Carsten M. Klingner

Behavioral correlates of negative BOLD signal changes in the primary somatosensory cortex

Functional magnetic resonance imaging (fMRI) hypothesis testing based on the blood oxygenation level dependent (BOLD) contrast mechanism typically involves a search for a positive effect during a specific task relative to a control state. However, aside from positive BOLD signal changes there is converging evidence that neuronal responses within various cortical areas also induce negative BOLD signals. Although it is commonly believed that these negative BOLD signal changes reflect suppression of neuronal activity direct evidence for this assumption is sparse. Since the somatosensory system offers the opportunity to quantitatively test sensory function during concomitant activation and has been well-characterized with fMRI in the past, the aim of this study was to determine the functional significance of ipsilateral negative BOLD signal changes during unilateral sensory stimulation. For this, we measured BOLD responses in the somatosensory system during unilateral electric stimulation of the right median nerve and additionally determined the current perception threshold of the left index finger during right-sided electrical median nerve stimulation as a quantitative measure of sensory function. As expected, positive BOLD signal changes were observed in the contralateral primary and bilateral secondary somatosensory areas, whereas a decreased BOLD signal was observed in the ipsilateral primary somatosensory cortex (SI). The negative BOLD signal changes were much more spatially extensive than the representation of the hand area within the ipsilateral SI. The negative BOLD signal changes in the area of the index finger highly correlated with an increase in current perception thresholds of the contralateral, unstimulated finger, thus supporting the notion that the ipsilateral negative BOLD response reflects a functionally effective inhibition in the somatosensory system.

Thalamocortical connectivity during resting state in schizophrenia.

Schizophrenia has been linked to disturbed connectivity between large-scale brain networks. Altered thalamocortical connectivity might be a major mechanism mediating regionally distributed dysfunction, yet it is only incompletely understood. We analysed functional magnetic resonance imaging data obtained during resting state from 22 DSM-IV schizophrenia patients and 22 matched healthy controls to directly assess the differences in thalamocortical functional connectivity. We identified significantly higher overall thalamocortical functional connectivity in patients, which was mostly accounted for by difference in thalamic connections to right ventrolateral prefrontal and bilateral secondary motor and sensory (superior temporal and lateral occipital) cortical areas. Voxelwise analysis showed group differences at the thalamic level to be mostly in medial and anterior thalamic nuclei and arising thalamocortical changes to be mostly due to higher positive correlations in prefrontal and superior temporal correlations, as well as absent negative correlations to sensory areas in patients. Our findings demonstrate that different types of thalamocortical dysfunction contribute to network alterations, including lack of inhibitory interaction attributed to the lack of significant negative thalamic/sensory cortical connections. These results emphasize the functional importance of the thalamus in the pathophysiology of schizophrenia.

Fiber anatomy of dorsal and ventral language streams

Recent advances in neuroimaging have led to new insights into the organization of language related networks. Increasing evidence supports the model of dorsal and ventral streams of information flow between language-related areas. Therefore, a review of the descriptions of language-related fiber anatomy in the human and monkey brain was performed. In addition, case studies of macroscopical fiber dissection and polarized light imaging (PLI) with special focus on the ventral stream were done. Several fiber structures can be identified to play a role in language, i.e. the arcuate fasciculus as a part of the superior longitudinal fasciculus, the middle longitudinal fasciculus, the inferior fronto-occipital fasciculus, and extreme and external capsules. Substantial differences between human and monkey fiber architecture have been identified. Despite inconsistencies based on different terminologies used, there can be no doubt that dorsal and ventral language streams have a clear correlation in the structure of white matter tracts.

Decreased Olfactory Bulb Volume in Idiopathic Parkinson's Disease Detected by 3.0-Tesla Magnetic Resonance Imaging

A number of neuropathological studies have demonstrated that the olfactory system is among the first brain regions affected in Parkinsons disease (PD). These findings correlate with pathophysiological and pathological data that show a loss in olfactory bulb (OB) volume in patients with PD. However, to date, MRI has not been a reliable method for the in vivo detection of this volumetric loss in PD. Using a 3.0‐Tesla MRI constructive interference in the steady‐state sequence, OB volume was evaluated in patients with PD (n = 16) and healthy control subjects (n = 16). A significant loss of OB volume was observed in patients with PD, compared to the healthy control group (91.2 ± 15.72 versus 131.4 ± 24.56 mm3, respectively). Specifically, decreased height of the left OB appears to be a reliable parameter that is adaptable to clinical practice and significantly correlates with OB volume loss in patients with idiopathic PD. Measuring both the volume and height of the OB by MRI may be a valuable method for the clinical investigation of PD.

