High-resolution EEG source localization in personalized segmentation-free head model with multi-dipole fitting.

Objective. Electroencephalograms (EEGs) are often used to monitor brain activity. Several source localization methods have been proposed to estimate the location of brain activity corresponding to EEG readings. However, only a few studies evaluated source localization accuracy from measured EEG using personalized head models in a millimeter resolution. In this study, based on a volume conductor analysis of a high-resolution personalized human head model constructed from magnetic resonance images, a finite difference method was used to solve the forward problem and to reconstruct the field distribution.Approach. We used a personalized segmentation-free head model developed using machine learning techniques, in which the abrupt change of electrical conductivity occurred at the tissue interface is suppressed. Using this model, a smooth field distribution was obtained to address the forward problem. Next, multi-dipole fitting was conducted using EEG measurements for each subject (N= 10 male subjects, age: 22.5 ± 0.5), and the source location and electric field distribution were estimated.Main results.For measured somatosensory evoked potential for electrostimulation to the wrist, a multi-dipole model with lead field matrix computed with the volume conductor model was found to be superior than a single dipole model when using personalized segmentation-free models (6/10). The correlation coefficient between measured and estimated scalp potentials was 0.89 for segmentation-free head models and 0.71 for conventional segmented models. The proposed method is straightforward model development and comparable localization difference of the maximum electric field from the target wrist reported using fMR (i.e. 16.4 ± 5.2 mm) in previous study. For comparison, DUNEuro based on sLORETA was (EEG: 17.0 ± 4.0 mm). In addition, somatosensory evoked magnetic fields obtained by Magnetoencephalography was 25.3 ± 8.5 mm using three-layer sphere and sLORETA.Significance. For measured EEG signals, our procedures using personalized head models demonstrated that effective localization of the somatosensory cortex, which is located in a non-shallower cortex region. This method may be potentially applied for imaging brain activity located in other non-shallow regions.

Distillation of Regional Activity Reveals Hidden Content of Neural Information in Visual Processing.

Multivoxel pattern analysis (MVPA) has become a standard tool for decoding mental states from brain activity patterns. Recent studies have demonstrated that MVPA can be applied to decode activity patterns of a certain region from those of the other regions. By applying a similar region-to-region decoding technique, we examined whether the information represented in the visual areas can be explained by those represented in the other visual areas. We first predicted the brain activity patterns of an area on the visual pathway from the others, then subtracted the predicted patterns from their originals. Subsequently, the visual features were derived from these residuals. During the visual perception task, the elimination of the top-down signals enhanced the simple visual features represented in the early visual cortices. By contrast, the elimination of the bottom-up signals enhanced the complex visual features represented in the higher visual cortices. The directions of such modulation effects varied across visual perception/imagery tasks, indicating that the information flow across the visual cortices is dynamically altered, reflecting the contents of visual processing. These results demonstrated that the distillation approach is a useful tool to estimate the hidden content of information conveyed across brain regions.

Cognitive control affects motor learning through local variations in GABA within the primary motor cortex.

The primary motor cortex (M1) is crucial for motor learning; however, its interaction with other brain areas during motor learning remains unclear. We hypothesized that the fronto-parietal execution network (FPN) provides learning-related information critical for the flexible cognitive control that is required for practice. We assessed network-level changes during sequential finger tapping learning under speed pressure by combining magnetic resonance spectroscopy and task and resting-state functional magnetic resonance imaging. There was a motor learning-related increase in preparatory activity in the fronto-parietal regions, including the right M1, overlapping the FPN and sensorimotor network (SMN). Learning-related increases in M1-seeded functional connectivity with the FPN, but not the SMN, were associated with decreased GABA/glutamate ratio in the M1, which were more prominent in the parietal than the frontal region. A decrease in the GABA/glutamate ratio in the right M1 was positively correlated with improvements in task performance (p = 0.042). Our findings indicate that motor learning driven by cognitive control is associated with local variations in the GABA/glutamate ratio in the M1 that reflects remote connectivity with the FPN, representing network-level motor sequence learning formations.

Brain networks of social action-outcome contingency: The role of the ventral striatum in integrating signals from the sensory cortex and medial prefrontal cortex.

