Hyperactive action monitoring during motor-initiation in conversion paralysis: an event-related potential study

Conversion paralysis (CP) is featured by a stress-induced tonic immobility. Although the neural correlates of this psychiatric condition remain largely unexplored, previous reports showed CP to be associated with anterior cingulate cortex (ACC) hyperactivity. We examined the ACC action monitoring function by recording event-related potentials (ERPs) when conversion patients (n = 6) with unilateral arm paresis made speeded responses with their affected and healthy arms on a flankers task. During this task, pre-response ACC action monitoring is reflected in the N2 ERP component, which is increased when incongruent stimuli lead to simultaneously activated competing response tendencies. The results showed that the N2 congruency effects were significantly increased for responses with affected hands compared to healthy hands. There were no such results for post-response monitoring. This study is the first to present electrophysiological correlates of action monitoring in CP and suggests ACC to be hyperactive when movements with affected arms are to be initiated.     

Non-target flanker effects on movement in a virtual action centred reference frame

Visual selective attention is thought to underly inhibitory control during pointing movements. Accounts of inhibitory control during pointing movements make differential predictions about movement deviations towards or away from highly salient non-target flankers based on their potential cortical activation and subsequent inhibition: (1) Tipper et al. (Vis Cogn 4:1–38, 1997) “response vector model” predicts movements away from highly salient flankers; (2) Welsh and Elliott’s (Q J Exp Psychol 57:1031–1057, 2004a and J Mot Behav 36:200–211, 2004b) “response activation model” predicts movements towards highly salient flankers early in the response, that is resolved by a race for inhibition. To eliminate the confounds of physical properties, such as obstacle avoidance and information cues of non-target objects, pointing was conducted in a virtual environment (graphical user interface). Participants were 14 skilled computer users who moved a computer cursor with a mouse to virtual targets. Analysis revealed non-target flankers significantly interfered with movement consistent with action centred selective attention, and reflecting a proximity-to-hand effect. Spatial analysis revealed evidence of highly salient flankers attracting movement, and less salient flankers repelling movement, supporting Welsh and Elliott’s response activation model. These effects were achieved in a virtual 2D environment where interference caused by the physical properties of objects was less cogent.     

ERP components on reaction errors and their functional significance: a tutorial

Some years ago we described a negative (Ne) and a later positive (Pe) deflection in the event-related brain potentials (ERPs) of incorrect choice reactions [Falkenstein, M., Hohnsbein, J., Hoormann, J., Blanke, L., 1990. In: Brunia, C.H.M., Gaillard, A.W.K., Kok, A. (Eds.), Psychophysiological Brain Research. Tilburg Univesity Press, Tilburg, pp. 192-195. Falkenstein, M., Hohnsbein, J., Hoormann, J., 1991. Electroencephalography and Clinical Neurophysiology, 78, 447-455]. Originally we assumed the Ne to represent a correlate of error detection in the sense of a mismatch signal when representations of the actual response and the required response are compared. This hypothesis was supported by the results of a variety of experiments from our own laboratory and that of Coles [Gehring, W. J., Goss, B., Coles, M.G.H., Meyer, D.E., Donchin, E., 1993. Psychological Science 4, 385-390. Bernstein, P.S., Scheffers, M.K., Coles, M.G.H., 1995. Journal of Experimental Psychology: Human Perception and Performance 21, 1312-1322. Scheffers, M.K., Coles, M. G.H., Bernstein, P., Gehring, W.J., Donchin, E., 1996. Psychophysiology 33, 42-54]. However, new data from our laboratory and that of Vidal et al. [Vidal, F., Hasbroucq, T., Bonnet, M., 1999. Biological Psychology, 2000] revealed a small negativity similar to the Ne also after correct responses. Since the above mentioned comparison process is also required after correct responses it is conceivable that the Ne reflects this comparison process itself rather than its outcome. As to the Pe, our results suggest that this is a further error-specific component, which is independent of the Ne, and hence associated with a later aspect of error processing or post-error processing. Our new results with different age groups argue against the hypotheses that the Pe reflects conscious error processing or the post-error adjustment of response strategies. Further research is necessary to specify the functional significance of the Pe.     

