Effective connectivity maps in the swine somatosensory cortex estimated from electrocorticography and validated with intracortical local field potential measurements.

Macroscopic techniques are increasingly being used to estimate functional connectivity in the brain, which provides valuable information about brain networks. In any such endeavors it is important to understand capabilities and limitations of each technique through direct validation, which is often lacking. This study evaluated a multiple dipole source analysis technique based on electrocorticography (ECOG) data in estimating effective connectivity maps and validated the technique with intracortical local field potential (LFP) recordings. The study was carried out in an animal model (swine) with a large brain to avoid complications caused by spreading of the volume current. The evaluation was carried out for the cortical projections from the trigeminal nerve and corticocortical connectivity from the first rostrum area (R1) in the primary somatosensory cortex. Stimulation of the snout and layer IV of the R1 did not activate all projection areas in each animal, although whenever an area was activated in a given animal, its location was consistent with the intracortical LFP. The two types of connectivity maps based on ECOG analysis were consistent with each other and also with those estimated from the intracortical LFP, although there were small discrepancies. The discrepancies in mean latency based on ECOG and LFP were all very small and nonsignificant: snout stimulation, -1.1-2.0 msec (contralateral hemisphere) and 3.9-8.5 msec (ipsilateral hemisphere); R1 stimulation, -1.4-2.2 msec for the ipsilateral and 0.6-1.4 msec for the contralateral hemisphere. Dipole source analysis based on ECOG appears to be quite useful for estimating effective connectivity maps in the brain.

Attention induces reciprocal activity in the human somatosensory cortex enhancing relevant- and suppressing irrelevant inputs from fingers.

OBJECTIVE: We studied whether attention regulates information processing in the human primary somatosensory cortex (SI) by selective enhancement of relevant- and suppression of irrelevant information. METHODS: Under successive and simultaneous electric stimuli to both the right index and middle fingers, tactile stimuli were randomly (20%) presented on one of the two fingers in separate two runs exchanging the finger. Subjects were requested to discriminate the tactile stimuli in an attention task to induce attention to one finger and to ignore the stimuli in a control task to avoid such an attention focus. Somatosensory evoked magnetic fields were measured only for the two-finger electric stimulation and an early component (M50) was analyzed. RESULTS: In spite of the two-finger simultaneous stimulation, attention to either the index or middle finger lowered or heightened the M50-sourse location, respectively. The attention task did not increase the M50 amplitude. CONCLUSIONS: Attention to a finger enhanced selectively the representation of the finger in the SI cortex. However, this SI activity did not increase the M50 amplitude, suggesting that the attention suppressed another finger region receiving the unattended inputs. SIGNIFICANCE: Attention regulates the SI activity by selectively enhancing the task-relevant information and by filtering out other noise inputs.

Functional connectivity between forearm and digits representations in human somatosensory area 3b.

OBJECTIVE: We compared the effects of tactile interference to the forearm on magnetic responses evoked by electric stimulation of the little finger (D5) and the thumb (D1). METHODS: Electric stimulation was delivered to D5 or D1 individually. In each stimulus session, magnetic recordings were conducted with or without concurrent tactile interference to the radial side of the anterior forearm. RESULTS: With forearm interference, the amplitude of the primary response (N20m) following D5 stimulation was reduced to 90.7% of the control value without interference, while that following D1 stimulation was not affected (100.7%). CONCLUSIONS: In human somatosensory area 3b, the representation of the forearm is immediately adjacent to that of the D5, and distant from that of the D1. Thus, the result suggests that the tactile interference effect on N20m depends on the cortical distance between electrically and mechanically activated 3b areas. SIGNIFICANCE: Intrinsic synaptic connections between the 3b hand representation and its surroundings have been hypothesized as a neural basis for plastic changes of the human brain, such as a phantom hand phenomenon. The present finding implies that these connections may play some physiological roles even in normal adult humans.

Serial N20m dipoles in somatosensory evoked magnetic fields move along the distal-proximal representation of the digit area 3b of the human cortex.

