Generators of visual evoked potentials for faces and eyes in the human brain as determined by dipole localization

Human visual evoked potentials were recorded during presentation of photos of human and animal faces and various face features. Negative waves with approximate peak latencies of 165 msec (N170) were bilaterally recorded from the occipito-temporal regions. Mean peak latencies of the N170 were shorter for faces than eyes only. Analyses of amplitudes of evoked potentials indicated that the N170 elicited by faces reflected activity of a specific neural system which was insensitive to detailed differences among individual faces regardless of species, and consequently suggest that this system might function to detect existence of faces in general. On the other hand, the mean amplitude of the N170 elicited by human eyes was significantly larger than those by animal eyes. These differences in response latencies and amplitudes of the N170 suggest existence of at least 2 different visual evoked potentials with similar latencies (i.e., N170) which are sensitive to faces in general and human eyes, respectively. Dipole source localization analysis indicated that dipoles for the N170 elicited by eyes were located in the posterior inferior temporal gyrus, and those for faces, located initially in the same region, but moved toward the fusiform and lingual gyri at the late phase of the N170. The results indicated that information processing of faces and eyes separated at least as early as the latency of the N170 at the posterior inferior temporal gyrus as well as the fusiform and lingual gyri, and might provide neurophysiological and anatomical bases to an initial structural encoding stage of human faces.     

Effects of Interleukin-12 on the Induction of Cytotoxic T Lymphocytes from the Regional Lymph Node Lymphocytes of Patients with Lung Adenocarcinoma

Lung cancer-specific cytotoxic T lymphocytes (CTL) were induced by repeated stimulations of regional lymph node lymphocytes (RLNL) in lung cancer patients with either autologous or HLA-A-locus-matched tumor cells. To investigate the effect of interleukin-12 (IL-12), IL-12 was added during the stimulation of RLNL from HLA A24 / adenocarcinoma patients with either autologous tumor cells or HLA A24-positive adenocarcinoma cells (PC-9) in combination with, or instead of interleukin-2 (IL-2), and then the cytotoxic activity, cytokine production and populations of the lymphocyte subsets were examined. The addition of IL-12, or the substitution of IL-2 by IL-12 was found to enhance the cytotoxic activity and the cytokine production (IFN-γ, GM-CSF) of the CTL as compared with IL-2 alone. The cytotoxic activity and cytokine production were both partially inhibited by anti-MHC-class I monoclonal antibody. The CTL thus induced by IL-12 had a higher proportion of CD3⁺/CD56⁺ cells than the CTL induced with IL-2 alone. The positively selected CD8⁺/CD56^– lymphocytes showed PC-9-specific cytotoxic activity, because the population did not show any cytotoxicity to K562 or A549 (HLA-A26/A30). However, the CD3⁺/CD56⁺ lymphocytes were cytotoxic to both PC-9 and K562. In conclusion, IL-12 is considered to be a useful cytokine for both the induction of lung-cancer specific CTL and the augmentation of non-MHC-restricted cytotoxicity against tumor cells, and may be applicable for adoptive immunotherapy using CTL.     

The Induction of Cytotoxic T Lymphocytes against HLA-A Locus-matched Lung Adenocarcinoma in Patients with Non-small Cell Lung Cancer

To induce cytotoxic T lymphocytes (CTL) against non-small cell lung cancer (NSCLC) efficiently, the induction of CTL was attempted using HLA-A locus-shared allogeneic NSCLC cells. T cells derived from either tumor tissue specimens or the regional lymph nodes of patients with NSCLC were stimulated twice or three times with an HLA-A2/A24-positive NSCLC cell line (PC-9), and thereafter the cytotoxic activity was examined by ⁵¹Cr-release assay. In patients with HLA-A24/ adenocarcinoma, anti-PC-9 cytotoxicity was induced in all 6 patients tested. Anti-PC-9 cytotoxicity was induced in 2 out of 5 patients with HLA-A2 (A24⁻)/adenocarcinoma, in 2 out of 4 patients with HLA-A24/squamous cell carcinoma, and 1 of 2 patients with HLA-A2/squamous cell carcinoma. The cytotoxic activity was observed to kill PC-9 selectively, not other NSCLC lines, and the activity was substantially blocked by anti-MHC class I antibody, but not by anti-MHC class II antibody. The PC-9-specific CTL produced γ-interferon in response to autologous tumor cells. These results indicated that the anti-PC-9 cytotoxicity was mediated by cytotoxic T lymphocytes that may recognize the T cell epitope(s) shared and presented by HLA-A2 and/or HLA-A24-positive NSCLC.     

