Global structure, robustness, and modulation of neuronal models.

The electrical characteristics of many neurons are remarkably robust in the face of changing internal and external conditions. At the same time, neurons can be highly sensitive to neuromodulators. We find correlates of this dual robustness and sensitivity in a global analysis of the structure of a conductance-based model neuron. We vary the maximal conductance parameters of the model neuron and, for each set of parameters tested, characterize the activity pattern generated by the cell as silent, tonically firing, or bursting. Within the parameter space of the five maximal conductances of the model, we find directions, representing concerted changes in multiple conductances, along which the basic pattern of neural activity does not change. In other directions, relatively small concurrent changes in a few conductances can induce transitions between these activity patterns. The global structure of the conductance-space maps implies that neuromodulators that alter a sensitive set of conductances will have powerful, and possibly state-dependent, effects. Other modulators that may have no direct impact on the activity of the neuron may nevertheless change the effects of such direct modulators via this state dependence. Some of the results and predictions arising from the model studies are replicated and verified in recordings of stomatogastric ganglion neurons using the dynamic clamp.

Alcoholism and memory: broadening the scope of alcohol-expectancy research.

Current biopsychosocial research on the etiology of alcoholism has begun to focus on memory processes as a possible common pathway for drinking decisions. The alcohol-expectancy construct is rooted both in cognitive psychology and alcohol research and can serve as a vehicle for this study. Reexamination of one recent review of issues in alcohol-expectancy research provides an opportunity to broaden the scope of this research with theoretical and methodological alternatives to those suggested in that review. Most importantly, this article shows that expectancy findings, discussed by Leigh (1989a) as reflecting "psychometric" limitations, are instead quite consistent with recent network models of memory structure. Such models can provide an informative guide to future research activities. It is also recommended that alcohol-expectancy research remain open to inputs from expectancy theories already developed in several psychological domains, as well as to theories of social cognition and attitude structure in addition to those advanced by Leigh.

Cortical petechial hemorrhage, leukoencephalopathy, and subacute dementia associated with seizures due to cerebral amyloid angiopathy.

Although cerebral amyloid angiopathy is a well-known cause of cerebral lobar hemorrhage, subacute dementia, seizures, and acute encephalopathy without lobar hemorrhage are infrequently recognized as manifestations of this disease. In this report, we describe a case of cerebral amyloid angiopathy in a 74-year-old woman who had subacute progressive dementia and a superimposed rapid acute neurologic deterioration associated with seizures and the presence of cerebral edema on computed tomographic scans and leukoencephalopathy and cortical petechial hemorrhages on magnetic resonance imaging. A diagnosis of cerebral amyloid angiopathy in conjunction with small cortical infarcts and petechial hemorrhages was confirmed by antemortem biopsy. This clinical and radiologic picture is being increasingly recognized as characteristic of cerebral amyloid angiopathy.

Repair of shattered solitary testicle.

A solitary shattered testicle with complete eventration of the seminiferous tubules was repaired with resultant satisfactory function. Principles of management in testicular trauma are reviewed briefly.

Spinal dural arteriovenous fistulas: MR and myelographic findings.

