Dose-dependent decrease of activation in bilateral amygdala and insula by lorazepam during emotion processing

BACKGROUND: Functional neuroimaging may elucidate the pathophysiologic features of anxiety disorders and the site of action of anxiolytic drugs. A large body of evidence suggests that the amygdala and associated limbic structures play a critical role in the expression of anxiety and may be treatment targets for anxiolytic drugs. OBJECTIVE: To determine whether lorazepam dose-dependently attenuates blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) activation in the amygdala and associated limbic structures during an emotion face assessment task. PARTICIPANTS AND DESIGN: Fifteen healthy volunteers participated in a double-blind, placebo-controlled, randomized dose-response study. Subjects underwent imaging 3 times (at least a week apart) and were given either a single-dose placebo or 0.25 mg or 1.0 mg of lorazepam 1 hour prior to an MRI session. During fMRI, subjects completed an emotion face assessment task, which has been shown to elicit amygdala activation. MAIN OUTCOME MEASURES: The BOLD-fMRI activation in amygdala, insula, and medial prefrontal cortex during the emotion face assessment task. RESULTS: Lorazepam significantly attenuated the BOLD-fMRI signal in a dose-dependent manner in bilateral amygdala and insula but not in the medial prefrontal cortex. Lorazepam did not affect the BOLD-fMRI signal in the primary visual cortex. CONCLUSIONS: The current finding provides the first neuroimaging evidence of a dose-dependent change induced by an established therapeutic agent in brain regions known to be critical for the mediation of anxiety. This investigation may help to support the use of BOLD-fMRI with pharmacological probes to investigate the neural circuits underlying anxiety and the use of fMRI as a tool in the development of new anxiolytic agents.     

Corticothalamic modulation during absence seizures in rats: a functional MRI assessment

PURPOSE: Functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during absence seizures in an awake animal model. METHODS: Blood-oxygenation-level-dependent (BOLD) fMRI in the brain was measured by using T2*-weighted echo planar imaging at 4.7 Tesla. BOLD imaging was performed before, during, and after absence seizure induction by using gamma-butyrolactone (GBL; 200 mg/kg, intraperitoneal). RESULTS: The corticothalamic circuitry, critical for spike-wave discharge (SWD) formation in absence seizure, showed robust BOLD signal changes after GBL administration, consistent with EEG recordings in the same animals. Predominantly positive BOLD changes occurred in the thalamus. Sensory and parietal cortices showed mixed positive and negative BOLD changes, whereas temporal and motor cortices showed only negative BOLD changes. CONCLUSIONS: With the BOLD fMRI technique, we demonstrated signal changes in brain areas that have been shown, with electrophysiology experiments, to be important for generating and maintaining the SWDs that characterize absence seizures. These results corroborate previous findings from lesion and electrophysiological experiments and show the technical feasibility of noninvasively imaging absence seizures in fully conscious rodents.     

Enhanced phase regression with savitzky‐golay filtering for high‐resolution BOLD fMRI

Phase regression exploits the temporal evolution of phase in individual voxels to suppress blood oxygenation level dependent (BOLD) signal fluctuations caused by larger vessels and draining veins while preserving signal changes from microvascular effects. However, this process does not perform well when phase time series have low signal‐to‐noise ratios because of high levels of physiological noise. We demonstrate that Savitzky‐Golay filters may be used to recover the underlying change in phase and completely restore the efficacy of phase regression. We do not make a priori assumptions regarding phase evolution and perform a data‐driven exploration of parameter space to select the Savitzky‐Golay filter parameters that minimize temporal variance in each voxel after phase regression. This approach is shown to work well on data acquired with single‐shot and multi‐shot pulse sequences, and should therefore be useful for both human and animal gradient‐echo fMRI at high spatial resolutions at high fields. The ability to improve the spatial specificity of BOLD activation may be especially advantageous for clinical applications of fMRI that rely upon the accuracy of individual subject's activation maps to assist with presurgical planning and clinical decision‐making. Enhanced phase regression with Savitzky‐Golay filtering may also find other uses in analyses of resting state functional connectivity. Hum Brain Mapp 35:3832–3840, 2014. © 2014 Wiley Periodicals, Inc.     

