Christine Preibisch

EEG-correlated fMRI of human alpha activity

Electroencephalography-correlated functional magnetic resonance imaging (EEG/fMRI) can be used to identify blood oxygen level-dependent (BOLD) signal changes associated with both physiological and pathological EEG events. Here, we implemented continuous and simultaneous EEG/fMRI to identify BOLD signal changes related to spontaneous power fluctuations in the alpha rhythm (8-12 Hz), the dominant EEG pattern during relaxed wakefulness. Thirty-two channels of EEG were recorded in 10 subjects during eyes-closed rest inside a 1.5-T magnet resonance (MR) scanner using an MR-compatible EEG recording system. Functional scanning by echoplanar imaging covered almost the entire cerebrum every 4 s. Off-line MRI artifact subtraction software was applied to obtain continuous EEG data during fMRI acquisition. The average alpha power over 1-s epochs was derived at several electrode positions using a Fast Fourier Transform. The power time course was then convolved with a canonical hemodynamic response function, down-sampled, and used for statistical parametric mapping of associated signal changes in the image time series. At all electrode positions studied, a strong negative correlation of parietal and frontal cortical activity with alpha power was found. Conversely, only sparse and nonsystematic positive correlation was detected. The relevance of these findings is discussed in view of the current theories on the generation and significance of the alpha rhythm and the related functional neuroimaging findings.

Severity of dysfluency correlates with basal ganglia activity in persistent developmental stuttering

Previous studies suggest that anatomical anomalies [Foundas, A. L., Bollich, A. M., Corey, D. M., Hurley, M., & Heilman, K. M. (2001). Anomalous anatomy of speech-language areas in adults with persistent developmental stuttering. Neurology, 57, 207-215; Foundas, A. L., Corey, D. M., Angeles, V., Bollich, A. M., Crabtree-Hartman, E., & Heilman, K. M. (2003). Atypical cerebral laterality in adults with persistent developmental stuttering. Neurology, 61, 1378-1385; Foundas, A. L., Bollich, A. M., Feldman, J., Corey, D. M., Hurley, M., & Lemen, L. C. et al., (2004). Aberrant auditory processing and atypical planum temporale in developmental stuttering. Neurology, 63, 1640-1646; Jancke, L., Hanggi, J., & Steinmetz, H. (2004). Morphological brain differences between adult stutterers and non-stutterers. BMC Neurology, 4, 23], in particular a reduction of the white matter anisotropy underlying the left sensorimotor cortex [Sommer, M., Koch, M. A., Paulus, W., Weiller, C., & Buchel, C. (2002). Disconnection of speech-relevant brain areas in persistent developmental stuttering. Lancet, 360, 380-383] could be at the origin of persistent developmental stuttering (PDS). Because neural connections between the motor cortex and basal ganglia are implicated in speech motor functions, PDS could also be associated with a dysfunction in basal ganglia activity [Alm, P. (2004). Stuttering and the basal ganglia circuits: a critical review of possible relations. Journal of Communication Disorders, 37, 325-369]. This fMRI study reports a correlation between severity of stuttering and activity in the basal ganglia and shows that this activity is modified by fluency shaping therapy through long-term therapy effects that reflect speech production improvement. A model of dysfunction in stuttering and possible repair modes is proposed that accommodates the data presented here and observations previously made by us and by others.

Evidence for compensation for stuttering by the right frontal operculum

There is recent evidence of focal alteration in fibre tracts underlying the left sensorimotor cortex in persistent developmental stuttering (PDS) [Lancet 360 (2002) 380]. If, as proposed, this anatomical abnormality is the cause of PDS, then overactivation in the right hemisphere seen with functional neuroimaging in stutterers may reflect a compensatory mechanism. To investigate this hypothesis, we performed two functional magnetic resonance imaging (fMRI) experiments. The first showed systematic activation of a single focus in the right frontal operculum (RFO) in PDS subjects during reading, which was not observed in controls. Responses in this region were negatively correlated with the severity of stuttering, suggesting compensation rather than primary dysfunction. Negative correlation was also observed during the baseline task that consisted in passive viewing of meaningless signs, indicating that RFO compensation acts independently of specific demands on motor speech output. The second experiment, that involved a covert semantic decision task, confirmed that RFO activation does not require overt utterances or motor output. In combination these findings suggest that the RFO serves a nonspecific compensatory role rather than one restricted to the final stages of speech production.

Influence of RF spoiling on the stability and accuracy of T1 mapping based on spoiled FLASH with varying flip angles.