PURPOSE: To examine the clinical and radiographic findings in a large group of patients having or suspected of having a spinal dural arteriovenous fistula. METHODS: An analysis of 240 spinal angiograms in 132 patients revealed 97 vascular malformations that included 66 spinal dural arteriovenous fistulas. Sixteen patients had 1 or more normal spinal angiograms that were performed for suspected spinal dural arteriovenous fistulas on other imaging studies. The imaging and clinical data were reviewed in all patients who had or were suspected of having a spinal dural arteriovenous fistula and who had a spinal MR (n = 44) and a myelogram (n = 37). RESULTS: Spinal dural arteriovenous fistulas were more common in males (3.4:1) with an average age of 62 years (range, 37 to 81 years). The average time from onset of symptoms to diagnosis was 27 months. Clinical findings included weakness (55%), a progressive clinical course (100%), and a myelopathy on exam (84%). The nidus of the fistula was located between T-6 and T-12 in 61%, in the sacrum in 9%, and intracranially in 8%. In the spinal dural arteriovenous fistula group, vessels were seen on supine myelography in all patients. MR findings in this group included increased T2 signal in the cord (100%), gadolinium enhancement (88%), mass effect (45%), and flow voids (T1, 35%; T2, 45%). The patients in the negative spinal angiogram group were younger (average age, 51 years), had symptoms longer (average time from symptom onset to spinal angiogram, 59 months), and presented with numbness or pain (76%). When compared with the patients with spinal dural arteriovenous fistula, acute or stable deficits were more common (31%), and myelopathy on exam was less common (56%). Although the angiogram-negative patients commonly had vessels on the myelogram (92%), abnormal T2 signal in the cord was unusual (17%). CONCLUSIONS: In the appropriate clinical setting, high T2 signal of the spinal cord is the most sensitive imaging finding in spinal dural arteriovenous fistula. The presence of mass effect and enhancement should not discourage this diagnosis. The likelihood of finding a spinal dural arteriovenous fistula in a patient without T2 signal on MR is low.

Expectancy challenge and drinking reduction: experimental evidence for a mediational process.

Substantial correlational evidence supports a causal (mediational) interpretation of alcohol expectancy operation, but definitive support requires a true experimental test. Thus, moderately to heavily drinking male college students were randomly assigned to 1 of 3 conditions in a pre-post design: Expectancy challenge (designed to manipulate expectancy levels), "traditional" information, and assessment-only control. Expectancy challenge produced significant drinking decreases, compared with the other 2 groups. Decreases in measured expectancies paralleled drinking decreases in the challenge condition. Significant increases in alcohol knowledge in the traditional program were not associated with decreased drinking. These experimental findings support a causal (mediational) interpretation of expectancy operation. The implications for a cognitive (memory) model of expectancies and for prevention and intervention programs for problem drinking and alcoholism are discussed.

Age and drinking-related differences in the memory organization of alcohol expectancies in 3rd-, 6th-, 9th-, and 12th-grade children.

To advance the theoretical modeling of the development of alcohol expectancies as a parallel processing memory network, this study assessed expectancies and alcohol consumption of 2,324 children in Grades 3, 6, 9, and 12 from a large suburban-rural school district. Individual-differences scaling (INDSCAL), a variant of multidimensional scaling, mapped expectancies into a hypothetical memory network format, and preference mapping (PREFMAP) modeled hypothetical paths of association within this network. Throughout this age range, older and higher drinking youth appeared to associate positive and arousing effects with alcohol cues, in contrast to lower drinking children, who appeared to mainly associate undesirable effects. These drinking-related differences in the organization of expectancy information are discernible well before onset of regular drinking habits and may influence the development of drinking in adolescence.

Experience-dependent neuropsychological recovery and the treatment of alcoholism.

Accumulating research has shown that some cognitive deficits in recently abstinent alcoholics (e.g., cognitive flexibility, acquisition of novel skills) improve only with remediation in contrast to the spontaneous, time-dependent rebound seen for other tasks. In principle, this facilitated or experience-dependent recovery should enhance acquisition of the content of alcoholism treatment programs, but this relationship has yet to be tested empirically; previous research assessed recovery using only neuropsychological tasks presented by an experimenter. The current investigation focused on treatment-relevant remediation (acquisition of the content of a relapse-prevention [RP] program) using tasks administered by self-guided workbooks. Four groups of male alcoholics received pre- and posttesting. Between the two testing sessions, the groups received neuropsychological remediation tasks (n = 15), ecologically relevant tasks (n = 15), attention-placebo tasks (n = 16), or no intervention (n = 15). Results showed that exposure to both types of remediation produced significant cognitive recovery, with skills transferring to posttest neuropsychological measures and RP acquisition. Hence, cognitive remediation may facilitate alcoholism treatment.

