M. Cornelia Stoeckel

A fronto-parietal circuit for tactile object discrimination: an event-related fMRI study.

Previous studies of somatosensory object discrimination have been focused on the primary and secondary sensorimotor cortices. However, we expected the prefrontal cortex to also become involved in sequential tactile discrimination on the basis of its role in working memory and stimulus discrimination as established in other domains. To investigate the contributions of the different cerebral structures to tactile discrimination of sequentially presented objects, we obtained event-related functional magnetic resonance images from seven healthy volunteers. Our results show that right hand object exploration involved left sensorimotor cortices, bilateral premotor, parietal and temporal cortex, putamen, thalamus, and cerebellum. Tactile exploration of parallelepipeds for subsequent object discrimination activated further areas in the dorsal and ventral portions of the premotor cortex, as well as parietal, midtemporal, and occipital areas of both cerebral hemispheres. Discriminating a parallelepiped from the preceding one involved a bilateral prefrontal-anterior cingulate-superior temporal-posterior parietal circuit. While the prefrontal cortex was active with right hemisphere dominance during discrimination, there was left hemispheric prefrontal activation during the delay period between object presentations. Delay related activity was further seen in the anterior intraparietal area and the fusiform gyrus. The results reveal a prominent role of the human prefrontal cortex for somatosensory object discrimination in correspondence with recent models on stimulus discrimination and working memory.

Congenitally altered motor experience alters somatotopic organization of human primary motor cortex

Human motor development is thought to result from a complex interaction between genes and experience. The well-known somatotopic organization of the primate primary motor cortex (M1) emerges postnatally. Although adaptive changes in response to learning and use occur throughout life, somatotopy is maintained as reorganization is restricted to modifications within major body part representations. We report of a unique opportunity to evaluate the influence of experience on the genetically determined somatotopic organization of motor cortex in humans. We examined the motor “foot” representation in subjects with congenitally compromised hand function and compensatory skillful foot use. Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) of M1 revealed that the foot was represented in the classical medial foot area of M1 and was several centimetres away in nonadjacent cortex in the vicinity of the lateral “hand” area. Both areas had direct output to the spinal motor neurons innervating foot muscles and were behaviorally relevant because experimental disruption of either area by TMS altered reaction times. We demonstrate a unique, nonsomatotopically organized M1 in humans, which emerged as a function of grossly altered motor behavior from the earliest stages of development. Our results imply that during early motor development experience may play a more critical role in the shaping of genetically determined neural networks than previously assumed.

Reduced somatosensory hand representation in thalidomide‐induced dysmelia as revealed by fMRI

The concept of cerebral plasticity suggests that the hand representation in somatosensory cortex is abnormal in congenital malformation disorders. To investigate this issue we studied 11 subjects with different degrees of upper extremity dysmelia due to thalidomide embryopathy in comparison to 10 control subjects. In the affected subjects fingers are typically missing in radio‐ulnar order beginning with the thumb. Haemodynamic responses to electrical stimulation of the radial‐most and ulnar‐most fingers were measured in each subject using functional magnetic resonance tomography. The size of the hand area in the primary somatosensory cortex was estimated by calculating the Euclidian distance between corresponding activation peaks on the lateral postcentral gyrus. The cortical somatosensory hand representation was found to be significantly smaller in dysmelic subjects as compared with the control subjects (P < 0.001). The shrinkage of the hand area was not proportional to the number of missing fingers. Furthermore, the cortical representation of the ulnar fingers in the dysmelic subjects was shifted towards the cortical thumb representation of the control group. We suggest that the unproportional reduction of the hand area together with the observed shift may reflect use‐dependent rather than malformation‐induced reorganization of the somatosensory hand area.

Brain Responses during the Anticipation of Dyspnea

Dyspnea is common in many cardiorespiratory diseases. Already the anticipation of this aversive symptom elicits fear in many patients resulting in unfavorable health behaviors such as activity avoidance and sedentary lifestyle. This study investigated brain mechanisms underlying these anticipatory processes. We induced dyspnea using resistive-load breathing in healthy subjects during functional magnetic resonance imaging. Blocks of severe and mild dyspnea alternated, each preceded by anticipation periods. Severe dyspnea activated a network of sensorimotor, cerebellar, and limbic areas. The left insular, parietal opercular, and cerebellar cortices showed increased activation already during dyspnea anticipation. Left insular and parietal opercular cortex showed increased connectivity with right insular and anterior cingulate cortex when severe dyspnea was anticipated, while the cerebellum showed increased connectivity with the amygdala. Notably, insular activation during dyspnea perception was positively correlated with midbrain activation during anticipation. Moreover, anticipatory fear was positively correlated with anticipatory activation in right insular and anterior cingulate cortex. The results demonstrate that dyspnea anticipation activates brain areas involved in dyspnea perception. The involvement of emotion-related areas such as insula, anterior cingulate cortex, and amygdala during dyspnea anticipation most likely reflects anticipatory fear and might underlie the development of unfavorable health behaviors in patients suffering from dyspnea.

Brain mechanisms of short-term habituation and sensitization toward dyspnea.