We studied the relationship between the distal-proximal representation of the digit in area 3b and moving dipoles of the primary magnetic response (N20m). By the use of ring electrodes, a distal or proximal portion of the middle finger was stimulated to elicit N20m. The dipole locations were sequentially analyzed around the N20m peak. The dipole locations did not differ between distal and proximal stimulation before the N20m peak. After 0.4 ms post-N20m peak, however, the dipoles following proximal stimulation substantially and progressively shifted laterally to those following distal stimulation. The result suggests that the N20m dipole moves from the distal representation toward the proximal representation of the digits in area 3b.

Is there training-dependent reorganization of digit representations in area 3b of string players?

OBJECTIVE: The digit representations in area 3b were studied to examine whether there is training-dependent reorganization in string players. METHODS: Somatosensory evoked magnetic fields were recorded following electrical stimulation of digits 1 (D1), 2 (D2) and 5 (D5) of both hands in 8 string players and of the left hand in 12 control subjects. The N20m and P30m responses, and high-frequency oscillations (HFOs) were separated by 3-300 Hz and 300-900 Hz bandpass filtering. RESULTS: The dipole locations on the coronal plane and strengths of D1, D2 and D5, and D1-D5 cortical distance estimated at the peak of N20m or P30m did not differ between left and right hand in string players or between left hand in string players and controls. On the other hand, the dipole locations of D2 estimated from N20m and P30m and of D1 from N20m were significantly anterior, the D2-D5 distance from P30m longer, and the number of HFO peaks larger for D5 in string players than controls. CONCLUSIONS/SIGNIFICANCE: With strong mutual competition among the fingering digits, the scale of reorganization should be much smaller as compared with the competition-free denervation-induced reorganizations. Taken together, the training-dependent reorganization of somatosensory cortex in string players is manifest not only in the enlarged cortical representation but also in the enhanced HFOs presumably representing activity of the fast-spiking interneurons.

Spatiotemporal characteristics of hemodynamic changes in the human lateral prefrontal cortex during working memory tasks.

The prefrontal cortex (PFC) is widely believed to subserve mental manipulation and monitoring processes ascribed to the central executive (CE) of working memory (WM). We attempted to examine and localize the CE by functional imaging of the frontal cortex during tasks designed to require the CE. Using near-infrared spectroscopy, we studied the spatiotemporal dynamics of oxygenated hemoglobin (oxy-Hb), an indicator of changes in regional cerebral blood flow, in both sides of lateral PFC during WM intensive tasks. In most participants, increases in oxy-Hb were localized within one subdivison during performance of the n-back task, whereas oxy-Hb increased more diffusely during the random number generation (RNG) task. Activation of the ventrolateral PFC (VLPFC) was prominent in the n-back task; both sustained and transient dynamics were observed. Transient dynamics means that oxy-Hb first increases but then decreases to less than 50% of the peak value or below the baseline level before the end of the task. For the RNG task sustained activity was also observed in the dorsolateral PFC (DLPFC), especially in the right hemisphere. However, details of patterns of activation varied across participants: subdivisions commonly activated during performance of the two tasks were the bilateral VLPFCs, either side of the VLPFC, and either side of the DLPFC in 4, 2, and 4 of the 12 participants, respectively. The remaining 2 of the 12 participants had no regions commonly activated by these tasks. These results suggest that although the PFC is implicated in the CE, there is no stereotyped anatomical PFC substrate for the CE.

Effect of stimulus frequency on human cerebral hemodynamic responses to electric median nerve stimulation: a near-infrared spectroscopic study.

We examined the effect of stimulus frequency on optically recorded hemodynamic responses to electric median nerve stimulation. Electric stimuli were delivered to the right median nerve with an intensity of 90% of motor threshold. Four different stimulus frequencies (2, 5, 10, and 20 Hz) were administered in each subject. By means of a multi-channel near-infrared spectroscopic instrument, changes in concentration of oxygenated hemoglobin were continuously measured over the left scalp. After 20 Hz stimulation, we found two spatially and temporally distinct hemodynamic responses. One lasted beyond 60 s, and the center of this response was located over the secondary somatosensory area. The other had a transient duration starting immediately after the stimulus onset and was located in the primary somatosensory hand area. Both responses were linearly augmented as a function of the stimulus frequency. Since temporal activation patterns are different in two somatosensory areas, real-time optical monitoring is necessary in evaluation of hemodynamic responses to electric nerve stimulation.

