A neurophysiologic model for aggressive behavior in the cat

A neurophysiologic model for aggessive behavior in the cat is proposed. Stimulus-bound and seizure-bound aggression was evaluated in relation to limbic and basal ganglia induced seizures (after-discharges). Electrically induced limbic and basal ganglia afterdischarges were used because they are known to implicate septohypothalamic sites from which aggression can be elicited by direct stimulation. The occurrence of behavioral aggression is correlated with the discharge characteristics of a single discharging system and with two interacting discharging systems. Aggression is composed of autonomic and somato-motor components which poses relatively low and high thresholds, respectively, for their activation. Aggression occurring during a combined septum and amygdala discharge was more intense and prolonged than with a septum discharge alone. Participation of a slow frequency discharging basal ganglia system activated seizurebound aggression in an otherwise nonaggressive limbic seizure. The limbic and basal ganglia stimulations and after-discharges lowered the excitability threshold of the aggression system and made it more vulnerable to being activated by external stimuli, such as visual and auditory stimuli. These observations are reminiscent of patients with aggressive behavior associated with psychomotor seizures.     

Kasuistik einer adoleszenten Frau mit NMDA-Rezeptor-antikörperpositiven Enzephalitis

Paraneoplastic encephalitis, an immune-mediated disease, has been known for a long time. In the last decade, several specific antibodies against cell membrane-located antigens causing limbic or diffuse encephalitis have been identified. Most of these cases are in fact non-paraneoplastic. These antibodies are likely primarily involved in the pathogenesis, in contrast to antineuronal antibodies against cytoplasmatic antigens (e.g., anti-Hu, anti-Yo, and anti-Ma2), which are more likely an epiphenomenon. The case reported here is an adolescent woman presenting with NMDAR (N-methyl D-aspartate receptor) antibody encephalitis, finally diagnosed during a relapse. The diagnostic and therapeutic approach to NMDAR antibody and limbic encephalitis is discussed.     

Aggression in temporal lobe epilepsy and limbic psychotic trigger reaction implicating vagus kindling of hippocampus/amygdala (in sinus abnormalites on MRIs)

Five aspects associated with potentially aggressive partial limbic seizures are interrelated: (1) Five out of six unselected (consecutively referred) White, male out-of-character aggressive felons (mean age 33) had histories of recurrent nasopharyngeal infections, four with congruent MRIs, two of these MRIs also showed cortical atrophy, three men had histories of various seizures, and one scalp EEG was “congruent with seizures in the temporal regions.” All men had histories of head injuries. The diagnoses of their bizarre acts during a brief psychosis were partial limbic seizures in an “exhibitionist” with temporal lobe epilepsy (TLE) and proposed limbic psychotic trigger reaction (LPTR) in four “murderers”, based on 13 specific symptoms and signs. (2) The men's nasopharyngeal (medical) conditions are hypothesized to be associated with intermittent mild stimulation of the vagus nerve. Supportive evidence shows that (3) experimental vagus stimulation has the most excitatory impact on hippocampus and amygdala, which are also (4) the most susceptible to limbic seizure kindling (by intermittent subthreshold stimuli). (5) even by contrast, high-voltage energy level and frequently applied vagus nerve stimulation (VNS), which is used as an antiepileptic treatment; however, VNS has elicited seizures in some patients.     

Wirkung vorgeburtlicher und früh-nachgeburtlicher Umwelteinflüsse auf Gehirn und Psyche

The psyche of a human being is formed in strict correlation with the development of the brain. Genetic, epigenetic regulatory and prenatal influences through the brain of the mother as well as postnatal influences, predominantly as early childhood attachment experiences are all intertwined with each other. This takes place at three “limbic levels”: a lower level at which the infantile temperament resides, a middle level of early childhood impressioning experiences and an upper limbic level of socialization. The cognitive language level develops in a relatively independent manner. At the three limbic levels six psychoneural systems are operative, namely the stress processing, the self-calming, the impulse inhibiting, the motivation, the attachment and the reality and risk perception systems. Mental disorders are characterized throughout by disorders of the first two systems, predominantly in the form of greatly increased cortisol levels and greatly reduced serotinin levels. These then induce deficits in other systems; however, in less severe cases compensatory processes can occur via an attachment-related increased release of oxytocin. Similar processes also occur within the “therapeutic alliance” in the patient-therapist relationship.     