Dyspnea is a prevalent and threatening cardinal symptom in many diseases including asthma. Whether patients suffering from dyspnea show habituation or sensitization toward repeated experiences of dyspnea is relevant for both quality of life and treatment success. Understanding the mechanisms, including the underlying brain activation patterns, that determine the dynamics of dyspnea perception seems crucial for the improvement of treatment and rehabilitation. Toward this aim, we investigated the interplay between short-term changes of dyspnea perception and changes of related brain activation. Healthy individuals underwent repeated blocks of resistive load induced dyspnea with parallel acquisition of functional magnetic resonance imaging data. Late vs. early ratings on dyspnea intensity and unpleasantness were correlated with late vs. early brain activation for both, dyspnea anticipation and dyspnea perception. Individual trait and state anxiety were determined using questionnaire data. Our results indicate an involvement of the orbitofrontal cortex (OFC), midbrain/periaqueductal gray (PAG) and anterior insular cortex in habituation/sensitization toward dyspnea. Changes in the anterior insular cortex were particularly linked to changes in dyspnea unpleasantness. Changes of both dyspnea intensity and unpleasantness were positively correlated with state and trait anxiety. Our findings are in line with the suggested relationship between the anterior insular cortex and dyspnea unpleasantness. They further support the notion that habituation/sensitization toward dyspnea is influenced by anxiety. Our study extends the known role of the midbrain/PAG in anti-nociception to an additional involvement in habituation/sensitization toward dyspnea and suggests an interplay with the OFC.

Dyspnea catastrophizing and neural activations during the anticipation and perception of dyspnea

Dyspnea is an aversive symptom in various diseases. High levels of negative affectivity are typically associated with increased dyspnea and changes in its neural processing. Recently, more dyspnea-specific forms of negative affectivity such as dyspnea catastrophizing were suggested to contribute to increased perception of dyspnea beyond effects of rather unspecific negative affectivity such as general anxiety levels. The involved neural mechanisms have not yet been explored. Therefore, the present retrospective analysis examined the associations of dyspnea catastrophizing with neural activations during the anticipation and perception of dyspnea. Sixty-six healthy volunteers underwent 20 blocks of inspiratory resistive load breathing with parallel acquisition of fMRI data. Loads inducing either severe or mild dyspnea (dyspnea conditions) were presented in alternating order, with each condition being visually cued (anticipation conditions). Dyspnea catastrophizing and general trait anxiety were measured with the Breathlessness Catastrophizing Scale (BCS) and the State-Trait Anxiety Inventory, respectively. Correlating the BCS scores with neural activations during the perception of dyspnea yielded no significant results. However, during the anticipation of dyspnea, BCS scores correlated positively with activations of the anterior cingulate cortex (ACC), even after controlling for general anxiety levels. These activations in the ACC were not related to concurrent respiratory parameters. Results suggest that dyspnea catastrophizing in healthy volunteers is associated with stronger ACC recruitment during dyspnea anticipation. Given the established role of the ACC in processing affective states, affect regulation, and antinociception, this might reflect increased affective and/or top-down modulatory processing in individuals with higher dyspnea catastrophizing when anticipating dyspnea.

Differential grey matter changes in sensorimotor cortex related to exceptional fine motor skills.

Functional changes in sensorimotor representation occur in response to use and lesion throughout life. Emerging evidence suggests that functional changes are paralleled by respective macroscopic structural changes. In the present study we used voxel-based morphometry to investigate sensorimotor cortex in subjects with congenitally malformed upper extremities. We expected increased or decreased grey matter to parallel the enlarged or reduced functional representations we reported previously. More specifically, we expected decreased grey matter values in lateral sensorimotor cortex related to compromised hand function and increased grey matter values in medial sensorimotor cortex due to compensatory foot use. We found a medial cluster of grey matter increase in subjects with frequent, hand-like compensatory foot use. This increase was predominantly seen for lateral premotor, supplementary motor, and motor areas and only marginally involved somatosensory cortex. Contrary to our expectation, subjects with a reduced number of fingers, who had shown shrinkage of the functional hand representation previously, did not show decreased grey matter values within lateral sensorimotor cortex. Our data suggest that functional plastic changes in sensorimotor cortex can be associated with increases in grey matter but may also occur in otherwise macroscopically normal appearing grey matter volumes. Furthermore, macroscopic structural changes in motor and premotor areas may be observed without respective changes in somatosensory cortex.

Breathlessness amplifies amygdala responses during affective processing

Breathlessness is an aversive symptom in many prevalent somatic and psychiatric diseases and is usually experienced as highly threatening. It is strongly associated with negative affect, but the underlying neural processes remain poorly understood. Therefore, using fMRI, the present study examined the effects of breathlessness on the neural processing of affective visual stimuli within candidate brain areas including the amygdala, insula, and anterior cingulate cortex (ACC). During scanning, 42 healthy volunteers, mean (SD) age: 29.0 (6.0) years, 14 female, were presented with affective picture series of negative, neutral, and positive valence while experiencing either no breathlessness (baseline conditions) or resistive-load induced breathlessness (breathlessness conditions). Respiratory measures and self-reports suggested successful induction of breathlessness and affective experiences. Self-reports of breathlessness intensity and unpleasantness were significantly higher during breathlessness conditions, mean (SD): 45.0 (16.6) and 32.3 (19.8), as compared to baseline conditions, mean (SD): 1.9 (3.0) and 2.9 (5.5). Compared to baseline conditions, stronger amygdala activations were observed during breathlessness conditions for both negative and positive affective picture series relative to neutral picture series, while no such effects were observed in insula and ACC. The present findings demonstrate that breathlessness amplifies amygdala responses during affective processing, suggesting an important role of the amygdala for mediating the interactions between breathlessness and affective states.