The hippocampus and memory for "what," "where," and "when"

Previous studies have indicated that nonhuman animals might have a capacity for episodic-like recall reflected in memory for "what" events that happened "where" and "when". These studies did not identify the brain structures that are critical to this capacity. Here we trained rats to remember single training episodes, each composed of a series of odors presented in different places on an open field. Additional assessments examined the individual contributions of odor and spatial cues to judgments about the order of events. The results indicated that normal rats used a combination of spatial ("where") and olfactory ("what") cues to distinguish "when" events occurred. Rats with lesions of the hippocampus failed in using combinations of spatial and olfactory cues, even as evidence from probe tests and initial sampling behavior indicated spared capacities for perception of spatial and odor cues, as well as some form of memory for those individual cues. These findings indicate that rats integrate "what," "where," and "when" information in memory for single experiences, and that the hippocampus is critical to this capacity.     

Activation-induced restoration of sensorimotor functions in rats with dopamine-depleting brain lesions.

Bilateral electrolytic lesions of the lateral hypothalamus or intraventricular 6-hydroxydopamine injections produced substantial depletions of striatal dopamine in rates. All animals with brain damage showed marked sensorimotor impairments. However, they began to move and respond appropriately to environmental stimuli when placed in a sink of water, in a shallow ice bath, or among a colony of cats or rats. A reversal of the sensorimotor dysfunctions was still apparent shortly after the animals were removed from each activating situation. However, the terapeutic effects dissipated rapidly, and by 4 hr after an exposure the rats responded as poorly as they had prior to activation. These findings are strikingly similar to the "paradoxical kinesia" seen in parkinsonism, a clinical disorder attributed to degeneration of central dopamine-containing neurons. Collectively, they suggest the importance of activation in maintaining responsiveness to senory stimuli in rats following dopamine-depleting brain lesions.     

Repeatedly reactivated memories become more resistant to hippocampal damage

We examined whether repeated reactivations of a context memory would prevent the typical amnesic effects of post-training damage to the hippocampus (HPC). Rats were given a single contextual fear-conditioning session followed by 10 reactivations, involving a brief return to the conditioning context (no shock). Subsequently, the rats received sham or complete lesions of the HPC. When tested for retention, the HPC rats that experienced the reactivations froze significantly more than nonreactivation HPC rats and did not significantly differ from their respective control group. These findings suggest that memory reactivations contribute to long-term memories becoming independent of the HPC.     

Using proton magnetic resonance imaging and spectroscopy to understand brain "activation"

Upon stimulation, areas of the brain associated with specific cognitive processing tasks may undergo observable physiological changes, and measures of such changes have been used to create brain maps for visualization of stimulated areas in task-related brain "activation" studies. These perturbations usually continue throughout the period of the stimulating event, and then subside when the event is terminated. In this communication, we consider the nature and meaning of these task-related brain activations. Since stimulation usually results in an increase in the frequency of neuron depolarizations or "spikes", an energy expensive activity that requires ATP for restoration of ionic gradients, additional energy supplies must be rapidly deployed to the stimulated areas or rates of re-polarization could be decreased, and refractory periods between spikes increased. As a result, maximum spiking rates may be decreased and some frequency-encoded information lost. The energy available to brain cells to re-synthesize ATP from ADP is a function of levels of glucose and oxygen in blood, and their availability to stimulated neurons is a function of the rate at which focal blood supplies can be increased (hyperemia). In this review we explore how neurons transmit meaningful encoded information; how the integrity of that information is dependent on a continuous supply of energy, and how proton magnetic imaging and spectroscopy may aid in understanding the process. Finally, evidence is presented that the neuropeptide, N-acetylaspartylglutamate, is a neuronal astrocyte-vascular feedback signal that regulates activation induced focal hyperemic responses.     

