Simone Lang

Context conditioning and extinction in humans: differential contribution of the hippocampus, amygdala and prefrontal cortex

Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty‐one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS− was found in the left hippocampus and anterior cingulate cortex (ACC). The amygdala, insula and inferior frontal cortex were differentially active during late acquisition. Extinction was accompanied by enhanced activation to CS+ vs. CS− in the dorsal anterior cingulate cortex (dACC). The results are in accordance with animal studies and provide evidence for the important role of the hippocampus in contextual learning in humans. Connectivity analyses revealed correlated activity between the left posterior hippocampus and dACC (BA32) during early acquisition and the dACC, left posterior hippocampus and right amygdala during extinction. These data are consistent with theoretical models that propose an inhibitory effect of the mPFC on the amygdala. The interaction of the mPFC with the hippocampus may reflect the context‐specificity of extinction learning.

Cognitive processing in completely paralyzed patients with amyotrophic lateral sclerosis

Cognitive functions have never been studied before in completely paralyzed patients, probably due to the lack of the appropriate method. In this study, three male patients in the last stage of amyotrophic lateral sclerosis (ALS) are examined. They were totally locked‐in, i.e., incapable of any voluntary response including eye movements. Given this complete lack of motor expression, the method of event‐related brain potentials (ERPs) was used. The ERP recording was carried out at the patients’ bedside. In one patient indications of preserved cognitive abilities including adequate language comprehension were obtained. The data of the second patient also demonstrate a high degree of intactness of complex cognitive functions, but some ERP phenomena were consistently abnormal, which may be interpreted as a consequence of disease‐related degenerative processes. In the third patient no electrocortical response which might indicate higher cortical processing was found. This first ERP study of totally paralyzed patients shows that some of them can possess high, perhaps even normal, information processing capacity after a long period of severe immobility and artificial ventilation.

Borderline personality disorder and psychosis: a review.

Early views of borderline personality disorder (BPD) were based on the idea that patients with this pathology were “on the border” of psychosis. However, more recent studies have not supported this view, although they have found evidence of a malevolent interpersonal evaluation and a significant proportion of BPD patients showing psychotic symptoms. For example, in one study, 24% of BPD patients reported severe psychotic symptoms and about 75% had dissociative experiences and paranoid ideation. Thus, we start with an overview regarding the prevalence of psychotic symptoms in BPD patients. Furthermore, we report findings of studies investigating the role of comorbidity (eg, post-traumatic stress disorder) in the severity and frequency of psychotic symptoms in BPD patients. We then present results of genetic and neurobiological studies comparing BPD patients with patients with schizophrenia or nonschizophrenic psychotic disorders. In conclusion, this review reveals that psychotic symptoms in BPD patients may not predict the development of a psychotic disorder but are often permanent and severe and need careful consideration by clinicians. Therefore, adequate diagnosis and treatment of psychotic symptoms in BPD patients is emphasized.

Hypersensitivity in Borderline Personality Disorder during Mindreading

Background One of the core symptoms of borderline personality disorder (BPD) is the instability in interpersonal relationships. This might be related to existent differences in mindreading between BPD patients and healthy individuals. Methods We examined the behavioural and neurophysiological (fMRI) responses of BPD patients and healthy controls (HC) during performance of the ‘Reading the Mind in the Eyes’ test (RMET). Results Mental state discrimination was significantly better and faster for affective eye gazes in BPD patients than in HC. At the neurophysiological level, this was manifested in a stronger activation of the amygdala and greater activity of the medial frontal gyrus, the left temporal pole and the middle temporal gyrus during affective eye gazes. In contrast, HC subjects showed a greater activation in the insula and the superior temporal gyri. Conclusion These findings indicate that BPD patients are highly vigilant to social stimuli, maybe because they resonate intuitively with mental states of others.