Social interactions can be facilitated by action-outcome contingency, in which self-actions result in relevant responses from others. Research has indicated that the striatal reward system plays a role in generating action-outcome contingency signals. However, the neural mechanisms wherein signals regarding self-action and others' responses are integrated to generate the contingency signal remain poorly understood. We conducted a functional MRI study to test the hypothesis that brain activity representing the self modulates connectivity between the striatal reward system and sensory regions involved in the processing of others' responses. We employed a contingency task in which participants made the listener laugh by telling jokes. Participants reported more pleasure when greater laughter followed their own jokes than those of another. Self-relevant listener's responses produced stronger activation in the medial prefrontal cortex (mPFC). Laughter was associated with activity in the auditory cortex. The ventral striatum exhibited stronger activation when participants made listeners laugh than when another did. In physio-physiological interaction analyses, the ventral striatum showed interaction effects for signals extracted from the mPFC and auditory cortex. These results support the hypothesis that the mPFC, which is implicated in self-related processing, gates sensory input associated with others' responses during value processing in the ventral striatum.

Abacus in the brain: a longitudinal functional MRI study of a skilled abacus user with a right hemispheric lesion.

The abacus, a traditional physical calculation device, is still widely used in Asian countries. Previous behavioral work has shown that skilled abacus users perform rapid and precise mental arithmetic by manipulating a mental representation of an abacus, which is based on visual imagery. However, its neurophysiological basis remains unclear. Here, we report the case of a patient who was a good abacus user, but transiently lost her "mental abacus" and superior arithmetic performance after a stroke owing to a right hemispheric lesion including the dorsal premotor cortex (PMd) and inferior parietal lobule (IPL). Functional magnetic resonance imaging experiments were conducted 6 and 13 months after her stroke. In the mental calculation task, her brain activity was shifted from the language-related areas, including Broca's area and the left dorsolateral prefrontal and IPLs, to the visuospatial-related brain areas including the left superior parietal lobule (SPL), according to the recovery of her arithmetic abilities. In the digit memory task, activities in the bilateral SPL, and right visual association cortex were also observed after recovery. The shift of brain activities was consistent with her subjective report that she was able to shift the calculation strategy from linguistic to visuospatial as her mental abacus became stable again. In a behavioral experiment using an interference paradigm, a visual presentation of an abacus picture, but not a human face picture, interfered with the performance of her digit memory, confirming her use of the mental abacus after recovery. This is the first case report on the impairment of the mental abacus by a brain lesion and on recovery-related brain activity. We named this rare case "abacus-based acalculia." Together with previous neuroimaging studies, the present result suggests an important role for the PMd and parietal cortex in the superior arithmetic ability of abacus users.

Movement initiation-locked activity of the anterior putamen predicts future movement instability in periodic bimanual movement.

In periodic bimanual movements, anti-phase-coordinated patterns often change into in-phase patterns suddenly and involuntarily. Because behavior in the initial period of a sequence of cycles often does not show any obvious errors, it is difficult to predict subsequent movement errors in the later period of the cyclical sequence. Here, we evaluated performance in the later period of the cyclical sequence of bimanual periodic movements using human brain activity measured with functional magnetic resonance imaging as well as using initial movement features. Eighteen subjects performed a 30 s bimanual finger-tapping task. We calculated differences in initiation-locked transient brain activity between antiphase and in-phase tapping conditions. Correlation analysis revealed that the difference in the anterior putamen activity during antiphase compared within-phase tapping conditions was strongly correlated with future instability as measured by the mean absolute deviation of the left-hand intertap interval during antiphase movements relative to in-phase movements (r = 0.81). Among the initial movement features we measured, only the number of taps to establish the antiphase movement pattern exhibited a significant correlation. However, the correlation efficient of 0.60 was not high enough to predict the characteristics of subsequent movement. There was no significant correlation between putamen activity and initial movement features. It is likely that initiating unskilled difficult movements requires increased anterior putamen activity, and this activity increase may facilitate the initiation of movement via the basal ganglia-thalamocortical circuit. Our results suggest that initiation-locked transient activity of the anterior putamen can be used to predict future motor performance.

Single session of transcranial direct current stimulation transiently increases knee extensor force in patients with hemiparetic stroke.

BACKGROUND: Transcranial direct current stimulation (tDCS) of the motor cortex can enhance the performance of a paretic upper extremity after stroke. Reported effects on lower limb (LL) function are sparse. OBJECTIVE: The authors examined whether tDCS can increase the force production of the paretic quadriceps. METHODS: In this double-blind, crossover, sham-controlled experimental design, 8 participants with chronic subcortical stroke performed knee extension using their hemiparetic leg before, during, and after anodal or sham tDCS of the LL motor cortex representation in the affected hemisphere. Affected hand-grip force was also recorded. RESULTS: The maximal knee-extension force increased by 21 N (13.2%, P < .01) during anodal tDCS compared with baseline and sham stimulation. The increase persisted less than 30 minutes. Maximal hand-grip force did not change. CONCLUSIONS: Anodal tDCS transiently enhanced knee extensor strength. The modest increase was specific to the LL. Thus, tDCS might augment the rehabilitation of stroke patients when combined with lower extremity strengthening or functional training.

