This study used functional magnetic resonance imaging (fMRI) to examine the association between brain activation during exposure to cocaine-related cues and relapse to drug use in cocaine-dependent (CD) patients. We imaged 17 CD subjects during a 2-week in-patient stay. The subjects then entered a 10-week outpatient placebo-controlled, double-blind randomized clinical trial where urine toxicologies were assessed three times weekly to calculate the treatment effectiveness score (TES). Worse TES correlated with BOLD activation in the left precentral, superior temporal, and posterior cingulate cortices (PCC), and right middle temporal and lingual cortices (R40.65; Po0.005). The left PCC activation also distinguished eight nonrelapsers (TES above mean and completed treatment) from nine relapsers. Cocaine-free urines were significantly greater in the nonrelapsers (92%) than in the relapsers (66%), who also remained in treatment for an average of only 3.2 weeks. Self-reports of craving during fMRI did not differ between nonrelapsers and relapsers and did not correlate with TES. Relapse to cocaine abuse was associated with increased activation in the sensory association cortex, the motor cortex, and PCC while viewing images of cocaine-related cues. These results suggest that relapse to cocaine abuse is associated with increased brain activation to cocaine cues in sensory, motor, and cognitive-emotional processing areas. This physiological activation was a better predictor of relapse than subjective reports of craving, and may be a useful target for treatment development.

ABSTRACT[123I][(lR)-2(3-carbomethoxy-3fl-(4-iodophenyl)tropane] ([123'IJ-CIT) labels dopamine transporters and is, therefore, a marker of neurons that degenerate in Parkinson disease. Single photon emission computed tomography imaging with [123I]P-CIT showed that radioactivity in striatal regions in healthy subjects increased during a 2-day imaging study, whereas that in Parkinsonian patients peaked earlier at reduced levels relative to healthy subjects. Kinetic analyses of radioactivity in plasma and brain suggest that this decrease was due to an =65% loss of target sites in patients compared with healthy subjects; greater losses occurred in putamen than in caudate. AU patients showed lateralized differences in striatal uptake, with greater losses in the striatum contralateral to the side of the body with initial symptoms. These preliminary results suggest that [123'IJ-CIT is a marker for the loss of striatal dopamine terminals in patients with Parkinson disease. Single photon emission computed tomographic imaging with [123'I-CIT may be useful for early diagnosis of the disorder, for monitoring the progression of the disease, and for distinguishing the idiopathic disorder from other Parkinsonian syndromes with more widespread pathology.Parkinson disease is a progressive, disabling neurodegenerative disorder characterized clinically by tremor at rest, bradykinesia, rigidity, and postural instability. The disorder is characterized pathologically by the degeneration of dopaminergic neurons in the substantia nigra, resulting in an 80-99% reduction in striatal dopamine concentrations (1) and a corresponding loss of dopamine transporters (2). Dopamine replacement with either the precursor L-dopa (L-dihydroxyphenylalanine) or direct dopamine-receptor agonists effectively reverses the motor deficits of the disease early in its course. However, as the disease progresses, patients develop disabilities from a number of drug-induced side effects, progression of motor dysfunction (due to continued degeneration of dopamine nerve terminals), and an array of nonmotor, non-dopamine responsive symptoms. Therefore, recent research has focused on developing therapeutic strategies to prevent progression of disease by halting neuronal death and/or restoring neuronal function. Several carbomethoxy-33-(4-iodophenyl)tropane ([123I]3-CIT) (4)[also designated RTI-55 (5)], which labels the dopamine transporter. This protein is located in the presynaptic membrane and transports dopamine from the synapse back into the terminal. That is, [123I]f3-CIT labels sites located on the terminals of dopamine neuronal projections from the substantia nigra to the striatum and may, therefore, provide a measure of dopamine terminal innervation. METHODS SPECT imaging of [123I]3-CIT was done in five patients withidiopathic Parkinson disease and five sex-matched healthy subjects; both groups had a similar mean age. All patients had symptoms that were responsive to L-dopa and had at least three of the following symptoms: resting tremor, bradykinesia, rigi...

Single sodium channel events were recorded from cell-attached patches on single canine cardiac Purkinje cells at 10-13~ Data from four patches containing two to four channels and one patch with one channel were selected for quantitative analysis. The channels showed prominent reopening behavior at voltages near threshold, and the number of reopenings declined steeply with depolarization. Mean channel open time was a biphasic function of voltage with the maximum value (1-1.5 ms) occurring between -50 and -40 mV and lower values at more and at less hyperpolarized levels. Inactivation without opening was also prominent near threshold, and this occurrence also declined with depolarization. The waiting time distributions and the probability of being open showed voltage and time dependence as expected from whole-cell current studies. The results were analyzed in terms of a five-state Markovian kinetic model using both histogram analysis and a maximum likelihood method to estimate kinetic parameters. The kinetic parameters of the model fits were similar to those of GHs pituitary cells (Horn, R., and C.

An NMR method is presented for separating blood volume and magnetic susceptibility effects in response to respiratory challenges such as hypoxia and hyperoxia. The technique employs high susceptibility contrast agents to enhance blood volume induced signal changes. The results show that for a rat model the dominant source of signal variation upon changing breathing gas from 100% oxygen to 10% oxygen/90% nitrogen is the change in blood magnetic susceptibility associated with the BOLD effect. The results imply that signal changes associated with respiratory challenges can be regarded as indicators of local blood oxygenation in vivo.