Posthypnotic suggestion and the modulation of Stroop interference under cycloplegia

Recent data indicate that under a specific posthypnotic suggestion to circumvent reading, highly suggestible subjects successfully eliminated the Stroop interference effect. The present study examined whether an optical explanation (e.g., visual blurring or looking away) could account for this finding. Using cyclopentolate hydrochloride eye drops to pharmacologically prevent visual accommodation in all subjects, behavioral Stroop data were collected from six highly hypnotizables and six less suggestibles using an optical setup that guaranteed either sharply focused or blurred vision. The highly suggestibles performed the Stroop task when naturally vigilant, under posthypnotic suggestion not to read, and while visually blurred; the less suggestibles ran naturally vigilant, while looking away, and while visually blurred. Although visual accommodation was precluded for all subjects, posthypnotic suggestion effectively eliminated Stroop interference and was comparable to looking away in controls. These data strengthen the view that Stroop interference is neither robust nor inevitable and support the hypothesis that posthypnotic suggestion may exert a top-down influence on neural processing.     

The clinician-investigator: unavoidable but manageable tension

The "difference position" holds that clinical research and therapeutic medical practice are sufficiently distinct activities to require different ethical rules and principles. The "similarity position" holds instead that clinical investigators ought to be bound by the same fundamental principles that govern therapeutic medicine--specifically, a duty to provide the optimal therapeutic benefit to each patient or subject. Some defenders of the similarity position defend it because of the overlap between the role of attending physician and the role of investigator in a research trial. This overlap is maximal when the same physician occupies both roles with respect to a particular patient-subject. We address the ethical tensions inherent in that role conflict and argue that the tensions are real but manageable. The difference position provides a sound ethical framework within which to manage those tensions, while the similarity position is unsatisfactory because it seeks to deny the existence of the tensions.     

Enhanced retention in the passive-avoidance task by 5-HT(1A) receptor blockade is not associated with increased activity of the central nucleus of the amygdala

The effect of blockade of 5-HT1A receptors was investigated on (1). retention in a mildly aversive passive-avoidance task, and (2). spontaneous single-unit activity of central nucleus of the amygdala (CeA) neurons, a brain site implicated in modulation of retention. Systemic administration of the selective 5-HT1A antagonist NAN-190 immediately after training markedly-and dose-dependently-facilitated retention in the passive-avoidance task; enhanced retention was time-dependent and was not attributable to variations in wattages of shock received by animals. Systemic administration of NAN-190 had mixed effects on spontaneous single-unit activity of CeA neurons recorded extracellularly in vivo; microiontophoretic application of 5-HT, in contrast, consistently and potently suppressed CeA activity. The present findings-that 5-HT1A receptor blockade by NAN-190 (1). enhances retention in the passive-avoidance task, and (2). does not consistently increase spontaneous neuronal activity of the CeA-provide evidence that a serotonergic system tonically inhibits modulation of retention in the passive-avoidance task through activation of the 5-HT1A receptor subtype at brain sites located outside the CeA.     

A pharmacological analysis of an associative learning task: 5-HT(1) to 5-HT(7) receptor subtypes function on a pavlovian/instrumental autoshaped memory

Recent studies using both invertebrates and mammals have revealed that endogenous serotonin (5-hydroxytryptamine [5-HT]) modulates plasticity processes, including learning and memory. However, little is currently known about the mechanisms, loci, or time window of the actions of 5-HT. The aim of this review is to discuss some recent results on the effects of systemic administration of selective agonists and antagonists of 5-HT on associative learning in a Pavlovian/instrumental autoshaping (P/I-A) task in rats. The results indicate that pharmacological manipulation of 5-HT1-7 receptors or 5-HT reuptake sites might modulate memory consolidation, which is consistent with the emerging notion that 5-HT plays a key role in memory formation.     

Complex effects of NMDA receptor antagonist APV in the basolateral amygdala on acquisition of two-way avoidance reaction and long-term fear memory

Although much has been learned about the role of the amygdala in Pavlovian fear conditioning, relatively little is known about an involvement of this structure in more complex aversive learning, such as acquisition of an active avoidance reaction. In the present study, rats with a pretraining injection of the N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonopentanoic acid (APV), into the basolateral amygdala (BLA) were found to be impaired in two-way active avoidance learning. During multitrial training in a shuttle box, the APV-injected rats were not different from the controls in sensitivity to shock or in acquisition of freezing to contextual cues. However, APV injection led to impaired retention of contextual fear when tested 48 h later, along with an attenuation of c-Fos expression in the amygdala. These results are consistent with the role of NMDA receptors of the BLA in long-term memory of fear, previously documented in Pavlovian conditioning paradigms. The APV-induced impairment in the active avoidance learning coincided with deficits in directionality of the escape reaction and in attention to conditioned stimuli. These data indicate that normal functioning of NMDA receptors in the basolateral amygdala is required during acquisition of adaptive instrumental responses in a shuttle box but is not necessary for acquisition of short-term contextual fear in this situation.     