Transient neural activation in human amygdala involved in aversive conditioning of face and voice.

Elucidating the neural mechanisms involved in aversive conditioning helps find effective treatments for psychiatric disorders such as anxiety disorder and phobia. Previous studies using fMRI and human subjects have reported that the amygdala plays a role in this phenomenon. However, the noxious stimuli that were used as unconditioned stimuli in previous studies (e.g., electric shock) might have been ecologically invalid because we seldom encounter such stimuli in daily life. Therefore, we investigated whether a face stimulus could be conditioned by using a voice that had negative emotional valence and was collected from a real-life environment. A skin conductance response showed that healthy subjects were conditioned by using these stimuli. In an fMRI study, there was greater amygdala activation in response to the faces that had been paired with the voice than to those that had not. The right amygdala showed transient activity in the early stage of acquisition. A psychophysiological interaction analysis indicated that the subcortical pathway from the medial geniculate body to the amygdala played a role in conditioning. Modulation of the subcortical pathway by voice stimuli preceded the transient activity in the amygdala. The finding that an ecologically valid stimulus elicited the conditioning and amygdala response suggests that our brain is automatically processing unpleasant stimuli in daily life.

Listening to rhythms activates motor and premotor cortices.

We used functional magnetic resonance imaging (fMRI) to identify brain areas involved in auditory rhythm perception. Participants listened to three rhythm sequences that varied in temporal predictability. The most predictable sequence was an isochronous rhythm sequence of a single interval (ISO). The other two sequences had nine intervals with unequal durations. One of these had interval durations of integer ratios relative to the shortest interval (METRIC). The other had interval durations of non-integer ratios relative to the shortest interval (NON-METRIC), and was thus perceptually more complex than the other two. In addition, we presented unpredictable sequences with randomly distributed intervals (RAN). We tested two hypotheses. Firstly, that areas involved in motor timing control would also process the temporal predictability of sensory cues. Therefore, there was no active task included in the experiment that could influence the participant perception or induce motor preparation. We found that dorsal premotor cortex (PMD), SMA, preSMA, and lateral cerebellum were more active when participants listen to rhythm sequences compared to random sequences. The activity pattern in supplementary motor area (SMA) and preSMA suggested a modulation dependent on sequence predictability, strongly suggesting a role in temporal sensory prediction. Secondly, we hypothesized that the more complex the rhythm sequence, the more it would engage short-term memory processes of the prefrontal cortex. We found that the superior prefrontal cortex was more active when listening to METRIC and NON-METRIC compared to ISO. We argue that the complexity of rhythm sequences is an important factor in modulating activity in many of the rhythm areas. However, the difference in complexity of our stimuli should be regarded as continuous.

Cross-modal integration during vowel identification in audiovisual speech: a functional magnetic resonance imaging study.

To investigate the neural substrates of the perception of audiovisual speech, we conducted a functional magnetic resonance imaging study with 28 normal volunteers. We hypothesized that the constraint provided by visually-presented articulatory speech (mouth movements) would lessen the workload for speech identification if the two were concordant, but would increase the workload if the two were discordant. In auditory attention sessions, subjects were required to identify vowels based on auditory speech. Auditory vowel stimuli were presented with concordant or discordant visible articulation movements, unrelated lip movements, and without visual input. In visual attention sessions, subjects were required to identify vowels based on the visually-presented vowel articulation movements. The movements were presented with concordant or discordant uttered vowels and noise, and without sound. Irrespective of the attended modality, concordant conditions significantly shortened the reaction time, whereas discordant conditions lengthened the reaction time. Within the neural substrates that were commonly activated by auditory and visual tasks, the mid superior temporal sulcus showed greater activity for discordant stimuli than concordant stimuli. These findings suggest that the mid superior temporal sulcus plays an important role in the auditory-visual integration process underlying vowel identification.

Human brain activation in response to olfactory stimulation by intravenous administration of odorants.