Dependence of the negative BOLD response on somatosensory stimulus intensity

The primary somatosensory cortex (SI) has been shown to encode the intensity of a stimulus applied to the contralateral side of the body. Recent studies have demonstrated that ipsilateral SI is also involved in the processing of somatosensory information. In this study, we investigated the dependence of the negative BOLD response in ipsilateral SI on the intensity of somatosensory stimulation. Functional MRI was performed in 12 healthy subjects during electrical median nerve stimulation at four different intensities. A monotonic relationship between stimulus intensity and the strength of the negative BOLD response in ipsilateral SI was found. Additionally, a psychophysiological experiment revealed tight coupling between the stimulus intensity applied to one hand and increased perceptual threshold of the other hand. These findings indicate a stimulus intensity-dependent inhibition of ipsilateral SI.

Functional deactivations: multiple ipsilateral brain areas engaged in the processing of somatosensory information.

Somatosensory signals modulate activity throughout a widespread network in both of the brain hemispheres: the contralateral as well as the ipsilateral side of the brain relative to the stimulated limb. To analyze the ipsilateral somatosensory brain areas that are engaged during limb stimulation, we performed functional magnetic resonance imaging (fMRI) in 12 healthy subjects during electrical median nerve stimulation using both a block‐ and an event‐related fMRI design. Data were analyzed through the use of model‐dependent (SPM) and model‐independent (ICA) approaches. Beyond the well‐known positive blood oxygenation level‐dependent (BOLD) responses, negative deflections of the BOLD response were found consistently in several ipsilateral brain areas, including the primary somatosensory cortex, the supplementary motor area, the insula, the dorsal part of the posterior cingulate cortex, and the contralateral cerebellum. Compared to their positive counterparts, the negative hemodynamic responses showed a different time course, with an onset time delay of 2.4 s and a peak delay of 0.7 s. This characteristic delay was observed in all investigated areas and verified by a second (purely tactile) event‐related paradigm, suggesting a systematic difference for brain areas involved in the processing of somatosensory information. These findings may indicate that the physiological basis of these deactivations differs from that of the positive BOLD responses. Therefore, an altered model for the negative BOLD response may be beneficial to further model‐dependent fMRI analyses. Hum Brain Mapp, 2010.

Age-related changes in the somatosensory processing of tactile stimulation—An fMRI study

Age-related changes in brain function are complex. Although ageing is associated with a reduction in cerebral blood flow and neuronal activity, task-related processing is often correlated with an enlargement of the corresponding and additionally recruited brain areas. This supplemental employment is considered an attempt to compensate for deficits in the ageing brain. Although there are contradictory reports regarding the role of the primary somatosensory cortex (SI), currently, there is little knowledge about age-related functional changes in other brain areas in the somatosensory network (secondary somatosensory cortex (SII), and insular, anterior (ACC) and posterior cingulate cortices (PCC)). We investigated 16 elderly (age range, 62-71 years) and 18 young subjects (age range, 21-28 years) by determining the current perception threshold (CPT) and applying functional magnetic resonance imaging (fMRI) using a 3.0 Tesla scanner under tactile stimulation of the right hand. CPT was positively correlated with age. fMRI analysis revealed significantly increased activation in the contralateral SI and ipsilateral motor cortex in elderly subjects. Furthermore, we demonstrated age-related reductions in the activity in the SII, ACC, PCC, and dorsal parts of the corpus callosum. Our study revealed dramatic age-related differences in the processing of a simple tactile stimulus in the somatosensory network. Specifically, we detected enhanced activation in the contralateral SI and ipsilateral motor cortex assumingly caused by deficient inhibition and decreased activation in later stages of somatosensory processing (SII, cingulate cortex) in elderly subjects. These results indicate that, in addition to over-activation to compensate for impaired brain functions, there are complex mechanisms of modified inhibition and excitability involved in somatosensory processing in the ageing brain.

