Resting-state functional magnetic resonance imaging indices are related to electrophysiological dysfunction in degenerative cervical myelopathy.

The age-related degenerative pathologies of the cervical spinal column that comprise degenerative cervical myelopathy (DCM) cause myelopathy due spinal cord compression. Functional neurological assessment of DCM can potentially reveal the severity and pathological mechanism of DCM. However, functional assessment by conventional MRI remains difficult. This study used resting-state functional MRI (rs-fMRI) to investigate the relationship between functional connectivity (FC) strength and neurophysiological indices and examined the feasibility of functional assessment by FC for DCM. Preoperatively, 34 patients with DCM underwent rs-fMRI scans. Preoperative central motor conduction time (CMCT) reflecting motor functional disability and intraoperative somatosensory evoked potentials (SEP) reflecting sensory functional disability were recorded as electrophysiological indices of severity of the cervical spinal cord impairment. We performed seed-to-voxel FC analysis and correlation analyses between FC strength and the two electrophysiological indices. We found that FC strength between the primary motor cortex and the precuneus correlated significantly positively with CMCT, and that between the lateral part of the sensorimotor cortex and the lateral occipital cortex also showed a significantly positive correlation with SEP amplitudes. These results suggest that we can evaluate neurological and electrophysiological severity in patients with DCM by analyzing FC strengths between certain brain regions.

Three weeks of exercise therapy altered brain functional connectivity in fibromyalgia inpatients.

Background: Fibromyalgia (FM) is a chronic pain syndrome characterized by widespread pain, tenderness, and fatigue. Patients with FM have no effective medication so far, and their activity of daily living and quality of life are remarkably impaired. Therefore, new therapeutic approaches are awaited. Recently, exercise therapy has been gathering much attention as a promising treatment for FM. However, the underlying mechanisms are not fully understood, particularly, in the central nervous system, including the brain. Therefore, we investigated functional connectivity changes and their relationship with clinical improvement in patients with FM after exercise therapy to investigate the underlying mechanisms in the brain using resting-state fMRI (rs-fMRI) and functional connectivity (FC) analysis. Methods: Seventeen patients with FM participated in this study. They underwent a 3-week exercise therapy on in-patient basis and a 5-min rs-fMRI scan before and after the exercise therapy. We compared the FC strength of sensorimotor regions and the mesocortico-limbic system between two scans. We also performed a multiple regression analysis to examine the relationship between pre-post differences in FC strength and improvement of patients' clinical symptoms or motor abilities. Results: Patients with FM showed significant improvement in clinical symptoms and motor abilities. They also showed a significant pre-post difference in FC of the anterior cingulate cortex and a significant correlation between pre-post FC changes and improvement of clinical symptoms and motor abilities. Although sensorimotor regions tended to be related to the improvement of general disease severity and depression, brain regions belonging to the mesocortico-limbic system tended to be related to the improvement of motor abilities. Conclusion: Our 3-week exercise therapy could ameliorate clinical symptoms and motor abilities of patients with FM, and lead to FC changes in sensorimotor regions and brain regions belonging to the mesocortico-limbic system. Furthermore, these changes were related to improvement of clinical symptoms and motor abilities. Our findings suggest that, as predicted by previous animal studies, spontaneous brain activities modified by exercise therapy, including the mesocortico-limbic system, improve clinical symptoms in patients with FM.

Verification of the brain network marker of major depressive disorder: Test-retest reliability and anterograde generalization performance for newly acquired data.

BACKGROUND: Recently, we developed a generalizable brain network marker for the diagnosis of major depressive disorder (MDD) across multiple imaging sites using resting-state functional magnetic resonance imaging. Here, we applied this brain network marker to newly acquired data to verify its test-retest reliability and anterograde generalization performance for new patients. METHODS: We tested the sensitivity and specificity of our brain network marker of MDD using data acquired from 43 new patients with MDD as well as new data from 33 healthy controls (HCs) who participated in our previous study. To examine the test-retest reliability of our brain network marker, we evaluated the intraclass correlation coefficients (ICCs) between the brain network marker-based classifier's output (probability of MDD) in two sets of HC data obtained at an interval of approximately 1 year. RESULTS: Test-retest correlation between the two sets of the classifier's output (probability of MDD) from HCs exhibited moderate reliability with an ICC of 0.45 (95 % confidence interval,0.13-0.68). The classifier distinguished patients with MDD and HCs with an accuracy of 69.7 % (sensitivity, 72.1 %; specificity, 66.7 %). LIMITATIONS: The data of patients with MDD in this study were cross-sectional, and the clinical significance of the marker, such as whether it is a state or trait marker of MDD and its association with treatment responsiveness, remains unclear. CONCLUSIONS: The results of this study reaffirmed the test-retest reliability and generalization performance of our brain network marker for the diagnosis of MDD.