The major histocompatibility complex and genetic control of antibody response to synthetic antigens in chickens

The genetic association of the B-F/B-L region of the chicken major histocompatibility complex (MHC) with the antibody responses to the hapten 2,4-dinitrophenol (DNP) conjugated to human gamma globulin and to the synthetic antigens, GAT and (T,G)-A-L were investigated using five inbred lines of White Leghorn chickens. Two of the five inbred lines of chickens J1 and M1, were found to be high responders to DNP and (T,G)-A-L, whilst L1, M4 and N1 chickens were found to be relatively low responders to both antigens. Chickens from all five inbred lines were low responders to GAT. Matings between the inbred lines. J1, M1 and N(1), showed that the magnitude of the antibody response to (T,G)-A-L in backcross chickens was regulated by a dominant gene or set of genes linked to the MHC. High antibody responsiveness to (T,G)-A-L was inherited as a dominant trait linked to the B113 and the B15 MHC alleles of the J1 and M1 inbred lines respectively. The similarity of the anti-(T,G)-A-L responses in chickens from the three B113 homozygous inbred lines L1, M4 and N1, also suggests that control of this response was linked to the MHC. The magnitude of the antibody response to DNP in backcross chickens from matings between the inbred lines N1 and J1 or M1 was also found to be regulated by a gene or set of genes linked to the MHC. Again, high antibody responsiveness to DNP was inherited as a dominant trait linked to the B113 and the B15 MHC alleles of the J1 and M1 inbred lines respectively.     

Perceptual factors affecting age-related differences in focused attention: Performance and psychophysiological analyses

In this study, the impact of two perceptual factors, feature similarity and spacing, on age-related differences in performance and psychophysiological measures were investigated within a focused attention paradigm. Young and old subjects performed an Eriksen letter identification task, in which centrally presented targets were flanked by response-compatible or response-incompatible letters. In feature similarity conditions, targets and flankers had a low or high amount of feature overlap. In spacing conditions, flankers were presented at four different lateral positions from the target. In the condition with high feature overlap and shortest target-flanker distance, old subjects showed greater interference by incompatible flankers than young subjects. Feature similarity was of little influence on age-related differences. However, spacing turned out to be of critical importance. Age-related interference effects disappeared when the target-flanker distance increased. This appears to be due to a decrease in response competition.     

Anticipated action consequences as a nexus between action and perception: evidence from event-related potentials

We used high-density event-related potentials (ERP) in a modified flanker paradigm to study the role of anticipated action consequences in action planning and the role of anticipation in the perception of action consequences. Prior to the experiment, participants were trained to classify target letters in a four-alternative forced-choice task; another letter was presented as an effect following each response. After participants had thus acquired the response-effect contingencies, in the experiment effect letters were presented as flankers to target letters. Effect-compatible flankers were letters that were learned as effects of the correct response to the target; effect-incompatible ones were learned as effects of other responses; neutral flankers were never presented as action effects. To help distinguish early and late effects of flankers on target processing, flankers were presented either simultaneously with the target or after a delay. We found that effect-incompatible flankers resulted in longer, than other flankers, time between the onset of the response-locked lateralized readiness potential and the response, indicating extended motor processing. ERP evoked by the effect-incompatible flankers differed from those evoked by other flankers in early perceptual component P1 and in later frontal component P2 reflecting stimulus evaluation and conflict detection. These results show that anticipating action consequences involves brain systems ranging from perceptual to executive; anticipated action effects constitute a link between perception and action.     

Age-related differences in the timing of stimulus and response processes during visual selective attention: Performance and psychophysiological analyses

In this study, age-related differences in the selection of visual information were investigated. Two groups of younger and older subjects performed focused- and divided-attention (i.e., visual search) tasks. In the focused-attention task, centrally presented target letters could be flanked by compatible or incompatible noise letters. In the visual search task, targets could be cued or uncued, and target locations could be spatially compatible or incompatible with the responding hand. P3 latency, lateralized readiness potentials, the electromyogram, and reaction times were used to detect possible age-related differences in the timing of stimulus- and response-related processes during selective processing of information. In the focused-attention task, performance of older subjects showed greater interference by incompatible flankers than did that of younger subjects because of stronger response competition caused by partial activation of the incorrect response channel by the incompatible flankers. No evidence was found of specific age-related differences in the efficiency of visual search in a divided-attention task. Furthermore, in both tasks, younger subjects showed an earlier start of response execution (in the electromyogram) relative to the onset of response preparation (lateralized readiness potential) and a higher percentage of incorrect electromyographic activity than did older subjects.     