Using alcohol expectancies to predict adolescent drinking behavior after one year.

An accumulating literature has shown the influence of childhood experiences associated with alcohol use on later drinking practices. Recent studies have suggested that alcohol-related expectancy may serve as an intervening variable to connect these early experiences with the later, proximal decision to drink when opportunities for actual alcohol consumption arise. Those studies, however, have collected expectancy and drinking data concurrently, whereas the present study for the first time reports on the power of expectancies measured in early adolescents (seventh and eighth grades) to predict self-reported drinking onset and drinking behavior measured a full year later. Results show that five of seven expectancy scores readily discriminated between nonproblem drinkers and those subsequently beginning problem drinking and accounted for a large portion of the variance in a continuous quantity/frequency index and a problem drinking index. The strength of these timelagged relations strengthens the case for inferring that expectancies have causal power on drinking behavior and suggests prevention strategies.

The influence of alcohol expectancy priming and mood manipulation on subsequent alcohol consumption.

Studies showing that verbal priming can implicitly affect alcohol consumption have been used to support cognitive models of expectancies. However, because expectancy words reflect affective states as well as drinking outcomes, mediation through an affective pathway remains theoretically plausible (i.e., such words inadvertently may affect mood, which in turn influences drinking). The primary pathway was identified (and expectancy theory was tested) by comparing memory priming (using alcohol expectancy or neutral words) with mood induction (using positive or neutral music); an unrelated experiment paradigm allowed the priming manipulation to implicitly affect drinking. Men in the alcohol priming group drank significantly more than men in each of the other conditions, and, consistent with theory, men with histories of heavier drinking drank the most when primed with alcohol expectancies, indicating that expectancies can function as automatic memory processes.

Empirical modeling of an alcohol expectancy memory network using multidimensional scaling.

Risk-related antecedent variables can be linked to later alcohol consumption by memory processes, and alcohol expectancies may be one relevant memory content. To advance research in this area, it would be useful to apply current memory models such as semantic network theory to explain drinking decision processes. We used multidimensional scaling (MDS) to empirically model a preliminary alcohol expectancy semantic network, from which a theoretical account of drinking decision making was generated. Subanalyses (PREFMAP) showed how individuals with differing alcohol consumption histories may have had different association pathways within the expectancy network. These pathways may have, in turn influenced future drinking levels and behaviors while the person was under the influence of alcohol. All individuals associated positive/prosocial effects with drinking, but heavier drinkers indicated arousing effects as their highest probability associates, whereas light drinkers expected sedation. An important early step in this MDS modeling process is the determination of iso-meaning expectancy adjective groups, which correspond to theoretical network nodes.

Expectancy for social facilitation from drinking: the divergent paths of high-expectancy and low-expectancy adolescents.

Using a 3-wave longitudinal design, adolescents were studied over a 2-year period during which many first began to drink. Covariance structure modeling showed that teens' expectancy for social facilitation from alcohol and their drinking experience influenced each other in a reciprocal, positive feedback fashion: the greater the expectancy endorsement, the higher subsequent drinking levels, and the higher the drinking levels, the greater the subsequent expectancy endorsement. This model fit the data quite well; comparison models, in which expectancy (or drinking) had no independent influence on future drinking (or expectancy), showed significantly poorer fit than the present model. Initial nondrinkers' social expectancy predicted individual differences in the rate of drinking increase over the 2 years. Results bolster the hypothesis that expectancy actively influences drinking and point to the importance of expectancy-based intervention efforts.

Effects of naloxone on ethanol dependence in rats.

Adult male Long-Evans rats were maintained on an ethanol-containing liquid diet. During development of ethanol dependence, the rats were given daily i.p. injections of either naloxone (2 mg/kg) or saline daily. At the beginning of ethanol withdrawal, the rats were injected with either naloxone (10 mg/kg) or saline i.p. Rats injected with naloxone during the development of ethanol dependence consumed significantly more of the ethanol diet and therefore more ethanol than rats injected with saline. Rats treated with naloxone throughout both the development of ethanol dependence and during ethanol-withdrawal showed delayed or reduced withdrawal symptomatology compared to rats injected with only saline, naloxone only during the development of dependence and naloxone only during ethanol withdrawal. These results indicate that naloxone can alter the effects of chronic ethanol exposure and further suggest that ethanol may exert some of its actions via the brain opioid system.

