Terminal Contingent Negative Variation Research Articles

Contingent negative variation for the periodicity of migraine attacks without aura.

Migraine is a primary neuropsychological disorder, although its etiology and pathogenesis are unknown. It has been reported that using contingent negative variation, the periodicity of migraine attacks is three days in adults. However, there is still a lack of relevant reports about the periodicity of migraine without aura in adults. Therefore, we investigated the changes of contingent negative variation in adults with migraine without aura from three to seven days after migraine attacks in order to provide the basis for exploring the circulation periodicity of migraine without aura. This prospective, observational study involved a group of 34 individuals with migraine without aura, who were screened during the three to seven days after a migraine attack without aura. A healthy group (31 individuals) was used as controls to assess the amplitudes of contingent negative variation and habituation of early contingent negative variation. Indices of the amplitudes included overall contingent negative variation, initial contingent negative variation, terminal contingent negative variation, and postoperative negative contingent variation. Differences between these indicators were analyzed. No significant difference was found between the patient and control groups for either the amplitudes of these measures of contingent negative variation or habituation of the early contingent negative variation for three to seven days after a migraine attack without aura (all P > 0.05). Thus, the study reported here found that the periodicity of migraine attacks without aura in adults is more than three days.

Executive control, ERP and pro-inflammatory activity in emotionally exhausted middle-aged employees. Comparison between subclinical burnout and mild to moderate depression

Burnout is a syndrome occurring mainly in individuals with long-term stressful work. The main complaints are emotional exhaustion and reduced performance. Burnout also largely overlaps with depression. Both are characterized by increased incidence of infections due to dysregulation of the immune system, overexpression of pro-inflammatory cytokines and cognitive deficits, particularly related to executive functions. To distinguish between burnout and depression already at the pre-clinical stage, the present double-blinded study compared immunological and cognitive parameters in seventy-six employees from emotionally demanding occupations who were post-hoc subdivided into two groups scoring low (EE−) and high (EE+) in emotional exhaustion and low (DE−) and high (DE+) in depression. Immunological parameters were measured from blood samples. Executive functions were studied by analyzing event-related brain potentials (ERPs) and performance during a task switching paradigm. Psychosocial job parameters were measured with standardized questionnaires.Burnout and mild to moderate depression largely overlapped. However, several subjects showed burnout without depressive symptoms. Higher levels of the pro-inflammatory cytokines IL-6 and IL-12 were correlated with burnout severity and depressive symptoms in male individuals. In the switch task a trend for lower performance in the EE+ vs. EE− group and no difference between DE+ and DE− groups were found. In the ERPs, however, differences were observed which distinguished between subclinical burnout and depression: the terminal contingent negative variation (CNV), indicating preparatory activity and the P3b, related to allocation of cognitive resources were generally reduced in EE+ vs. EE−, whereas no differences were found in the DE+ vs. DE− groups. The frontal P3a was selectively reduced in switch trials in the EE+ vs. EE− group and showed only a trend in DE+ vs. DE−, indicating impairment of executive control in subclinical burnout. Taken together, the results unveil specific immunological changes and declines in brain functions in employees with subclinical burnout that are not apparent in persons with moderate depression. Hence, the combination of immunological, behavioral and ERP methods renders a promising method for distinguishing both syndromes and for improving an early diagnosis of burnout before a clinical stage is reached.

Midbrain raphe hypoechogenicity in migraineurs: An indicator for the use of analgesics but not triptans.

