Biomedical subjects

M Lotze

Publications and source records attributed to M Lotze.

At least 19 recordsLinked to original sources

PubMed2006

Evidence for a different role of the ventral and dorsal medial prefrontal cortex for social reactive aggression: An interactive fMRI study.

Interactive paradigms inducing reactive aggression are absent in the brain mapping literature. We used a competitive reaction time task to investigate brain regions involved in social interaction and reactive aggression in sixteen healthy male subjects with fMRI. Subjects were provoked by increasingly aversive stimuli and were given the opportunity to respond aggressively against their opponent by administering a stimulus as retaliation. fMRI revealed an increase of medial prefrontal cortex (mPFC) activity during retaliation. The dorsal mPFC was active when subjects had to select the intensity of the retaliation stimulus, and its activity correlated with the selected stimulus strength. In contrast, ventral mPFC was active during observing the opponent suffering but also during retaliation independent of the stimulus strength. Ventral mPFC activation, stronger in low callous subjects, correlated positively with skin conductance response during observation of the suffering opponent. In conclusion, dorsal mPFC activation seems to represent cognitive operations related to more intense social interaction processes whereas the ventral mPFC might be involved in affective processes associated with compassion to the suffering opponent.

Adult↗

PubMed2006

Differential cerebral activation during observation of expressive gestures and motor acts.

We compared brain activation involved in the observation of isolated right hand movements (e.g. twisting a lid), body-referred movements (e.g. brushing teeth) and expressive gestures (e.g. threatening) in 20 healthy subjects by using functional magnetic resonance imaging (fMRI). Perception-related areas in the occipital and inferior temporal lobe but also the mirror neuron system in the lateral frontal (ventral premotor cortex and BA 44) and superior parietal lobe were active during all three conditions. Observation of body-referred compared to common hand actions induced increased activity in the bilateral posterior superior temporal sulcus (STS), the left temporo-parietal lobe and left BA 45. Expressive gestures involved additional areas related to social perception (bilateral STS, temporal poles, medial prefrontal lobe), emotional processing (bilateral amygdala, bilateral ventrolateral prefrontal cortex (VLPFC), speech and language processing (Broca's and Wernicke's areas) and the pre-supplementary motor area (pre-SMA). In comparison to body-referred actions, expressive gestures evoked additional activity only in the left VLPFC (BA 47). The valence-ratings for expressive gestures correlated significantly with activation intensity in the VLPFC during expressive gesture observation. Valence-ratings for negative expressive gestures correlated with right STS-activity. Our data suggest that both, the VLPFC and the STS are coding for differential emotional valence during the observation of expressive gestures.

Adult↗

PubMed2006

Cross-modal plasticity of the motor cortex while listening to a rehearsed musical piece.

Learning a musical piece requires the development of a strong linkage between sensory and motor representations. Audition plays a central role and a tight cortical auditory-motor corepresentation is a characteristic feature of music processing. Recent works have indicated the establishment of a functional connection between auditory and motor cortices during the learning of a novel piece, although no causal relation has yet been demonstrated. Here transcranial magnetic stimulation of the cortical motor representation involved in musical performance was used to test excitability changes in piano players during auditory presentation of a rehearsed and a non-rehearsed piece. Results showed an increased motor excitability for the rehearsed but not for the non-rehearsed piece. Moreover, we observed an increase of excitability over time as intracortical facilitation was already present after 30 min of training whereas cortico-spinal facilitation increased after a longer training period (5 days).

Acoustic Stimulation↗

PubMed2006

Neuroimaging patterns associated with motor control in traumatic brain injury.