Muscle afferent inputs from the hand activate human cerebellum sequentially through parallel and climbing fiber systems.

OBJECTIVE: Spatio-temporal response characteristics of the human cerebellum to median nerve stimulation (MNS) were studied with the use of a whole-head magnetoencephalographic (MEG) system covering the cerebellum and upper cervical spine. METHODS: Neuromagnetic responses from the cerebellum were recorded following electric stimulation of the right median nerve in 12 subjects. In 6 out of 12 subjects, the responses to the left median nerve and to the right index or middle finger stimulation were also recorded. RESULTS: The medial part of the cerebellum (spinocerebellum) was activated by MNS. In contrast, there were no responses from the cerebellum to the finger stimulation, suggesting that muscle afferent inputs are the source of cerebellar activation for MNS. The cerebellar responses consisted of 3 or 4 components of alternating polarity within 90 ms post-stimulus: the current direction for the first component was from the depth to the surface of the anterior lobe. CONCLUSIONS: From the timing and current direction, we speculate that the 4 components reflect, respectively, (1) excitatory postsynaptic potentials (EPSPs) of granule cells, (2) Purkinje cell EPSPs at the distal dendrites driven by parallel fibers, (3) Purkinje cell EPSPs at the soma and the proximal dendrites mediated by climbing fibers and (4) second Purkinje cell EPSPs at the distal dendrites driven by parallel fibers. SIGNIFICANCE: We first visualized serial activation of the human spinocerebellum following MNS noninvasively with MEG.

Tactile interference to the face affects magnetic responses elicited by electric thumb stimulation.

OBJECTIVE: We examined the effect of tactile interference to the face on somatosensory evoked magnetic fields (SEFs) following electric thumb stimulation. METHODS: SEFs were elicited by electric stimulation of the right thumb in a control and two interference conditions. In the interference conditions, continuous tactile stimuli were delivered to the skin surface over the right upper face or the right thumb. RESULTS: The face interference significantly attenuated N20m and enhanced P30m. The amplitudes of N20m in the face and thumb interference conditions were 90.3 and 70.3% of the value in the control condition, respectively, while those of P30m were 120.2 and 74.4%. CONCLUSIONS: In human somatosensory area 3b, the representation of the thumb is immediately adjacent to that of the face although the thumb and face are physically distant. We suggest, therefore, that the effect of tactile interference on N20m depends on a cortical distance between electrically and mechanically activated 3b areas, rather than a physical distance between the body parts to which these two stimuli were administered. Although it is unclear why the face interference specifically enhanced the P30m, it is suggested that the generating mechanism of the interference effect on P30m may be different from that on N20m. SIGNIFICANCE: The tactile interference effect on N20m does not depend on the physical distance between electrically and mechanically activated skin areas, but on the distance of the 3b cortex receiving these two inputs.

Acute cholecystitis and duodenitis associated with Churg-Strauss syndrome.

We describe a patient with acute cholecystitis and duodenitis associated with Churg-Strauss syndrome. A 36-year-old male, who had been healthy, had abdominal pain following high fever. He had marked hypereosinophilia of 17,000/mm3. Radiographs of the chest disclosed a transient infiltrated lesion in the left lower lung. Ultrasonographic and gastroendoscopic examinations revealed acute cholecystitis and duodenitis, respectively. Endoscopic retrograde cholangiopancreatography demonstrated a filling defect suspecting aberrant ascariasis in the common bile duct. The patient suddenly developed distally dominant mononeuritis multiplex, especially in the upper limbs. Muscle biopsy revealed vasculitis of intramuscular arteries with infiltration of eosinophils. These findings fulfilled the diagnostic criteria of Churg-Strauss syndrome. Corticosteroid dramatically resolved the abdominal symptoms. Cholecystectomy and removal of the foreign body were performed. Histological examinations revealed that necrosis of the gallbladder was caused by occlusion due to thrombosed arteries and that the foreign body in the common bile duct was an aggregate of necrotic epithelium of the bile duct wall surrounded by inflammatory cells. Although abdominal complaints rarely appeared as an initial symptom in the patients with Churg-Strauss syndrome, this syndrome should be taken into consideration for an accurate diagnosis when the patients with abdominal pain of unknown origin had eosinophilia, asthma, or allergic rhinitis.

