Dynamic activation of distinct cytoarchitectonic areas of the human SI cortex after median nerve stimulation.

MEG recordings visualized non-invasively a serial mediolateral activation of the human somatosensory 3b area followed by a stationary activation of area 1 after median nerve stimulation. Somatosensory evoked fields (SEFs) were recorded over the hand area contralateral to the right median nerve stimulation at the wrist in six normal subjects. A newly developed MEG vector beamformer technique applied to the SEFs revealed two distinct sources (areas 3b and 1) in the primary somatosensory cortex (SI) during the primary N20m-P22m response in all subjects. The first source was located in area 3b, which started to move sequentially toward mediolateral direction 0.7 ms prior to the peak of N20m and ended its movement 1.4 ms after the peak with a total distance of 11.2 mm. We speculate that the movement reflects a sequential mediolateral activation of the pyramidal cells in area 3b, which is mediated by horizontal connections running parallel to the cortical surface. The second source in area 1, located 5.6 mm medial and 4.2 mm posterior to the first source, was active 1.0 ms after the N20m peak. Then, the first source became inactive and the second source was dominant. In sharp contrast with the first source, the second source was stationary. The different behavior of these two components (moving vs stationary) indicates independent parallel inputs to area 3b and area 1 from the thalamus.

Specific somatosensory processing in somatosensory area 3b for human thumb: a neuromagnetic study.

OBJECTIVES: We examined the relation between somatosensory N20m primary responses and high-frequency oscillations (HFOs) after thumb and middle finger stimulation. METHODS: Somatosensory evoked fields (SEFs) from 12 subjects were measured following electric stimulation of the thumb and middle finger. SEFs were recorded with a wide bandpass (3-2000 Hz) and then N20m and HFOs were separated by subsequent 3-300 and 300-900 Hz bandpass filtering. RESULTS: The N20m peak-to-peak amplitude did not differ significantly between thumb and middle finger SEFs. In contrast, HFOs had a significantly larger number of peaks and were higher in the maximum amplitude and the total amplitude after thumb stimulation than after middle finger stimulation. CONCLUSIONS: Our present data demonstrate a different relation between N20m and HFOs after thumb and middle finger stimulation. In view of the fact that the human thumb has uniquely evolved functionally and morphologically, the somatosensory information from the thumb will be processed differently for a fine motor control. We speculate that HFOs are generated by inhibitory interneurons in layer 4 in area 3b. Thus, enhanced activity of interneurons reflected by high amplitude HFOs exerts stronger inhibition on downstream pyramidal cells in area 3b for thumb stimulation.

What and when: parallel and convergent processing in motor control.

Successful motor behavior requires making appropriate response (response selection) at the right time (timing adjustment). Earlier psychological studies have suggested that the response selection and timing adjustment processes are performed serially in separate stages. We tested this hypothesis using functional magnetic resonance imaging. The subjects performed a choice reaction time task in four conditions: two (on-line response selection required or not) by two (on-line timing adjustment required or not). We found that the neural correlates for the two processes were indeed separate: the anterior medial premotor cortex (presupplementary motor area) was selectively active in response selection, whereas the cerebellar posterior lobe was selectively active in timing adjustment. However, the functional separation was only partial in that the lateral premotor cortex and the intraparietal sulcus were active equally for response selection and timing adjustment. The lateral premotor cortex was most active when both processes were required, suggesting that it integrates the information on response selection and the information on timing adjustment; alternatively, it might contribute to the allocation of attentional resources during dual information processing. The intraparietal sulcus was equally active when either response selection or timing adjustment was required, suggesting that it modifies, rather than integrates, these processes. Furthermore, our results suggest that these activations related to response selection and timing adjustment were distinct from sensory or motor processes.

Human cerebellar activity reflecting an acquired internal model of a new tool.

Theories of motor control postulate that the brain uses internal models of the body to control movements accurately. Internal models are neural representations of how, for instance, the arm would respond to a neural command, given its current position and velocity. Previous studies have shown that the cerebellar cortex can acquire internal models through motor learning. Because the human cerebellum is involved in higher cognitive function as well as in motor control, we propose a coherent computational theory in which the phylogenetically newer part of the cerebellum similarly acquires internal models of objects in the external world. While human subjects learned to use a new tool (a computer mouse with a novel rotational transformation), cerebellar activity was measured by functional magnetic resonance imaging. As predicted by our theory, two types of activity were observed. One was spread over wide areas of the cerebellum and was precisely proportional to the error signal that guides the acquisition of internal models during learning. The other was confined to the area near the posterior superior fissure and remained even after learning, when the error levels had been equalized, thus probably reflecting an acquired internal model of the new tool.

Neural representation of a rhythm depends on its interval ratio.