Performing the hand laterality judgement task does not necessarily require motor imagery.

When people judge the laterality of rotated hand images, that is they perform the laterality judgement task (LJT), they are thought to use motor imagery. However, recent studies have suggested that its completion does not necessarily require the use of motor imagery. In this study, we investigated whether and how many people preferentially use motor imagery to perform the LJT in 37 healthy adults. We assessed the presence of behavioural features associated with motor imagery at the individual level, namely, the linear angle-response time (RT) relationship and the biomechanical constraints effect in the LJT and in the same-different judgement task (SDJT), in which people are not thought to use motor imagery. We found that at most 50% of participants showed both behavioural features in the palmar view condition of the LJT. Moreover, this proportion did not differ from that in the dorsal view condition of the LJT or that in both view conditions of the SDJT. These results demonstrate that a motor imagery-based strategy is not universally and specifically used to perform the LJT. Therefore, previous results of the LJT, in particular, regarding the biomechanical constraints effect, should be reinterpreted in light of our findings.

Resting-state Amplitude of Low-frequency Fluctuation is a Potentially Useful Prognostic Functional Biomarker in Cervical Myelopathy.

BACKGROUND: Cervical MRI is the standard diagnostic imaging technique for patients with cervical myelopathy. However, the utility of conventional cervical MRI as a predictive biomarker for surgical recovery remains unclear, partly because of the limited information obtained from this anatomically small area. Brain resting-state functional MRI (rs-fMRI) may help identify candidate predictive biomarkers. Two analytical methods that assess local spontaneous brain activity are widely used for rs-fMRI: functional connectivity between two brain regions and amplitude of low-frequency fluctuation (ALFF). In our previous analysis of functional connectivity, we discovered that brain functional connectivity may be a predictive biomarker for neurologic recovery in patients with cervical myelopathy; however, the functional connectivity analysis identified a correlation with only one clinical outcome (the 10-second test). To establish a comprehensive prediction measure, we need to explore other brain biomarkers that can predict recovery of other clinical outcomes in patients with cervical myelopathy. QUESTIONS/PURPOSES: We aimed to (1) elucidate preoperative ALFF alterations in patients with cervical myelopathy and how ALFF changes after surgery, with a focus on postoperative normalization and (2) establish a predictive model using preoperative ALFF by investigating the correlation between preoperative ALFF and postoperative clinical recovery in patients with cervical myelopathy. METHODS: Between August 2015 and June 2017, we treated 40 patients with cervical myelopathy. Thirty patients met our prespecified inclusion criteria, all were invited to participate, and 28 patients opted to do so (93%; 14 men and 14 women; mean age: 67 years). The 28 patients and 28 age- and sex-matched controls underwent rs-fMRI (twice for patients with cervical myelopathy: before and 6 months after cervical decompression surgery). We analyzed the same study population that was used in our earlier study investigating functional connectivity. Controls had none of the following abnormalities: neck or arm pain, visual or auditory disorders, cognitive disorder, structural brain disorder, a history of brain surgery, mental and neurologic disorders, and medications for the central nervous system. We performed ALFF comparisons between preoperative patients with cervical myelopathy and controls, analyzed postoperative ALFF changes in patients with cervical myelopathy, and performed a correlation analysis between preoperative ALFF and clinical recovery in these patients. Clinical outcomes in the cervical myelopathy group were assessed using the 10-second test, the Japanese Orthopaedic Association upper-extremity motor (JOA-UEM) score, JOA upper-extremity sensory score (JOA-UES), and Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire for upper-extremity function (JOACMEQ-UEF) score before and 6 months after surgery, which is when we believe these scores generally reach a plateau. A total of 93% of those enrolled (26 of 28 patients) were analyzed both preoperatively and postoperatively; the other two were lost to follow-up. RESULTS: The cervical myelopathy group had an increase in ALFF in the bilateral primary sensorimotor cortices (right, cluster size = 850 voxels, t-value = 6.10; left, cluster size = 370 voxels, t-value = 4.84) and left visual cortex (cluster size = 556 voxels, t-value = 4.21) compared with the control group. The cervical myelopathy group had a decrease in ALFF in the bilateral posterior supramarginal gyrus (right, cluster size = 222 voxels, t-value = 5.09; left, cluster size = 436 voxels, t-value = 5.28). After surgery, the bilateral sensorimotor cortices (right, cluster size = 468 voxels, t-value = 6.74; left, cluster size = 167 voxels, t-value = 5.40) and left visual cortex (cluster size = 3748 voxels, t-value = 6.66) showed decreased ALFF compared with preoperative ALFF, indicating postoperative normalization of spontaneous brain activities in these regions. However, the bilateral posterior supramarginal gyrus did not show an increase in ALFF postoperatively, although ALFF in this region decreased preoperatively. Greater levels of ALFF at the left and right frontal pole and left pars opercularis of the inferior frontal gyrus before surgery in the cervical myelopathy group were correlated with larger improvements in the JOACMEQ-UEF score 6 months after surgery (r = 0.784; p < 0.001, r = 0.734; p < 0.001 and r = 0.770, respectively; p < 0.001). The prediction formula, based on preoperative ALFF values in the left frontal pole, was as follows: the predicted postoperative improvement in the JOACMEQ-UEF score = 34.6 × preoperative ALFF value - 7.0 (r = 0.614; p < 0.001). CONCLUSIONS: Our findings suggest that preoperative ALFF may be a biomarker for postoperative recovery in that it predicted postoperative JOACMEQ-UEF scores. To establish a comprehensive prediction measure for neurologic recovery in patients with cervical myelopathy, a multicenter study is underway. LEVEL OF EVIDENCE: Level II, diagnostic study.

