Ernst Nennig

fMRI reflects functional connectivity of human somatosensory cortex.

Unilateral sensory stimulation reliably elicits contralateral somatotopic activation of primary (SI) and secondary (SII) somatosensory cortex. There is an ongoing debate about the occurrence and nature of concomitant ipsilateral SI and SII activation. Here we used functional magnetic resonance imaging (fMRI) in healthy human subjects with unilateral tactile stimulation of fingers and lips, to compare somatosensory activation patterns from distal and proximal body parts. We hypothesized that fMRI in humans should reflect the functional connectivity of somatosensory cortex as predicted by animal studies. We show that both unilateral finger and lip stimulations activate contra- and ipsilateral SI and SII cortices with high detection frequency. Correlations of BOLD-signals to the applied hemodynamic reference function were significantly higher in contralateral as compared to ipsilateral SI and SII cortices for both finger and lip stimulation, reflecting strong contribution of contralateral thalamocortical input. Furthermore, BOLD-signal correlations were higher in SI than in SII activations on the contralateral but not on the ipsilateral side. While these asymmetries within and across hemispheres were consistent for finger and lip stimulations, indicating analogous underlying organizing principles, they were less prominent for lip stimulation. Somatotopic organization was detected in SI but not in SII representations of fingers and lips. These results qualitatively and quantitatively support the prevalent concepts of anatomical and functional connectivity in the somatosensory system and therefore may allow interpretation of sensory evoked fMRI signals in terms of normal human brain function. Thus, the assessment of human somatosensory function with fMRI may permit in the future investigations of pathological conditions.

Gender-specific strategy use and neural correlates in a spatial perspective taking task.

In the context of the present study spatial perspective taking refers to the ability to translocate ones own egocentric viewpoint to somebody elses viewpoint in space. We adopted a spatial perspective taking paradigm and performed a functional magnetic resonance imaging study to assess gender differences of neural activity during perspective taking. 24 healthy subjects (12 male/12 female) were asked to systematically either take their own (first-person-perspective, 1PP) or another persons perspective (third-person-perspective, 3PP). Presented stimuli consisted of a virtual scenery with an avatar and red balls around him that had to be counted, if visible, from 1PP or 3PP. Reaction time was increased and correctness scores were decreased during the cognitively more effortful 3PP condition. Correctness scores showed a trend towards a more pronounced decline of performance during 3PP as compared to 1PP in female subjects. Female subjects correctness scores declined by 6.7% from 1PP to 3PP, while in male subjects this performance decline was only 2.7%. Debriefings after the experiment, reaction times depending on angle of rotation and error rates suggest that males are more likely to employ an object-based strategy in contrast to a consistently employed egocentric perspective transformation in females. In the whole group, neural activity was increased in the parieto-occipital, right inferior frontal and supplementary motor areas, confirming previous studies. With respect to gender, male subjects showed stronger activation in the precuneus and the right inferior frontal gyrus than female subjects in a region-of-interest approach. In a subgroup of male subjects whose strategy reports suggest object-based strategies these differences seem to be more pronounced. In conclusion, the differential recruitment of brain regions most likely reflects different strategies in solving this spatial perspective taking task.

DTI of commissural fibers in patients with Chiari II-malformation.

Chiari II-malformation is a complex congenital deformity of the brain which is frequently associated with hydrocephalus. Abnormalities of the corpus callosum are known to occur in the majority of patients. The objective of the present study was to study the microstructure of the corpus callosum (CC) and the anterior commissure (AC) to differentiate between different mechanisms of damage to these structures. We investigated 6 patients with Chiari II-malformation and 6 well-matched healthy volunteers employing T1-weighted 3D imaging and diffusion tensor imaging (DTI) to determine the fractional anisotropy (FA) and cross-sectional area of the CC and AC, as well as with neuropsychological testing. Four patients showed hydrocephalus, two patients had callosal dysplasia and four had a hypoplastic CC. The callosal FA in the patients was significantly reduced which was less pronounced for the genu alone. The area of CC was also reduced in Chiari II-patients. There was a strong correlation between the size and FA of the CC in the patients. In contrast, the thickness of the AC was significantly increased and was associated with higher FA in the patients. In psychological tests all patients showed reduced verbal memory; all but one patient showed reduced IQ as well as impaired visuo-spatial performance, indicating deficits in tasks requiring parieto-occipital integration. The existence of callosal dysplasia in two patients, the diminished FA reduction in the genu and the correlation of the cross-sectional area and FA in the patients point to a developmental white matter damage beside that exerted by hydrocephalus alone.