Introduction The involvement of the serotonergic system of the brainstem raphe in the pathogenesis of migraine is discussed. Here we studied brainstem alterations in migraineurs using transcranial sonography and examined their relation to clinical features and self-medication. Methods We investigated 51 migraineurs (11 men, 40 women, mean age 29.7 ± 11.9 years) and 32 healthy individuals without history of headache or depressive disorder (eight men, 24 women, mean age 34.4 ± 13.0 years). Transcranial sonography was performed in an investigator-blinded fashion. Midbrain raphe echogenicity was quantified using digitized analysis. Migraine characteristics and the use of analgesics were evaluated by applying validated questionnaires. Eight migraineurs underwent neurophysiologic evaluation of contingent stimulus-related cortical potentials. Results Echo-reduced midbrain raphe was detected in 27 (53%) migraineurs, but only six (19%) control subjects (odds ratio = 4.87, p = 0.002). Lower raphe echogenicity correlated with both higher amplitude of terminal contingent negative variation (Spearman test, r = 0.76, p = 0.028) and higher use of analgesic drugs ( r = -0.45, p = 0.011), but not with use of triptans or with migraine frequency or severity (all p > 0.2). Compared to migraineurs without aura, migraineurs with aura had enlarged third ventricles (t-test, p = 0.014), while the lateral ventricle widths did not differ ( p = 0.62). Conclusions Midbrain raphe alteration is frequent in migraineurs and relates to self-medication behavior. This alteration may reflect the dysfunction of serotonergic raphe nuclei.

Deficient fear conditioning in psychopathy as a function of interpersonal and affective disturbances

The diminished fear reactivity is one of the most valid physiological findings in psychopathy research. In a fear conditioning paradigm, with faces as conditioned stimulus (CS) and electric shock as unconditioned stimulus (US), we investigated a sample of 14 high psychopathic violent offenders. Event related potentials, skin conductance responses (SCR) as well as subjective ratings of the CSs were collected. This study assessed to which extent the different facets of the psychopathy construct contribute to the fear conditioning deficits observed in psychopaths. Participants with high scores on the affective facet subscale of the Psychopathy Checklist-Revised (PCL-R) showed weaker conditioned fear responses and lower N100 amplitudes compared to low scorers. In contrast, high scorers on the affective facet rated the CS+ (paired) more negatively than low scorers regarding the CS− (unpaired). Regarding the P300, high scores on the interpersonal facet were associated with increased amplitudes to the CS+ compared to the CS−, while the opposed pattern was found for the antisocial facet. Both, the initial and terminal contingent negative variation indicated a divergent pattern: participants with pronounced interpersonal deficits, showed increased cortical negativity to the CS+ compared to the CS−, whereas a reversed CS+/CS− differentiation was found in offenders scoring high on the antisocial facet. The present study revealed that deficient fear conditioning in psychopathy was most pronounced in offenders with high scores on the affective facet. Event related potentials suggest that participants with distinct interpersonal deficits showed increased information processing, whereas the antisocial facet was linked to decreased attention and interest to the CS+. These data indicate that an approach to the facets of psychopathy can help to resolve ambiguous findings in psychopathy research and enables a more precise and useful description of this disorder.

Cortical Habituation Deficit in Tinnitus Sufferers: Contingent Negative Variation as an Indicator of Duration of the Disease

Cortical attention and habituation parameters are altered in patients suffering from tinnitus. The aim of the study was to quantify cortical attention and habituation parameters in tinnitus patients by recording the contingent negative variation (CNV) response and to correlate amplitudes of different CNV parameters with duration of disease. Twenty patients suffering from tinnitus (median: 44years) and twenty age- and sex-matched healthy controls (median: 41years) were tested by a CNV paradigm. We recorded overall CNV, initial CNV, and terminal CNV and calculated habituation slopes. All CNV parameters were Spearman-correlated with individual duration of disease. Highly significant between groups differences emerged in total (tinnitus: -8.4uV vs. controls: -3.8uV), initial (-11.2 vs. -6.0uV), and terminal CNV (-11.9 vs. -6.5uV) demonstrating higher negative amplitudes in tinnitus patients. Habituation differed in total and terminal CNV, indicating missing habituation in tinnitus patients. Overall CNV (ϱ=-.365) and initial CNV (ϱ=-.529) showed a medium Spearman correlation with duration of disease. We conclude that the correlation between duration of tinnitus and the initial CNV amplitudes indicates an altered state of cortical excitability that can also be observed in more negative CNV-amplitudes in tinnitus patients. We assume that this state indicates a chronicity process in tinnitus disease.