The category test perseveration, loss of set, and memory scales: three new scales and their relationship to executive functioning measures

The Category Test (CT) is a neuropsychological measure that taps into multiple domains of complex reasoning but yields a single error score, limiting the use of the test. In this study, three new CT scales were developed to assess specific aspects of executive dysfunction: Perseveration, Failure to Maintain Cognitive Set, and Inability to Recall and Re-Initiate Past Behavior. The relationship of these scales to well-established neuropsychological measures was examined in head-injured individuals and schizophrenia patients. The CT Perseveration score was correlated with the Wisconsin Card Sorting Test (WCST) Perseverative Responses score, but also with measures from the Wechsler Memory Scale-Revised and the California Verbal Learning Test. The CT Memory score correlated with other memory measures, but also with the WCST Perseveration measure. Although future studies designed to test discriminant and convergent validity are warranted, these scales may be useful in determining specific aspects of impaired CT performance.     

Involvement of BDNF receptor TrkB in spatial memory formation

The N-methyl-D-aspartate (NMDA) receptors are involved in long-term potentiation (LTP), and are phosphorylated by several tyrosine kinases including a Src-family tyrosine kinase Fyn. Brain-derived neurotrophic factor (BDNF) is a neurotrophin, which also enhances hippocampal synaptic transmission and efficacy by increasing NMDA receptor activity. Here, we show that Fyn is a key molecule linking the BDNF receptor TrkB with NMDA receptors, which play an important role in spatial memory formation in a radial arm maze. Spatial learning induced phosphorylation of TrkB, Fyn, and NR2B, but not NR2A, in the hippocampus. Fyn was coimmunoprecipitated with TrkB and NR2B, and this association was increased in well-trained rats compared with control animals. Continuous intracerebroventricular infusion of PP2, a tyrosine kinase inhibitor, in rats delayed memory acquisition in the radial arm maze, but PP2-treated animals reached the same level of learning as the controls. The phosphorylation of Fyn and NR2B, but not TrkB, was diminished by PP2 treatment. Our findings suggest the importance of interaction between BDNF/TrkB signaling and NMDA receptors for spatial memory in the hippocampus.     

Emotional risk factors and postconcussional disorder

Emotional risk factors were examined in 129 litigant and nonlitigant patients diagnosed with Postconcussional Disorder (PCD) following Mild Traumatic Brain Injury (MTBI). According to Millon Clinical Multiaxial Inventory (MCMI) criteria, four subgroups emerged: (a) 14.7% met criteria for an Axis I disorder, (b) 24.8% for an Axis II disorder, (c) 24.0% for bout Axis I and II disorders, and (d) 36.4% fell below threshold for psychopathology. Thus, 63.5% endorsed emotional pathology. Of the four groups, those with both Axis I and II psychopathology presented the greatest number of emotional complaints in a clinical interview and manifested the lowest neurocognitive test scores. Motor skills, verbal abilities, memory functioning, and IQ were primarily affected. With the exception of post-morbid emotional complaints, no significant differences were identified between litigants and nonlitigants. Our analysis suggests that the combination of both Axis I and II psychopathology is associated with greater impairment following MTBI.     

Emerging therapeutics for Alzheimer's disease: an avenue of hope

Emerging therapies for Alzheimer's disease offer hope to patients and their caregivers. Future treatments will probably include combination approaches with agents that modify amyloid processing, deposition, and clearance. One example, the AD vaccine, reduced amyloid burden and changed behavior in animal models of AD, but the human trial was halted when several subjects developed brain inflammation. Anti-inflammatory agents have epidemiologic support, but clinical trials have been disappointing, possibly related to inadequate study with anti-inflammatory agents that modify amyloid processing. Agents that target known cardiovascular risk factors, such as hypercholesterolemia, hypertension, and insulin resistance, have epidemiologic, preclinical, and clinical evidence to warrant further investigation. Heavy metal chelators, antioxidants, neurotrophic factors, glutaminergic modulators, and agents that modify hyperphosphorylation of Tau are other approaches in research and development.