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Cognitive deficits affecting memory, attention and speed of information processing are common in multiple sclerosis (MS). The mechanisms of cognitive impairment remain unclear. Here, we examined the association between neuropsychological test performance and brain atrophy in a group of mildly disabled patients with relapsing-remitting MS. We applied voxel-based morphometry (SPM2) to investigate the distribution of brain atrophy in relation to cognitive performance. Patients had lower scores than control subjects on tests of memory and executive function, including the PASAT, Digit Span Backward and a test of short-term verbal memory (Memo). Among patients, but not healthy controls, performance on the PASAT, a comprehensive measure of cognitive function and reference task for the cognitive evaluation of MS-patients, correlated with global grey matter volume as well as with grey matter volume in regions associated with working memory and executive function, including bilateral prefrontal cortex, precentral gyrus and superior parietal cortex as well as right cerebellum. Compared to healthy subjects, patients showed a volume reduction in left temporal and prefrontal cortex, recently identified as areas predominantly affected by diffuse brain atrophy in MS. A comparison of low performers in the patient group with their matched control subjects showed more extensive and bilateral temporal and frontal volume reductions as well as bilateral parietal volume loss, compatible with the progression of atrophy found in more advanced MS-patients. These findings indicate that MS-related deficits in cognition are closely associated with cortical atrophy.
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Cerebral reorganization may limit the effects of central nervous system tissue damage on cognition in patients with multiple sclerosis (MS). This study investigated fMRI activation patterns in patients with relapsing-remitting MS and healthy control subjects during performance of a delayed recognition task. As intended, fMRI task performance was similar in the MS and the control group, whereas neuropsychological testing revealed reduced performance in the patient group on the Paced Serial Addition Test, a reference task for the assessment of cognitive function in MS. Patients overall showed more activation in left posterior parietal cortex than healthy control subjects. Global gray matter atrophy in the patient group was associated with low PASAT scores. In a multiple regression analysis including white matter lesion load and gray matter atrophy as covariates, PASAT performance correlated with activation in left posterior parietal cortex and right anterior midfrontal gyrus, indicating a reallocation of neuronal resources to help preserve function. Global gray matter atrophy correlated with activation in bilateral prefrontal cortex, dorsal ACC and left posterior parietal cortex and, furthermore, was associated with a low degree of deactivation in rostral ACC, suggesting neural inefficiency and consistent with a reduced capacity to modulate between frontoparietal task-associated activation and 'default network' activity. The current study provides evidence that altered brain activation in MS patients has two distinct components, one related to compensatory processes and one to neural inefficiency associated with tissue damage.
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We investigated subjective and hemodynamic responses towards disgust-inducing, fear-inducing, and neutral pictures in a functional magnetic resonance imaging study. Within an interval of 1 week, 24 male subjects underwent the same block design twice in order to analyze possible response changes to the repeated picture presentation. The results showed that disgust-inducing and fear-inducing scenes provoked a similar activation pattern in comparison to neutral scenes. This included the thalamus, primary and secondary visual fields, the amygdala, the hippocampus, and various regions of the prefrontal cortex. During the retest, the affective ratings hardly changed. In contrast, most of the previously observed brain activations disappeared, with the exception of the temporo-occipital activation. An additional analysis, which compared the emotion-related activation patterns during the two presentations, showed that the responses to the fear-inducing pictures were more stable than the responses to the disgust-inducing ones.
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The perception of action is influenced by the observer's familiarity with its movement. However, how does motor familiarity with own movement patterns modulate the visual perception of action effects? Cortical activation was examined with fMRI while 20 observers were watching videotaped point-light displays of markers on the shoulders, the right elbow, and wrist of an opposing table tennis player. The racket and ball were not displayed. Participants were asked to predict the invisible effect of the stroke, that is, the ball flight direction. Different table tennis models were used without the observers knowing and being informed in advance that some of the presented videos displayed their own movements from earlier training sessions. Prediction had to be made irrespective of the identity of the player represented by the four moving markers. Results showed that participants performed better when observing their "own" strokes. Using a region-of-interest approach, fMRI data showed that observing own videos was accompanied by stronger activation (compared to other videos) in the left angular gyrus of the inferior parietal lobe and the anterior rostral medial frontal cortex. Other videos elicited stronger activation than own videos in the left intraparietal sulcus and right supramarginal gyrus. We suggest that during action observation of motorically familiar movements, the compatibility between the observed action and the observers' motor representation is already coded in the parietal angular gyrus--in addition to the paracingulate gyrus. The activation in angular gyrus is presumably part of an action-specific effect retrieval that accompanies actor-specific prefrontal processing. The intraparietal sulcus seems to be sensitive to incongruence between observed kinematics and internal model representations, and this also influences processing in the supramarginal gyrus.
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We investigated subjective and hemodynamic responses towards disgust-inducing, fear-inducing, and neutral pictures in a functional magnetic resonance imaging study. Within an interval of 1 week, 24 male subjects underwent the same block design twice in order to analyze possible response changes to the repeated picture presentation. The results showed that disgust-inducing and fear-inducing scenes provoked a similar activation pattern in comparison to neutral scenes. This included the thalamus, primary and secondary visual fields, the amygdala, the hippocampus, and various regions of the prefrontal cortex. During the retest, the affective ratings hardly changed. In contrast, most of the previously observed brain activations disappeared, with the exception of the temporo-occipital activation. An additional analysis, which compared the emotion-related activation patterns during the two presentations, showed that the responses to the fear-inducing pictures were more stable than the responses to the disgust-inducing ones.
