents the utility of the picture-identification task for poststroke language recovery evaluation. Our data suggest that adult stroke patients use functional peristroke areas to perform language functions.

The core network in absence epilepsy

We used EEG-fMRI to study epileptiform activity in a cohort of untreated children with typical absence seizures (AS). Our aim was to identify cortical and subcortical regions involved in spike and wave events and to explore the timing of activity in these regions. Eleven children with AS confirmed on video-EEG underwent EEG-fMRI. An event-related analysis of epileptiform activity was performed. Regions of interest (ROIs), identified in the event-related analysis, were used to study the time course of the blood oxygen level-dependent (BOLD) signal prior to and immediately following events of interest in these ROIs. Group analysis confirmed positive BOLD in the thalamus and negative BOLD in the lateral and mesial parietal lobe, caudate nuclei, and additionally the brainstem reticular formation. The event-related time course differed between the thalamus, the parietal cortex, and the pons and caudate nuclei. In the subcortical structures, BOLD signal change occurred at, or immediately after, electrographic onset. Importantly, in the parietal cortex, but not in other cortical regions, there was a subtle BOLD signal increase for 10 seconds prior to the onset of epileptiform activity. In children with typical AS, we have confirmed a core network of structures involved in generalized epileptiform activity that includes the reticular structures of the brainstem. Furthermore, we have identified changes in parietal BOLD signal which precede the onset of epileptiform activity, suggesting the parietal cortex has a role in the initiation of epileptiform activity.

Early Suppressive Mechanisms and the Negative Blood Oxygenation Level-Dependent Response in Human Visual Cortex

Functional magnetic resonance imaging (fMRI) studies of early sensory cortex often measure stimulus-driven increases in the blood oxygenation level-dependent (BOLD) signal. However, these positive responses are frequently accompanied by reductions in the BOLD signal in adjacent regions of cortex. Although this negative BOLD response (NBR) is thought to result from neuronal suppression, the precise relationship between local activity, suppression, and perception remains unknown. By measuring BOLD signals in human primary visual cortex while varying the baseline contrast levels in the region affected by the NBR, we tested three physiologically plausible computational models of neuronal modulation that could explain this phenomenon: a subtractive model, a response gain model, and a contrast gain model. We also measured the ability of isoluminant contrast to generate an NBR. We show that the NBR can be modeled as a pathway-specific contrast gain modulation that is strongest outside the fovea. We found a similar spatial bias in a psychophysical study using identical stimuli, although these data indicated a response gain rather than a contrast gain mechanism. We reconcile these findings by proposing (1) that the NBR is associated with a long-range suppressive mechanism that hyperpolarizes a subset of magnocellularly driven neurons at the input to V1, (2) that this suppression is broadly tuned to match the spatial features of the mask region, and (3) that increasing the baseline contrast in the suppressed region drives all neurons in the input layer, reducing the relative contribution of the suppressing subpopulation in the fMRI signal.

Negative Blood Oxygen Level Dependence in the Rat:A Model for Investigating the Role of Suppression in Neurovascular Coupling

Modern neuroimaging techniques rely on neurovascular coupling to show regions of increased brain activation. However, little is known of the neurovascular coupling relationships that exist for inhibitory signals. To address this issue directly we developed a preparation to investigate the signal sources of one of these proposed inhibitory neurovascular signals, the negative blood oxygen level-dependent (BOLD) response (NBR), in rat somatosensory cortex. We found a reliable NBR measured in rat somatosensory cortex in response to unilateral electrical whisker stimulation, which was located in deeper cortical layers relative to the positive BOLD response. Separate optical measurements (two-dimensional optical imaging spectroscopy and laser Doppler flowmetry) revealed that the NBR was a result of decreased blood volume and flow and increased levels of deoxyhemoglobin. Neural activity in the NBR region, measured by multichannel electrodes, varied considerably as a function of cortical depth. There was a decrease in neuronal activity in deep cortical laminae. After cessation of whisker stimulation there was a large increase in neural activity above baseline. Both the decrease in neuronal activity and increase above baseline after stimulation cessation correlated well with the simultaneous measurement of blood flow suggesting that the NBR is related to decreases in neural activity in deep cortical layers. Interestingly, the magnitude of the neural decrease was largest in regions showing stimulus-evoked positive BOLD responses. Since a similar type of neural suppression in surround regions was associated with a negative BOLD signal, the increased levels of suppression in positive BOLD regions could importantly moderate the size of the observed BOLD response.

Blood oxygenation level dependent effect of cerebral ischemic penumbra in monkey reversible middle cerebral artery occlusion model