OBJECTIVE: To determine if patients with traumatic brain injury (TBI) and motor deficits show differences in functional activation maps during repetitive hand movements relative to healthy controls. Are there predictors for motor outcome in the functional maps of these patients? METHODS: In an exploratory cross-sectional study, functional magnetic resonance imaging (fMRI) was used to study the blood-oxygenation-level-dependent (BOLD) response in cortical motor areas of 34 patients suffering from moderate motor deficits after TBI as they performed unilateral fist-clenching motions. Twelve of these patients with unilateral motor deficits were studied 3 months after TBI and a 2nd time approximately 4 months later. RESULTS: Compared to age-matched, healthy controls performing the same task, TBI patients showed diminished fMRI-signal change in the primary sensorimotor cortex contralateral to the moving hand (cSM1), the contralateral dorsal premotor cortex, and bilaterally in the supplementary motor areas (SMAs). Clinical impairment and the magnitude of the fMRI-signal change in cSM1 and SMA were negatively correlated. Patients with poor and good motor recovery showed comparable motor impairment at baseline. Only patients who evolved to "poor clinical outcome" had decreased fMRI-signal change in the cSM1 during baseline. CONCLUSIONS: These observations raise the hypothesis that the magnitude of the fMRI-signal change in the cSM1 region could have prognostic value in the evaluation of patients with TBI.

Adolescent↗

PubMed2006

Combination of TMS and fMRI reveals a specific pattern of reorganization in M1 in patients after complete spinal cord injury.

PURPOSE: After a spinal cord injury (SCI), which was complete, deafferentation of the body representation caudal to the lesion height results in drastic changes in the cortical representation. The underlaying processes are poorly understood. METHODS: We investigated cortical representation sites of upper limb muscles using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in five patients suffering from thoracic complete SCI and one with an incomplete SCI in the height of L1. RESULTS: In comparison to healthy controls fMRI demonstrated a displacement of elbow movement representations in the precentral gyrus in patients with complete SCI into the direction of the deafferented cortical thoracic representation. Changes increased with time after the incidence of SCI. TMS revealed reduced excitability and prolonged silent periods for muscles more distant to the deafferented area. CONCLUSIONS: Whereas fMRI demonstrated changes in representation sites adjacent to the deafferented area, TMS excitability changes were also observed more distant to the deafferented area and silent periods were prolonged in comparison to healthy controls. TMS changes might depend on both: the distance to the deafferented area and the time of persistence of deafferentation.

Adult↗

PubMed2003

The musician's brain: functional imaging of amateurs and professionals during performance and imagery.

We compared activation maps of professional and amateur violinists during actual and imagined performance of Mozart's violin concerto in G major (KV216). Execution and imagination of (left hand) fingering movements of the first 16 bars of the concerto were performed. Electromyography (EMG) feedback was used during imagery training to avoid actual movement execution and EMG recording was employed during the scanning of both executed and imagined musical performances. We observed that professional musicians generated higher EMG amplitudes during movement execution and showed focused cerebral activations in the contralateral primary sensorimotor cortex, the bilateral superior parietal lobes, and the ipsilateral anterior cerebellar hemisphere. The finding that professionals exhibited higher activity of the right primary auditory cortex during execution may reflect an increased strength of audio-motor associative connectivity. It appears that during execution of musical sequences in professionals, a higher economy of motor areas frees resources for increased connectivity between the finger sequences and auditory as well as somatosensory loops, which may account for the superior musical performance. Professionals also demonstrated more focused activation patterns during imagined musical performance. However, the auditory-motor loop was not involved during imagined performances in either musician group. It seems that the motor and auditory systems are coactivated as a consequence of musical training but only if one system (motor or auditory) becomes activated by actual movement execution or live musical auditory stimuli.

Acoustic Stimulation↗

PubMed2003

Comparison of representational maps using functional magnetic resonance imaging and transcranial magnetic stimulation.