To identify the BOLD effects related to olfaction in humans, we recorded functional magnetic resonance imaging (fMRI) scans in response intravenously instilled thiamine propyl disulfide (TPD) and thiamine tetrahydrofurfuryl disulfide monohydrochloride (TTFD). TPD and TTFD evoked a strong and weak odor sensation, respectively. Since we did not spray the odor stimuli directly, this method is expected to reduce the effect caused by direct stimulation of the trigeminal nerve. For the analysis of fMRI data, statistical parametric mapping (SPM2) was employed and the areas significantly activated during olfactory processing were located. Both strong and weak odorants induced brain activities mainly in the orbitofrontal gyrus (Brodmann's area: BA 11) in the left hemisphere. TPD (a strong odorant) induced activity in the subthalamic nucleus in the left hemisphere and the precentral gyrus (BA 6) and insula in the right hemisphere. TTFD (a weak odorant) induced activity in the superior frontal gyrus (BA 11) in the right hemisphere. In both circumstances, there was an increase in blood flow at the secondary olfactory cortex (SOC) but not the primary olfactory cortex (POC), probably due to a habituation effect in the POC. From the present results, we found brain activity in not only odor-specific regions but also regions whose levels of activity were changed by an intensity difference of odor stimuli.

Neural correlates of perceptual difference between itching and pain: a human fMRI study.

It has been wondered why we can discriminate between itching and pain as different sensations. Several researchers have investigated neural mechanisms underlying their perceptual differences, and found that some C fibers and spinothalamic tract neurons had different sensitivity between itching and pain. These findings suggest that such differences in ascending pathways are partly associated with perceptual difference between itching and pain. However, it was still unclear how our brains distinguish itching from pain. Thus, by functional magnetic resonance imaging (fMRI) time series analysis, we investigated the neural substrates of perceptual differences between itching and pain. The anterior cingulate cortex, the anterior insula, the basal ganglia and the pre-supplementary motor area were commonly activated by itching and pain. Neural activity in the posterior cingulate cortex (PCC) and the posterior insula associated with itching was significantly higher than that associated with pain and significantly proportional to itching sensation. Pain, but not itching, induced an activation of the thalamus for several minutes, and neural activity of this brain region significantly correlated to pain sensation. These findings demonstrate that the difference in the sensitivity of PCC, the posterior insula and the thalamus between itching and pain would be responsible for the perceptual difference between these sensations. The previous itching studies did not observe an activation of the secondary somatosensory cortex (S2) by itching. However, we observed that an activation of S2 by pain was not significantly different from that by itching, indicating that S2 was associated with not only pain but also itching.

Neural correlates of counting of sequential sensory and motor events in the human brain.

Little is known about the ability to enumerate small numbers of successive stimuli and movements. It is possible that there exist neural substrates that are consistently recruited both to count sensory stimuli from different modalities and for counting movements executed by different effectors. Here, we identify a network of areas that was involved in enumerating small numbers of auditory, visual, and somatosensory stimuli, and in enumerating sequential movements of hands and feet, in the bilateral premotor cortex, presupplementary motor area, posterior temporal cortex, and thalamus. The most significant consistent activation across sensory and motor counting conditions was found in the lateral premotor cortex. Lateral premotor activation was not dependent on movement preparation, stimulus presentation timing, or number word verbalization. Movement counting, but not sensory counting, activated the anterior parietal cortex. This anterior parietal area may correspond to an area recruited for movement counting identified by recent single-neuron studies in monkeys. These results suggest that overlapping but not identical networks of areas are involved in counting sequences of sensory stimuli and sequences of movements in the human brain.

Intracerebral pain processing in a Yoga Master who claims not to feel pain during meditation.

We recorded magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) following noxious laser stimulation in a Yoga Master who claims not to feel pain when meditating. As for background MEG activity, the power of alpha frequency bands peaking at around 10 Hz was much increased during meditation over occipital, parietal and temporal regions, when compared with the non-meditative state, which might mean the subject was very relaxed, though he did not fall asleep, during meditation. Primary pain-related cortical activities recorded from primary (SI) and secondary somatosensory cortices (SII) by MEG were very weak or absent during meditation. As for fMRI recording, there were remarkable changes in levels of activity in the thalamus, SII-insula (mainly the insula) and cingulate cortex between meditation and non-meditation. Activities in all three regions were increased during non-meditation, similar to results in normal subjects. In contrast, activities in all three regions were weaker during meditation, and the level was lower than the baseline in the thalamus. Recent neuroimaging and electrophysiological studies have clarified that the emotional aspect of pain perception mainly involves the insula and cingulate cortex. Though we cannot clearly explain this unusual condition in the Yoga Master, a change of multiple regions relating to pain perception could be responsible, since pain is a complex sensory and emotional experience.

Functionally segregated neural substrates for arbitrary audiovisual paired-association learning.

