Hallucinations, perceptions in the absence of external stimuli, are prominent among the core symptoms of schizophrenia. The neural correlates of these brief, involuntary experiences are not well understood, and have not been imaged selectively. We have used new positron emission tomography (PET) methods to study the brain state associated with the occurrence of hallucinations in six schizophrenic patients. Here we present a group study of five patients with classic auditory verbal hallucinations despite medication, demonstrating activations in subcortical nuclei (thalamic, striatal), limbic structures (especially hippocampus), and paralimbic regions (parahippocampal and cingulate gyri, as well as orbitofrontal cortex). We also present a case study of a unique, drug-naive patient with visual as well as auditory verbal hallucinations, demonstrating activations in visual and auditory/linguistic association cortices as part of a distributed cortical-subcortical network. Activity in deep brain structures, identified with group analysis, may generate or modulate hallucinations, and the particular neocortical regions entrained in individual patients may affect their specific perceptual content. The interaction of these distributed neural systems provides a biological basis for the bizarre reports of schizophrenic patients.

A method is described to monitor the motion of the head during neurological positron emission tomography (PET) acquisitions and to correct the data post acquisition for the recorded motion prior to image reconstruction. The technique uses an optical tracking system, Polaris, to accurately monitor the position of the head during the PET acquisition. The PET data are acquired in list mode where the events are written directly to disk during acquisition. The motion tracking information is aligned to the PET data using a sequence of pseudo-random numbers, which are inserted into the time tags in the list mode event stream through the gating input interface on the tomograph. The position of the head is monitored during the transmission acquisition, and it is assumed that there is minimal head motion during this measurement. Each event, prompt and delayed, in the list mode event stream is corrected for motion and transformed into the transmission space. For a given line of response, normalization, including corrections for detector efficiency, geometry and crystal interference and dead time are applied prior to motion correction and rebinning in the sinogram. A series of phantom experiments were performed to confirm the accuracy of the method: (a) a point source located in three discrete axial positions in the tomograph field of view, 0 mm, 10 mm and 20 mm from a reference point, (b) a multi-line source phantom rotated in both discrete and gradual rotations through +/- 5 degrees and +/- 15 degrees, including a vertical and horizontal movement in the plane. For both phantom experiments images were reconstructed for both the fixed and motion corrected data. Measurements for resolution, full width at half maximum (FWHM) and full width at tenth maximum (FWTM), were calculated from these images and a comparison made between the fixedand motion corrected datasets. From the point source measurements, the FWHM at each axial position was 7.1 mm in the horizontal direction, and increasing from 4.7 mm at the 0 mm position, to 4.8 mm, 20 mm offset, in the vertical direction. The results from the multi-line source phantom with +/- 5 degrees rotations showed a maximum degradation in FWHM, when compared with the stationary phantom, of 0.6 mm, in the horizontal direction, and 0.3 mm in the vertical direction. The corresponding values for the larger rotation, +/- 15 degrees, were 0.7 mm and 1.1 mm, respectively. The performance of the method was confirmed with a Hoffman brain phantom moved continuously, and a clinical acquisition using [11C]raclopride (normal volunteer). A visual comparison of both the motion and non-motion corrected images of the Hoffman brain phantom clearly demonstrated the efficacy of the method. A sample time-activity curve extracted from the clinical study showed irregularities prior to motion correction, which were removed after correction. A method has been developed to accurately monitor the motion of the head during a neurological PET acquisition, and correct for this motion prior to image reconstruction. The...

The long term effects of GH replacement in adult GH-deficient (GHD) patients have not yet been clarified. We studied 21 GHD adults who originally took part in a randomized, double blind, placebo-controlled trial of GH treatment in 1987. After completion of that trial, 10 patients received continuous GH replacement for the subsequent 10 yr, whereas 11 did not. A group of 11 age- and sex-matched normal controls were also studied in 1987 and 1997. Lean body mass, as assessed by total body potassium measurement and computed tomography scanning of the dominant thigh, increased in the GH-treated group (P < 0.01 for both) only (P < 0.05 between groups for total body potassium). Low density lipoprotein cholesterol decreased in the GH-treated group (P < 0.05) only. Carotid intima media thickness was significantly greater (P < 0.05) in the untreated group than in the GH-treated group. Assessment of psychological well-being using the Nottingham Health Profile revealed improvement in overall score, energy levels, and emotional reaction in the GH-treated group compared with those in the untreated group (P < 0.02). In conclusion, GH treatment for 10 yr in GHD adults resulted in increased lean body and muscle mass, a less atherogenic lipid profile, reduced carotid intima media thickness, and improved psychological well-being.

Summary: Positron emission tomography regional CBF (rCBF) studies of cognitive processes have traditionally required 30--60 mCi of H21S0 per scan and intersubject averaging to achieve statistical significance. However, in tersubject anatomical, functional, and disease variability can make such an approach problematic. A new method that produces significant results in single subjects is pre sented. It is based upon high-sensitivity three dimensional imaging and a "slow" bolus administration of < 15 mCi of H21S0 per scan. The method is validated in four normal volunteers using control and auditory language activation tasks with four scans per condition and statistical parametric mapping analysis. It is demon strated that the rCBF distribution associated with the Functional brain imaging of regional CBF (rCBF) with positron emission tomography (PET) provides an in vivo index of localized synaptic activity asso ciated with cognitive and behavioral states in hu mans (Raichle, 1987). 150-labeled water, despite some limitation in diffusion (Eichling et aI., 1974), is currently the preferred CBF tracer because of its short half-life (2.05 min), ease of production and use, and low toxicity (Lammert sma and Mazoyer, Received November 4, 1992; final revision received January 21, 1993; accepted January 25, 1993 . Address correspondence and reprint requests to Dr. D. A. Silbersweig at MRC Cyclotron Unit, Hammersmith Hospital, DuCane Road, London WI2 OHS, England.Abbreviations used: BA, Brodmann's area; 3-D, three dimensional; NEC, noise equivalent count rate; PET, positron emission tomography; rCBF, regional CBF; SMA, supplemen tary motor area; SPM, statistical parametric map . 617cognitive state is detected during the arrival of radio tracer in the brain. This occurs over 30 s and constitutes a crit ical temporal window during which stimulation should be performed. A 90-s acquisition time is found to produce results of greater significance than a 60-s acquisition time. The implications of the results and the functional neuro anatomical findings are discussed. This method is suitable for the study of individual functional neuroanatomy in many neuropsychological, pharmacologic, and symptom states in normal subjects and in patients with psychiatric and neurologic disorders. Key Words: Functional brain imaging-ISO-labeled water-Positron emission tomog raphy-Regional cerebral blood flow-Single-subject analysis-Slow bolus technique. 1990). Qualitative subtraction studies utilizing 30-60 mCi of H2150 per scan and a two-dimensional scanning technique (with interplane septa) have provided valuable information concerning func tional neuroanatomy (Posner et aI., 1988; Zeki et aI. , 1991). However, limitations on acceptable doses of administered radioactivity and limitations of scanner sensitivity have necessitated the use of multiple subjects to obtain results of statistical sig nificance. While intersubject averaging may in crease the generalizability of results, it introduces additional problems associated with intersubject an at...