Statistical evaluation of time-dependent metabolite concentrations: estimation of post-mortem intervals based on in situ 1H-MRS of the brain

Knowledge of the time interval from death (post-mortem interval, PMI) has an enormous legal, criminological and psychological impact. Aiming to find an objective method for the determination of PMIs in forensic medicine, 1H-MR spectroscopy (1H-MRS) was used in a sheep head model to follow changes in brain metabolite concentrations after death. Following the characterization of newly observed metabolites (Ith et al., Magn. Reson. Med. 2002; 5: 915-920), the full set of acquired spectra was analyzed statistically to provide a quantitative estimation of PMIs with their respective confidence limits. In a first step, analytical mathematical functions are proposed to describe the time courses of 10 metabolites in the decomposing brain up to 3 weeks post-mortem. Subsequently, the inverted functions are used to predict PMIs based on the measured metabolite concentrations. Individual PMIs calculated from five different metabolites are then pooled, being weighted by their inverse variances. The predicted PMIs from all individual examinations in the sheep model are compared with known true times. In addition, four human cases with forensically estimated PMIs are compared with predictions based on single in situ MRS measurements. Interpretation of the individual sheep examinations gave a good correlation up to 250 h post-mortem, demonstrating that the predicted PMIs are consistent with the data used to generate the model. Comparison of the estimated PMIs with the forensically determined PMIs in the four human cases shows an adequate correlation. Current PMI estimations based on forensic methods typically suffer from uncertainties in the order of days to weeks without mathematically defined confidence information. In turn, a single 1H-MRS measurement of brain tissue in situ results in PMIs with defined and favorable confidence intervals in the range of hours, thus offering a quantitative and objective method for the determination of PMIs.

Cross-modal plasticity in the human thalamus: evidence from intraoperative macrostimulations

During stereotactic functional neurosurgery, stimulation procedure to control for proper target localization provides a unique opportunity to investigate pathophysiological phenomena that cannot be addressed in experimental setups. Here we report on the distribution of response modalities to 487 intraoperative thalamic stimulations performed in 24 neurogenic pain (NP), 17 parkinsonian (PD) and 10 neuropsychiatric (Npsy) patients. Threshold responses were subdivided into somatosensory, motor and affective, and compared between medial (central lateral nucleus) and lateral (ventral anterior, ventral lateral and ventral medial) thalamic nuclei and between patients groups. Major findings were as follows: in the medial thalamus, evoked responses were for a large majority (95%) somatosensory in NP patients, 47% were motor in PD patients, and 54% affective in Npsy patients. In the lateral thalamus, a much higher proportion of somatosensory (83%) than motor responses (5%) was evoked in NP patients, while the proportion was reversed in PD patients (69% motor vs. 21% somatosensory). These results provide the first evidence for functional cross-modal changes in lateral and medial thalamic nuclei in response to intraoperative stimulations in different functional disorders. This extensive functional reorganization sheds new light on wide-range plasticity in the adult human thalamocortical system.