Autoimmun-Enzephalitiden – eine Erkrankungsgruppe mit vielen Gesichtern

During the last 10 years a number of syndromes with antibodies against neuronal surface antigens have been characterized. Adults as well as children can be affected. Patients may suffer from amnestic syndrome, other cognitive deficits, seizures, or psychiatric symptoms. Some patients develop generalized encephalopathy with altered levels of consciousness, hyperkinesias, and hypothalamic disorders. In some patients, ovarial teratoma, thymoma, or small cell lung cancer can be diagnosed. However, in most patients no tumor is found. These syndromes were previously called autoimmune channelopathies. In fact, most antigens are not part of an ion channel but proteins or part of protein complexes on the cell surface of neurons, axons, dendrites, or synaptic terminals. These proteins are expressed throughout the nervous system. Interestingly, in limbic encephalitis very circumscribed brain regions are affected. This may be due to an increased vulnerability or accessibility of the affected brain regions. Limbic encephalitis is a well-characterized form of autoimmune encephalitis, which can be associated with different antibodies. Anti-NMDA-receptor encephalitis is not restricted to the limbic system. Characterization of other syndromes and auto-antibodies are expected in the future. In this review, aspects of limbic encephalitis and anti-NMDA-receptor encephalitis will be discussed.     

Effects of normal aging and Alzheimer's disease on emotional memory

Recall is typically better for emotional than for neutral stimuli. This enhancement is believed to rely on limbic regions. Memory is also better for neutral stimuli embedded in an emotional context. The neural substrate supporting this effect has not been thoroughly investigated but may include frontal lobe, as well as limbic circuits. Alzheimer's disease (AD) results in atrophy of limbic structures, whereas normal aging relatively spares limbic regions but affects prefrontal areas. The authors hypothesized that AD would reduce all enhancement effects, whereas aging would disproportionately affect enhancement based on emotional context. The results confirmed the authors' hypotheses: Young and older adults, but not AD patients, showed better memory for emotional versus neutral pictures and words. Older adults and AD patients showed no benefit from emotional context, whereas young adults remembered more items embedded in an emotional versus neutral context.     

Comparison between two opposite homicidal syndromes (Syndrome e vs. limbic psychotic trigger reaction)

Two syndromes with opposite kinds of homicidal acts also implicate opposite activation of frontal lobe and limbic systems. I. Fried's “Syndrome E” refers to planned, ideologically-motivated mass murders, committed in groups and accompanied by “elation.” Implicated are heightened functioning of certain frontal lobe regions with certain reduced limbic involvement . In contrast, A. A. Pontius' “Limbic Psychotic Trigger Reaction” delineates unplanned, motiveless homicidal acts (so far 17 cases) committed by a single loner with flat affect, implicating a partial limbic seizure hyperactivation with fleeting psychosis and brief secondary dysfunctioning of certain frontal regions.     

Glutamate-mediated neuroplasticity in a limbic input to the hypothalamus

Emotionally-salient stressors are processed by cortical and limbic circuits that provide important regulatory input to the hypothalamic-pituitary-adrenal (HPA) axis. However, exposure to chronic or severe stress may cause disregulation of the axis and a variety of physiological and psychological symptoms. The mechanisms that underlie stress-induced alterations in HPA axis function are not well characterized, but one possibility is that severe stress causes plastic changes in limbic inputs to the hypothalamus. We examined plasticity within the bed nucleus of stria terminalis (BNST) and the hypothalamic paraventricular nucleus (PVN) with a stimulating electrode in the BNST and a recording electrode in the PVN. High-frequency BNST stimulation produced long-lasting suppression of evoked field potentials recorded from the PVN, and this effect was blocked by administration of MK-801. Accordingly, rapid glutamate-mediated neuroplasticity in the BNST to PVN neurocircuitry may contribute to plasticity in limbic regulation of the HPA axis.     