Resting-state brain functional connectivity in patients with chronic pain who responded to subanesthetic-dose ketamine.

Ketamine has been used to treat chronic pain; however, it is still unknown as to what types of chronic pain is ketamine effective against. To identify the effect of administration of subanesthetic-dose ketamine in patients with chronic pain and to clarify the mechanism of the effect, we retrospectively investigated brain functional connectivity using resting-state functional magnetic resonance imaging (rs-fMRI). Patients were divided into responders (Group R: ≥50% improvement on Numerical Rating Scale) and non-responders (Group NR). We compared the differences in terms of brain functional connectivity by seed-to-voxel correlation analysis. Two-sample t-test revealed significant lower connectivity between the medial prefrontal cortex (mPFC) and precuneus in Group R. We also found a significant negative correlation between the improvement rate and functional connectivity strength between the mPFC and precuneus. These findings suggest that subanesthetic-dose ketamine is effective in patients with chronic pain whose brain functional connectivity between the mPFC and precuneus is low. We believe that the current study explored for the first time the correlation between brain functional connectivity and the effect of subanesthetic-dose ketamine for chronic pain and indicated the possibility of use of the predictive marker in pharmacological treatment of chronic pain.

Towards prognostic functional brain biomarkers for cervical myelopathy: A resting-state fMRI study.

Recently, there has been increasing interest in strategies to predict neurological recovery in cervical myelopathy (CM) based on clinical images of the cervical spine. In this study, we aimed to explore potential preoperative brain biomarkers that can predict postoperative neurological recovery in CM patients by using resting-state functional magnetic resonance imaging (rs-fMRI) and functional connectivity (FC) analysis. Twenty-eight patients with CM and 28 age- and sex-matched healthy controls (HCs) underwent rs-fMRI (twice for CM patients, before and six months after surgery). A seed-to-voxel analysis was performed, and the following three statistical analyses were conducted: (i) FC comparisons between preoperative CM and HC; (ii) correlation analysis between preoperative FCs and clinical scores; and (iii) postoperative FC changes in CM. Our analyses identified three FCs between the visual cortex and the right superior frontal gyrus based on the conjunction of the first two analyses [(i) and (ii)]. These FCs may act as potential biomarkers for postoperative gain in the 10-second test and might be sufficient to provide a prediction formula for potential recovery. Our findings provide preliminary evidence supporting the possibility of novel predictive measures for neurological recovery in CM using rs-fMRI.

Verbal Instruction Can Induce Extinction of Fear of Movement-Related Pain.