Generation of autologous tumor-specific T cell clones from a patient with adenosquamous carcinoma of the lung

BACKGROUND: Adenosquamous carcinoma of the lung is not a common cancer, but its prognosis is worse than that of adenocarcinoma or squamous cell carcinoma. Therefore, new therapeutic strategies need to be developed to treat this type of lung cancer. Recently, vaccination using tumor antigens which are recognized by cytotoxic T lymphocytes (CTL) has been applied mainly to melanoma patients. We therefore attempted to establish T cell clones specific for autologous tumor cells (AT) from a patient with adenosquamous carcinoma in order to analyze the specific immune responses against AT. METHODS: A lung adenosquamous carcinoma cell line was established from a resected tumor obtained from a 72-year-old patient. Regional lymph node lymphocytes were stimulated weekly with CD80-transfected AT to induce CTL. The CTL activities were assessed by a standard (51)Cr release assay and by cytokine release. RESULTS: We succeeded in inducing an AT-specific CTL line. Using a limiting dilution method, eight T cell clones were established. AT-specific activity was observed in three CD8(+) T cell clones and one CD4(+) T cell clone out of the eight clones tested. Anti-HLA class I and anti-HLA-B/C mAbs inhibited IFN-gamma production from the AT-specific CD8(+) clones co-cultured with AT, thus indicating the restriction element to be HLA-B*5201 or HLA-Cw*1202. In contrast, the CD4(+) T cell clone recognized AT in an HLA class II-restricted manner. CONCLUSIONS: These results are the first demonstration of a successful induction of AT-specific T cell clones from a patient with lung adenosquamous carcinoma. It may therefore supply a possible way to apply specific immunotherapy to this type of lung cancer.     

Neuronal responses to a delayed-response delayed-reward go/nogo task in the monkey posterior insular cortex

Anatomical connections of the insular cortex suggest its involvement in cognition, emotion, memory, and behavioral manifestation. However, there have been few neurophysiological studies on the insular cortex in primates, in relation to such higher cognitive functions. In the present study, neural activity was recorded from the monkey insular cortex during performance of a delayed-response delayed-reward go/nogo task. In this task, visual stimuli indicating go or nogo responses associated with reward (reward trials) and with no reward (no-reward trials) were presented after eye fixation. In the reward trials, the monkey was required to release a button during presentation of the 2nd visual stimuli after a delay period (delay 1). Then, a juice reward was delivered after another delay (delay 2). The results indicated that the neurons responding in each epoch of the task were topographically localized within the insular cortex, consistent with the previous anatomical studies indicating topographical distributions of afferent inputs from other subcortical and cortical sensory areas. Furthermore, some insular neurons 1) nonspecifically responded to the visual cues and during fixation; 2) responded to the visual cues predicting reward and during the delay period before reward delivery; 3) responded differentially in go/nogo trials during the delay 2; and 4) responded around button manipulation. The observed patterns of insular-neuron responses and the correspondence of their topographical localization to those in previous anatomical studies suggest that the insular cortex is involved in attention- and reward-related functions and might monitor and integrate activities of other brain regions during cognition and behavioral manifestation.     

Induction of tumor-specific cytotoxic T lymphocytes from regional lymph node lymphocytes of human breast cancer

Background  In this study we activated breast cancer-specific cytotoxic T lymphocytes (CTL) from regional lymph node lymphocytes (RLNL) of HLA-A2-positive patients with breast cancer. Melthods  Freshly isolated RLNL were stimulated with solid phase anti-CD3 monoclonal antibody followed by expansion with recombinant interleukin-2. Subsequently, the RLNL were stimulated with an irradiated HLA 0201 breast cancer cell line, MCF-7, at a responder/stimulator ratio of 10/1 once a week for 2 weeks. Results  The cultured RLNL exhibited specific lysis against MCF-7 in all 5 HLA-A2-positive patients tested, but not in 2 HLA-A2-negative patients. Cytotoxicity against MCF-7 was substantially inhibited by addition of anti-HLA-A2 mAb. In 3 of 5 HLA-A2-positive patients, anti-MCF-7 CTL also exhibited a substantial level of reactivity against PC-9, an HLA-A0206-positive lung adenocarcinoma cell line. Conversely, anti-PC-9-specific CTL were inducible by multiple stimulations of RLNL with PC-9 cells in 2 of 3 patients. Conclusions  These results suggest that several common tumor antigens might exist among HLA-A2-positive breast cancers, some of which may be shared with lung adenocarcinomas.     