Clinical functional MRI of sensorimotor cortex using passive motor and sensory stimulation at 3 tesla

To establish a passive motor paradigm for clinical functional MRI (fMRI) that could be beneficial for patients with motor or attention deficits who are not able to perform active motor tasks.

Fully automated localization of the human primary somatosensory cortex in one minute by functional magnetic resonance imaging.

A clinical functional magnetic resonance imaging (fMRI) protocol based on a fully automated tactile stimulation was optimized in 10 right-handed volunteers at 1.5 T for minimum scan time, high BOLD-signals and robust localization of the primary somatosensory cortex (S1) by systematically varying the applied block design. All volunteers had six different fMRI measurements of 5 stimulation/baseline cycles each with equal block duration that was changed between the measurements from 6 to 30 s. Data sets of 4, 3 and 2 cycles were generated post hoc resulting in a total of 240 data sets that were evaluated individually for BOLD-signal intensity (dS%), correlation to the hemodynamic reference function (r) and Euclidean coordinates (x, y, z). The protocol with 5 cycles, a block duration of 6 s and a total scan time of 66 s provided the best BOLD-signal characteristics (dS% = 1.15, r = 0.78). Compared to the mean scan time of other clinical fMRI protocols (174 s) a reduction of 62% was achieved.

Time-efficient localization of the human secondary somatosensory cortex by functional magnetic resonance imaging

Standardized, robust and time-efficient localization of the human secondary somatosensory cortex (S2) is a challenge in clinical blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). A fully automated tactile stimulation was optimized in seven right-handed volunteers at 1.5 T for minimum scan time, high BOLD signals and robust localization of S2 by systematically varying the applied block-design. All volunteers had six different fMRI measurements of five stimulation-baseline-cycles (sbc) each with equal block duration that was changed between the measurements from 6 s to 30 s. Additional data sets of 4, 3 and 2 cycles were generated post hoc resulting in a total of 168 data sets that were evaluated individually for BOLD-signal intensity (dS%), correlation to the hemodynamic reference function (r) and Euclidean coordinates (x, y, z). Using different block-designs the S2 activation was highly variable regarding the localization rate (lr), the hemispheric symmetry and the BOLD-signals. The protocol with 3 cycles, a block duration (dp) of 15 s and a total scan time (dt) of 105 s most robustly localized S2 (contralateral: lr=71.4%, r=0.65, dS=1.01%; ipsilateral: lr=100%, r=0.6, dS=1.14%) whereas the most time-efficient protocol to localize SI (sbc=5, dp=6 s, dt=66 s) provided no robust localization of S2. Compared to other published fMRI protocols a scan time reduction up to 86% was achieved.

Effects of Covert and Overt Paradigms in Clinical Language fMRI

RATIONALE AND OBJECTIVES The aim of this study was to assess the intrasubject and intersubject reproducibility of functional magnetic resonance imaging (fMRI) language paradigms on language localization and lateralization. MATERIALS AND METHODS Fourteen healthy volunteers were enrolled prospectively and underwent language fMRI using visually triggered covert and overt sentence generation (SG) and word generation (WG) paradigms. Semiautomated analysis of all functional data was performed using Brain Voyager on an individual basis. Regions of interest for Brocas area, Wernickes area, and their contralateral homologues were drawn. The Euclidean coordinates of the center of gravidity (x, y, and z) of the respective blood oxygenation level-dependent (BOLD) activation cluster, and the correlation of the measured hemodynamic response to the applied reference function (r), relative BOLD signal change as BOLD signal characteristics were measured in each region of interest. Regional lateralization indexes were calculated for Brocas area, Wernickes area, and their contralateral homologues separately. Wilcoxons signed-rank test was applied for statistical comparisons (P values < .05 were considered significant). Ten of the 14 volunteers had three repeated measurements to test intrasession reproducibility and intersession reproducibility. RESULTS Overall activation rates for the four paradigms were 89% for covert SG, 82% for overt SG, 89% for covert WG, and 100% for overt WG. When comparing covert and overt paradigms, language localization was significantly different in 17% (Euclidean coordinates) and 19% (BOLD signal characteristics), respectively. Language lateralization was significantly different in 75%. Intrasubject and intersubject reproducibility was excellent, with 3.3% significant differences among all five parameters for language localization and 0% significant differences for language lateralization using covert paradigms. CONCLUSIONS Covert language paradigms (SG and WG) provided highly robust and reproducible localization and lateralization of essential language centers for scans performed on the same and different days. Their overt counterparts achieved confirmatory localization but lower lateralization capabilities. Reference data for presurgical application are provided.