Rhythm is determined solely by the relationship between the time intervals of a series of events. Psychological studies have proposed two types of rhythm representation depending on the interval ratio of the rhythm: metrical and nonmetrical representation for rhythms formed with small integer ratios and noninteger ratios, respectively. We used functional magnetic resonance imaging to test whether there are two neural representations of rhythm depending on the interval ratio. The subjects performed a short-term memory task for a seven-tone rhythm sequence, which was formed with 1:2:4, 1:2:3, or 1:2.5:3.5 ratios. The brain activities during the memory delay period were measured and compared with those during the retention of a control tone sequence, which had constant intertone intervals. The results showed two patterns of brain activations; the left premotor and parietal areas and right cerebellar anterior lobe were active for 1:2:4 and 1:2:3 rhythms, whereas the right prefrontal, premotor, and parietal areas together with the bilateral cerebellar posterior lobe were active for 1:2.5:3.5 rhythm. Analysis on individual subjects revealed that these activation patterns depended on the ratio of the rhythms that were produced by the subjects rather than the ratio of the presented rhythms, suggesting that the observed activations reflected the internal representation of rhythm. These results suggested that there are two neural representations for rhythm depending on the interval ratio, which correspond to metrical and nonmetrical representations.

Functional magnetic resonance imaging of neural activity related to orthographic, phonological, and lexico-semantic judgments of visually presented characters and words.

Functional magnetic resonance imaging was used to investigate neural activity during the judgment of visual stimuli in two groups of experiments using seven and five normal subjects. The subjects were given tasks designed differentially to involve orthographic (more generally, visual form), phonological, and lexico-semantic processes. These tasks included the judgments of whether a line was horizontal, whether a pseudocharacter or pseudocharacter string included a horizontal line, whether a Japanese katakana (phonogram) character or character string included a certain vowel, or whether a character string was meaningful (noun or verb) or meaningless. Neural activity related to the visual form process was commonly observed during judgments of both single real-characters and single pseudocharacters in lateral extrastriate visual cortex, the posterior ventral or medial occipito-temporal area, and the posterior inferior temporal area of both hemispheres. In contrast, left-lateralized activation was observed in the latter two areas during judgments of real- and pseudo-character strings. These results show that there is no katakana "word form center" whose activity is specific to real words. Activation related to the phonological process was observed, in Broca's area, the insula, the supramarginal gyrus, and the posterior superior temporal area, with greater activation in the left hemisphere. These activation foci for visual form and phonological processes of katakana also were reported for the English alphabet in previous studies. The present activation showed no additional areas for contrasts of noun judgment with other conditions and was similar between noun and verb judgment tasks, suggesting two possibilities: no strong semantic activation was produced, or the semantic process shared activation foci with the phonological process.

Localizing the site of magnetic brain stimulation by functional MRI.

In order to locate the site of action of transcranial magnetic stimulation (TMS) within the human motor cortices, we investigated how the optimal positions for evoking motor responses over the scalp corresponded to the hand and leg primary-motor areas. TMS was delivered with a figure-8 shaped coil over each point of a grid system constructed on the skull surface, each separated by 1 cm, to find the optimal site for obtaining motor-evoked potentials (MEPs) in the contralateral first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. Magnetic resonance imaging scans of the brain were taken for each subject with markers placed over these sites, the positions of which were projected onto the cortical region just beneath. On the other hand, cortical areas where blood flow increased during finger tapping or leg movements were identified on functional magnetic resonance images (fMRI), which should include the hand and leg primary-motor areas. The optimal location for eliciting MEPs in FDI, regardless of their latency, lay just above the bank of the precentral gyrus, which coincided with the activated region during finger tapping in fMRI studies. The direction of induced current preferentially eliciting MEPs with the shortest latency in each subject was nearly perpendicular to the course of the precentral gyrus at this position. The optimal site for evoking motor responses in TA was also located just above the activated area during leg movements identified within the anterior portion of the paracentral lobule. The results suggest that, for magnetic stimulation, activation occurs in the primary hand and leg motor area (Brodmann area 4), which is closest in distance to the optimal scalp position for evoking motor responses.

Separate cerebellar areas for motor control.

Cerebellar activation was measured using functional magnetic resonance imaging, while seven normal subjects tapped their fingers paced by tone sequences with or without tone omission. The cerebellar anterior lobe (Larsell's H IV-V) ipsilateral to the movement was activated to a similar degree irrespective of the presence or absence of the tone omission. In contrast, the lateral part of the bilateral posterior lobe (H VIIa) was significantly highly activated for the tone sequence with random omission, compared with either that without omission or that with regular omission. The result suggests that the H IV-V is involved in motor execution, while the lateral part of H VIIa is involved in on-line motor adjustment to unpredictable sensory stimuli.

Attention-regulated activity in human primary visual cortex.