OBJECTIVE: Comparison of functional magnetic resonance imaging (fMRI) representational maps, that were generated during voluntary thumb abduction, hand dorsiflexion and foot elevation to amplitude maps of motor-evoked potentials (MEPs) elicited by single transcranial magnetic stimulation (TMS) administered to cortical motor representation areas of the muscles of the thenar eminence, extensor carpi radialis and tibialis anterior muscles. METHODS: Stimulus locations that produced maximal motor-evoked potential amplitudes were compared to fMRI activation maxima in three-dimensional (3D)-space and in a 2D-projection using a novel technique that allowed fMRI activation sites to be projected onto the surface of the brain. RESULTS AND CONCLUSIONS: When analyzing pooled data from all target muscles, the location of projected fMRI and TMS activation maxima on the cortical surface differed by an average 13.9 mm. The differences in 3D distances were particularly large for representation areas of lower leg muscles. 3D distances between fMRI activation maxima and highest MEP site in TMS correlated significantly with higher TMS thresholds. These observations strongly suggest that higher TMS excitation thresholds and lower MEP amplitudes are largely due to the absolute distance between the stimulation site and the excitable cortical tissue targeting this muscle. After the projection 4 out of 5 representation sites as evaluated by TMS were located anterior to the fMRI activation maxima, an observation which may due to the orientation of the magnetic field induced by the current in the coil. The representation sites as evaluated with both methods were specific for the type of movement: distances between representation maxima of the same movements were significantly smaller than those within different movements. Nevertheless, fMRI and TMS provide complementary information, which is discussed on the basis of the functional map observed with both methods.

Adult↗

PubMed2001

Outpatient biochemotherapy with interleukin-2 and interferon alfa-2b in patients with metastatic malignant melanoma: results of two phase II cytokine working group trials.

PURPOSE: The Cytokine Working Group performed a randomized phase II trial of two outpatient biochemotherapy regimens to identify an outpatient regimen with high antitumor activity and less toxicity than inpatient regimens which might be compared with chemotherapy or inpatient biochemotherapy regimens in future phase III trials. PATIENTS AND METHODS: Eighty-one patients with metastatic malignant melanoma received dacarbazine 250 mg/m(2)/d intravenously (IV) and cisplatin 25 mg/m(2)/d IV on days 1, 2, and 3, plus interferon (IFN) alfa-2b 5 mU/m(2) subcutaneously (SC) on days 6, 8, 10, 13, and 15, given every 28 days. Interleukin-2 (IL-2) was given daily on days 6 to 10 and 13 to 15. In group 1, IV IL-2 was given at 18.0 MU/m(2), and in group 2, SC IL-2 was given at 5.0 mU/m(2). RESULTS: In group 1 (IV IL-2), there were five complete responses (CRs) and 11 partial responses (PRs) among 44 patients (objective response rate [ORR], 36%; 95% confidence interval [CI], 22% to 51%). In group 2 (SC IL-2), there was one CR and five PRs among the 36 patients (ORR, 17%; 95% CI, 4% to 29%). The median survival was 10.7 months in group 1 and 7.3 months in group 2. Eleven patients in group 1 and four patients in group 2 remain alive as of the last follow-up. Toxicities in both groups were similar. No patient required hospitalization for neutropenic fever. CONCLUSION: Biochemotherapy has activity in these outpatient regimens with acceptable toxicity. The antitumor activity observed with the IV IL-2 regimen seems similar to that of inpatient biochemotherapy regimens. If inpatient biochemotherapy regimens develop an established role in the management of melanoma, future phase III trial comparisons with this outpatient IV IL-2 regimen would be appropriate.

Adult↗

PubMed2001

Sensorimotor mapping of the human cerebellum: fMRI evidence of somatotopic organization.

Functional magnetic resonance imaging (fMRI) was employed to determine areas of activation in the cerebellar cortex in 46 human subjects during a series of motor tasks. To reduce the variance due to differences in individual anatomy, a specific transformational procedure for the cerebellum was introduced. The activation areas for movements of lips, tongue, hands, and feet were determined and found to be sharply confined to lobules and sublobules and their sagittal zones in the rostral and caudal spino-cerebellar cortex. There was a clear symmetry mirroring at the midline. The activation mapped as two distinct homunculoid representations. One, a more extended representation, was located upside down in the superior cerebellum, and a second one, doubled and smaller, in the inferior cerebellum. The two representations were remarkably similar to those proposed by Snider and Eldred [1951] five decades ago. In the upper representation, an intralimb somatotopy for the right elbow, wrist, and fingers was revealed. The maps seem to confirm earlier electrophysiological findings of sagittal zones in animals. They differ, however, from micromapping reports on fractured somatotopic maps in the cerebellar cortex of mammals. We assume that the representations that we observed are not solely the result of spatial integration of hemodynamic events underlying the fMRI method and may reflect integration of afferent peripheral and central information in the cerebellar cortex.