Response to motion in extrastriate area MSTl: disparity sensitivity

Many neurons in the lateral-ventral region of the medial superior temporal area (MSTl) have a clear center surround separation in their receptive fields. Either moving or stationary stimuli in the surround modulates the response to moving stimuli in the center, and this modulation could facilitate the perceptual segmentation of a moving object from its background. Another mechanism that could facilitate such segmentation would be sensitivity to binocular disparity in the center and surround regions of the receptive fields of these neurons. We therefore investigated the sensitivity of these MSTl neurons to disparity ranging from three degrees crossed disparity (near) to three degrees uncrossed disparity (far) applied to both the center and the surround regions. Many neurons showed clear disparity sensitivity to stimulus motion in the center of the receptive field. About (1)/(3) of 104 neurons had a clear peak in their response, whereas another (1)/(3) had broader tuning. Monocular stimulation abolished the tuning. The prevalence of cells broadly tuned to near and far disparity and the reversal of preferred directions at different disparities observed in MSTd were not found in MSTl. A stationary surround at zero disparity simply modulated up or down the response to moving stimuli at different disparities in the receptive field (RF) center but did not alter the disparity tuning curve. When the RF center motion was held at zero disparity and the disparity of the stationary surround was varied, some surround disparities produced greater modulation of MSTl neuron response than did others. Some neurons with different disparity preferences in center and surround responded best to the relative disparity differences between center and surround, whereas others were related to the absolute difference between center and surround. The combination of modulatory surrounds and the sensitivity to relative difference between center and surround disparity make these MSTl neurons particularly well suited for the segmentation of a moving object from the background.     

Neural correlates of stimulus-reward association in the rat mediodorsal thalamus

Neural activity was recorded from the mediodorsal thalamic nucleus of behaving rats during the discrimination of olfactory cues associated with or without a reward. Approximately 10% of mediodorsal thalamic neurons showed significant responses during the presentation of cues. Most of these neurons responded strongly to cues associated with a reward. These neurons also differentiated between cues, even in the same reinforcement (reward/nonreward) group. All of the neurons tested in extinction, relearning, and/or new-learning trials changed their responses flexibly according to the reward contingency. These neurons were located primarily in the central and medial segments of the mediodorsal thalamus. These results suggest that these mediodorsal thalamic neurons are the neural substrates for association learning of olfactory stimuli with rewards.     

Motivation-related neuronal activity in the object discrimination task in monkey septal nuclei

Septal nuclei are suggested to work as an interface between the hippocampal formation, involved in higher cognitive functions, and the hypothalamus, involved in motivational behaviors such as feeding, drinking, and intracranial self-stimulation. In the present study, to elucidate a role of the septal nuclei in motivational behaviors, single neuron activity was recorded from water- and food-deprived monkeys during discrimination of objects associated with juice, and during ingestion of juice. Of 349 neurons recorded from two monkeys, 67 responded in the ingestion phase of the object discrimination task. Of these 67 neurons, 31 were further tested with the noncontingent liquid (juice or water) test in which liquid was provided until the animals became satiated. These 31 septal neurons were classified into two groups: type I neurons (n = 10) responded to juice ingestion with inhibition, and type II neurons (n = 21) responded with excitation. The spontaneous firing rates of the type I neurons were higher in the deprived condition and decreased as the animal became satiated by intake of liquid. Nine type II neurons responded to the sight of a white object associated with juice as well as ingestion of juice. The response magnitudes of the type II neurons to both the sight of the white object and ingestion of juice also decreased by satiation. However, spontaneous firing rates of the type II neurons did not change. These activity changes of both type I and II neurons were well correlated with changes in motivational state of the monkey estimated by the behavioral test. The results suggest that the activity of type I neurons reflects thirst or hunger drive levels, and that responses of type II neurons are related to reward perception. These type I and II neurons were located mainly in the anterior part of the septal nuclei. Results of the present study suggest, along with previous lesion and anatomical studies, that the septal nuclei exert a powerful influence on the motivational/drive systems through the projection to the hypothalamus. Hippocampus 1997;7:536–548. © 1997 Wiley-Liss, Inc.