Induction of Cell-Mediated Immunity against Mycobacterium tuberculosis Using DNA Vaccines Encoding Cytotoxic and Helper T-Cell Epitopes of the 38-Kilodalton Protein

Cell-mediated immune responses are crucial in the protection against tuberculosis. In this study, we constructed DNA vaccines encoding cytotoxic T lymphocytes (CTL) and T helper cell (Th) epitopes of the 38-kDa lipoglycoprotein of Mycobacterium tuberculosis and analyzed and compared their immunogenicities with that of pXJ38, a DNA vaccine encoding the entire 38-kDa protein (X. Zhu, N. Venkataprasad, H. S. Thangaraj, M. Hill, M. Singh, J. Ivanyi, and H. M. Vordermeier, J. Immunol. 158:5921-5926, 1997). Plasmid DNAs encoding a CTL epitope, P3 (pP3), a Th epitope (vTh), or both the Th and the P3 epitopes (pThP3) were prepared and tested in C57BL6/J (H-2(b)) mice. Our results confirmed that DNA immunization with pXJ38 induces strong CD8(+) CTL and Th1 responses (high gamma interferon [IFN-gamma], low interleukin-4 [IL-4]). Coadministration of plasmid DNAs encoding a Th epitope with those encoding a CTL epitope (vTh+pP3) elicited both antigen-specific CD8(+) CTL and Th1 responses. High levels of IFN-gamma were secreted by spleen cells from all plasmid DNA-vaccinated mice after in vitro stimulation with the recombinant 38-kDa protein. Small or undetectable amounts of IL-4 were observed, which indicates the induction of a Th1-like response. Multiple-epitope vaccination by vTh+pP3 or pThP3 resulted in a broader Th1 response to peptide or epitopes than the single-epitope plasmid DNAs. Antigen-specific immunoglobulin G2a was only detected in sera from mice immunized with the plasmid pXJ38, and not in mice immunized with the epitope-based DNA vaccines. Thus, the absence of an antibody response after immunization with epitope plasmid DNAs and their ability to trigger only a specific cellular immune response may prove to be important advantages for a vaccine against tuberculosis.     

Impaired perception of facial emotions following bilateral damage to the anterior temporal lobe

Two patients (E.P. and G.T.) were previously described with damage to amygdala and anterior temporal cortex (S.B. Hamann et al., 1996). Both rated emotions in facial expressions normally (the rating task) when the data analysis followed a method that had revealed an impairment in the well-studied patient S.M. The present study reports findings for a 3rd patient (G.P.) with the rating task and reexamines the data for E.P. and G.T. All 3 patients were also given a labeling task in which they selected, from a list of 6 words, which word they thought best described the emotion expressed by a face. All 3 patients were unmistakably impaired on both tasks. However, the impairment exhibited by these patients is different from S.M.'s impairment. The difference may depend on the etiology (congenital vs. adult-onset lesion) or the site of the damage (relatively selective amygdala damage vs. damage to amygdala as well as anterior temporal cortex).     

T cell activation by anti-CD3 antibodies: function of Fc receptors on B cell blasts, but not resting B cells, and CD18 on the responding T cells

Mouse anti-human CD3 (T3) antibodies can induce T cell proliferation in the presence of Fc receptor (FcR)-bearing accessory cells. Depending on whether the particular antibody can interact with the FcR, it can be mitogenic or otherwise. Previously, some of us (Smith, K. G. C. et al., Eur. J. Immunol. 1986. 16:478) examined human T cell responses to the murine anti-CD3 antibody switch variants UCHT1 (IgG1) and UCHT1B (IgG2b). Using a novel xenogeneic system with mouse macrophages (M phi) and an anti-FcR antibody, 2.4G2, we obtained direct evidence for accessory function of FcR in these responses. However, mouse B cells which also possess FcR were not accessory cells. Here we show that resting B cells do not inhibit anti-CD3 responses in the presence of other accessory cells, and they do not synergize with them. They appear to be inert in these responses but this is not simply because of their radiosensitivity. In contrast, B cell blasts proved to be potent stimulators of responses with UCHT1, UCHT1B and OKT3 (IgG2a). All three responses were inhibited by 2.4G2, whereas we have shown previously that the OKT3 response with M phi was not, in keeping with the known specificities of B cell and M phi FcR. These findings are discussed in relation to the molecular cloning of FcR, and we consider the possibility that distinct FcR could be expressed on resting and activated B cells. A report that anti-CD18 (LFA-1) antibodies blocked the UCHT1 response with human monocytes raised the possibility that this molecule might also be involved in accessory function. However, we show that this inhibition is in fact at the level of the T cell, since anti-human, but not anti-mouse CD18 antibodies, inhibited proliferative responses and clustering with both human and mouse accessory cells. Our results demonstrate that the principal contribution of accessory cells to anti-CD3 responses may be the provision of an FcR, and that CD18 is most probably required at the level of the T cell.     