Adolescent↗

PubMed2001

Cerebral activation during anal and rectal stimulation.

While the rectum is innervated by visceral afferents, the anal canal is innervated by the somatosensory pudendal nerve. The representation of these two central domains of intestinal sensations in the human brain is largely unknown. Nonpainful pneumatic stimulation of the anal canal and the distal rectum using event-related functional magnetic resonance imaging (fMRI) was performed in eight healthy subjects. Subjective scaling of sensations revealed no differences in unpleasantness and pain during both stimuli. Both types of stimuli revealed fMRI activation in secondary somatosensory, insula, cingular gyrus, left inferior parietal, and right orbitofrontal cortex. Anal stimulation resulted in additional activation of primary sensory and motor cortex, supplementary motor area, and left cerebellum. We concluded that viscerorectal and somatosensory anal stimulation predominantly differ in their primary sensory activation and additional activation in motor areas. This motor response following aversive somatosensory stimuli may be caused by a reflexive avoidance reaction which is not observed after the more diffuse experienced visceral stimulation.

Adult↗

PubMed2001

Phantom movements and pain. An fMRI study in upper limb amputees.

Using functional MRI, we investigated 14 upper limb amputees and seven healthy controls during the execution of hand and lip movements and imagined movements of the phantom limb or left hand. Only patients with phantom limb pain showed a shift of the lip representation into the deafferented primary motor and somatosensory hand areas during lip movements. Displacement of the lip representation in the primary motor and somatosensory cortex was positively correlated to the amount of phantom limb pain. Thalamic activation was only present during executed movements in the healthy controls. The cerebellum showed no evidence of reorganizational changes. In amputees, movement of the intact hand showed a level of activation similar to movement of the right dominant hand in the healthy controls. During imagination of moving the phantom hand, all patients showed significantly higher activation in the contralateral primary motor and somatosensory cortices compared with imagination of hand movements in the controls. In the patients with phantom limb pain but not the pain-free amputees, imagined movement of the phantom hand activated the neighbouring face area. These data suggest selective coactivation of the cortical hand and mouth areas in patients with phantom limb pain. This reorganizational change may be the neural correlate of phantom limb pain.

Adult↗

PubMed2001

Decreased zeta chain expression and apoptosis in CD3+ peripheral blood T lymphocytes of patients with melanoma.

Expression of T-cell receptor- or Fcgamma receptor III-associated signal-transducing zeta chain is important for the functional integrity of immune cells. We found that significantly higher proportions of circulating CD3+ T cells as well as natural killer cells had low or absent expression of the zeta chain in patients with advanced melanoma than in normal donors (P < 0.0005). Decreased zeta expression was always observed in a small subset of circulating CD3+ T cells that were in the process of apoptosis, i.e., bound Annexin V or were terminal deoxynucleotidyl transferase-mediated nick end labeling positive. Up to 80% of T cells in the peripheral blood of patients with melanoma were Fas+, with the mean percentage of Fas+CD3+ cells significantly higher in patients (P < 0.004) than normal controls. These Fas+CD3+ T cells were found to preferentially undergo apoptosis. Annexin V binding, the loss of Fas expression from the cell surface as well as zeta down-regulation, which are associated with early apoptosis, were detected in a proportion of circulating Fas+CD3+. In Jurkat cells incubated with agonistic anti-Fas antibody (CH-11), a rapid loss of Fas expression from the cell surface coincided with Annexin V binding and preceded the loss of zeta chain during early apoptosis. In a subset of Jurkat cells coincubated with human melanoma cells, Annexin V binding and zeta degradation as well as DNA fragmentation were observed, indicating that the tumor induced T-cell death. Triggering of death receptors expressed on activated T lymphocytes was accompanied by the loss of zeta expression. On the other hand, soluble factors secreted by melanoma cells induced down-regulation but no apoptosis in activated normal T cells. In the circulation of patients with melanoma, apoptosis of immune effector cells may be related to the state of chronic activation, resulting in the up-regulation of death receptors and increased susceptibility to apoptosis.

