Klaus Scheffler

Processing of Temporal Unpredictability in Human and Animal Amygdala

The amygdala has been studied extensively for its critical role in associative fear conditioning in animals and humans. Noxious stimuli, such as those used for fear conditioning, are most effective in eliciting behavioral responses and amygdala activation when experienced in an unpredictable manner. Here, we show, using a translational approach in mice and humans, that unpredictability per se without interaction with motivational information is sufficient to induce sustained neural activity in the amygdala and to elicit anxiety-like behavior. Exposing mice to mere temporal unpredictability within a time series of neutral sound pulses in an otherwise neutral sensory environment increased expression of the immediate-early gene c-fos and prevented rapid habituation of single neuron activity in the basolateral amygdala. At the behavioral level, unpredictable, but not predictable, auditory stimulation induced avoidance and anxiety-like behavior. In humans, functional magnetic resonance imaging revealed that temporal unpredictably causes sustained neural activity in amygdala and anxiety-like behavior as quantified by enhanced attention toward emotional faces. Our findings show that unpredictability per se is an important feature of the sensory environment influencing habituation of neuronal activity in amygdala and emotional behavior and indicate that regulation of amygdala habituation represents an evolutionary-conserved mechanism for adapting behavior in anticipation of temporally unpredictable events.

Multiecho Sequences with Variable Refocusing Flip Angles: Optimization of Signal Behavior Using Smooth Transitions between Pseudo Steady States (TRAPS)

A variation of the rapid acquisition with relaxation enhancement (RARE) sequence (also called turbo spin‐echo (TSE) or fast spin‐echo (FSE)) is presented. This technique uses variable flip angles along the echo train such that magnetization is initially prepared into the static pseudo steady state (PSS) for a low refocusing flip angle (α < 180°). It is shown that after such a preparation, magnetization will always stay very close to the static PSS even after significant variation of the subsequent refocusing flip angles. This allows the design of TSE sequences in which high refocusing flip angles yielding 100% of the attainable signal are applied only for the important echoes encoding for the center of k‐space. It is demonstrated that a reduction of the RF power (RFP) by a factor of 2.5–6 can be achieved without any loss in signal intensity. The contribution of stimulated‐echo pathways leads to a reduction of the effective TE by a factor ft, which for typical implementations is on the order of 0.5–0.8. This allows the use of longer echo readout times, and thus longer echo trains, for acquiring images with a given T2 contrast. Magn Reson Med 49:527–535, 2003.

Magnetization preparation during the steady state: Fat-saturated 3D TrueFISP

A novel fat saturation scheme is proposed which combines spectral fat saturation with a steady‐state 3D true Fast Imaging with Steady Precesson (TrueFISP) sequence. Fat saturation consisted of a conventional frequency‐selective excitation pulse surrounded by spoiler gradients. This saturation block was periodically repeated within a continuously running TrueFISP sequence. Except for the fat signals, the steady‐state signal formation and the resulting image contrast of TrueFISP was not modified by the periodically inserted fat saturation block. This was achieved by a α/2 flip‐back pulse before the fat saturation block, which stores the established steady‐state transverse magnetization as pure longitudinal magnetization. After fat saturation this longitudinal magnetization was excited by a α/2 preparation pulse to continue the TrueFISP acquisition. The resulting images show contrast identical to conventional TrueFISP images, but without the usually very bright fat signals. The short repetition time allows acquisition of a 3D data set of the abdomen within a single breath‐hold. Magn Reson Med 45:1075–1080, 2001.

T1 quantification with inversion recovery TrueFISP

A snapshot FLASH sequence can be used to acquire the time course of longitudinal magnetization during its recovery after a single inversion pulse. However, excitation pulses disturb the exponential recovery of longitudinal magnetization and may produce systematic errors in T1 estimations. In this context the possibility of using the TrueFISP sequence to detect the recovery of longitudinal magnetization for quantitative T1 measurements was examined. Experiments were performed on different Gd‐doped water phantoms and on humans. T1 values derived from inversion recovery TrueFISP were in excellent agreement with the single‐point method even for flip angles up to 50°. In terms of T1 accuracy and SNR, the proposed method seems to be superior to the conventional inversion recovery snapshot FLASH technique. Magn Reson Med 45:720–723, 2001.

Tonotopic organization of the human auditory cortex as detected by BOLD-FMRI

Functional magnetic resonance imaging is a noninvasive and nonradioactive method for the detection of focal brain activity. In the present study the auditory cortex was investigated in nine normal subjects who were binaurally stimulated using pulsed sine tones of 500 Hz and 4000 Hz. The BOLD (blood oxygenation level dependent) signal change coincided with the stimulation paradigm and was detected in the plane of the superior temporal gyrus. The comparison of the spatial distribution of activated areas revealed a different behavior for the two frequencies. The present findings underline the existence of a frequency specific organization in the medio-lateral, fronto-occipital and cranio-caudal extension in both hemispheres of the auditory cortex in human. The activated areas for the high tone were found more frontally and medially orientated than the low tone stimulated areas. Furthermore, a slight cranio-caudal shift was observed for the higher frequency, more pronounced in the right than in the left temporal lobe. Finally, for most of the subjects investigated the BOLD activation area of the 500 Hz sine tone was larger than that of the 4000 Hz stimulation. Both frequencies showed a lateralization of signal response to the left temporal lobe.

Is TrueFISP a gradient‐echo or a spin‐echo sequence?