Selective attention regulates spatial and intensity information processing in the human primary somatosensory cortex.

Attention-related cognitive processes in the primary somatosensory cortex (SI) were studied by measuring somatosensory evoked magnetic fields (SEFs). Twenty-one normal adult human subjects participated in this study for investigating effects of attention and stimulus intensity on cortical finger representation in the SI cortex. Electric stimuli at low and high intensity were delivered to the index or middle finger in finger discrimination and non-discrimination task. For the low intensity stimulation at 1.25 times sensory threshold, an early component (M50) showed clear segregation of the sources for the two fingers and an increase of the amplitude specific to the finger discrimination task. Such an attentional effect on the SI cortex was masked by the high intensity stimulation (2.5 times sensory threshold); the M50 source separation by the fingers was induced irrespective of the discrimination or non-discrimination task. The results suggest that a conscious regulation of stimulus intensity coding in the SI cortex underlies the attention-dependent enhancement of spatial finger information processing.

Contribution of primary somatosensory area 3b to somatic cognition: a neuromagnetic study.

Interference effects on somatic cognition were compared with those on primary magnetic N20m responses. During tactile interference to various sets of digits, sensory thresholds for electric middle finger stimulation were measured, and then N20m was elicited with the intensity 4 mA above the sensory threshold measured without interference. After the recording, subjective magnitudes for the test stimuli were reported. Modifications of N20m and above psychophysical measures were dependent on the distance between electrically and mechanically activated areas. The differential N20m attenuation is considered to be generated within the neural circuitry in area 3b consisting of mechanically and electrically activated pyramidal neurons. The result indicates that such circuitry plays a fundamental role in magnitude estimation of somatic stimuli.

Movement interference attenuates somatosensory high-frequency oscillations: contribution of local axon collaterals of 3b pyramidal neurons.

OBJECTIVES: We examined the effects of movement interference on high-frequency oscillations (HFOs) and N20m in 10 healthy subjects. METHODS: For the movement interference condition, somatosensory evoked magnetic fields (SEFs) following electric median nerve stimulation were recorded during voluntary movement of the digits. For the control condition, the SEFs were recorded without interference. The N20m and HFOs were separated by 3-300Hz and 300-900Hz bandpass filtering. Then, the peak-to-peak amplitudes were measured. RESULTS: Both interference/control amplitude ratios for the N20m and HFOs were smaller than 100%. In contrast, the HFO/N20m amplitude index, which was calculated by dividing the interference/control amplitude ratio for the HFOs with that for the N20m, was significantly greater in the movement interference condition than in the control condition. CONCLUSIONS: Although the overall amplitude of the HFOs was decreased by movement, enhancement of the HFOs by the movement was revealed by the HFO/N20m amplitude index. Thus, we suggest that the HFOs represent activity of the inhibitory interneurons excited by both thalamocortical afferent impulses and excitatory synaptic inputs from pyramidal neurons in area 3b through their local axon collaterals, thereby reflecting both feed-forward and feedback inhibitory effects onto the post-synaptic pyramidal neurons.

Neural mechanisms for generation of tactile interference effects on somatosensory evoked magnetic fields in humans.

OBJECTIVES: We examined modification of somatosensory evoked fields following electric middle finger stimulation with interference to the same and surrounding digits in 13 subjects. METHODS: During electric middle finger stimulation, concurrent tactile stimulation was applied to the middle finger, to the index and ring fingers, and to the thumb and the little finger, individually. RESULTS: The amplitudes of the N20m and the P30m were significantly reduced by the interference to the middle finger, and to the index and ring fingers. The former interference induced more prominent attenuation than the latter. The amplitudes of the P60m did not show significant changes by any kind of the interference. CONCLUSIONS: The N20m and the P30m were attenuated according to the cortical distance between electrically and mechanically activated 3b areas. Pyramidal neurons are interconnected by intrinsic horizontal collaterals, even if their representations are segregated. The activation of the intrinsic collaterals induces direct excitation and indirect inhibition (via inhibitory interneurons) to the target pyramidal neurons. The result indicates that the activation of the intrinsic collaterals inhibits, on balance, the postsynaptic pyramidal targets, thereby generating the attenuation of the N20m and P30m.