Annexin A5↗

PubMed2000

The representation of articulation in the primary sensorimotor cortex.

Bilabial, alveolar and velar sounds are produced at different locations around the oral cavity. fMRI was used to localize cortical representation of articulation in seven healthy subjects during repetitive lip and vertical tongue movements as well as repetitive articulation of /pa/ (bilabial), /ta/ (alveolar), /ka/ (velar consonants) and a combination of all three in /pataka/. Centers of gravity (COG) analysis of fMRI activation in the primary motor (M1) and sensory cortex (S1) revealed /pa/- adjacent to lip representation and /ta/- articulation to tongue representation. The articulation of /pataka/ showed an activation pattern with a combination of the two M1/S1-components and additional activation in the supplementary motor area.

Adult↗

PubMed2000

fMRI evaluation of somatotopic representation in human primary motor cortex.

We used fMRI to map foot, elbow, fist, thumb, index finger, and lip movements in 30 healthy subjects. For each movement type confidence intervals of representational sites in the primary motor cortex (M1) were evaluated. In order to improve the precision of their anatomical localization and to optimize the mapping of cortical activation sites, we used both the assessment of locations in the conventional 3D system and a 2D projection method. In addition to the computation of activation maxima of activation clusters within the precentral gyrus, centers of gravity were determined. Both methods showed a high overlap of their representational confidence intervals. The 2D-projection method revealed statistically significant distinct intralimb locations, e.g., elbow versus index finger movements and index finger versus thumb movements. Increased degree of complexity of finger movements resulted in a spread of the somatotopic location toward the arm representation. The 2D-projection method-based fMRI evaluation of limb movements showed high precision and was able to reveal differences in intralimb movement comparisons. fMRI activation revealed a clear somatotopic order of movement representation in M1 and also reflected different degrees of complexity of movement.

Adult↗

PubMed2000

Daily rhythm of vigilance assessed by temporal resolution of the visual system.

To assess the daily distribution of temporal resolution in visual detection, binocular double-pulse resolution (DPR) was measured over a 24 h period in six healthy subjects. DPR showed a significant daily variation with an amplitude for the foveal stimulus of up to 60%. Like in other vigilance-dependent daily rhythms, optimal performance occurred around midday. The DPR measurements described here are an excellent method for assessment of vigilance and mental alertness (e.g. in pharmacological studies). They show strong time-of-day differences, are highly reliable across successive measurements, and can be fully automated.

Adult↗

PubMed2000

Phase II trial of interleukin 2, interferon alpha, and 5-fluorouracil in metastatic renal cell cancer: a cytokine working group study.