There is increasing interest in quantitative T1 mapping techniques for a variety of applications. Several methods for T1 quantification have been described. The acquisition of two spoiled gradient‐echo data sets with different flip angles allows for the calculation of T1 maps with a high spatial resolution and a relatively short experimental duration. However, the method requires complete spoiling of transverse magnetization. To achieve this goal, RF spoiling has to be applied. In this work it is investigated whether common RF spoiling techniques are sufficiently effective to allow for accurate T1 quantification. It is shown that for most phase increments the apparent T1 can deviate considerably from the true value. Correct results may be achieved with phase increments of 118.2° or 121.8°. However, for these values the method suffers from instabilities. In contrast, stable results are obtained with a phase increment of 50°. An algorithm is presented that allows for the calculation of corrected T1 maps from the apparent values. The method is tested both in phantom experiments and in vivo by acquiring whole‐brain T1 maps of the human brain. Magn Reson Med 61:125–135, 2009.

Functional MRI using sensitivity-encoded echo planar imaging (SENSE-EPI)

Parallel imaging methods become increasingly available on clinical MR scanners. To investigate the potential of sensitivity-encoded single-shot EPI (SENSE-EPI) for functional MRI, five imaging protocols at different SENSE reduction factors (R) and matrix sizes were compared with respect to their noise characteristics and their sensitivity toward functional activation in a motor task examination. At constant echo times, SENSE-EPI was either used to shorten the single volume acquisition times (TR(min)) at matrix size 128 x 100 (22 slices) from 3.9 s (no SENSE) to 2.0 s at R = 3, or to increase the matrix size to 192 x 153 (22 slices), resulting in TR(min) = 5.3 s for R = 2 or TR(min) = 3.4 s for R = 3. At the lower resolution, the bisection of echo train length (R = 2) substantially reduced distortions and blurring, while signal-to-noise and statistical power (measured by cluster size and maximum t value per unit time) were hardly reduced. At R = 3 the additional gain in speed and distortion reduction was quite small, while signal-to-noise and statistical power dropped significantly. With enhanced spatial resolution the time course signal-to-noise was better than expected from theory for purely thermal noise because of a reduced contribution of physiological noise, and statistical power almost reached that of the regular, low-resolution single-shot EPI, with a slight drop off toward R = 3. Thus, SENSE-EPI allows to substantially increase speed and spatial resolution in fMRI. At SENSE reduction factors up to R = 2, the potential drawbacks regarding signal-to-noise and statistical power are almost negligible.

Differential Opioid Action on Sensory and Affective Cerebral Pain Processing

Low doses of morphine, the most commonly used opioid analgesic, have been shown to significantly reduce the affective but not the sensory intensive dimension of pain. This suggests differential dose–response relationships of opioid analgesia on the sensory and affective components of pain. We investigated the effects of different alfentanil plasma concentration levels (0, 19.6±2.7, 47.2±7.6, and 76.6±11.3 ng/ml) on pain‐related brain activation achieved by short pulses of gaseous CO2 delivered to the nasal mucosa, using functional magnetic resonance imaging (fMRI) on a 3.0 T MRI scanner in 16 non‐carriers and 9 homozygous carriers of the μ‐opioid receptor gene variant OPRM1 118A>G. Increasing opioid concentrations had differential effects in brain regions processing the sensory and affective dimensions of pain. In brain regions associated with the processing of the sensory intensity of pain (primary and secondary somatosensory cortices, posterior insular cortex), activation decreased linearly in relation to alfentanil concentrations, which was significantly less pronounced in OPRM1 118G carriers. In contrast, in brain regions known to process the affective dimension of pain (parahippocampal gyrus, amygdala, anterior insula), pain‐related activation disappeared at the lowest alfentanil dose, without genotype differences.

Time course in the development of cerebral vasospasm after experimental subarachnoid hemorrhage: clinical and neuroradiological assessment of the rat double hemorrhage model.