Physiological changes during operations on the limbic system in man

The limbic system is a phylogenetically old part of the brain which is concerned with a variety of emotional and viscerosomatic functions. It has been found that small discrete lesions, placed by stereotaxis in this system during limbic leukotomy, may result in marked clinical improvement in severely incapacitated psychiatric patients who have failed to respond to any other type of treatment. In one patient, electrical stimulation of the anterior cingulate gyrus was carried out under local anesthesia to locate a suitable site for a limbic lesion. Physiological arousal was produced, as evidenced by changes in heart rate, forearm blood flow, sweat gland activity and respiration. Bilateral lesions, 8 mm in diameter, produced by freezing this site, resulted in marked clinical improvement. Peripheral physiological changes are now being used to aid in the selection of target sites in various parts of the limbic system. Under general anesthesia marked respiratory changes have been found on stimulation of the lower medial quadrant of the frontal lobe, anterior cingulate gyrus, above the roof of the lateral ventricle, and in the amygdala nucleus of the temporal lobe. Lesions are made with a cryogenic probe at sites of maximum physiological response. It is postulated that physiological monitoring during electrical stimulation of target areas will improve the accuracy of lesion placement. Some of the results of this procedure are described.     

The Limbic System and the Soul: Evolution and the Neuroanatomy of Religious Experience

The evolutionary neurological foundations of religious experience are detailed. Human beings have been burying and preparing their dead for the Hereafter for more than 100,000 years. These behaviors and beliefs are related to activation of the amygdala, hippocampus, and temporal lobe, which are responsible for religious, spiritual, and mystical trancelike states, dreaming, astral projection, near-death and out-of-body experiences, and the hallucination of ghosts, demons, angels, and gods. Abraham, Moses, Muhammad, and Jesus Christ, and others who have communed with angels or gods display limbic system hyperactivity, whereas patients report religious hallucinations or out-of-body experiences when limbic structures are stimulated or excessively activated. It is postulated that limbic and temporal lobe structures account for the sexual and violent aspects of religious behavior and also serve as a "transmitter to God," and that the evolution of these structures made spiritual experience possible.     

A theory of alpha/theta neurofeedback, creative performance enhancement, long distance functional connectivity and psychological integration

Professionally significant enhancement of music and dance performance and mood has followed training with an EEG-neurofeedback protocol which increases the ratio of theta to alpha waves using auditory feedback with eyes closed. While originally the protocol was designed to induce hypnogogia, a state historically associated with creativity, the outcome was psychological integration, while subsequent applications focusing on raising the theta–alpha ratio, reduced depression and anxiety in alcoholism and resolved post traumatic stress syndrome (PTSD). In optimal performance studies we confirmed associations with creativity in musical performance, but effects also included technique and communication. We extended efficacy to dance and social anxiety. Diversity of outcome has a counterpart in wide ranging associations between theta oscillations and behaviour in cognitive and affective neuroscience: in animals with sensory-motor activity in exploration, effort, working memory, learning, retention and REM sleep; in man with meditative concentration, reduced anxiety and sympathetic autonomic activation, as well as task demands in virtual spatial navigation, focussed and sustained attention, working and recognition memory, and having implications for synaptic plasticity and long term potentiation. Neuroanatomical circuitry involves the ascending mescencephalic-cortical arousal system, and limbic circuits subserving cognitive as well as affective/motivational functions. Working memory and meditative bliss, representing cognitive and affective domains, respectively, involve coupling between frontal and posterior cortices, exemplify a role for theta and alpha waves in mediating the interaction between distal and widely distributed connections. It is posited that this mediation in part underpins the integrational attributes of alpha–theta training in optimal performance and psychotherapy, creative associations in hypnogogia, and enhancement of technical, communication and artistic domains of performance in the arts.     

Aberrant paralimbic gray matter in criminal psychopathy

Psychopaths impose large costs on society, as they are frequently habitual, violent criminals. The pervasive nature of emotional and behavioral symptoms in psychopathy suggests that several associated brain regions may contribute to the disorder. Studies employing a variety of methods have converged on a set of brain regions in paralimbic cortex and limbic areas that appear to be dysfunctional in psychopathy. The present study further tests this hypothesis by investigating structural abnormalities using voxel-based morphometry in a sample of incarcerated men (N=296). Psychopathy was associated with decreased regional gray matter in several paralimbic and limbic areas, including bilateral parahippocampal, amygdala, and hippocampal regions, bilateral temporal pole, posterior cingulate cortex, and orbitofrontal cortex. The consistent identification of paralimbic cortex and limbic structures in psychopathy across diverse methodologies strengthens the interpretation that these regions are crucial for understanding neural dysfunction in psychopathy.     