Symptomatic and functional outcome of stereotactic ventralis lateralis thalamotomy for intention tremor.

In the past, intention tremor has responded well to selected neuroablative procedures; however, objective symptomatic and functional outcomes of ventralis lateralis (VL) thalamotomy specifically for intention tremor in the post-computerized tomography era has rarely been reported. This series explored the symptomatic and functional impact of VL thalamotomy on 14 patients presenting at the Mayo Clinic with severe, refractory intention tremor due to multiple sclerosis (five patients), trauma (four patients), or stroke (five patients). General neurological examinations, psychometric evaluations, speech pathology assessments, and neuroradiological scans were performed. Pre- and postoperative disability were graded according to a modified form of an established rating scale for tremor. All patients received VL radiofrequency thalamotomies utilizing neurophysiological recording and stimulation control. Contralateral targeted upper-extremity tremor remained symptomatically absent or markedly reduced in 81.8% of cases (mean follow-up period 23.4 months). The median disability score was reduced by 12 points (0.02 less than p less than 0.05). Persistent surgical morbidity was limited to two patients with mild, nondisabling dysarthrias. One elderly patient died of pulmonary complications 2 weeks postoperatively. There were no reported surgically induced exacerbations in multiple sclerosis; however, some of these patients exhibited difficulties with electrophysiological localization. These results compare favorably with those reported in the literature and confirm that stereotactic VL thalamotomy for debilitating intention tremor carries a low surgical risk and can be an effective treatment option for properly selected patients.

Effects of intermittent reperfusion during temporal focal ischemia.

There is controversy regarding the role of intermittent reperfusion employed as a cerebroprotective measure when temporary arterial occlusion is necessary during repair of difficult aneurysms. The intraluminal suture middle cerebral artery (MCA) occlusion technique was used in 23 Wistar rats under barbiturate anesthesia to induce 60, 90, or 120 minutes of uninterrupted MCA occlusion. The total infarcted areas obtained were compared to those occurring in 27 animals subjected to identical cumulative ischemic periods but with 5 minutes of reperfusion after every 10-minute ischemic period. The mean total infarcted areas in the groups with 60-minute (1.8 +/- 0.89 sq mm), 90-minute (1.08 +/- 1.02 sq mm), and 120-minute (8.72 +/- 5.89 sq mm) intermittent reperfusion were significantly smaller than those occurring in the 60-minute (12.02 +/- 3.10 sq mm), 90-minute (11.54 +/- 2.68 sq mm), or 120-minute (30.43 +/- 6.51 sq mm) control groups, respectively (p < 0.05). Furthermore, there was no difference in the occurrence of blood-brain barrier breakdown, intraparenchymal hemorrhage, hemispheric edema, or seizures between control and intermittent reperfusion groups. The results support the hypothesis that intermittent reperfusion is beneficial if vessel occlusion is required during aneurysm repair.

The symptomatic and functional outcome of stereotactic thalamotomy for medically intractable essential tremor.

Eight patients with medically refractory disabling essential tremor underwent ventralis lateralis (VL) thalamotomies; the procedure was unilateral in seven cases and bilateral (staged) in the other. Contralateral tremor remained absent or markedly reduced in all patients at the time of the most recent follow-up examinations, at a mean of 17.3 months after surgery. Disability was determined by a modified form of an established rating scale for tremor, and was reduced from a mean score of 21.1 (moderate grade) to 3.9 (absent grade) (p less than 0.001). Interestingly, voice tremor was abolished or significantly improved in 71.4% of patients with preoperative voice tremor. This feature has not been reported previously. Persistent surgical morbidity was limited to two patients with mild dysarthria and one with a mild cognitive impairment. There were no surgically related deaths. It is concluded that stereotactic VL thalamotomy is a treatment option for medically intractable disabling essential tremor.