The fear avoidance model of chronic musculoskeletal pain highlights the importance of pain-related fear in chronification of pain. Although several interventions have been developed on the basis of this model, the following issues remain unresolved: first, whether movement conditioned to pain can evoke fear responses particularly sympathetic activation, and second, whether verbal instructions can attenuate conditioned fear of movement-related pain as with direct experience. To investigate these issues, we induced proprioceptive conditioning (learning the relationship between proprioceptive sensations and an aversive event) and extinction learning in healthy volunteers, and we compared psychophysiological and subjective indices of fear between an instructed and a normal extinction group. Using paired presentation of painful heat stimuli as an unconditioned stimulus and flexion of the wrist as a conditioned stimulus, all participants acquired the conditioned fear response (skin potential response) to the conditioned stimulus. The instructed extinction group was then told that the movement was no longer followed by painful stimulus at the beginning of the extinction phase, and only this group showed significant decreases on both indices of fear. This finding indicates that verbal instruction can attenuate conditioned fear of movement-related pain, supporting the clinical importance of providing information regarding the relationship between movement and pain. PERSPECTIVE: This article presents evidence that, in a laboratory setting, verbal instructions rapidly decrease conditioned fear of movement-related pain on psychophysiological as well as subjective indices. This result indicates that it is important for chronic musculoskeletal pain patients to precisely understand the relationship between movement and pain in clinical situations.

[Cortical Midline Structures: "Self" and "Pain"].

Emerging evidence indicates that cortical midline structures (CMS) (which consist of the orbitomedial prefrontal cortex (OMPFC), dorsomedial prefrontal cortex (DMPFC), anterior cingulate cortex (ACC), and precuneus/posterior cingulate cortex (pC/PCC)) have a critical role in generating a model of the self. These regions also serve as hub regions for the default mode network (DMN) or salience network (SN). Furthermore, regions of the CMS overlap with pain-related regions such as the so-called "pain matrix," suggesting that pain has unique attributes compared to other sensations like vision. Previous studies have reported that disturbances of the CMS relate to chronic pain, as well as neurological and psychiatric diseases. The considerable overlap between regions involved in pain and those involved in self-cognition may provide important insights not only into the pathology of chronic pain and cognitive aspects of pain, but also for understanding self-representation in the brain.

Pain-Related Brain Activity Evoked by Active and Dynamic Arm Movement: Delayed-Onset Muscle Soreness as a Promising Model for Studying Movement-Related Pain in Humans.

OBJECTIVE: To demonstrate delayed-onset muscle soreness (DOMS) is a suitable model for the study of movement-evoked pain, we attempted to identify brain regions specifically involved in pain evoked by active and dynamic movement under DOMS condition. SUBJECT: Twelve healthy volunteers METHODS: DOMS was induced in the left upper-arm flexor muscles by an eccentric elbow contraction exercise. Movement-evoked pain in the affected muscles was evaluated just before (day 0) and after (days 1-7 and 30) the exercise using a visual analog scale. Subjects underwent functional magnetic resonance imaging scans while performing repeated elbow flexion on day 2 (DOMS condition) and day 30 (painless condition). We compared brain activity between the DOMS and painless conditions. RESULTS: Movement-evoked pain reached peak intensity on day 2 and disappeared by day 30 in all subjects. No subject felt pain at rest on either of these days. Contralateral primary motor cortex (M1), parietal operculum and bilateral presupplementary motor area (pre-SMA) showed greater activity during active and dynamic arm movement with DOMS than during the same movement without pain. There was no difference in activation of brain regions known collectively as the "pain matrix," except for the parietal operculum, between the two conditions. CONCLUSION: Active and dynamic movement with pain selectively evoked activation of M1, pre-SMA, and parietal operculum, as assessed using DOMS. Our results demonstrate that DOMS is a promising experimental model for the study of movement-evoked pain in humans.

fMRI evidence of improved visual function in patients with progressive retinitis pigmentosa by eye-movement training.

To evaluate changes in the visual processing of patients with progressive retinitis pigmentosa (RP) who acquired improved reading capability by eye-movement training (EMT), we performed functional magnetic resonance imaging (fMRI) before and after EMT. Six patients with bilateral concentric contraction caused by pigmentary degeneration of the retina and 6 normal volunteers were recruited. Patients were given EMT for 5 min every day for 8-10 months. fMRI data were acquired on a 3.0-Tesla scanner while subjects were performing reading tasks. In separate experiments (before fMRI scanning), visual performances for readings were measured by the number of letters read correctly in 5 min. Before EMT, activation areas of the primary visual cortex of patients were 48.8% of those of the controls. The number of letters read correctly in 5 min was 36.6% of those by the normal volunteers. After EMT, the activation areas of patients were not changed or slightly decreased; however, reading performance increased in 5 of 6 patients, which was 46.6% of that of the normal volunteers (p< 0.05). After EMT, increased activity was observed in the frontal eye fields (FEFs) of all patients; however, increases in the activity of the parietal eye fields (PEFs) were observed only in patients who showed greater improvement in reading capability. The improvement in reading ability of the patients after EMT is regarded as an effect of the increased activity of FEF and PEF, which play important roles in attention and working memory as well as the regulation of eye movements.