To clarify the neural substrates and their dynamics during crossmodal association learning, we conducted functional magnetic resonance imaging (MRI) during audiovisual paired-association learning of delayed matching-to-sample tasks. Thirty subjects were involved in the study; 15 performed an audiovisual paired-association learning task, and the remainder completed a control visuo-visual task. Each trial consisted of the successive presentation of a pair of stimuli. Subjects were asked to identify predefined audiovisual or visuo-visual pairs by trial and error. Feedback for each trial was given regardless of whether the response was correct or incorrect. During the delay period, several areas showed an increase in the MRI signal as learning proceeded: crossmodal activity increased in unimodal areas corresponding to visual or auditory areas, and polymodal responses increased in the occipitotemporal junction and parahippocampal gyrus. This pattern was not observed in the visuo-visual intramodal paired-association learning task, suggesting that crossmodal associations might be formed by binding unimodal sensory areas via polymodal regions. In both the audiovisual and visuo-visual tasks, the MRI signal in the superior temporal sulcus (STS) in response to the second stimulus and feedback peaked during the early phase of learning and then decreased, indicating that the STS might be key to the creation of paired associations, regardless of stimulus type. In contrast to the activity changes in the regions discussed above, there was constant activity in the frontoparietal circuit during the delay period in both tasks, implying that the neural substrates for the formation and storage of paired associates are distinct from working memory circuits.

Activation of the primary and association auditory cortex by the transition of sound intensity: a new method for functional examination of the auditory cortex in humans.

During functional MRI image acquisition, the scanning equipment generates substantial auditory noise, the effects of which are usually ignored. To investigate the neural activity in response to the transition of noise, we measured cerebral responses to short silent periods (1 and 5 s) during which the slice readout gradients were switched off. In all 15 normal volunteers, the 1 s silence bilaterally activated the primary and association auditory cortex. Subtraction of the response to the 1 s silent period from that to the 5 s silent period revealed the activation related to the onset (transition of sound from OFF to ON) event, indicating that the 1 s response is offset (transition of sound from ON to OFF) related. The complex response of the auditory cortex to the transition of the noise should be considered in designing functional MRI with auditory tasks.

Prospective comparison of 18F-FDG PET with conventional imaging modalities (MRI, CT, and 67Ga scintigraphy) in assessment of combined intraarterial chemotherapy and radiotherapy for head and neck carcinoma.

UNLABELLED: To preserve the oral organs and functions in patients with head and neck carcinoma, accurate determination of the appropriate treatment after neoadjuvant chemotherapy and radiotherapy is of critical importance. We evaluated the diagnostic accuracy of (18)F-FDG PET relative to that of other conventional imaging modalities in the assessment of therapeutic response after combined intraarterial chemotherapy and radiotherapy as an organ preservation protocol. METHODS: The study was prospectively performed on 23 consecutive patients with head and neck squamous cell carcinoma who completed the treatment regimen and underwent 2 (18)F-FDG PET studies before and after neoadjuvant chemoradiotherapy. (67)Ga scintigraphy (only before therapy) as well as MRI and CT (both before and after therapy) were also performed. All images were blindly and independently interpreted without knowledge of histologic findings. The level of confidence in image interpretation was graded by means of a 5-point rating system (0 = definitely no tumor to 4 = definite tumor). RESULTS: Before treatment, (18)F-FDG PET detected primary tumors in all 23 patients and was more sensitive (100%) than MRI (18/23; 78.3%), CT (15/22; 68.2%), and (67)Ga scintigraphy (8/20; 40%), with a confidence level of 3 or 4 as a positive tumor finding. After chemoradiotherapy, residual tumors were histologically confirmed in 4 patients (pathologic complete response rate, 19/23; 82.6%). Although posttreatment (18)F-FDG PET showed almost equal sensitivity (4/4; 100%) compared with MRI (3/3; 100%) or CT (3/4; 75%), its specificity (17/19; 89.5%) was superior to MRI (7/17, 41.2%) and to CT (10/17; 58.8%) for primary lesions. Regarding metastases to neck lymph nodes, only specificity for posttreatment images was calculated because no metastasis was confirmed in any patients after treatment. Six subjects had (18)F-FDG PET-positive lymph nodes, which had pathologically no tumor cells and suggested an inflammatory reactive change after therapy. Therefore, the specificity of posttreatment (18)F-FDG PET (17/23; 73.9%) was almost identical to that of MRI (17/20; 85%) and CT (16/21; 76.2%) for neck metastasis. With combined chemoradiotherapy monitored with (18)F-FDG PET, 8 patients avoided surgery and the remaining 15 patients underwent a reduced form of surgery. CONCLUSION: (18)F-FDG PET facilitates differentiation of residual tumors from treatment-related changes after chemoradiotherapy, which may be occasionally difficult to characterize by anatomic images. (18)F-FDG PET has a clinical impact for the management of patients with head and neck cancers after neoadjuvant chemoradiotherapy by optimizing surgical treatment for each patient and contributes to the improvement of the patient's quality of life.