The culture of science and the ethics of alcohol administration in research.

The failure of ethicists to develop an absolute ethical code has led to the consideration of ethics in particular contexts. In the alcohol field, such consideration has resulted in considerable controversy, because this field has been influenced by parallel cultural contexts: a scientific research culture and a layman's spiritual culture (represented by Alcoholics Anonymous). Both cultures can inform ethical decisions, but for scientific decisions to be made the influence of these cultures must be disentangled. This article reviews issues pertaining to this disentangling in connection with the use of alcohol administration in research.

Experience-dependent recovery of block design performance in male alcoholics: strategy training versus unstructured practice.

Neuropsychological functioning in alcoholics has been known to improve with length of abstinence. However, recovery in some areas is limited in the absence of specific cognitive stimulation. In order to better identify the factor(s) responsible for experience-dependent recovery in alcoholics, the current investigation compared a strategy training approach to the unstructured practice approach used in previous studies. Results showed that both treatments improved Block Design performance in abstinent male alcoholics to levels comparable to nonalcoholic controls, while unremediated alcoholics remained significantly impaired. Unstructured practice was sufficient to improve Block Design performance, with no additional advantage evident in alcoholics receiving strategy training. Hence, forced use of cognitive skills appears to be the important factor in experience-dependent recovery.

Experience-dependent cognitive recovery in alcoholics: a task component strategy.

Visuospatial problem-solving deficits following chronic alcohol abuse may not readily recover spontaneously after drinking cessation but may reverse with appropriate environmental stimulation. To determine if such recovery in alcoholics under age 40 may be accelerated by training with components of an initially impaired task (Trails B), this study employed four groups of alcoholics (N = 53) and a group of matched controls (N = 13). Two alcoholic groups received two consecutive cognitive remediation sessions during the latter 2 weeks of a 1-month treatment program, and two groups of alcoholics received no remediation. Results confirmed that recovery of visuospatial problem-solving skills is facilitated by training with task components (experience-dependent recovery) while spontaneous recovery during the first month of abstinence is minimal for this task. These findings demonstrate the efficacy of cognitive remediation in reversing some alcohol-induced cognitive impairment and have important implications for improving alcohol treatment outcome and adaptive functioning.

Self-reported drinking and alcohol-related problems among early adolescents: dimensionality and validity over 24 months.

OBJECTIVE: Researchers rely on adolescents' self-reports of alcohol consumption and alcohol-related problems, despite little evidence concerning their validity. We assessed the reliability and validity of adolescents' self-reports, employing collateral validation and focusing on the understudied transitional years of early adolescence. METHOD: Subjects were 214 boys and 247 girls who participated in school-wide surveys that assessed drinking, drunkenness and alcohol-related problems each year for 3 years. These measures were validated by collateral (peer) reports and by separate, 7-day drinking calenders. Internal consistency and test-retest reliability were also assessed. RESULTS: Results replicated findings with older adolescents that drinking/drunkenness and alcohol-related problems fall on two partially overlapping dimensions. Scales assessing each dimension had moderate to high internal consistency and high test-retest stability. Correlations with collateral reports were relatively strong for the drinking/drunkenness scale, moderate for a dichotomous variable reflecting the presence or absence of alcohol-related problems, and more modest for the alcohol-related problems scale. Correlations with diary reports of drinking behavior were strong for drinking/drunkenness. Results generally replicated across gender and over time. CONCLUSIONS: Researchers can have some confidence in the reliability and validity of early adolescents' survey self-reports, particularly of alcohol consumption (alcohol-related problems occurred with low base rates, perhaps limiting validity coefficients). Because drinking/drunkenness and alcohol-related problems shared 30% of their variance, factors other than consumption (e.g., personality factors) apparently influenced the experience of alcohol-related problems.