Network-dependent modulation of brain activity during sleep.

Brain activity dynamically changes even during sleep. A line of neuroimaging studies has reported changes in functional connectivity and regional activity across different sleep stages such as slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. However, it remains unclear whether and how the large-scale network activity of human brains changes within a given sleep stage. Here, we investigated modulation of network activity within sleep stages by applying the pairwise maximum entropy model to brain activity obtained by functional magnetic resonance imaging from sleeping healthy subjects. We found that the brain activity of individual brain regions and functional interactions between pairs of regions significantly increased in the default-mode network during SWS and decreased during REM sleep. In contrast, the network activity of the fronto-parietal and sensory-motor networks showed the opposite pattern. Furthermore, in the three networks, the amount of the activity changes throughout REM sleep was negatively correlated with that throughout SWS. The present findings suggest that the brain activity is dynamically modulated even in a sleep stage and that the pattern of modulation depends on the type of the large-scale brain networks.

Efficiency of a "small-world" brain network depends on consciousness level: a resting-state FMRI study.

It has been revealed that spontaneous coherent brain activity during rest, measured by functional magnetic resonance imaging (fMRI), self-organizes a "small-world" network by which the human brain could sustain higher communication efficiency across global brain regions with lower energy consumption. However, the state-dependent dynamics of the network, especially the dependency on the conscious state, remain poorly understood. In this study, we conducted simultaneous electroencephalographic recording with resting-state fMRI to explore whether functional network organization reflects differences in the conscious state between an awake state and stage 1 sleep. We then evaluated whole-brain functional network properties with fine spatial resolution (3781 regions of interest) using graph theoretical analysis. We found that the efficiency of the functional network evaluated by path length decreased not only at the global level, but also in several specific regions depending on the conscious state. Furthermore, almost two-thirds of nodes that showed a significant decrease in nodal efficiency during stage 1 sleep were categorized as the default-mode network. These results suggest that brain functional network organizations are dynamically optimized for a higher level of information integration in the fully conscious awake state, and that the default-mode network plays a pivotal role in information integration for maintaining conscious awareness.

Distinct role of spatial frequency in dissociative reading of ideograms and phonograms: an fMRI study.

It has been proposed that distinct neural circuits are activated by reading Japanese ideograms (Kanji) and phonograms (Kana). By measuring high-density event-related potentials, we recently reported that spatial frequency (SF) information is responsible for the dissociation between Kanji and Kana reading. In particular, we found close links between Kana and low SF (LSF) information and between Kanji and high SF (HSF) information. However, it remains unclear which brain regions contribute to this dissociation. To determine this, we performed functional magnetic resonance imaging while presenting unfiltered or spatially filtered Kanji and Kana word stimuli to healthy native Japanese subjects. Fourier analysis revealed that Kanji and Kana stimuli were characterized by HSF and LSF information, respectively. When presented with either type of unfiltered stimulus (Kanji or Kana), the bilateral inferior temporal (IT, BA 37) regions were activated compared to the resting condition. Kana but not Kanji reading also activated the bilateral inferior parietal lobules (IPL, BA 40). When we compared Kanji and Kana reading directly, the left IT region was significantly activated by Kanji reading, while significant activation of the left IPL was observed during Kana reading. In response to filtered HSF stimuli, the Kanji reading minus Kana reading comparison revealed significant activation of the left IT region but not the left IPL. Conversely, significant activation of the left IPL but not the left IT region occurred in the Kana reading minus Kanji reading comparison for filtered LSF stimuli. These results suggest that Kanji and Kana engage a relatively overlapping network, within which the left IT is more involved in Kanji processing, while the left IPL contributes more to Kana processing. The preferential engagements of these brain regions could reflect the close links between Kana and LSF information, and between Kanji and HSF information. Therefore, this study provides further evidence that SF contributes to the dissociation between Kanji and Kana reading.

Activation in left primary visual cortex representing parafoveal visual field during reading Japanese texts.