Sensitivity and specificity of reliable digit span in malingered pain-related disability

The reliable digit span (RDS) performance of chronic pain patients with unambiguous spinal injuries and no evidence of exaggeration or response bias (n = 53) was compared to that of chronic pain patients meeting criteria for definite malingered neurocognitive dysfunction (n = 35), and a group of nonmalingering moderate-severe traumatic brain injury (TBI) patients (n = 69). The results demonstrated that scores of 7 or lower were associated with high specificity (> .90) and sensitivity (up to .60) even when moderate to severe TBI are included. Multiple studies have demonstrated that RDS scores of 7 or lower rarely occur in TBI and pain patients who are not intentionally performing poorly on cognitive testing. This study supports the use of the RDS in detecting response bias in neuropsychological patients complaining of pain as well as in the assessment of pain-related cognitive impairment in patients whose primary complaint is pain.     

Patterns of motor disability in very preterm children

Motor development in very preterm children differs in several important ways from that of children born at full term. Variability is common, although the anatomic and physiologic bases for that variability are often poorly understood. Motor patterns over the first postnatal year may depend on behaviours learned during often long periods of neonatal intensive care. The normal pattern of development may be modified by disturbances of brain function caused both by the interruption of normal brain maturation ex-utero and the superimposition of focal brain injuries following very preterm birth. Abnormal patterns of development over the first year may evolve into clear neuromotor patterns of cerebral palsy or resolve, as "transient dystonias." Cerebral palsy is associated with identified patterns of brain injury secondary to ischaemic or haemorrhagic lesions, perhaps modified by activation of inflammatory cytokines. Cerebral palsy rates have not fallen as might be expected over the past 10 years as survival has improved, perhaps because of increasing survival at low gestations, which is associated with the highest prevalence of cerebral palsy. Children who escape cerebral palsy are also at risk of motor impairments during the school years. The relationship of these impairments to perinatal factors or to neurological progress over the first postnatal year is debated. Neuromotor abnormalities are the most frequent of the "hidden disabilities" among ex-preterm children and are thus frequently associated with poorer cognitive ability and attention deficit disorders. Interventions to prevent cerebral palsy or to reduce these late disabilities in very preterm children are needed.     

A comparison of the effects of fimbria-fornix, hippocampal, or entorhinal cortex lesions on spatial reference and working memory in rats: short versus long postsurgical recovery period.

Using a radial maze task and different postoperative recovery periods, this experiment assessed and compared the reference and working memory performances of adult Long-Evans male rats subjected to entorhinal cortex, fimbria-fornix, and hippocampus lesions. Sham-operated rats were used as controls. In order to see whether the duration of the postsurgical recovery period would influence acquisition of the complex radial maze task, training began 1 month following surgery (Delay 1) for half the rats in each group, while for the other half training was started 6.5 months following surgery (Delay 2). The results indicated that at both recovery periods the entorhinal cortex lesions failed to affect either working or reference memory in the spatial task. Conversely, both fimbria-fornix and hippocampus lesions impaired both reference and working memory. While the reference memory deficit was generally similar in both fimbria-fornix and hippocampal lesion groups, analysis of the results for working memory indicated that at the longer delay rats with fimbria-fornix lesions were still impaired but in animals that had the hippocampus removed, working memory did not differ from that of controls. These results suggest that there was some recovery in those rats with hippocampal lesions (e.g., on the working memory task) but both hippocampal and fimbria-fornix animals were still impaired compared to controls when training was delayed 6.5 months following the operations.     

Influence of acetaminophen consumption on perceived exertion at the lactate concentration threshold

The purpose of this investigation was to study effects of acetaminophen consumption on ratings of perceived exertion and estimated time limit responses at the lactate threshold. 98 young regional to national level athletes performed a graded exhausting exercise on an outdoor running track to estimate their maximal aerobic velocity and the velocity associated with their lactate concentration threshold. Urine (30 mL) was collected during this test and analysed for numerous substances. During urinary screening for doping substances, 9 acetaminophen consumers (9.2%) among the 98 included athletes were detected. These acetaminophen consumers have significantly lower perceived exertion at velocity corresponding to the lactate concentration threshold than nonconsumers (11.9 +/- 2.1 vs 13.6 +/- 2.1, respectively) although they were at the same relative exercise intensity. This result shows that acetaminophen consumption may have mediated the perceived exertion response at the lactate concentration threshold. This may then suggest that the pain induced by training load could be a factor in use of self-prescribed pain relievers. Such consumption must be taken into account by medical staff, trainers, or educators who have to give information on the use and adverse effects of this substance and to propose palliative methods to their athletes.     

The effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage

Clozapine is an atypical antipsychotic drug that has been shown to improve spatial memory in some animal models; however its efficacy in reversing spatial memory impairment in rats with hippocampal lesions is unknown. To address this issue, we tested the effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage in three separate experiments. In each experiment, adult male rats received sham surgery or direct stereotaxic infusions of the excitotoxin, NMDA, into the hippocampus. In the first study, seven days after surgery, the sham control animals received daily saline injections while the lesioned animals were split into two groups that received daily saline or clozapine (2.0 mg/kg, sc) injections. During the fifth week of injections, all animals were tested in a food-motivated delayed spatial alternation task. Saline-treated rats with excitotoxic hippocampal damage displayed significant deficits in delayed spatial alternation. Daily clozapine injections completely reversed this deficit. In a second experiment, it was found that clozapine treatment limited to the testing days only did not improve alternation performance in lesioned rats. Finally, in a third experiment, chronic clozapine treatment did not improve alternation performance in lesioned rats that were pre-trained in the alternation task prior to surgery. These results suggest that chronic, but not acute, clozapine treatment enables rats with hippocampal damage to develop new spatial learning, but can not rescue old spatial learning established prior to damage. These results may have implications for the treatment of cognitive deficits caused by hippocampal dysfunction in disorders such as schizophrenia, Alzheimer's disease, and others.     

From countertransference to "passion"

Bion's ideas may be extended to describe an emotional phenomenology of the analyst's subjectivity and a methodology which helps differentiate countertransference enactments from fuller emotional participation. Bion called the process of integrating and utilizing one's most basic and important emotions to make meaning, "passion." The analyst's primal feelings--of love, hate, and curiosity--serve as a central organizer of meaning in the analytic interaction. These feelings involve pain, and to the extent the analyst unconsciously decides to evade or foreclose the evolution of the feelings, such that they remain unintegrated in the thinking process, the analyst is liable to become mired in repetitive transference-countertransference experiences without establishing fresh meaning. A case example illustrates the relevance of "passion" to contemporary relational theory and practice.     

Using the Millon Behavioral Medicine Diagnostic to Delineate Treatment Outcomes in Rehabilitation

Patients undergoing rehabilitation have been evidenced to improve in different ways depending on their coping styles. Amplifiers, Repressors, and Social Copers are examples of patients who present differently in rehabilitation settings and tend to have differing levels of success in their response to treatment. The current study examined the differential treatment outcomes of three coping style groups undergoing multidisciplinary rehabilitation. A sample of 59 patients suffering from injuries associated with chronic pain were assessed using the Multidimensional Pain Inventory, Beck Depression Inventory, and Beck Anxiety Inventory before, during, and after multidisciplinary pain management treatment. Coping style groups derived from the Millon Behavioral Medicine Diagnostic consisting of Amplifiers, Repressors, and Social Copers were compared with regard to reductions in depression, anxiety, pain, functional impairment, and associated outcomes. Repeated measures ANOVA revealed that Amplifiers, Repressors, and Social Copers had varying levels of success in the treatment program. Hierarchical linear modeling analyses revealed the coping style groups to have significantly different change curves from pre to post-treatment in depression, anxiety, pain severity, functional impairment, affective distress, life control, social support, and soliciting help from others. These findings support prior research emphasizing the value of tailoring treatments in rehabilitation settings toward patients’ coping styles in order to maximize outcomes. A program (provided in either SAS or SPSS syntax) that will compute MBMD coping style group membership will be provided upon request. Request by e-mail to: dcipher@hsc.unt.edu or by fax to: +1-817-7352270.     