Volumetric measurement of the pontomesencephalic cistern in patients with trigeminal neuralgia and healthy controls.

OBJECTIVE:Most so-called idiopathic trigeminal neuralgias (TN) are caused by neurovascular compression. Does the size of the cerebellopontine cistern play a role in favoring a neurovascular conflict? The aim of this prospective study was to measure the volume of the parapontine cistern in patients with idiopathic TN and to perform a comparison with healthy controls. METHODS:In 25 patients with unilateral idiopathic TN and 17 healthy participants, high-resolution 1.5-T magnetic resonance imaging scans of the parapontine region and the trigeminal nerve were performed. A coronal T2-weighted, true fast imaging steady-state precession sequence with a slice thickness of 0.9 mm was used to define the surrounding cerebrospinal fluid space from the trigeminal root entry zone to Meckel’s cave. The volume of the pontomesencephalic cistern was calculated using a standardized method. RESULTS:The mean difference of the volume of the affected and opposite side was 13% in patients with TN. In all patients, a significantly smaller volume of the cistern was found on the affected side (P < 0.01). Healthy controls showed a mean volumetric side difference of 9%, which was not significant (P > 0.05). CONCLUSION:High-resolution magnetic resonance imaging scans are able to demonstrate significant volumetric differences of the pontomesencephalic cistern in patients with unilateral TN. A smaller cistern may be correlated with the occurrence of a neurovascular compression, and these findings support the neurovascular compression theory in idiopathic TN.

Altered somatosensory processing in trigeminal neuralgia.

Trigeminal neuralgia (TN) is a pain state characterized by intermittent unilateral pain attacks in one or several facial areas innervated by the trigeminal nerve. The somatosensory cortex is heavily involved in the perception of sensory features of pain, but it is also the primary target for thalamic input of nonpainful somatosensory information. Thus, pain and somatosensory processing are accomplished in overlapping cortical structures raising the question whether pain states are associated with alteration of somatosensory function itself. To test this hypothesis, we used functional magnetic resonance imaging to assess activation of primary (SI) and secondary (SII) somatosensory cortices upon nonpainful tactile stimulation of lips and fingers in 18 patients with TN and 10 patients with TN relieved from pain after successful neurosurgical intervention in comparison with 13 healthy subjects. We found that SI and SII activations in patients did neither depend on the affected side of TN nor differ between operated and nonoperated patients. However, SI and SII activations, but not thalamic activations, were significantly reduced in patients as compared to controls. These differences were most prominent for finger stimulation, an area not associated with TN. For lip stimulation SI and SII activations were reduced in patients with TN on the contra‐ but not on the ipsilateral side to the stimulus. These findings suggest a general reduction of SI and SII processing in patients with TN, indicating a long‐term modulation of somatosensory function and pointing to an attempt of cortical adaptation to potentially painful stimuli. Hum Brain Mapp, 2009.

Primary motor cortex activation and lateralization in patients with tumors of the central region.

Hemispheric lateralization is a frequently encountered phenomenon of cortical function. It describes the functional specialization of a region on one side of the brain for a given task. It is well characterized in motor and sensory, as well as language systems and becomes more and more known for various cognitive domains. While in the adult healthy brain hemispheric lateralization is mostly set, pathological processes may lead to cortical reorganization. In these cases neuroplasticity of the corresponding region in the non-dominant hemisphere seems to play an important role. In a previous study we investigated language associated regions in right-handed patients with frontal and temporal tumors of the left hemisphere. We observed a marked change of language lateralization in these patients towards the non-dominant hemisphere as measured by functional MRI (Partovi et al., 2012). In the present study we evaluated activation and lateralization of cortical motor areas in patients with tumors of the central region. BOLD fMRI was performed during unilateral voluntary movements of the contralesional hand in 87 patients. Individual correlations of measured BOLD-signals with the model hemodynamic reference function were determined on a ROI basis in single subjects and compared to those of 16 healthy volunteers. In volunteers the strongest activation is usually found in the M1 hand representation contralateral to the movement, while a weaker homotopic co-activation is observed in ipsilateral M1 (Stippich et al., 2007a). In the patient group our results show significant changes of motor activations, ranging from a reduction of M1 lateralization to equalization of M1 activations or even inversion of M1 lateralization during contralesional movements. This study corroborates in a large patient group the idea that lesions affecting M1 may lead to functional reorganization of cortical motor systems and in particular equalize hemispheric lateralization. However, it is not yet clear whether these changes are only an epiphenomenon or indeed reflect an attempt of recovery of brain function.