Activation in the left primary visual cortex (V1) representing the parafoveal field during text reading has been interpreted as attentional modulation in the process of deciding saccadic target for reading ahead. Kanji words serve the main cue to decide the goal of saccades in Japanese. We aimed to determine the exact location of this modulation in the V1 and to determine whether the area of the modulation changes according to the location where the next Kanji word appears or it is fixed on a certain region in V1. Using functional magnetic resonance imaging, we determined the area in V1 representing each eccentricity on the horizontal meridian of the visual field for each participant. Then we investigated brain activation while they were reading two sets of Japanese texts that scrolled leftward as the participants. In set 1, the distance between the heads of adjacent Kanji words was about 3°. In set 2, the distance was about 5°. From the results of these experiments, we obtained activation amplitude of the area corresponding to each eccentricity. We recorded eye movements simultaneously with the acquisition of fMRI data. The maximum peak of the activation was found in the region representing about 4.5° of eccentricity on the horizontal meridian in the left V1 for each participant. The activation pattern did not essentially differ between the two text conditions, although the location of the saccades made for reading next section of the text corresponds to the head of the next Kanji word. The activation modulation during reading Japanese texts occurs in the parafoveal V1 of the left hemisphere. The attentional modulation did not change with the distance to the next goal of saccade but was fixed on the area representing about 4.5° of eccentricity.

Connectivity pattern changes in default-mode network with deep non-REM and REM sleep.

Recent studies have compared default-mode network (DMN) connectivity in different arousal levels to investigate the relationship between consciousness and DMN. The comparison between the DMN in rapid eye movement (REM) sleep with that in non-REM (NREM) sleep is useful for revealing the relationship between arousal level and DMN, because the arousal level is at its lowest during deep NREM, while during REM sleep it is as high as wakefulness. Functional magnetic resonance imaging (fMRI) and polysomnogram data were acquired from participants in REM, deep NREM, and light NREM sleep, and the DMN was compared using functional connectivity analysis. Our analysis revealed that functional connectivity among the DMN core regions - the posterior cingulate cortex, rostral anterior cingulate cortex, and inferior parietal lobule - remained consistent across sleep states. In contrast, connectivity involving the DMN subsystems of REM sleep differs from that of NREM sleep, and the change well accounts for the characteristics of REM sleep. Our results suggest that both the DMN core region and subsystems may not relate to the maintenance of arousal. The DMN core network and subsystems may respectively serve to integrate brain regions and perform function specific to each level of arousal.

Human brain activity time-locked to rapid eye movements during REM sleep.

To identify the neural substrate of rapid eye movements (REMs) during REM sleep in humans, we conducted simultaneous functional magnetic resonance imaging (fMRI) and polysomnographic recording during REM sleep. Event-related fMRI analysis time-locked to the occurrence of REMs revealed that the pontine tegmentum, ventroposterior thalamus, primary visual cortex, putamen and limbic areas (the anterior cingulate, parahippocampal gyrus and amygdala) were activated in association with REMs. A control experiment during which subjects made self-paced saccades in total darkness showed no activation in the visual cortex. The REM-related activation of the primary visual cortex without visual input from the retina provides neural evidence for the existence of human ponto-geniculo-occipital waves (PGO waves) and a link between REMs and dreaming. Furthermore, the time-course analysis of blood oxygenation level-dependent responses indicated that the activation of the pontine tegmentum, ventroposterior thalamus and primary visual cortex started before the occurrence of REMs. On the other hand, the activation of the putamen and limbic areas accompanied REMs. The activation of the parahippocampal gyrus and amygdala simultaneously with REMs suggests that REMs and/or their generating mechanism are not merely an epiphenomenon of PGO waves, but may be linked to the triggering activation of these areas.

Different modulation of medial superior temporal activity across saccades: a functional magnetic resonance imaging study.

Studies on saccadic eye movements in humans and animals reported decreased cortical activation accompanying saccades in visual motion sensitive area MT+/V5, implying that the region is the neural basis of saccadic suppression. This, however, conflicts with findings that MT+/V5 is activated by saccades. As MT+/V5 can be subdivided into middle temporal (MT) and medial superior temporal (MST), these regions may have distinct functional roles that cause the discrepancy. To test this hypothesis, we compared the activation of MT with that of MST during exploratory saccades and visually guided saccades. MST was activated only during visually guided saccades, whereas MT was not activated by either. These findings support our hypothesis and suggest that the activity of these regions is differentially modulated depending on extraretinal information.