Locus of Psychological Control and Peculiarities of Event-Related EEG Potentials

In a group including 74 adults of both sexes, we examined interrelations between the locus of psychological control (diagnosed using the Rotter questionnaire) and parameters of event-related EEG potentials, ERPs, recorded in the course of performance of two behavioral test acts with a motor component. Task A corresponded to maximally fast pushing on the button after a signal with warning; the time of the sensorimotor reaction was measured. Task B included internal counting of a definite time interval limited by two pushings on the button. Under these conditions, we recorded the contingent negative variation (CNV), the P300 potential, and, in task B, the readiness potential (RP). EEG leads C3 and C4, according to the 10-20 system, were used. Internals (estimates by the questionnaire, 6 stens or higher) were characterized by higher amplitudes of the terminal CNV (CNV-T), integral CNV, and P300 in task A, by greater RP and CNV amplitudes in task B, and also by shorter reaction times and their smaller dispersion. It should be supposed that the corresponding peculiarities of the neurodynamic constitution of an individual are determined, to a considerable extent, by the specificity of organization and functioning of a few neurotransmitter (aminergic in particular) and neurohumoral systems.

Retrieval and emotional processing of traumatic memories in posttraumatic stress disorder: Peripheral and central correlates

Posttraumatic stress disorder (PTSD) is thought to be characterized by dysfunctional memory processes, i.e., the automatic re-experiencing of the traumatic event and the inability to consciously recall facts about the traumatic event, as well as altered emotional processing of trauma-relevant cues. The present study examined the cerebral mechanisms underlying the cued recall of trauma-specific memories and the emotional processing of the presented cues in 16 PTSD patients, 15 trauma-exposed subjects without PTSD and 16 healthy controls. Subjects received questions about their specific trauma as well as other disastrous and neutral events while the electroencephalogram and heart rate were measured. The PTSD patients showed no impairment in trauma-specific declarative memory compared to non-PTSD subjects but had some deficits in general declarative memory as assessed by the Wechsler Memory Scale-Revised. Compared to healthy control subjects, PTSD patients displayed increased P300 and late positive complex amplitudes to trauma-specific questions, indicating enhanced emotional processing of these cues. In line with their behavioral performance, both trauma-exposed groups showed decreased terminal contingent negative variation amplitudes to trauma-specific questions over frontal electrodes reflecting altered memory retrieval. Within-group comparisons revealed that only the PTSD group but not the other groups showed a differentiation between trauma-specific and neutral questions with respect to the LPC, tCNV and P300. Concordantly with previous studies, PTSD patients showed elevated resting heart rate compared to the healthy controls. These findings are discussed in the context of current models of the role of declarative memory in the development and maintenance of PTSD.

Aversive Pavlovian conditioning in psychopaths: Peripheral and central correlates

Differential aversive Pavlovian conditioning with a foul odor as unconditioned stimulus (US) and neutral faces as conditioned stimuli (CS) was compared between 9 noncriminal psychopaths as defined by the Hare Psychopathy Checklist Revised and 12 healthy controls. Event-related potentials (ERP), heart rate, skin conductance response, corrugator EMG, and startle response potentiation as well as valence, arousal, and contingency of the CS were assessed. Whereas the healthy controls (HC) showed significant CS +/CS- differentiation, the psychopaths (PP) failed to exhibit a conditioned response although unconditioned responses were comparable between the groups. N100, P200, and P300 to the CSs revealed that psychopaths were not deficient in information processing and showed even better anticipatory responding than the HC group indicated by the terminal contingent negative variation (tCNV), that lacked, however, CS+ and CS- differentiation. These data indicate a deficit in association formation in psychopaths that may be related to deficient interaction of limbic-subcortical and cortical structures.