It is commonly accepted that TrueFISP (balanced FFE, FIESTA) belongs to the class of gradient‐echo (GRE) sequences. GRE sequences are sensitive to dephasing effects of the transverse magnetization between the excitation pulse and echo acquisition, and phase coherence is only established directly after and before excitation pulses. However, an analysis of the phase evolution of transverse magnetization in a TrueFISP experiment shows very close similarities to the echo formation of a spin‐echo (SE) experiment. If dephasing between excitation pulses is below ±π, TrueFISP exhibits a nearly complete refocusing of transverse magnetization at TE = TR/2. Only signals acquired before and after TR/2 show an additional T  *2 sensitivity. Magn Reson Med 49:395–397, 2003.

A pictorial description of steady-states in rapid magnetic resonance imaging

Magnetic resonance imaging in biochemical and clinical research requires rapid imaging sequences. Time-resolved imaging of heart movement and the acquisition of a three-dimensional image block within the circulation time of a contrast agent bolus are two typical examples. Rapid imaging sequences are characterized by a very fast train of radiofre- quency (rf) and gradient pulses. Between these rf pulses, the excited magnetization is unable to return to its thermal equilibrium. As a consequence, further rf pulses will influence both the remaining transversal and the remaining equilibrium state. The steady-state magnetization of a multi-rf pulse and gradient pulse experiment is thus a mixture or superposition of different transversal and longitudinal states and the acquired image amplitude becomes a complex func- tion of the investigated tissues relaxation properties. Based on the works of Woessner, Kaiser, and Hennig, this article intends to give a pictorial description of rapid multipulse imaging ex- periments. It also provides an extension of this theory applied to modern imaging sequences such as TRUE FISP and rf-spoiled techniques.

Neural Processing of Auditory Looming in the Human Brain

Acoustic intensity change, along with interaural, spectral, and reverberation information, is an important cue for the perception of auditory motion. Approaching sound sources produce increases in intensity, and receding sound sources produce corresponding decreases. Human listeners typically overestimate increasing compared to equivalent decreasing sound intensity and underestimate the time to contact of approaching sound sources. These characteristics could provide a selective advantage by increasing the margin of safety for response to looming objects. Here, we used dynamic intensity and functional magnetic resonance imaging to examine the neural underpinnings of the perceptual priority for rising intensity. We found that, consistent with activation by horizontal and vertical auditory apparent motion paradigms, rising and falling intensity activated the right temporal plane more than constant intensity. Rising compared to falling intensity activated a distributed neural network subserving space recognition, auditory motion perception, and attention and comprising the superior temporal sulci and the middle temporal gyri, the right temporoparietal junction, the right motor and premotor cortices, the left cerebellar cortex, and a circumscribed region in the midbrain. This anisotropic processing of acoustic intensity change may reflect the salience of rising intensity produced by looming sources in natural environments.

On the transient phase of balanced SSFP sequences

The signal intensity of balanced steady‐state free precession (SSFP) imaging is a function of the proton density, T1, T2, flip angle (α), and repetition time (TR). The steady‐state signal intensity that is established after about 5*T1/TR can be described analytically. The transient phase or the approach of the echo amplitudes to the steady state is an exponential decay from the initial amplitude after the first excitation pulse to the steady‐state signal. An analytical expression of the decay rate of this transient phase is presented that is based on a simple analysis derived from the Bloch equations. The decay rate is a weighted average of the T1 and T2 relaxation times, where the weighting is determined by the flip angle of the excitation pulses. Thus, balanced SSFP imaging during the transient phase can provide various contrasts depending on the flip angle and the number of excitation pulses applied before the acquisition of the central k‐space line. In addition, transient imaging of hyperpolarized nuclei, such as 3He, 129Xe, or 13C, can be optimized according to their T1 and T2 relaxation times. Magn Reson Med 49:781–783, 2003.

Blood Oxygenation Level–Dependent Magnetic Resonance Imaging of the Skeletal Muscle in Patients With Peripheral Arterial Occlusive Disease

Background— Blood oxygenation level–dependent (BOLD) magnetic resonance imaging (MRI) has been used to measure T2* changes in skeletal muscle tissue of healthy volunteers. The BOLD effect is assumed to primarily reflect changes in blood oxygenation at the tissue level. We compared the calf muscle BOLD response of patients with peripheral arterial occlusive disease (PAOD) to that of an age-matched non-PAOD group during postischemic reactive hyperemia. Methods and Results— PAOD patients (n=17) with symptoms of intermittent calf claudication and an age-matched non-PAOD group (n=11) underwent T2*-weighted single-shot multiecho planar imaging on a whole-body magnetic resonance scanner at 1.5 T. Muscle BOLD MRI of the calf was performed during reactive hyperemia provoked by a cuff-compression paradigm. T2* maps were generated with an automated fitting procedure. Maximal T2* change (&Dgr;T2*max) and time to peak to reach &Dgr;T2*max for gastrocnemius, soleus, tibial anterior, and peroneal muscle were evaluated. Compared with the non-PAOD group, patients revealed significantly lower &Dgr;T2*max-values, with a mean of 7.3±5.3% versus 13.1±5.6% (P<0.001), and significantly delayed time-to-peak values, with a mean of 109.3±79.3 versus 32.2±13.3 seconds (P<0.001). Conclusions— T2* time courses of the muscle BOLD MRI signal during postocclusive reactive hyperemia revealed statistically significant differences in the key parameters (&Dgr;T2*max; time to peak) in PAOD patients compared with age-matched non-PAOD controls.