For an indeterministic ethics. The emptiness of the rule in dubio pro vita and life cessation decisions

It is generally claimed that there exist exceptional circumstances when taking human life may be approved and when such actions may be justified on moral grounds. Precise guidelines in the medical field for making such decisions concerning patients who are terminally ill or have irreparable injuries incompatible with a bearable life, are difficult to establish. Recommendations that take the particular logical form of a rule, such as "in dubio pro vita", "when in doubt favour life") have been suggested and in some countries incorporated into legal texts (Germany). We claim here that such a rule is of no value since it is open-ended and always allows for doubt, and a decision to employ measures that would support human life could always be argued to be a valid choice. Preservation of this rule could be encouraged, but giving it the force of law may put physicians at risk, as they may be challenged for choosing to terminate life in otherwise ethically and medically uncontroversial circumstances.     

From "in the air" to "under the skin": cortisol responses to social identity threat

The authors examined women's neuroendocrine stress responses associated with sexism. They predicted that, when being evaluated by a man, women who chronically perceive more sexism would experience more stress unless the situation contained overt cues that sexism would not occur. The authors measured stress as the end product of the primary stress system linked to social evaluative threat-the hypothalamic-pituitary-adrenal cortical axis. In Study 1, female participants were rejected by a male confederate in favor of another male for sexist reasons or in favor of another female for merit-based reasons. In Study 2, female participants interacted with a male confederate who they learned held sexist attitudes or whose attitudes were unknown. Participants with higher chronic perceptions of sexism had higher cortisol, unless the situation contained cues that sexism was not possible. These results illustrate the powerful interactive effects of chronic perceptions of sexism and situational cues on women's stress reactivity.     

The effects of lateral, medial, or complete septal lesions on positive conditioned suppression in rats

This study investigated the effects of lateral, medial, or complete septal lesions in rats on lever pressing and US-approach behaviors during the presentation of a light followed by two free food pellets. Ten days after surgery, groups of rats received 20 sessions of a random interval (RI) 60-s schedule of food reinforcement. The positive conditioned suppression paradigm consisted of 20 sessions of a 10-s light paired with free food while the rats were responding on the RI 60-s schedule. All groups of rats significantly suppressed lever pressing during the 10-s light presentation. During the last four sessions of the 10-s light condition, rats with lateral septal lesions had a significant increase in food-tray entries during the light presentation, while the other groups decreased lever pressing without a change in food-tray entries during the 10-s light presentation. Although rats with septal damage generally have difficulty inhibiting responses in a variety of operant situations, rats with lateral, medial, or complete septal lesions showed no impairment in positive conditioned suppression. This study also suggests that when the spatial arrangement of the CS and the type of US were manipulated to minimize sign-tracking and goal-tracking behaviors, emotional reactions during the presentation of the CS must be considered a factor influencing positive conditioned suppression.     

The GM1 ganglioside hastens the reduction of hyperemotionality after septal lesions

The purpose of the present study was to assess the effects of ganglioside treatment on changes in emotional, activity, and avoidance behaviors following septal brain damage. Rats were treated with GM1-gangliosides either before and after septal lesions, or only after septal lesions and tested for emotionality on 10 consecutive days beginning on the second day after surgery. The ganglioside treatment decreased the emotionality of rats with septal damage on the first test day, and enhanced their rate of recovery to control levels of emotionality. Septal rats treated with gangliosides had activity, rearing, and avoidance behaviors equivalent to nontreated septal rats; however, lesioned rats treated with GM1 showed reduced intertrial crossings during avoidance conditioning. These results suggest that the changes in emotional behavior of septal rats treated with GM1 occur shortly after the lesion.     