Comparative Distribution of the Cortical Generators of the Readiness Potential and the Terminal Contingent Negative Variation in Human Subjects

Comparative Distribution of the Cortical Generators of the Readiness Potential and the Terminal Contingent Negative Variation in Human Subjects

The effects of risperidone on memory function in schizophrenia

Posttraumatic stress disorder (PTSD) is thought to be characterized by dysfunctional memory processes, i.e., the automatic re-experiencing of the traumatic event and the inability to consciously recall facts about the traumatic event, as well as altered emotional processing of trauma-relevant cues.The present study examined the cerebral mechanisms underlying the cued recall of trauma-specific memories and the emotional processing of the presented cues in 16 PTSD patients, 15 trauma-exposed subjects without PTSD and 16 healthy controls. Subjects received questions about their specific trauma as well as other disastrous and neutral events while the electroencephalogram and heart rate were measured. The PTSD patients showed no impairment in trauma-specific declarative memory compared to non-PTSD subjects but had some deficits in general declarative memory as assessed by the Wechsler Memory Scale-Revised. Compared to healthy control subjects, PTSD patients displayed increased P300 and late positive complex amplitudes to trauma-specific questions, indicating enhanced emotional processing of these cues. In line with their behavioral performance, both trauma-exposed groups showed decreased terminal contingent negative variation amplitudes to trauma-specific questions over frontal electrodes reflecting altered memory retrieval. Within-group comparisons revealed that only the PTSD group but not the other groups showed a differentiation between trauma-specific and neutral questions with respect to the LPC, tCNV and P300. Concordantly with previous studies, PTSD patients showed elevated resting heart rate compared to the healthy controls. These findings are discussed in the context of current models of the role of declarative memory in the development and maintenance of PTSD.

Slow potentials, event-related potentials, "gamma-band" activity, and motor responses during aversive conditioning in humans.

We examined slow potentials, transient event-related potentials, and oscillatory-like responses in the electroencephalogram during aversive conditioning in humans, in order to determine what is happening in the neocortex when behavioral adaptations are learned. Pictures of an angry and a happy human face served as reinforced (CS+) and unreinforced (CS-) conditioned stimuli, respectively, in one group, and either the reversed condition or two discriminably different neutral faces in two other groups (total n = 48 subjects). The unconditioned stimulus (US) was intracutaneous shock delivered to the left hand 5 s after CS+ onset. The electroencephalographic (EEG) activity was recorded from Fz, Cz, Pz, C3, and C4, electromyographic (EMG) activity from bilateral forearm and corrugator muscles, and skin conductance from the right hand. During acquisition a negative slow potential developed after CS+ (not CS-), which was more pronounced when a neutral face served as CS+. Early (iCNV, initial contingent negative variation) and late (tCNV, terminal contingent negative variation) components of the slow-potential response were positively related to the magnitude of conditioned EMG responses. Differentiation of tCNV was larger when neutral faces signaled the US; iCNV persisted during extinction when a happy face served as CS+. Late-occurring event-related potentials (ERPs) elicited by the US diminished over conditioning, whereas short-latency US components and ERPs elicited by CS events did not. Fourier analysis revealed oscillatory ("gamma-band") activity between 30 and 40 Hz, which persisted up to 3 s after US delivery and diminished as conditioning progressed. Our findings indicate that learning is expressed in neocortical structures at the earliest stages of conditioning. The functional roles of the three types of EEG response in learning are discussed.

CNV, PINV and probe-evoked potentials in schizophrenics

Distractibility and temporal modulation of attention in schizophrenics were studied using a visual reaction time task with additional auditory probe stimuli during the forewarning period or between trials. The probes were thought to exert a distracting influence, especially on schizophrenics, and at the same time they generated auditory EPs which allowed to track the modulation of cortical excitability during response preparation. The midline distribution of the terminal contingent negative variation (tCNV) and the amplitude of the postimperative negative variation (PINV) were clearly different in 20 DSM III-R schizophrenics, as compared with 20 alcoholics and 20 normal controls. In schizophrenics, the more frontal distribution of the tCNV was associated with a higher degree of psychopathology (measured with the Brief Psychiatric Rating Scale) and with delayed reactions. Probes between trials reduced tCNV and PINV in all subjects alike. However, this effect could not be attributed to distraction, because reaction times were faster in these trials, possibly due to an alerting effect of the auditory probes. The N100 and P300 amplitudes to probes in the forewarning period, i.e., during the negative potential shift of the CNV, were significantly enhanced in all groups. Apparently there is a state of increased cortical excitability during the CNV which is not selectively “tuned” toward relevant stimuli. In schizophrenia, the temporal and topographical regulation of this excitability is disturbed.