Cognitive reappraisal in trauma-exposed women with borderline personality disorder

Borderline personality disorder (BPD) is characterized by emotional dysregulation and a high prevalence of traumatic stress. Recent estimates suggest that 2-6% of non-clinical populations suffer from BPD. Despite this relevance, this is the first study considering the neural mechanisms underlying trauma-history and temporal features of cognitive reappraisal in non-clinical BPD patients using script-driven stimuli. Using functional magnetic resonance imaging (fMRI), we examined subjective ratings of negative emotional experience and brain activity following up- and down-regulation of emotional responses to standardized negative scripts in 43 women: 14 trauma-exposed BPD patients (BPD), 14 trauma-exposed healthy subjects without posttraumatic stress disorder (non-PTSD), and 15 non-traumatized healthy subjects (HC). Behaviorally, all groups were able to use cognitive reappraisal to up- and down-regulate negative emotions. HC subjects showed increased early activation in the prefrontal cortex (PFC) and the amygdala following up-regulation of emotions to negative scripts, whereas BPD and non-PTSD subjects showed early deactivation in the PFC. Additionally, the anterior cingulate cortex was more activated in HC subjects than in BPD and non-PTSD subjects during up- and down-regulation. No significant group differences were found between BPD patients and non-PTSD. BPD patients and healthy individuals with trauma history do not engage the cognitive control regions to the extent than HC subjects do when employing down-regulation of negative emotions. They also do not activate the brain regions associated with emotional up-regulation. These findings may reflect compensatory changes associated with trauma-exposure.

Event-related potentials in an auditory semantic oddball task in humans

Whenever rare target stimuli are presented interspersed by frequent irrelevant stimuli (standards), the targets elicit a late parieto-central positive wave called P3. Usually standards and targets differ by a simple physical feature (e.g. tone pitch). Less consistent are the data obtained in semantic tasks, in which standards and targets are represented by different word classes. Given an equal number of words in the target and standard categories, each individual standard is more frequent than each target, that is, the frequency of the category is confounded with that of individual stimuli. In the present study participants were presented five semantic classes each being represented by 15 words. Words belonging to one particular class should be counted. Thus targets were rare (20%), although the frequencies of each word and of each semantic class were equal. A highly significant P3 was recorded. Its latency was longer, and the amplitude was smaller, than when standards and targets were two tones. These data indicate that brain waves recorded in semantic tasks are not necessarily manifestations of specific semantic processing.

Hearing others' pain: neural activity related to empathy.

The human voice is one of the principal conveyers of social and affective communication. Recent neuroimaging studies have suggested that observing pain in others activates neural representations similar to those from the first-hand experience of pain; however, studies on pain expressions in the auditory channel are lacking. We conducted a functional magnetic resonance imaging study to examine brain responses to emotional exclamations of others’ pain. The control condition comprised positive (e.g., laughing) or negative (e.g., snoring) stimuli of the human voice that were not associated with pain and suffering. Compared to these control stimuli, pain-related exclamations elicited increased activation in the superior and middle temporal gyri, left insula, secondary somatosensory cortices, thalamus, and right cerebellum, as well as deactivation in the anterior cingulate cortex. The left anterior insular and thalamic activations correlated significantly with the Empathic Concern subscale of the Interpersonal Reactivity Index. Thus, the brain regions involved in hearing others’ pain are similar to those activated in the empathic processing of visual stimuli. Additionally, the findings emphasise the modulating role of interindividual differences in affective empathy.

Precursors of Insight in Event-related Brain Potentials

Event-related potentials (ERPs) were investigated to find precursors of insightful behavior. Participants had to process successive pairs in strings of digits to obtain a final response in each trial. Within the sequence of five responses required in each trial, the last two responses mirrored the two preceding ones. This hidden regularity, allowing for shortcutting each trial from five to two responses, was discovered by 6 out of 26 participants. Both groups, solvers and nonsolvers, implicitly learned the regularity, reflected by faster responses to the repeated, predictable responses, but this differential effect was larger in solvers, whereas nonsolvers became unspecifically faster with all responses. Several ERP components were larger in solvers than in nonsolvers from the outset: slow positive wave, frontocentral P3a, anterior N1 to those digits that triggered the critical repeating responses, and P3b to the digit that evoked the immediately repeating response. Being already present in the first block, these effects were early precursors of insightful behavior. This early occurrence suggests that participants who will gain insight may be distinguished beforehand by their individual characteristics.