Effects of attention to a local contour of a moving object on the activation of human primary visual cortex (area V1) were examined. Local cerebral oxygenation changes (an index of neuronal activity) in human area V1 were measured with functional magnetic resonance imaging (fMRI) in conditions including the following two: 1) when attention was selectively directed toward one side of a moving wedge (the attention condition) and 2) when the wedges were viewed passively (the passive condition). Activation in area V1 was found to be higher in the attention condition than in the passive condition. To our knowledge, this is the first finding that attention to motion activates as early as area V1. We suggest that attentional activation of area V1 is task dependent.

Transition of brain activation from frontal to parietal areas in visuomotor sequence learning.

We studied the neural correlates of visuomotor sequence learning using functional magnetic resonance imaging (fMRI). In the test condition, subjects learned, by trial and error, the correct order of pressing two buttons consecutively for 10 pairs of buttons (2 x 10 task); in the control condition, they pressed buttons in any order. Comparison between the test condition and the control condition revealed four brain areas specifically related to learning: the dorsolateral prefrontal cortex (DLPFC), the presupplementary motor area (pre-SMA), the precuneus, and the intraparietal sulcus (IPS). We found that the time course of activation during learning was different between these areas. To normalize the individual differences in the speed of learning, we classified the performance of each subject into three learning stages: early, intermediate, and advanced stages. Both the relative increase of signal intensity and the number of activated pixels within the four areas showed significant changes across the learning stages, with different time courses. The two frontal areas, DLPFC and pre-SMA, were activated in the earlier stages of learning, whereas the two parietal areas, precuneus and IPS, were activated in the later stages. Specifically, DLPFC, pre-SMA, precuneus, and IPS were most highly activated in the early stage, in both the early and intermediate stages, in the intermediate stage, and in both the intermediate and advanced stages, respectively. The results suggest that the acquisition of visuomotor sequences requires frontal activation, whereas the retrieval of visuomotor sequences requires parietal activation, which might reflect the transition from the declarative stage to the procedural stage.

Activation of human presupplementary motor area in learning of sequential procedures: a functional MRI study.

1. Using functional magnetic resonance imaging, we investigated the neural correlates of sequential procedural learning. During the test scans the subjects learned a new sequence (position or color) of button presses; during the control scans they pressed the buttons in any order. The comparison of the test and control scans was expected to reveal the neural activities related to learning, not sensory-motor processes. 2. We found that a localized area in what we regard to be the human homologue of the presupplementary motor area (pre-SMA) was particularly active for learning of new sequential procedures (either position or color sequences), not movements per se. 3. In contrast, the SMA proper (posterior to pre-SMA) was active for the performance of sequential movements, not learning. This was shown in another paradigm in which the subjects pressed the buttons in any order in the test scans and just watched the sequence in the control scans. 4. The learning-related pre-SMA region, which was consistent across different experiments in single subjects, was identified on only one side in each subject.

Evoked potentials during REM sleep reflect dreaming.

Polygraphic recordings were collected for 11 normal subjects during sleep and wakefulness in order to investigate characteristics of the rapid eye movement (REM) associated potentials. EEGs were averaged using 5 different triggering points: (1) saccade onset under the normal ambient illumination, (2) saccade onset in the total darkness, (3) onset of REMs during REM sleep, (4) flash during REM sleep, and (5) flash during stage 2 sleep. In the central area, positive potentials appeared with waking saccades under the normal ambient illumination (P240L) and REMs (P185R). The latency of P185R associated with REMs was significantly shorter than that of P240L associated with waking saccades. These findings suggest that P185R is evoked by PGO waves occurring just before the REM. A small positive potential appeared in the occipital area with waking saccade under the normal ambient illumination (P260L) and REMs in the total darkness (P250R). Conspicuous absence of these waves for waking saccades in the total darkness suggests that P250R accompanied with REMs reflects activities involved with the cognitive processes occurring when a subject scans a dream image during REM sleep.

Electrophysiological evidence for dreaming: human cerebral potentials associated with rapid eye movement during REM sleep.

In order to examine the relationship between rapid eye movement (REM) during REM sleep and dreaming, scalp EEGs (Fz, Cz, Pz and Oz) of 4 normal human subjects, time-locked to REM onset, to saccade onset toward fixation targets and to saccade onset in total darkness, were averaged. The results include the following: Three positive potentials were associated with REM: a sharp potential in the parieto-occipital area just before REM onset; a large, slow potential in the vertex area 140-180 msec after REM onset; and a potential in the occipital area 210-280 msec after REM onset. Three positive potentials, one being the so-called EM-antecedent potential and the others being the lambda response, were associated with the waking saccades toward targets: a sharp potential in the parieto-occipital area just before the saccade onset and two potentials in the occipital area with latencies of 140-150 and 260-310 msec from the saccade onset. Only the EM-antecedent potential appearing just before saccade onset was found in association with saccades in total darkness. The similarities between the 3 positive potentials during REM sleep and the lambda response during wakefulness, and the relationship between those potentials and dreaming, are discussed in terms of the neural processes occurring during REM sleep.