Transcranial magnetic stimulation of the primary motor cortex modulates response interference in a flanker task

In a typical flanker task, responses to a central target (“S” or “N”) are modulated by whether the flankers are compatible (“SSSSS”) or incompatible (“NNSNN”), with increased reaction times and decreased accuracy on incompatible trials. The role of the motor system in response interference under these conditions remains unclear, however. Here we show that transcranial magnetic stimulation (TMS) of the left primary motor cortex modulates the amount of flanker interference depending on the hand used for the response. Left motor TMS delivered at 200 ms after the onset of the array increased interference from incompatible flankers (“SSNSS”) when the target response was associated with the contralateral motor response (i.e. for “N” responses with the right hand), relative to when responses were to targets using the (left) hand ipsilateral to the site of TMS. Interestingly, under identical conditions, the degree of flanker interference was reduced when the TMS pulse was applied later in time. The analyses of the TMS-induced motor evoked potentials pointed to motor activity varying in the same conditions. We discuss the implications for understanding response interference and the role of the primary motor cortex in response selection.     

Enhanced error‐related negativity on flanker errors: Error expectancy or error significance?

The present study investigated whether the error-related negativity, an electrophysiological marker for performance monitoring, reflects (1) the expectancy of errors, or (2) the significance of errors for the current task goal. In the first case, a larger error-related negativity is predicted for less expected errors, whereas in the second case, a larger error-related negativity is predicted for errors with greater significance. To test these predictions, we varied flanker size in a flanker task. With large flankers, more errors occurred by executing the response associated with the flankers (flanker errors) leading to a greater expectancy of flanker errors. As revealed by a multinomial model, these additional flanker errors represented highly significant attention errors, leading to an increased error significance. The error-related negativity was larger for flanker errors with large flankers, which supports the error significance account.     

Social and emotional functions in three patients with medial frontal lobe damage including the anterior cingulate cortex

Introduction. The aim of this study was to explore social and emotional functions in patients with medial frontal damage including the anterior cingulate cortex (ACC).

Methods. Three patients with medial frontal lobe lesions primarily involving the ACC performed tasks on motivational decision making, emotional facial expression recognition, and social cognition, including theory of mind (ToM). Their performance on these tasks was compared with age and education matched healthy controls.

Results. Patient performance on the motivational decision making and social situations tasks did not differ from controls. Selective emotional facial expression recognition impairment for fear was evident in one patient with a unilateral right ACC lesion (patient 3). ToM impairment was present in only one patient with a bilateral ACC lesion (patient 2). In contrast, the two patients with unilateral right ACC lesions had intact ToM (patients 1 and 3).

Conclusions. These findings suggest that medial frontal lobe lesions primarily involving the ACC do not appear to critically disrupt motivational decision making or social situation processing. The ACC plays a role in processing particular types of emotion (fear). Bilateral ACC damage impairs ToM processing, but unilateral damage to the right ACC is not sufficient to disrupt ToM.     

Response selection in the human anterior cingulate cortex.

The anterior cingulate cortex (ACC) has been proposed as part of the brain's attentional control network, but the exact nature of its involvement in cognitive and motor operations is under debate. Assessing effects of human ACC damage directly addresses the problem of ACC function. We report that executive control processes of a patient with a focal right hemisphere anterior cingulate lesion were not compromised. However, her performance level depended on the response modality used. Under the same task requirements, she was impaired when giving manual responses, but not vocal responses. Thus, we provide neuropsychological evidence for functional specialization within the human ACC.     

Response activation impairments in schizophrenia: evidence from the lateralized readiness potential

Previous research has demonstrated deficits in preresponse motor activity in schizophrenia, as evidenced by a reduced lateralized readiness potential (LRP). The LRP deficit could be due to increased activation of the incorrect response (e.g., failure to suppress competition) or to reduced activation of the correct response (e.g., a low-level impairment in response preparation). To distinguish these possibilities, we asked whether the LRP impairment is increased under conditions of strong response competition. We manipulated the compatibility of stimulus-response mappings (Experiment 1) and the compatibility of the target with flankers (Experiment 2). In both experiments, the patient LRP was reduced as much under conditions of low response competition as under high competition. These results are incompatible with a failure of patients to suppress competition and are instead consistent with a deficit in activating the correct response.     