A comparison of 'Early' and 'Late' stage brain activation during brief practice of a simple motor task

This research study addresses the question: does the neural circuit implementing a motor task undergo change as a function of even limited practice? To detect potential neural changes associated with limited practice we compared brain activation at the early and late stages of motor performance on a simple task over one relatively brief session. Single-finger opposition served as cognitive stimulation during collection of BOLD fMRI signal. We predicted prefrontal cortex activation would be prominent early, with basal ganglia activation becoming prominent during late stage performance. Results revealed that both early and late performance involve areas in the cerebellum, prefrontal, mid-temporal, extrastriate, and parietal cortices, but that the particular regions within these broad areas differed for the two points of performance. The strongest dissociation between early and late performance involved the corpus striatum, thalamus, and cingulate gyrus. The findings suggested the neural circuit implementing this simple task varied over a relatively brief window of practice. Implications for defining the neurocognitive function of the structures involved, particularly the cerebellum, are discussed.     

fMRI studies of associative encoding in young and elderly controls and mild Alzheimer's disease

OBJECTIVE: To examine alterations in patterns of brain activation seen in normal aging and in mild Alzheimer's disease by functional magnetic resonance imaging (fMRI) during an associative encoding task. METHODS: 10 young controls, 10 elderly controls, and seven patients with mild Alzheimer's disease were studied using fMRI during a face-name association encoding task. The fMRI paradigm used a block design with three conditions: novel face-name pairs, repeated face-name pairs, and visual fixation. RESULTS: The young and elderly controls differed primarily in the pattern of activation seen in prefrontal and parietal cortices: elderly controls showed significantly less activation in both superior and inferior prefrontal cortices but greater activation in parietal regions than younger controls during the encoding of novel face-name pairs. Compared with elderly controls, the Alzheimer patients showed significantly less activation in the hippocampal formation but greater activation in the medial parietal and posterior cingulate regions. CONCLUSIONS: The pattern of fMRI activation during the encoding of novel associations is differentially altered in the early stages of Alzheimer's disease compared with normal aging.     

Pathophysiology of encephalopathy related to continuous spike and waves during sleep: the contribution of neuroimaging

In the last three decades, studies on functional neuroimaging have helped us to understand pathophysiological mechanisms responsible for electro‐clinical patterns associated with epileptic encephalopathies with continuous spikes and waves during slow sleep (ECSWS). MEG and EEG source reconstruction have revealed sources of pathological brain activity associated with epileptiform discharges in the perisylvian region pointing to the significance of this brain area for ECSWS. PET studies have revealed areas of focal hypermetabolism in perisylvian, superior temporal and inferior parietal regions as well as central cortices which were related to epileptic activity. The widespread hypometabolism in regions that belong to the default network (prefrontal and posterior cingulate cortices, parahippocampal gyrus and precuneus) was interpreted as remote inhibition following epileptic activity, which could contribute to cognitive deficits in affected individuals. Note that the described metabolic changes were functional and disappeared after successful treatment and recovery of ECSWS and were found in both sleep and wakefulness which may account for cognitive deficits in patients during the day. EEG‐fMRI studies have revealed a functional fingerprint of epileptic encephalopathy: significant positive BOLD signal changes were identified in the perisylvian regions, prefrontal cortex and anterior cingulate as well as thalamus and negative BOLD signal changes in the regions of the default mode network. The pattern of activation represents a propagation of epileptic activity specific to encephalopathy, which is independent of etiology and type of seizure associated with ECSWS. In summary, methods of neuroimaging have shed light on pathogenic mechanisms of ECSWS which may account for a number of clinical phenomena associated with this condition.     

Functional MRI studies of word-stem completion: Reliability across laboratories and comparison to blood flow imaging with PET

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an increasingly popular technique for mapping the brain. The relationship between BOLD-fMRI imaging and imaging of blood flow activation with positron emission tomography (PET) remains unclear. Moreover, BOLD imaging strategies and analysis procedures vary widely across laboratories. To examine the relationship between these different methods, we compared brain activation maps of a word-stem completion task obtained both using PET and using fMRI across two separate institutions (Washington University and Massachusetts General Hospital) with different acquisitions (gradient-refocused echo and asymmetric spin echo) and different analysis techniques. Overall, activation maps were highly similar across both fMRI methods and PET. A set of activated brain areas, in consistent locations in Talairach atlas space, were identified across all three studies, including visual striate and extrastriate, left prefrontal, supplementary motor area (SMA), and right cerebellar areas. Decreases in activation were also consistently observed in medial parietal, posterior insular, and medial inferior frontal areas. Some differences were noted that may be related to the silent performance of the task with fMRI. The largely consistent results suggest that comparisons can be made appropriately across imaging modalities and laboratory methods. A further implication of the consistencies, which extended to both increases and decreases in signal, is that the underlying brain physiology leading to BOLD contrast may be more similar to blood flow than originally appreciated. Hum. Brain Mapping 6:203–215, 1998. © 1998 Wiley-Liss, Inc.     

Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients

BACKGROUND/OBJECTIVES: A previous fMRI study demonstrated increased brain activation during working memory tasks in patients with HIV with mild dementia. The current study aims to determine whether patients who are HIV-1 positive and have normal cognitive function also show increased brain activation on fMRI. METHODS: Blood oxygenation level-dependent (BOLD) fMRI was performed in 10 patients with HIV (CD <500) and 10 age-, sex-, education-, and handedness-matched seronegative subjects. Each subject performed a battery of neuropsychological tests and fMRI with three tasks (0-back, 1-back, and 2-back) that required different levels of attention for working memory. RESULTS: Compared with control subjects, patients with HIV showed greater magnitude of brain activation (BOLD signal intensity changes, p 相似文献   

BOLD responses in somatosensory cortices better reflect heat sensation than pain

The discovery of cortical networks that participate in pain processing has led to the common generalization that blood oxygen level-dependent (BOLD) responses in these areas indicate the processing of pain. Physical stimuli have fundamental properties that elicit sensations distinguishable from pain, such as heat. We hypothesized that pain intensity coding may reflect the intensity coding of heat sensation during the presentation of thermal stimuli during fMRI. Six 3T fMRI heat scans were collected for 16 healthy subjects, corresponding to perceptual levels of "low innocuous heat," "moderate innocuous heat," "high innocuous heat," "low painful heat," "moderate painful heat," and "high painful heat" delivered by a contact thermode to the face. Subjects rated pain and heat intensity separately after each scan. A general linear model analysis detected different patterns of brain activation for the different phases of the biphasic response to heat. During high painful heat, the early phase was associated with significant anterior insula and anterior cingulate cortex activation. Persistent responses were detected in the right dorsolateral prefrontal cortex and inferior parietal lobule. Only the late phase showed significant correlations with perceptual ratings. Significant heat intensity correlated activation was identified in contralateral primary and secondary somatosensory cortices, motor cortex, and superior temporal lobe. These areas were significantly more related to heat ratings than pain. These results indicate that heat intensity is encoded by the somatosensory cortices, and that pain evaluation may either arise from multimodal evaluative processes, or is a distributed process.     

Highly focal BOLD activation on functional MRI in a patient with progressive myoclonic epilepsy and diffuse giant somatosensory evoked potentials

We analyzed the effect of afferent input on patterns of brain electrical activation in a 31-year-old man with progressive myoclonic epilepsy (PME) by measuring the somatosensory evoked potential (SSEP) amplitude at the scalp after median nerve stimulation and examining the changes in the functional magnetic resonance imaging blood oxygen level-dependent (fMRI BOLD) signal. High-amplitude SSEPs were elicited at the wrist in association with highly focal BOLD activation of the contralateral sensorimotor areas. By contrast, no diffuse activation of either the frontal or the posterior parietal cortical areas was observed, as seen in previously recorded data on SSEPs from a healthy control group. The highly focal BOLD activation in this patient suggests that cortex hyperexcitability might be limited to the sensorimotor cortex in PME. The combined EEG-fMRI findings highlight a dissociation between BOLD activation and neurophysiological findings.     

Assembling and encoding word representations: fMRI subsequent memory effects implicate a role for phonological control

Novel word learning is central to the flexibility inherent in the human language capacity. Word learning may partially depend on long-term memory formation during the assembly of phonological representations from orthographic inputs. In the present study, event-related functional magnetic resonance imaging (fMRI) examined the contributions of phonological control-a component of the verbal working memory system-to phonological assembly and word learning. Subjects were scanned while making syllable decisions about visually presented familiar (English) and novel (pseudo-English and Foreign) words, a task that required retrieval and analysis of existing phonological codes or the assembly and analysis of novel representations. Results revealed that left inferior prefrontal cortex (LIPC) and bilateral parietal cortices were differentially engaged during the processing of novel words, suggesting that this circuit is recruited during phonological assembly. A subsequent memory analysis that examined the relation between fMRI signal and the subject's ability to later remember the words (a measure of effective memory formation) revealed that the magnitude of activation in LIPC, bilateral superior parietal, and left inferior parietal cortices was positively correlated with later memory. Moreover, although the magnitude of the subsequent memory effect in parietal cortex was not significantly affected by word type, this effect was greater in posterior LIPC for novel (pseudo-English) than for familiar (English) words. In the course of subserving the assembly of novel word representations, the phonological (articulatory) control component of the phonological system appears to play a central role in the encoding of novel words into long-term memory.     