Personality effects on brain potentials in an S1-S2 paradigm

Event-related brain potentials (ERPs) were recorded in an S1-S2 paradigm. S1 was a warning signal that indicated whether subjects had to respond as quickly as possible, or had to delay their responses until 1 sec after S2. The amplitudes of the frontal N1, the negative slow wave (NSW) and the terminal contingent negative variation (CNV) were larger following the speed-instruction than after the delay-instruction. To investigate the influence of personality, comparisons were made between groups differing in negative affectivity, positive affectivity, sensation seeking, and impulsivity. Persons scoring high on sensation seeking (SS) showed larger NSW amplitudes than low-scorers on SS. This finding is interpreted as suggesting that larger NSW amplitudes reflects emotions that were approach-related rather than avoidance-related. It is suggested that mechanisms generating the NSW are influenced by the affective characteristics of S1.

Contingent negative variation in adults with Gilles de la Tourette syndrome.

Three deflections or waves of the Contingent Negative Variation (CNV): the Slow Negative Wave (SNW), the Terminal CNV (TCNV) and the Post Imperative Negative Variation (PINV) were studied in 18 adults with Gilles de la Tourette syndrome and in 15 controls. The patients showed a reduced SNW, a normal TCNV and an increased PINV. Moreover, at the right parietal region the patients demonstrated a decreased SNW, TCNV and PINV. The results are discussed in relation to behavioral and neuropsychological disturbances found in Gilles de la Tourette syndrome.

Alpha 1- and alpha 2-adrenoceptive modulation of vigilance and sleep : P.T.S. Putkonen, I. Hilakivi and A. Leppävouri (Helsinki, Finland)

Distractibility and temporal modulation of attention in schizophrenics were studied using a visual reaction time task with additional auditory probe stimuli during the forewarning period or between trials. The probes were thought to exert a distracting influence, especially on schizophrenics, and at the same time they generated auditory EPs which allowed to track the modulation of cortical excitability during response preparation. The midline distribution of the terminal contingent negative variation (tCNV) and the amplitude of the postimperative negative variation (PINV) were clearly different in 20 DSM III-R schizophrenics, as compared with 20 alcoholics and 20 normal controls. In schizophrenics, the more frontal distribution of the tCNV was associated with a higher degree of psychopathology (measured with the Brief Psychiatric Rating Scale) and with delayed reactions. Probes between trials reduced tCNV and PINV in all subjects alike. However, this effect could not be attributed to distraction, because reaction times were faster in these trials, possibly due to an alerting effect of the auditory probes. The N100 and P300 amplitudes to probes in the forewarning period, i.e., during the negative potential shift of the CNV, were significantly enhanced in all groups. Apparently there is a state of increased cortical excitability during the CNV which is not selectively “tuned” toward relevant stimuli. In schizophrenia, the temporal and topographical regulation of this excitability is disturbed.

The terminal CNV and stimulus discriminability in motor and sensory tasks

Slow EEG potentials were recorded during the foreperiod of a signal detection task which involved different levels of discrimination difficulty. The subject was required to react to S 2 as quickly as possible or to delay his response by 1 s. It was found that the contingent negative variation (CNV) was attenuated when no speeded response was required and that larger amplitudes preceded the easy rather than the difficult discrimination. In addition, no differences were found between correct and incorrect detections. On these grounds it is concluded that the CNV is not positively correlated with perceptual sensitivity.