The purpose of this study was to evaluate the potential efficacy of alternating two outpatient regimens for the treatment of metastatic renal cell cancer. These regimens consisted of 4 weeks of recombinant interleukin 2 (rIL-2) plus IFN-alpha2B followed by 4 weeks of 5-fluorouracil plus IFN-alpha2B. Fifty patients meeting eligibility criteria of previous Cytokine Working Group studies were treated on an outpatient basis. Patients received s.c. rIL-2 (Proleukin; Chiron, Emeryville, CA) during weeks 1-4 of the 8-week regimen. During weeks 1 and 4, the dosage for rIL-2 was 10 MIU/m2 twice daily on days 3-5, and the dosage for IFN-alpha2B (Intron; Schering Plough, Kenilworth, NJ) was 6 MIU/m2 on day 1. During weeks 2 and 3, the dosage for rIL-2 was 5 MIU/m2 on days 1, 3, and 5, and the dosage for IFN-alpha2B was 6 MIU/m2 on days 1, 3, 5. During weeks 5-8, 5-fluorouracil (750 mg/m2) was administered once weekly by i.v. infusion, and IFN-alpha2B (9 MIU/mZ) was administered as a s.c. injection three times weekly. Throughout the treatment, an assessment of quality of life was made and a symptom-distress scale was evaluated. There were two patients with complete responses (CRs) and seven with partial responses (PRs) for an objective response rate of 18% (95% confidence interval, 10-25). The median response duration was 8 months (range, 3-51+ months). The CRs lasted 5 months and 51+ months and the PRs ranged from 3+ to 18 months. After completing at least one course of treatment, eight patients (three with PR, one with minor response, four with stable disease) became CRs after surgery for remaining metastatic disease. Six remain alive at 43+ to 53+ months, and 5 remain disease-free since surgery. The median survival of the study group is 17.5 months, with a maximal follow-up of 53+ months. The range in survival is 1-53+ months. Toxicity was primarily constitutional. and treatment modifications were designed to maintain toxicity at grade 2/3. The most common toxicities during treatment with IL-2/IFN were fatigue, nausea/vomiting, anorexia, skin reaction, diarrhea, fever, and liver enzyme elevations. One-third had central nervous system toxicity (headache, depression, insomnia). During 5FU/IFN treatment, 49 of 50 patients experienced grade 2/3 myelosuppression during course 1. Eight patients experienced grade 4 toxicities. In conclusion, the activity of this alternating regimen is similar to that of IL-2/IFN alone, given in 4-week cycles. The addition of 5FU/IFN failed to increase the efficacy and added new toxicity (myelosuppression). This report does not confirm the results previously reported for either alternating or simultaneous administration of these three agents. Because 5FU does not appear to add to the antitumor activity of IL-2-based therapy for renal cancer, current efforts are directed toward a Phase III randomized comparison of high-dose i.v. bolus inpatient IL-2 treatment versus treatment with outpatient s.c. injection of IL-2 plus IFN.

Adult↗

PubMed1999

Activation of human language processing brain regions after the presentation of random letter strings demonstrated with event-related functional magnetic resonance imaging.

This study addresses the question, to what extent the processing of meaningless random letter strings involves classical language related brain regions. Using event-related functional magnetic resonance imaging (fMRI), which allows random stimulus presentation, we could demonstrate activation in the left inferior frontal gyrus, the left superior temporal gyrus, left parietal and occipital regions after the presentation of random letter strings compared to real words. The activation in these classical language related brain areas reflects an intense lexical evaluation process of the meaningless stimuli. Real words contrasted with random letter strings activated the left angular gyrus, bilateral precuneus and the left posterior cingulate gyrus, which may reflect the access of higher semantic associations.

Adult↗

PubMed1999

Functional MRI of cerebral activation during encoding and retrieval of words.

The aims of the present study were to identify the cerebral structures associated with encoding and retrieval of verbal material. To circumvent the inherent disadvantages of the conventional block designs used in functional magnetic resonance imaging (MRI), an event-related design compared activation related to randomly intermixed old and new words during recognition. To support the validity of results, both nonparametric analyses in regions of interest (ROI) and statistical parametric mapping (SPM 96) were used. Twelve healthy volunteers, ages 22-35 years, performed three tasks: intentional encoding of words, recognition of old (previously learned) words, and discrimination between words and nonwords, a task to control for visual input and motor output during recognition. Echo-planar magnetic resonance imaging of blood-level, oxygen-dependent, task-related changes was used to compare cerebral activity under active and resting conditions as well as to detect event-related activity within blocks of trials. Comparable results were obtained following nonparametric statistical analysis of selected ROI and SPM. Encoding of words was associated with increased activity in the left inferior frontal gyrus, including Broca's area and in the left parietal association cortex. Event-related data analysis revealed activation of the right medial frontal gyrus, the right anterior cingulate gyrus, and parietal association cortices during recognition of previously presented words. In the lexical decision task, words in comparison with nonwords were associated with activation of the left parietal association cortex. The right medial frontal gyrus, the right anterior cingulate gyrus, and the right parietal association cortex are likely to be involved in episodic memory functions during recognition of previously presented verbal material. The comparison of event-related activation occurring within one trial block instead of among several trial blocks may significantly improve the performance of memory studies.

Adult↗