OBJECTIVE:The “double hemorrhage” model in the rat is frequently used to simulate delayed cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) in humans. However, an exact neurological and angiographic characterization of the CVS is not available for this model so far and is provided in the present investigation. Additionally, perfusion weighted imaging (PWI) at 3 tesla magnetic resonance (MR) tomography was implemented to assess the reduction in cerebral blood flow (CBF). METHODS:In a prospective, randomized setting CVS was induced by injection of 0.2 ml autologous blood twice in the cisterna magna of 45 male Sprague-Dawley rats. The surviving animals were examined on Days 2, 3, 5, 7 and 9 and compared to a sham operated control group (n = 9). Rats were neurologically graded between 0 and 3, followed by MRI and selective digital subtraction angiography (DSA). The relative CBF was set in relation to the perfusion of the masseter muscle. RESULTS:The neurological state was significantly worsened on Day 2 (Grade 3), 3 (Grade 3), and 5 (Grade 2) (medians). The relative CBF/muscle BF ratio (2.5 ± 0.8 (SAH) versus 9.2 ± 1.3 (sham) (mean ± SEM) and the basilar artery (BA) diameter (0.15 ± 0.02 mm (SAH) versus 0.32 ± 0.01 mm (sham) were significantly decreased on Day 5. Correlation between relative CBF/muscle BF ratio and BA diameter was 0.70. CONCLUSION:A valid and reproducible CVS simulation was proven by neurological score, DSA, and PWI on Day 5. Furthermore, our data demonstrate the practicability and validity of MR PWI for the monitoring of CVS in a rat SAH model.

Separating brain processing of pain fromthat of stimulus intensity.

Regions of the brain network activated by painful stimuli are also activated by nonpainful and even nonsomatosensory stimuli. We therefore analyzed where the qualitative change from nonpainful to painful perception at the pain thresholds is coded. Noxious stimuli of gaseous carbon dioxide (n = 50) were applied to the nasal mucosa of 24 healthy volunteers at various concentrations from 10% below to 10% above the individual pain threshold. Functional magnetic resonance images showed that these trigeminal stimuli activated brain regions regarded as the “pain matrix.” However, most of these activations, including the posterior insula, the primary and secondary somatosensory cortex, the amygdala, and the middle cingulate cortex, were associated with quantitative changes in stimulus intensity and did not exclusively reflect the qualitative change from nonpainful to pain. After subtracting brain activations associated with quantitative changes in the stimuli, the qualitative change, reflecting pain‐exclusive activations, could be localized mainly in the posterior insular cortex. This shows that cerebral processing of noxious stimuli focuses predominately on the quantitative properties of stimulus intensity in both their sensory and affective dimensions, whereas the integration of this information into the perception of pain is restricted to a small part of the pain matrix. Hum Brain Mapp, 2012.

Rapid single‐scan T 2*‐mapping using exponential excitation pulses and image‐based correction for linear background gradients

A method for fast quantitative T  2* mapping based on multiple gradient‐echo (multi‐GE) imaging with correction for static magnetic field inhomogeneities is described, using an exponential excitation pulse. Field gradient maps are obtained from the phase information and modulus data are subsequently corrected, allowing for simple monoexponential T  2* fitting. Echoes with long echo times suffering from major signal losses due to field inhomogeneities are excluded from the analysis. The acquisition time for a matrix size of 256 × 256, 1 mm in‐plane resolution, and 2 mm slice thickness amounts to 15 s per slice. An additional correction for in‐plane field gradients further improves accuracy. Phantom experiments show that the method provides accurate T  2* values for field gradients up to 200 μT/m; for gradients up to 300 μT/m errors do not exceed 15%. In vivo T  2* values acquired on healthy volunteers at 3T are in excellent agreement with results from the literature. Magn Reson Med, 2009.

Event-related fMRI for the suppression of speech-associated artifacts in stuttering

The purpose of this study was to establish functional magnetic resonance imaging (fMRI) for the investigation of brain function during overt speech production in stuttering. Up to now this technique has rarely been used for the investigation of speech production paradigms because artifacts related to overt speaking largely impair the sensitivity toward task-related activation. Recently, the temporal delay of the hemodynamic response has been exploited to achieve a suppression of speech-related artifacts. By the limitation to very short utterances (one word), a temporal segregation of the respective effects was accomplished by means of an event-related experimental design. However, the investigation of speech production in persons who stutter requires a more extensive speaking situation. Since longer and more complex utterances evoke more symptoms of stuttering than reading of single words, a useful task should at least include the reading of full sentences. In this study we performed simulations to investigate the correlation of speech-related artifacts with the respective hemodynamic response in dependency on speech duration and rate of data sampling. Furthermore, we show that prolonged stimulus durations and repetition times of 3 s still allow an effective suppression of speech-related artifacts in fluent as well as in nonfluent speakers. Not only were obvious false activations at high contrast cerebrospinal fluid tissue borders widely eliminated, subjects also displayed consistent activation in speech-related and motor areas. As these results widely resemble those obtained by earlier neuroimaging studies on language production, event-related fMRI seems to be capable of recording neurophysiological correlates of overt speech production.