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Fear learning is a crucial process in the pathogeneses of psychiatric disorders, which highlights the need to identify specific factors contributing to interindividual variation. We hypothesized variation in the serotonin transporter gene (5-HTTLPR) and stressful life events (SLEs) to be associated with neural correlates of fear conditioning in a sample of healthy male adults (n = 47). Subjects were exposed to a differential fear conditioning paradigm after being preselected regarding 5-HTTLPR genotype and SLEs. Individual differences in brain activity as measured by functional magnetic resonance imaging (fMRI), skin conductance responses and preference ratings were assessed. We report significant variation in neural correlates of fear conditioning as a function of 5-HTTLPR genotype. Specifically, the conditioned stimulus (CS(+)) elicited elevated activity within the fear-network (amygdala, insula, thalamus, occipital cortex) in subjects carrying two copies of the 5-HTTLPR S' allele. Moreover, our results revealed preliminary evidence for a significant gene-by-environment interaction, such as homozygous carriers of the 5-HTTLPR S' allele with a history of SLEs demonstrated elevated reactivity to the CS(+) in the occipital cortex and the insula. Our findings contribute to the current debate on 5-HTTLPR x SLEs interaction by investigating crucial alterations on an intermediate phenotype level which may convey an elevated vulnerability for the development of psychopathology.
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The aim of this fMRI study was to explore brain structures that are involved in the processing of erotic and disgust-inducing pictures. The stimuli were chosen to trigger approach and withdrawal tendencies, respectively. By adding sadomasochistic (SM) scenes to the design and examining 12 subjects with and 12 subjects without sadomasochistic preferences, we introduced a picture category that induced erotic pleasure in one sample and disgust in the other sample. Since we also presented neutral pictures, all subjects viewed pictures of four different categories: neutral, disgust-inducing, erotic, and SM erotic pictures. The analysis indicated that several brain structures are commonly involved in the processing of disgust-inducing and erotic pictures (occipital cortex, hippocampus, thalamus, and the amygdala). The ventral striatum was specifically activated when subjects saw highly sexually arousing pictures. This indicates the involvement of the human reward system during the processing of visual erotica.
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The aim of this fMRI study was to explore brain structures that are involved in the processing of erotic and disgust-inducing pictures. The stimuli were chosen to trigger approach and withdrawal tendencies, respectively. By adding sadomasochistic (SM) scenes to the design and examining 12 subjects with and 12 subjects without sadomasochistic preferences, we introduced a picture category that induced erotic pleasure in one sample and disgust in the other sample. Since we also presented neutral pictures, all subjects viewed pictures of four different categories: neutral, disgust-inducing, erotic, and SM erotic pictures. The analysis indicated that several brain structures are commonly involved in the processing of disgust-inducing and erotic pictures (occipital cortex, hippocampus, thalamus, and the amygdala). The ventral striatum was specifically activated when subjects saw highly sexually arousing pictures. This indicates the involvement of the human reward system during the processing of visual erotica.
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Mindfulness training aims to impact emotion regulation. Generalized anxiety disorder (GAD) symptoms can be successfully addressed through mindfulness-based interventions. This preliminary study is the first to investigate neural mechanisms of symptom improvements in GAD following mindfulness training. Furthermore, we compared brain activation between GAD patients and healthy participants at baseline. 26 patients with a current DSM-IV GAD diagnosis were randomized to an 8-week Mindfulness Based Stress Reduction (MBSR, N = 15) or a stress management education (SME, N = 11) active control program. 26 healthy participants were included for baseline comparisons. BOLD response was assessed with fMRI during affect labeling of angry and neutral facial expressions. At baseline, GAD patients showed higher amygdala activation than healthy participants in response to neutral, but not angry faces, suggesting that ambiguous stimuli reveal stronger reactivity in GAD patients. In patients, amygdala activation in response to neutral faces decreased following both interventions. BOLD response in ventrolateral prefrontal regions (VLPFC) showed greater increase in MBSR than SME participants. Functional connectivity between amygdala and PFC regions increased significantly pre- to post-intervention within the MBSR, but not SME group. Both, change in VLPFC activation and amygdala-prefrontal connectivity were correlated with change in Beck Anxiety Inventory (BAI) scores, suggesting clinical relevance of these changes. Amygdala-prefrontal connectivity turned from negative coupling (typically seen in down-regulation of emotions), to positive coupling; potentially suggesting a unique mechanism of mindfulness. Findings suggest that in GAD, mindfulness training leads to changes in fronto-limbic areas crucial for the regulation of emotion; these changes correspond with reported symptom improvements.
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The article reviews the current knowledge regarding altered states of consciousness (ASC) (a) occurring spontaneously, (b) evoked by physical and physiological stimulation, (c) induced by psychological means, and (d) caused by diseases. The emphasis is laid on psychological and neurobiological approaches. The phenomenological analysis of the multiple ASC resulted in 4 dimensions by which they can be characterized: activation, awareness span, self-awareness, and sensory dynamics. The neurophysiological approach revealed that the different states of consciousness are mainly brought about by a compromised brain structure, transient changes in brain dynamics (disconnectivity), and neurochemical and metabolic processes. Besides these severe alterations, environmental stimuli, mental practices, and techniques of self-control can also temporarily alter brain functioning and conscious experience.
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