Contribution of intraperitoneal immunization to the local immune response in the respiratory tract of sheep

The contribution of gut-associated lymphoid tissue (GALT) to the local immune response in the respiratory mucosa of sheep has been investigated. Sheep were primed intraperitoneally (i.p.) with antigen in Freund's complete adjuvant, a procedure known to produce a large IgA-specific antibody-containing cell (ACC) response in intestinal lymph. ACC and their class specificity were then enumerated by double fluorochrome immunofluorescence in respiratory tissues after intratracheal (i.t.) antigen administration. This immunization procedure produced an enhanced IgA-specific ACC response in the upper respiratory tract mucosa compared with either i.t. or i.p. immunization alone and this was not reflected in the regional lymph nodes. Furthermore, chronic drainage of the intestinal efferent lymphatic duct for the duration of the immunization period abrogated the enhanced response in the respiratory mucosa. These data are consistent with the concept of an intermucosal cell circuit with respect to IgA cell precursors, and provide indirect evidence that IgA responses in the respiratory tract can be enhanced by harnessing the immune potential of GALT as a source of IgA precursors by appropriate immunization strategies.     

The immune response in the rat to Streptococcus pneumoniae type 3 and type 4 capsular polysaccharide. Detection by double immunocytochemical staining of antibody-containing cells in situ and ELISA.

Two different methods have been used to study immune responses in the rat to Streptococcus pneumoniae type 3 and type 4 capsular polysaccharides (PPS). First, for simultaneous detection of the specificity and isotype of anti-PPS antibody-containing cells (ACC) in cryostat sections of lymphoid tissue, a double immunocytochemical method was developed. This method is a combination of a three-step immunoperoxidase method to demonstrate specific anti-PPS ACC as bright red cells and a two-step immunophosphatase method to detect the isotype of ACC as blue cells. Double positive cells appear violet. Using this staining procedure, the detection of antigen was also possible. Second, to study the anti-PPS response in serum, an ELISA procedure was modified. In this ELISA, polyvinylchloride microtiter plates are coated directly with type-specific pneumococcal polysaccharide. After intraperitoneal (i.p.) immunization of rats with PPS-3 or PPS-4, both antigen (PPS) and specific ACC could be detected. Specific ACC were found in the spleen and mesenteric lymph nodes. In the spleen, the specific ACC were found in the red pulp, marginal zone, outer PALS, and follicles. Most of these ACC were IgM-positive and to a lesser extent IgG-positive and IgA-positive. However, specific ACC in mesenteric lymph nodes were predominantly of the IgA isotype, with only few IgM or IgG positive cells. The anti-PPS response in serum, as measured by the ELISA, consisted mainly of IgM antibodies with small amounts of IgG and IgA. Both methods were found to be valuable in studies of immune responses against bacterial polysaccharides.     

The aminoglycoside G418 suppresses muscarinic receptor-activated calcium release in stably transfected murine N1E-115 neuroblastoma cells

The aminoglycoside G418 inhibited the release of calcium (Ca²⁺) from internal stores coupled to muscarinic receptors in murine N1E-115 neuroblastoma cells carrying the aminoglycoside resistance gene neomycin phosphotransferase (NPT). No significant effect was observed on responses coupled to histamine or bradykinin receptors. Cells were transfected using the eukaryotic expression vector pHβAPr-1-neo and selected using G418. Two groups were differentiated either in the continued presence of G418 or in the absence of G418. Carbachol (1 mM), histamine (200 μM) and bradykinin (100 nM) were administered to cells for thirty seconds and changes in [Ca²⁺]_i were measured with fluorescence video microscopy of single cells loaded with the Ca²⁺ indicator fura-2. The effects of G418 on carbachol evoked Ca²⁺ release included a 73% reduction in the number of cells responding, a two fold increase in the time to reach half-maximal response, a 35% reduction of the peak [Ca²⁺]_i in response to agonist and an elevation of resting [Ca²⁺]_i from 99± 14 nM (mean ± S.E.M.) to 155 ± 27 nM. Acute application (20 min) of G418 to transfected cells differentiated without G418 also reduced the percentage of cells responding to carbachol. This effect was less pronounced in non-transfected parent cells. Thus, the mechanism might involve a metabolite of G418 produced in cells expressing NPT. These results indicate that G418 attenuates Ca²⁺ release coupled to muscarinic receptors.