Objective To investigate the value of blood oxygenation level dependent (BOLD) MRI in detecting monkey cerebral ischemic penumbra (IP). Methods Six monkeys were used to make reversible middle cerebral artery occlusion (MCAO) model by an interventional microcatheter method. MR DWI, PWI mean transit time (MTT), T_2WI and quantitative T_2 map, T_2~* map were performed at MCAO (0 h) and 1,3,6,12,24,48 h after reperfusion. Reversible transverse relaxation rate (R_2') BOLD imaging was calculated using quantitative T_2 and T_2~* maps. Lesion volume percentage (lesion volume/bilateral hemispheres volume) were measured on 0 h DWI,48 h T_2WI and TTC staining. Ischemic area was subdivided into infracted core (high signal area on both 0 h DWI and 48 h T_2 WI), IP (high signal on 0 h DWI, iso on 48 h T_2 WI) and oligemia (0 h delayed MTT, iso signal on both 0 h DWI and 48 h T_2 WI). Relative R_2' (rR_2') was calculated to get ratio between the lesion and mirror area in contralateral healthyhemisphere. Paired t test and correlation analysis were used for comparison of lesion volume percentage. rR_2' values at each time point were compared by ANOVA. Results Reversible MCAO models were made successfully in 4 of 6 monkeys. Lesion volume porcentage on 48 h T_2 WI was reduced compared to that on Oh DWI [ (8.16±0.55)% vs (11.37±1.41)% ,t=6.472,P 0.05], which showed significant positive correlation (r=0.98, P<0.05). rR_2' values were significant different at each time point, with highest in ohgemia followed by IP and infarcted core (P< 0.05). rR_2' values in infracted core, IP and oligemia were: 0 h(1.129±0.108,1.329±0.081,1.584± 0.103,F=36.19,P<0.05),1 h(0.668±0.082,1.237±0.072,1.435±0.066,F=134.09,P<0.05), 3 h (0.536±0.075,1.453±0.081,1.770±0.141, F=256.30, P<0.05), 6 h (0.259±0.050,2.435± 0.131,2.957±0.177,F=803.25,P<0.05), 12 h(0.385±0.054,2.447±0.148,3.254±0.184,F= 743.74,P<0.05),24 h(0.083±0.026,1.968±0.127,3.101±0.144,F=1236.26,P<0.05),48 h (0.246±0.058,3.694±0.218,4.297±0.322, F=557.02, P<0.05). After reperfusion, rR_2' values in IP and oligemia showed increased trend with time evolution and reflected positive BOLD effect, while the infracted core showed decreased trend, reflecting negative BOLD effect. Conclusion R_2' BOLD can delineate IP from infracted core according to the difference of oxygen metabolic status in ischemic brain tissue. Key words: Infarction,middle cerebral artery; Magnetic resonance imaging; Animal experimentation

Chronic Exposure to Manganese Alters Brain Responses to Amphetamine: A Pharmacological Magnetic Resonance Imaging Study

The parkinsonian symptoms and increased Mn accumulation in dopaminergic (DAergic) neurons of the basal ganglia implicate impaired dopamine signaling in the neurotoxic effects of chronic manganese overexposure. Using blood oxygenation level-dependent (BOLD) pharmacological magnetic resonance imaging (phMRI), we mapped brain responses to acute amphetamine (AMPH; 3 mg/kg, ip), which stimulates midbrain DAergic systems, in male Sprague-Dawley rats following 6 weeks of chronic MnCl(2) (5 mg Mn/kg, one per week, iv) or saline treatment. Plasma Mn content, measured immediately following phMRI, was elevated twofold in Mn-treated animals (p < 0.05), but the twofold increase in mean striatal Mn content did not reach significance. In saline-treated animals, AMPH stimulated robust positive BOLD responses throughout the basal ganglia and their reciprocally innervated connections. In contrast, acute AMPH stimulated a negative BOLD response in many of these structures in the Mn-treated group, resulting in significant differences between saline- and Mn-treated AMPH-evoked BOLD responses within caudate putamen, globus pallidus, substantia nigra, mediodorsal thalamic nucleus, and somatosensory cortex. These results demonstrate the utility of AMPH-evoked phMRI as readout of the DAergic signaling in vivo and confirm the vulnerability of DAergic systems to Mn.

Negative BOLD during tongue movement: A functional magnetic resonance imaging study

The aim of this functional magnetic resonance imaging (fMRI) study was to evaluate negative blood oxygen level-dependent (BOLD) signals during voluntary tongue movement. Deactivated (Negative BOLD) regions included the posterior parietal cortex (PPC), precuneus, and middle temporal gyrus. Activated (Positive BOLD) regions included the primary somatosensory-motor area (SMI), inferior parietal lobule, medial frontal gyrus, superior temporal gyrus, insula, lentiform nucleus, and thalamus. The results were not consistent with previous studies involving unilateral hand and finger movements showing the deactivation of motor-related cortical areas including the ipsilateral MI. The areas of Negative BOLD in the PPC and precuneus might reflect specific neural networks relating to voluntary tongue movement.

Acoustic Oddball during NREM Sleep: A Combined EEG/fMRI Study

BackgroundA condition vital for the consolidation and maintenance of sleep is generally reduced responsiveness to external stimuli. Despite this, the sleeper maintains a level of stimulus processing that allows to respond to potentially dangerous environmental signals. The mechanisms that subserve these contradictory functions are only incompletely understood.Methodology/Principal FindingsUsing combined EEG/fMRI we investigated the neural substrate of sleep protection by applying an acoustic oddball paradigm during light NREM sleep. Further, we studied the role of evoked K-complexes (KCs), an electroencephalographic hallmark of NREM sleep with a still unknown role for sleep protection. Our main results were: (1) Other than in wakefulness, rare tones did not induce a blood oxygenation level dependent (BOLD) signal increase in the auditory pathway but a strong negative BOLD response in motor areas and the amygdala. (2) Stratification of rare tones by the presence of evoked KCs detected activation of the auditory cortex, hippocampus, superior and middle frontal gyri and posterior cingulate only for rare tones followed by a KC. (3) The typical high frontocentral EEG deflections of KCs were not paralleled by a BOLD equivalent.Conclusions/SignificanceWe observed that rare tones lead to transient disengagement of motor and amygdala responses during light NREM sleep. We interpret this as a sleep protective mechanism to delimit motor responses and to reduce the sensitivity of the amygdala towards further incoming stimuli. Evoked KCs are suggested to originate from a brain state with relatively increased stimulus processing, revealing an activity pattern resembling novelty processing as previously reported during wakefulness. The KC itself is not reflected by increased metabolic demand in BOLD based imaging, arguing that evoked KCs result from increased neural synchronicity without altered metabolic demand.