Failure to delay gratification following septal lesions in rats: Implications for an animal model of disinhibitory psychopathology

It has been proposed that dysfunction within a neural system composed of the medial septum, the posterior hippocampus and the orbito-frontal cortex (SHF system) may constitute the physiological basis of several disinhibitory syndromes in humans—psychopathy, hyperkinesis, alcoholism and extraversion. Consequently, the syndrome produced by lesions of the SHF system in animals is offered as a tentative behavioral model that may elucidate basic psychological components of human disinhibitory psychopathology. As predicted from this model, rats with septal lesions, like disinhibited humans, were less likely to delay gratification than controls when given a choice between waiting 10 sec for an assured reinforcement and an immediately available, though infrequently delivered, reinforcement. Inquiry into the nature of this deficit suggested that these rats are subject to an interference effect, such that the influence of future rewards on behavior could be disrupted or ‘eclipsed’ by the presence of more immediate, prominent, motivationally significant cues. The possibility that various disinhibitory syndromes in humans may also be due to a similar rigid focus of attention upon the most immediate or prominent motivationally significant event was briefly discussed.     

Schmerz ist nicht gleich Schmerz

Pain is an emotional state that is inextricably linked to the mental state and sociocultural background of the person experiencing the pain. The basis of our current understanding of the pain are the bio-psycho-social model and knowledge regarding complex physiological and pathophysiological mechanisms. Nociceptive pain is caused by a painful stimulus; upon activation of peripheral nociceptors, signals are sent to the brain for processing. It has a protective function because it leads to reflexes or behavior-based reactions to minimize damage to tissue. Neuropathic pain is—apart from a few exceptions—a chronic, non-malignant pain condition that is caused by diseases of the central and peripheral nervous system. In contrast to acute pain, the causes of chronic pain are usually not known and remain even when no tissue damage is present.     

Visual discrimination learning in rats with lesions of superior colliculus: Door-push and approach errors in modified jumping stand

It has been suggested that, for some species, lesions of the superior colliculus affect visual discrimination learning, but only in certain conditions: (a) when problems are first learnt only after operation, or (b) when discriminanda require detailed scanning, or (c) when “approach” responses to the discriminanda are measured, rather than the response of actually touching them. These suggestions were examined in rats learning visual discriminations in a modified jumping-stand apparatus, after sustaining large lesions of the superior colliculus (and in some cases also of the pretectum). The lesions produced open-field hyperactivity and reduced exploration, indicating effective tectal damage, but the rats learnt a series of difficult discriminations in a door-push task as fast as normal rats, and they did not make more approach errors. Their main abnormality in the discrimination apparatus was that they looked less often between the stimulus doors before stepping across to one of them from the central platform. It is suggested that in rats, as in other animals, lesions of the superior colliculus disrupt the control of scanning head and eye movements; in rats, however, such disruption need not affect discrimination learning (at least in some kinds of apparatus), possibly because the retina of the rat has a relatively poorly developed area centralis.     

Gastric pathology and feeding deficits induced by hypothalamic damage in rats: effects of lesion type, size, and placement.

Three doses each of cathodal or anodal direct current were delivered to coagulate lateral hypothalamic tissue bilaterally in rats. Increases in hypothalamic tissue damage were associated with more instances of aphagia, greater amounts of glandular, but not rumenal, gastric pathology, and greater weight loss. Both anodal and cathodal lesions produced aphagia and similar amounts of gastric pathology, but anodal lesions also appeared to facilitate weight loss independently of the tissue damage. Extensive chromatolysis surrounding anodal lesion cavities may be importantly related to the postoperative effects. In additional experiments, anodal electrolytic lesions or cortical suction ablations were used to vary the location of neural damage. Fedding deficits and gastric pathology resulted from the destruction of several brain areas. In particular, eating of dry food in the presence of high gastric pathology was observed in rats with lesions ventral and medial to an area in the dorsolateral hypothalamus that was associated with aphagia. When aphagia was accompained by severe gastric pathology, the brain lesions typically encroached extensively on more ventromedial areas. Moreover, aphagia sometimes was observed with only negligible gastric pathology. It is suggested that gastric pathology is not primary to the expression of the aphagia that follows lateral hypothalamic damage.