Cortical reorganization in Bell's palsy

PURPOSE Bells palsy, a unilateral, idiopathic facial nerve palsy, is a common disorder that is generally followed by a good recovery of function. The aim of this study was to investigate the impact of such a transiently decreased motor control (without deafferentation) on the functional reorganization of the brain. METHODS To address this issue, functional MRI was applied to 10 patients in the acute state of Bells palsy and after their complete clinical recovery. The functional paradigm consisted of unilateral facial movements with the affected as well as the non-affected side. RESULTS We found an overactivity of several brain areas contralateral to the palsy that are related to error detection and sensory-motor integration in the acute stage and motor integration and control in the follow-up. Functional connectivity was disrupted in the affected cortical motor system during the acute stage of Bells palsy compared to the follow-up. This altered connectivity was found mostly between motor areas in the hemisphere contralateral to the paretic side, whereas the interhemispherical connectivity remained largely stable. CONCLUSION Our results indicate that a transient peripheral deefferentation causes functional reorganization in the brain that partly persists even after an apparently complete clinical recovery.

Prognostication of recovery time after acute peripheral facial palsy: a prospective cohort study

Objective Owing to a lack of prospective studies, our aim was to evaluate diagnostic factors, in particular, motor and non-motor function tests, for prognostication of recovery time in patients with acute facial palsy (AFP). Design Prospective cohort study. Setting University hospital. Participants 259 patients with AFP. Measurements Clinical data, facial grading, electrophysiological motor function tests and other non-motor function tests were assessed for their contribution to recovery time. Results The predominant origin of AFP was idiopathic (59%) and traumatic (21%). At baseline, the House-Brackmann scale (HB) was >III in 46% of patients. Follow-up time was 5.6±9.8 months with a complete recovery rate of 49%. The median recovery time was 3.5 months (95% CI 2.2 to 4.7 months). The following variables were associated with faster recovery: Interval between onset of AFP and treatment <6 days versus ≥6 days (median recovery time in months 2.1 vs 6.5; p<0.0001); HB ≤III vs >III (2.2 vs 4.6; p=0.001); no versus presence of pathological spontaneous activity in first electromyography (EMG; 2.8 vs probability of recovery <50%; p<0.0001); no versus voluntary activity in EMG (probability of recovery <50% vs 3.1; p<0.0001); normal versus pathological ipsilateral electroneurography (1.9 vs 6.5; p=0.008), normal versus pathological stapedius reflexes (1.6 vs 3.3; p=0.003). Conclusions Start of treatment and grading, but most importantly EMG evaluated for pathological spontaneous activity and the stapedius reflex test are powerful prognosticators for estimating the recovery time from AFP. These results need confirmation in larger datasets.

Time Course of Cortical Plasticity After Facial Nerve Palsy A Single-Case Study

Background. Functional connectivity is defined as the temporal correlation between spatially remote neurophysiological events. This method has become particularly useful for studying neuroplasticity to detect changes in the collaboration of brain areas during cortical reorganization. Methods. In this article, the authors longitudinally studied voxel-based morphometry and resting state functional magnetic resonance imaging 10 times in 1 patient during the course of Bell palsy (idiopathic facial nerve palsy) up to complete clinical recovery. Results. Morphometric analysis revealed a significant alteration in the face area of the primary motor cortex (M1) contralateral to the paretic face, with an initial increase in gray matter concentration. Functional connectivity analysis between the M1 and other parts of the facial motor network revealed acutely disrupted intrahemispheric connectivity but unaltered interhemispheric connectivity. The disrupted functional connectivity was most pronounced on the day of the onset of symptoms, with a subsequent return toward normal during the course of recovery. This time course was found to differ between the selected parts of the facial motor network. However, the increase in functional connectivity strength preceded clinical recovery in all areas and reached a stable level before the patient fully recovered. Conclusion. These results demonstrate that recovery from facial nerve palsy is complemented by cortical reorganization, with pronounced changes of functional connectivity that precede clinical recovery.