Lars J. Kemna

Modulation of the neuronal circuitry subserving working memory in healthy human subjects by repetitive transcranial magnetic stimulation

We studied the effect of repetitive transcranial magnetic stimulation (rTMS) on changes in regional cerebral blood flow (rCBF) as revealed by positron emission tomography (PET) while subjects performed a 2-back verbal working memory (WM) task. rTMS to the right or left dorsolateral prefrontal cortex (DLPFC), but not to the midline frontal cortex, significantly worsened performance in the WM task while inducing significant reductions in rCBF at the stimulation site and in distant brain regions. These results for the first time demonstrate the ability of rTMS to produce temporary functional lesions in elements of a neuronal network thus changing its distributed activations and resulting in behavioral consequences.

Effect of graded hypo‐ and hypercapnia on fMRI contrast in visual cortex: Quantification of T *2 changes by multiecho EPI

The sensitivity of functional magnetic resonance imaging (fMRI) in visual cortex to graded hypo‐ and hypercapnia was quantified in 10 normal subjects using single‐shot multiecho echo‐planar imaging (Turbo‐PEPSI) with eight equidistant echo times (TEs) between 12 and 140 ms. Visual stimulation was combined with controlled hyperventilation and carbon dioxide inhalation to perform fMRI at six levels of end‐expiratory pCO2 (PETCO2) between 20 and 70 mm Hg. T  *2 in visual cortex during baseline conditions (light off) increased nonlinearly from 20 to 70 mm Hg, from 61.1 ± 4.2 ms to 72.0 ± 4.6 ms. Changes in T  *2 due to visual stimulation increased 2.1‐fold, from 1.2 ± 0.6 ms at 20 mm Hg to 2.5 ± 0.7 ms at 50 mm Hg. An almost complete loss of functional contrast was measured at 70 mm Hg. The model of MR signal dephasing by Yablonskiy and Haacke (Mag Reson Med 1994;32:749–763) was used to predict changes in cerebral blood flow (CBF), which were found to be consistent with results from previous positron emission tomography (PET) studies. This study further emphasizes that global CBF changes (due to PETCO2 changes even in the physiological range) strongly influence fMRI contrast and need to be controlled for. Magn Reson Med 46:264–271, 2001.

Modulation of a brain-behavior relationship in verbal working memory by rTMS.

We investigated whether the brain-behavior relationship (BBR) between regional cerebral blood flow (rCBF) as measured by positron emission tomography (PET) and individual accuracy in verbal working memory (WM) can be modulated by repetitive transcranial magnetic stimulation (rTMS) of the left or right middle frontal gyrus (MFG). Fourteen right-handed male subjects received a 30-s rTMS train (4 Hz, 110% motor threshold) to the left or right MFG during a 2-back WM task using letters as stimuli. Simultaneously an rCBF PET tracer was injected and whole-brain functional images were acquired. A hypothesis-driven region-of-interest-analysis of the left and right MFG BBR as well as an explorative whole-brain analysis correlating the individual accuracy with rCBF was carried out. Without rTMS we found a negative BBR in the left but no significant BBR in the right MFG. This negative BBR is best explained by an increased effort of volunteers with an inferior task performance. Left-sided rTMS led to a shift of the BBR towards the superior frontal gyrus (SFG) and to a positive BBR in anterior parts of the left SFG. With rTMS of the right MFG the BBR was posterior and inferior in the left inferior frontal gyrus. Beyond the cognitive subtraction approach this correlation analysis provides information on how the prefrontal cortex is involved based on individual performance in working memory. The results are discussed along the idea of a short-term plasticity in an active neuronal network that reacts to an rTMS-induced temporary disruption of two different network modules.

Single-shot T2* mapping with 3D compensation of local susceptibility gradients in multiple regions

Macroscopic magnetic field inhomogeneities severely limit sensitivity of blood oxygenation level-dependent (BOLD) functional MRI (fMRI) in frontal and central brain regions close to brain stem. A single-shot multiecho echo-planar imaging method (TurboPEPSI) was developed that combines quantitative T(2)* mapping with gradient compensation of local susceptibility inhomogeneities in multiple volumes of interest (VOIs). Gradient compensation was optimized in individual subjects based on magnetic field mapping and applied at selected echo times, interleaved with acquisition of uncompensated echoes. Intrinsic T(2)* values from uncompensated echoes were obtained in real-time simultaneously with effective T(2)* values from gradient compensated echoes. It is demonstrated that up to three VOIs can be compensated in a single excitation, in addition to collecting uncompensated data, using 8-echo acquisition on a clinical 1.5 Tesla scanner. A theory was developed to optimize the sequence of uncompensated and compensated echoes to achieve maximum BOLD sensitivity. Gradient compensation increased effective T(2)* values in left and right amygdala on average by 18.8 +/- 7.5 ms, while maintaining sensitivity in uncompensated brain areas. In orbitofrontal cortex effective T(2)* values increased by 22.2 +/- 5.3 ms. A CO(2) challenge paradigm was used to demonstrate that this gradient compensation method significantly enhances BOLD signal changes in amygdala as compared to conventional echo-planar imaging (EPI) and uncompensated TurboPEPSI.

Interdependence of regional and global cerebral blood flow during visual stimulation: an O-15-butanol positron emission tomography study.

The authors investigated the influence of variations in global cerebral blood flow (gCBF) on regional flow changes during visual stimulation. Global flow was varied using different end-expiratory CO2 values (Petco2) between 20 and 70 mm Hg. Visual stimulation was performed with a red LED-array flashing at 8 Hz. Blood flow was measured with O-15-butanol, continuous arterial blood sampling, and positron emission tomography (PET). Global flow changes surpassed the published values of O-15-H2O studies, better fitting the results of the inert gas technique (gCBF at 20, 40, and 70 mm Hg Petco2 ± SD was 31 ± 4, 48 ± 13, and 160 ± 50 mL 100 g−1 min−1, respectively). The relation between Petco2 and CBF in the current study was best described by an exponential rather than a linear function. At low Petco2, the activation-induced flow changes are moderately damped, whereas at high Petco2, they are nearly lost (ΔCBF (±SD): 52% ± 25%, 68% ± 22%, 16% ± 25% at Petco2 = 20, 40, 70 mm Hg, respectively).

O-15-butanol is superior to O-15-water in detecting visual activation

Introduction: Two radiotracers, 0-15-water and 0-15-butanol are typically employed to assess cerebral blood flow, the first much more frequently, although butanol seems to be better suited because of its better extraction and therefore better capabilities for measuring high flows. We compared the uptake and the kinetics of the two tracers in the same subjects during visual stimulation using a well-defined parametric approach.