Technical note: gold marker implants and high-frequency jet ventilation for stereotactic, single-dose irradiation of liver tumors.

With reference to radiosurgery of the liver, we describe techniques designed to solve the methodological problem of striking targets subject to respiratory motion with the necessary precision. Implanting a gold marker in the vicinity of the liver tumor was the first step in ensuring the reproducibility of the isocenter's position. An 18-karat gold rod measuring 1.9 x 3 mm was implanted approximately 2 cm from the edge of the tumor as this was displayed in the spiral, thin-slice CT with contrast media. Both the implantation of the marker and the required, CT-controlled biopsy of the liver tumor can be achieved simultaneously with the same puncture needle. The efficiency of high-frequency jet ventilation (HFJV) in neutralizing the targeted organ's respiratory motion during stereotactic single-dose irradiation was evaluated. The procedure was carried out on ten patients without any complications. In the time between treatment planning and irradiation (3 days), no significant marker migration was observable. In all cases, the gold marker (volume: 7.5 mm(3)) was readily observable in the treatment beam using portal imaging. HFJV provided reliable immobilization. The liver motion in each anesthetized patient was limited to under 3.0 mm in all directions. Thus, the correct field settings and target reproducibility were able to be analyzed and documented during the irradiation. The combination of marker and HFJV enables the determination of stereotactic coordinates directly related to the liver itself and, in this way, stereotactic radiation treatment of liver tumors is freed from the uncertainties involved in orientation to bony landmarks, in respiratory motion, and in changes of position in the stereotactic body frame. The method is feasible and can improve the accuracy of stereotactic body radiation therapy.

Remote activation of referred phantom sensation and cortical reorganization in human upper extremity amputees.

Phantom limb sensation, whether painful or not, frequently occurs after peripheral nerve lesions. It can be elicited by stimulating body parts adjacent to the amputation site (referred to as phantom sensation) and it is often similar in quality to the stimulation at the remote site. The present study induced referred phantom sensations in two upper limb amputees. Neuroelectric source imaging (ESI) as well as functional magnetic resonance imaging (fMRI) was used to assess reorganization in primary somatosensory cortex (SI). Whereas recent studies found mislocalization of sensation related to stimulation mainly in regions adjacent and ipsilateral to the amputation site, we report here the elicitation of phantom sensation in the arm by stimulation in the lower body part both ipsi- and contralateral to the amputation in two arm amputees. The fMRI evaluation of one patient showed no shift in the location of the foot whereas ESI revealed major reorganization of the mouth region in primary somatosensory cortex in both patients. These data suggest that cortical structures other than SI might be contributing to the phenomenon of referred sensation. Candidate structures are the thalamus, secondary somatosensory cortex, posterior parietal cortex and prefrontal cortex.

The relationship of perceptual phenomena and cortical reorganization in upper extremity amputees.

In this study 16 unilateral upper extremity amputees participated in a comprehensive psychophysiological examination that included the assessment of painful and non-painful phantom and stump sensations, thermal and electric perception as well as two-point discrimination thresholds, the detailed analysis of referred sensation and the measurement of reorganizational changes in primary somatosensory cortex using neuroelectric source imaging. Reorganization of the primary somatosensory cortex was associated with increased habitual phantom limb pain, telescoping, non-painful stump sensations and painful referred sensation induced by painful stimulation. It was unrelated to non-painful phantom sensations, non-painful referred sensation elicited by painful or non-painful stimulation, painful referred sensation elicited by non-painful stimulation, perception thresholds and stump pain. These data substantiate the hypothesis that painful and non-painful phantom phenomena are mediated by different neural substrates.

Steady-state movement-related potentials evoked by fast repetitive movements.

We investigated steady-state movement-related cortical potentials elicited by fast repetitive movements (1/sec) with 50-channel EEG. The experimental design comprised a comparison (a) between unilateral movements of the digits and the toes and (b) between metronome-paced and self-paced initiation of the movements. A distinct biphasic pattern of electrical activity following movement onset was observed, namely a frontal negative peak at a latency of 90 ms (post-MP100) anda frontal positive peak at a latency of 310ms (post-MP300). Pacing exerted its effects mainly on the amplitude and on the latency of the post-MP300. Source analysis revealed that both peaks could be modelled by a single source. The source locations were highly reproducible across the metronome-paced and self-paced conditions, and, they followed the expected somatotopic organisation.

A neural substrate for nonpainful phantom limb phenomena.

Activity in the cerebral cortex associated with non-painful phantom limb sensation was studied in 14 upper extremity amputees. In four subjects, repetitive tactile stimulation of the digits or the lower corner of the mouth elicited non-painful phantom sensation in the amputated limb, in the remaining 10 patients no sensation could be evoked. Neuroelectric source imaging revealed significantly elevated activity in SI and posterior parietal cortex, and significantly decreased activity in ipsilateral SII cortex when referred sensations were present. However, nonpainful referred phantom sensations were not associated with a shift of the cortical representation of the mouth into the hand region, as previously suggested. Nonpainful phantom limb experiences seem to have widely distributed neural networks in multiple cortical regions.