Investigation of BOLD fMRI resonance frequency shifts and quantitative susceptibility changes at 7 T

Although blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) experiments of brain activity generally rely on the magnitude of the signal, they also provide frequency information that can be derived from the phase of the signal. However, because of confounding effects of instrumental and physiological origin, BOLD related frequency information is difficult to extract and therefore rarely used. Here, we explored the use of high field (7 T) and dedicated signal processing methods to extract frequency information and use it to quantify and interpret blood oxygenation and blood volume changes. We found that optimized preprocessing improves detection of task‐evoked and spontaneous changes in phase signals and resonance frequency shifts over large areas of the cortex with sensitivity comparable to that of magnitude signals. Moreover, our results suggest the feasibility of mapping BOLD quantitative susceptibility changes in at least part of the activated area and its largest draining veins. Comparison with magnitude data suggests that the observed susceptibility changes originate from neuronal activity through induced blood volume and oxygenation changes in pial and intracortical veins. Further, from frequency shifts and susceptibility values, we estimated that, relative to baseline, the fractional oxygen saturation in large vessels increased by 0.02–0.05 during stimulation, which is consistent to previously published estimates. Together, these findings demonstrate that valuable information can be derived from fMRI imaging of BOLD frequency shifts and quantitative susceptibility changes. Hum Brain Mapp 35:2191–2205, 2014. © 2013 Wiley Periodicals, Inc .     

Frontal and parietal participation in problem solving in the Tower of London: fMRI and computational modeling of planning and high-level perception

This study triangulates executive planning and visuo-spatial reasoning in the context of the Tower of London (TOL) task by using a variety of methodological approaches. These approaches include functional magnetic resonance imaging (fMRI), functional connectivity analysis, individual difference analysis, and computational modeling. A graded fMRI paradigm compared the brain activation during the solution of problems with varying path lengths: easy (1 and 2 moves), moderate (3 and 4 moves) and difficult (5 and 6 moves). There were three central findings regarding the prefrontal cortex: (1) while both the left and right prefrontal cortices were equally involved during the solution of moderate and difficult problems, the activation on the right was differentially attenuated during the solution of the easy problems; (2) the activation observed in the right prefrontal cortex was highly correlated with individual differences in working memory (measured independently by the reading span task); and (3) different patterns of functional connectivity were observed in the left and right prefrontal cortices. Results obtained from the superior parietal region also revealed left/right differences; only the left superior parietal region revealed an effect of difficulty. These fMRI results converged upon two hypotheses: (1) the right prefrontal area may be more involved in the generation of a plan, whereas the left prefrontal area may be more involved in plan execution; and (2) the right superior parietal region is more involved in attention processes while the left homologue is more of a visuo-spatial workspace. A 4CAPS computational model of the cognitive processes and brain activation in the TOL task integrated these hypothesized mechanisms, and provided a reasonably good fit to the observed behavioral and brain activation data. The multiple research approaches presented here converge on a deepening understanding of the combination of perceptual and conceptual processes in this type of visual problem solving.     

Central representation of the RIII flexion reflex associated with overt motor reaction: an fMRI study.

Recent neuroimaging studies precised the functions of the brain regions included in the so-called "pain-matrix". They isolated brain structures mediating attentional, emotional, anticipatory, cognitive, and discriminative aspects of pain perception. Surprisingly, little attention was devoted to isolate the cerebral network associated with the motor response to pain. In this study, we used fMRI to measure BOLD signal changes in nine volunteers while they received low- (L-) and high- (H-) intensity painful electrical shocks on the (left) lower limb. High-intensity stimulation was associated with a significantly stronger pain sensation and with a pronounced motor (withdrawal) reflex. BOLD responses common to L- and H-stimulation intensities were found in the right prefrontal and right posterior parietal cortices. These did not correlate with subjective pain ratings and probably mediate attentional processes unrelated to pain intensity and withdrawal. In contrast, signal changes in insula, left SII cortices and right amygdala did correlate with pain ratings and are therefore likely to encode for pain intensity. High-intensity shocks selectively recruited a motor network, including vermis, MI, SI, and paracentral cortices bilaterally, right premotor, right SII and posterior cingulate cortices. These responses, assessed for the first time in a functional imaging study, emphazised on the presence of a motor component in what has been described as the pain-matrix. They should be considered as a motor component of pain-related processes activated in case of intense pain.     

Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals

After its discovery in 1990, blood oxygenation level-dependent (BOLD) contrast in functional magnetic resonance imaging (fMRI) has been widely used to map brain activation in humans and animals. Since fMRI relies on signal changes induced by neural activity, its signal source can be complex and is also dependent on imaging parameters and techniques. In this review, we identify and describe the origins of BOLD fMRI signals, including the topics of (1) effects of spin density, volume fraction, inflow, perfusion, and susceptibility as potential contributors to BOLD fMRI, (2) intravascular and extravascular contributions to conventional gradient-echo and spin-echo BOLD fMRI, (3) spatial specificity of hemodynamic-based fMRI related to vascular architecture and intrinsic hemodynamic responses, (4) BOLD signal contributions from functional changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of O(2) utilization (CMRO(2)), (5) dynamic responses of BOLD, CBF, CMRO(2), and arterial and venous CBV, (6) potential sources of initial BOLD dips, poststimulus BOLD undershoots, and prolonged negative BOLD fMRI signals, (7) dependence of stimulus-evoked BOLD signals on baseline physiology, and (8) basis of resting-state BOLD fluctuations. These discussions are highly relevant to interpreting BOLD fMRI signals as physiological means.     

Focusing effects of L‐dopa in Parkinson's disease

Previous fMRI motor studies in Parkinson's disease (PD) have suggested that L ‐dopa may “normalize” areas of hypo‐ and hyperactivity. However, results from these studies, which were largely based on analyzing BOLD signal amplitude, have been conflicting. Examining only amplitude changes at distinct loci may thus be inadequate in fully capturing the activation changes induced by L ‐dopa. In this article, we extended prior analyses on the effects of L ‐dopa by investigating both amplitude and spatial changes of brain activation before and after L ‐dopa. Ten subjects with PD, both on and off medication, and ten healthy, age‐matched controls performed a visuo‐motor tracking task in which they sinusoidally squeezed a bulb at 0.25, 0.5, and 0.75 Hz. This task was contrasted with static squeezing to generate fMRI activation maps. To investigate the effects of L ‐dopa, we examined the amplitude and spatial variance of the BOLD response within anatomically‐defined regions of interest (ROIs). L ‐dopa had significant main effects on the amplitude of BOLD signal in bilateral primary motor cortex and left SMA. In contrast, L ‐dopa‐mediated spatial changes were apparent in bilateral cerebellar hemispheres, M1, SMA, and right prefrontal cortex. Moreover, L ‐dopa appeared to normalize the spatial distribution of ROI activation in PD to that of the controls. Specifically, L ‐dopa had a “focusing” effect on activity—an effect more pronounced than the typically‐measured fMRI amplitude changes. This observation is consistent with modeling studies, which demonstrated that dopamine increases the signal‐to‐noise ratio at the neuronal level with a resultant focusing of representations at the macroscopic level. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

The less BOLD, the wiser: support for the latent resource hypothesis after traumatic brain injury

Previous studies of the BOLD response in the injured brain have revealed neural recruitment relative to controls during working memory tasks in several brain regions, most consistently the right prefrontal cortex and anterior cingulate cortices. We previously proposed that the recruitment observed in this literature represents auxiliary support resources, and that recruitment of PFC is not abnormal or injury specific and should reduce as novelty and challenge decrease. The current study directly tests this hypothesis in the context of practice of a working memory task. It was hypothesized that individuals with brain injury would demonstrate recruitment of previously indicated regions, behavioral improvement following task practice, and a reduction in the BOLD signal in recruited regions after practice. Individuals with traumatic brain injury and healthy controls performed the n-back during fMRI acquisition, practiced each task out of the scanner, and returned to the scanner for additional fMRI n-back acquisition. Statistical parametric maps demonstrated a number of regions of recruitment in the 1-back in individuals with brain injury and a number of corresponding regions of reduced activation in individuals with brain injury following practice in both the 1-back and 2-back. Regions of interest demonstrated reduced activation following practice, including the anterior cingulate and right prefrontal cortices. Individuals with brain injury demonstrated modest behavioral improvements following practice. These findings suggest that neural recruitment in brain injury does not represent reorganization but a natural extension of latent mechanisms that engage transiently and are contingent upon cerebral challenge.     