Patients with unresponsive wakefulness syndrome respond to the pain cries of other people

Objective: Recent publications show that using imagery instructions, brain activation patterns indicating consciousness can be found in approximately 10% of patients with unresponsive wakefulness syndrome (UWS; previously called vegetative state). It is possible, however, that patients who cannot follow instructions (because of limited memory/attention capacities, for example) are nevertheless conscious and retain emotional abilities to feel pain and pleasure. The aim of this study was to assess residual affective consciousness in a specific network of brain structures, the so-called pain matrix (PM) of the brain. Methods: We examined 44 carefully diagnosed UWS patients at 2 imaging centers. fMRI was used to investigate the brain hemodynamic responses to (a) imagery instructions, and (b) pain cries as opposed to neutral human vocalizations. Results: In line with the data of other groups, consistent responses to imagery instructions were obtained in 5 patients. In contrast, the PM was activated by pain cries in 24 patients. The PM consists of a sensory subsystem, which underlies pain sensation, and an affective subsystem, which underlies the characteristic aversive emotional tone of pain. The former was activated in 34% of patients, the latter in 30% of patients. Conclusion: Although there is debate about whether patients with UWS can perceive their own pain, our data indicate that many of them respond to the signals of pain in others. One can speculate that “affective consciousness” can remain even in patients with very severe brain damage who have no capacity for cognition.

Evidence of cortical learning in vegetative state

Sirs: Vegetative state (VS) is the complete lack of coherent behavior despite the presence of a sleepwakefulness cycle and normal or even exaggerated reflexes [3]. The same clinical condition was previously described as apallic syndrome [4]. Recent imaging studies repeatedly report remaining cortical functions in some patients [2, 7, 10]. These reports, however, mostly concern small patient samples. Given the difficulty of the differential diagnosis of VS [1], a sceptic might suggest that the described patients presented diagnostic errors, borderline cases, or otherwise exceptions from the VS population. A learning process in form of the habituation of blink reflex has been reported [11, 12] in a selected subgroup of VS patients with better behavioral responsiveness. However, blink reflex is a simple brain stem reflex which persists even in decorticated preparations. A study of a large group of VS patients [12] mentioned that the habituation of the cortical component N1 of auditory evoked potentials (EPs) was also examined; however, the authors did not report whether the habituation process was really observed in VS. We examined thirty-three VS patients (14 females), aged 19–62 years (mean 42.1). The clinical diagnosis was based on the complete absence of goal-directed behavioral responses. Patients with apparent but inconsistent responses (in whom a diagnosis of minimally conscious state might be suggested) were excluded, as were patients younger than 14 years and those with severely disturbed brain stem auditory EPs. The Disability Rating Scale [9] was > 21. Disease duration ranged from 2–70 months (mean 6.8). Etiological factors were head injury (16 patients), subarachnoidal hemorrhage (8), or brain anoxia (9). Ten runs of 50-ms 800-Hz sine frequencies were presented, one per 400 ms, with the intervals between runs being 5 s. An additional, 11th run contained tones of 1500 Hz. Auditory EPs were recorded from Fz and Cz sites, referred to mastoids. The electrooculogram was recorded using electrodes attached to the left and right orbital rim, and above and below the right eye. Ocular artifacts were removed by means of a regression technique [6]. EPs were averaged, firstly, across trials in each run (resulting in 11 averages, the last of them to the deviant 1500 Hz tone), and secondly, across the ten 800 Hz runs for each trial number (i.e., 10 first trials, 10 second trials, etc.). Thus each average contained 10 trials. The amplitude of the N1 component was measured, and the rate of its change across trials and runs was taken as a measure of short-term and long-term habituation, respectively (Fig. 1). The N1 amplitude decreased with repetition across trials with a rate of 0.13 lV/trial (t = 2.05, p < 0.05) and 0.24 lV/trial (t = 3.60, p < 0.001), for Cz and Fz, respectively (Fig. 2, top). The amplitude decrement across runs was less steep (0.07 to 0.15 lV/run) and attained significance at Fz only (t = 2.59, p < .02). Given the short interstimulus interval, the amplitude decrease across trials might be accounted for by refractoriness, rather than habituation as a central learning process. However, refractoriness should have an even stronger effect on P2 (due to its larger latency), but the P2 amplitude did not change with stimulus repetition, which is in line with habituation data [5]. Further, the refractoriness hypothesis predicts that patients with a faster N1 decrement (i.e., unstable responses) would have a smaller N1 averaged across all 100 trials. Exactly the opposite was the case: patients with a faster N1 decrement had a higher N1 across all trials (p < 0.001). LETTER TO THE EDITORS J Neurol (2006) 253 : 1374–1376 DOI 10.1007/s00415-006-0221-0