Plasticity in the motor system related to therapy-induced improvement of movement after stroke.

Neuroplasticity might play a beneficial role in the recovery of function after stroke but empirical evidence for this is lacking thus far. Constraint-induced (CI) therapy was used to increase the use of a paretic upper extremity in four hemiparetic stroke patients. Dipole modeling of steady-state movement-related cortical potentials was applied before and after training and 3 months later. The source locations associated with affected hand movement were unusual at follow-up because activation of the ipsilateral hemisphere was found in the absence of mirror movements of the unaffected hand. This long-term change may be considered as an initial demonstration of large-scale neuroplasticity associated with increased use of the paretic limb after application of CI therapy.

Localization of somatosensory evoked potentials in primary somatosensory cortex: a comparison between PCA and MUSIC.

The aim of this study was to test source modeling strategies for EEG-data from a clinical group of amputees. The experimental conditions (measuring time, age and condition of the patients) resulted in low quality EEG-data. Noise reduction was achieved by a principal component analysis (PCA) and a multiple signal classification (MUSIC). A comparison of the results of these two methods with traditional signal handling yielded superior results for the MUSIC algorithm.

Tinnitus and event-related activity of the auditory cortex.

A neuromagnetic study in tinnitus patients and normal-hearing controls was performed with a modified contingent negative variation (CNV) paradigm. While the warning stimulus S1 was a tone burst at an intensity well above threshold, the imperative stimulus S2 was presented at a near threshold intensity because, in the majority of cases, the perceived loudness of tinnitus is very close to the threshold for a pure tone of the same frequency. Subjects had to respond to S2 by pressing a button until its offset was detected. In this case, instead of the usual sudden cut-off of the CNV after the perception of S2, a slow negative deflection develops, the post-imperative negative variation (PINV). Its initial portion probably indicates the development of a second initial CNV because the subject had to attend also to the offset of S2. The neuromagnetic data were analysed both in the time domain and in the frequency domain (short-time spectral analysis of the classical EEG bands). The time domain waveform as well as the spectrotemporal patterns of the MEG bands exhibited deviations from the normal pattern in several tinnitus subgroups, depending on the characteristics of tinnitus (tonal vs. noisiform, monaural vs. binaural) and on the stimulation conditions (tinnitus side vs. non-tinnitus side).

Reorganization of auditory cortex in tinnitus.

Magnetic source imaging was used to determine whether tonotopy in auditory cortex of individuals with tinnitus diverges from normative functional organization. Ten tinnitus subjects and 15 healthy controls were exposed to four sets of tones while magnetoencephalographic recordings were obtained from the two cortical hemispheres in sequence. A marked shift of the cortical representation of the tinnitus frequency into an area adjacent to the expected tonotopic location was observed. The Euclidean distance of the tinnitus frequency from the trajectory of the tonotopic map was 5.3 mm (SD = 3.1) compared with a distance of 2.5 mm (SD = 1.3) of a corresponding frequency in the healthy controls (t = 3.13, P < 0.01). In addition, a strong positive correlation was found between the subjective strength of the tinnitus and the amount of cortical reorganization (r = 0.82, P < 0.01). These results demonstrate that tinnitus is related to plastic alterations in auditory cortex. Similarities between these data and the previous demonstrations that phantom limb pain is highly correlated with cortical reorganization suggest that tinnitus may be an auditory phantom phenomenon.

Cortical reorganization and phantom phenomena in congenital and traumatic upper-extremity amputees.

The relationship between phantom limb phenomena and cortical reorganization was examined in five subjects with congenital absence of an upper limb and nine traumatic amputees. Neuromagnetic source imaging revealed minimal reorganization of primary somatosensory cortex in the congenital amputees (M=0.69 cm, SD 0.24) and the traumatic amputees without phantom limb pain (M=0.27 cm, SD 0.25); the amputees with phantom limb pain showed massive cortical reorganization (M=2.22 cm, SD 0.78). Phantom limb pain and nonpainful phantom limb phenomena were absent in the congenital amputees. Whereas phantom limb pain was positively related to cortical reorganization (r=0.87), nonpainful phantom phenomena were not significantly correlated with cortical reorganization (r=0.34). Sensory discrimination was normal and mislocalization (referral of stimulation-induced sensation to a phantom limb) was absent in the congenital amputees. The role of peripheral and central factors in the understanding of phantom limb pain and phantom limb phenomena is discussed in view of these findings.

Non-invasive functional mapping of the human motor cortex using near-infrared spectroscopy.

We applied non-invasive multisite near-infrared spectroscopy (NIRS) to assess oxygenation changes during performance of a sequential finger opposition task in five healthy human adults. Oxygenation response was localized anatomically using three-dimensional high-resolution magnetic resonance imaging (3D MRI). NIRS measurements showed a localized increase in [oxy-Hb] and a decrease in [deoxy-Hb] in all subjects. The largest response was obtained when the measurement position was over the primary motor and sensory cortex hand area. Interestingly, changes in [deoxy-Hb] seemed to be more localized than changes in [oxy-Hb]. We conclude that this simple, non-invasive and flexible optical bedside method may be used for functional brain mapping.