Imaging cocaine-induced changes in the mesocorticolimbic dopaminergic system of conscious rats

Functional magnetic resonance imaging (fMRI) was used to assess the effects of cocaine on brain activation in fully conscious rats. Methods were developed to image cocaine-induced changes in blood-oxygen-level-dependent (BOLD) signal without the peripheral cardiac and respiratory complications associated with psychostimulant administration. Using spin echo planar imaging (EPI), conscious rats were imaged in a 4.7 T spectrometer prior to and following the intracerebroventricular injection of cocaine (20 microg) in artificial cerebrospinal fluid (10 uL). Within 5 min of injection, there was a significant increase in BOLD signal intensity in the substantia nigra, ventral tegmental area, nucleus accumbens, dorsal striatum and prefrontal cortex, as compared to vehicle controls. Minimal negative BOLD signal changes were observed in response to cocaine and no significant perturbations in normal cardiovascular and respiratory function. These findings demonstrate the technical feasibility of studying psychostimulant-induced brain activity using functional MRI in conscious rats.     

Functional localization in the human brain: Gradient‐echo,spin‐echo,and arterial spin‐labeling fMRI compared with neuronavigated TMS

A spatial mismatch of up to 14 mm between optimal transcranial magnetic stimulation (TMS) site and functional magnetic resonance imaging (fMRI) signal has consistently been reported for the primary motor cortex. The underlying cause might be the effect of magnetic susceptibility around large draining veins in Gradient‐Echo blood oxygenation level‐dependent (GRE‐BOLD) fMRI. We tested whether alternative fMRI sequences such as Spin‐Echo (SE‐BOLD) or Arterial Spin‐Labeling (ASL) assessing cerebral blood flow (ASL‐CBF) may localize neural activity closer to optimal TMS positions and primary motor cortex than GRE‐BOLD. GRE‐BOLD, SE‐BOLD, and ASL‐CBF signal changes during right thumb abductions were obtained from 15 healthy subjects at 3 Tesla. In 12 subjects, tissue at fMRI maxima was stimulated with neuronavigated TMS to compare motor‐evoked potentials (MEPs). Euclidean distances between the fMRI center‐of‐gravity (CoG) and the TMS motor mapping CoG were calculated. Highest SE‐BOLD and ASL‐CBF signal changes were located in the anterior wall of the central sulcus [Brodmann Area 4 (BA4)], whereas highest GRE‐BOLD signal changes were significantly closer to the gyral surface. TMS at GRE‐BOLD maxima resulted in higher MEPs which might be attributed to significantly higher electric field strengths. TMS‐CoGs were significantly anterior to fMRI‐CoGs but distances were not statistically different across sequences. Our findings imply that spatial differences between fMRI and TMS are unlikely to be caused by spatial unspecificity of GRE‐BOLD fMRI but might be attributed to other factors, e.g., interactions between TMS‐induced electric field and neural tissue. Differences between techniques should be kept in mind when using fMRI coordinates as TMS (intervention) targets. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Losing the struggle to stay awake: Divergent thalamic and cortical activity during microsleeps

Maintaining alertness is critical for safe and successful performance of most human activities. Consequently, microsleeps during continuous visuomotor tasks, such as driving, can be very serious, not only disrupting performance but sometimes leading to injury or death due to accidents. We have investigated the neural activity underlying behavioral microsleeps – brief (0.5–15 s) episodes of complete failure to respond accompanied by slow eye‐closures – and EEG theta activity during drowsiness in a continuous task. Twenty healthy normally‐rested participants performed a 50‐min continuous tracking task while fMRI, EEG, eye‐video, and responses were simultaneously recorded. Visual rating of performance and eye‐video revealed that 70% of the participants had frequent microsleeps. fMRI analysis revealed a transient decrease in thalamic, posterior cingulate, and occipital cortex activity and an increase in frontal, posterior parietal, and parahippocampal activity during microsleeps. The transient activity was modulated by the duration of the microsleep. In subjects with frequent microsleeps, power in the post‐central EEG theta was positively correlated with the BOLD signal in the thalamus, basal forebrain, and visual, posterior parietal, and prefrontal cortices. These results provide evidence for distinct neural changes associated with microsleeps and with EEG theta activity during drowsiness in a continuous task. They also suggest that the occurrence of microsleeps during an active task is not a global deactivation process but involves localized activation of fronto‐parietal cortex, which, despite a transient loss of arousal, may constitute a mechanism by which these regions try to restore responsiveness. Hum Brain Mapp 35:257–269, 2014. © 2012 Wiley Periodicals, Inc.