A theory of alpha/theta neurofeedback,creative performance enhancement,long distance functional connectivity and psychological integration

Professionally significant enhancement of music and dance performance and mood has followed training with an EEG-neurofeedback protocol which increases the ratio of theta to alpha waves using auditory feedback with eyes closed. While originally the protocol was designed to induce hypnogogia, a state historically associated with creativity, the outcome was psychological integration, while subsequent applications focusing on raising the theta–alpha ratio, reduced depression and anxiety in alcoholism and resolved post traumatic stress syndrome (PTSD). In optimal performance studies we confirmed associations with creativity in musical performance, but effects also included technique and communication. We extended efficacy to dance and social anxiety. Diversity of outcome has a counterpart in wide ranging associations between theta oscillations and behaviour in cognitive and affective neuroscience: in animals with sensory-motor activity in exploration, effort, working memory, learning, retention and REM sleep; in man with meditative concentration, reduced anxiety and sympathetic autonomic activation, as well as task demands in virtual spatial navigation, focussed and sustained attention, working and recognition memory, and having implications for synaptic plasticity and long term potentiation. Neuroanatomical circuitry involves the ascending mescencephalic-cortical arousal system, and limbic circuits subserving cognitive as well as affective/motivational functions. Working memory and meditative bliss, representing cognitive and affective domains, respectively, involve coupling between frontal and posterior cortices, exemplify a role for theta and alpha waves in mediating the interaction between distal and widely distributed connections. It is posited that this mediation in part underpins the integrational attributes of alpha–theta training in optimal performance and psychotherapy, creative associations in hypnogogia, and enhancement of technical, communication and artistic domains of performance in the arts.     

Subtypes of limbic system dysfunction evoking homicide in limbic (?) Psychotic trigger reaction and temporal lobe epilepsy--evolutionary constraints

Within an evolutionary context two subtypes of limbic system dysfunctioning are compared: (1) the previously proposed limbic psychotic trigger reaction, in which nondrive motivated homicide is triggered by a specific individualized external stimulus, which evokes a brief-lasting active reliving of past (moderately) stressful, frequently repeated ("kindled"?) situations. The brief-lasting out-of-character homicidal episode with flat affect is typically associated with first-time formed or unformed hallucinations of various modalities and with overactivation of the autonomic nervous system. There is no (noticeable) loss of consciousness, enabling the patient's full recall (at times with suicidal attempts) (Pontius, 1981, 1984, 1987). (2) A rare case of homicide during a fugue state with echopraxia in temporal lobe epilepsy is discussed.     

Sensitization as a mechanism for multiple chemical sensitivity: relationship to evolutionary theory

Multiple chemical sensitivity (MCS) is a disorder in humans attributed to prior chemical exposure. Sensitization is an amplification of neuronal responsiveness that elicits increased behavioral responding to stimuli, and occurs in a recently developed rat model of MCS. Rats were exposed to repeated formaldehyde (Form) and their response in three behavioral tests, including locomotor activity after a cocaine challenge, conditioned fear, and behavioral avoidance of Form, was assessed. In all three tests, rats demonstrated sensitized behaviors, implicating amplified responding within specific limbic brain regions. Evolutionary theory in the context of MCS specifies how the behavioral strategies of those with MCS are consistent with the notion that their self-perceived sense of survival and reproductive fitness may be threatened by chemical exposures. This behavior may be mediated by the same limbic brain regions that become sensitized after repeated chemical exposure in animals.     

Cholinergic rebound after chlorpromazine exacerbates lithium muscarinic-induced limbic seizures in rats: implications for psychiatric treatment.

When lithium serum levels were within the (human) therapeutic range, young and old adult male and female rats (housed singly or in groups) all displayed faster limbic seizure onset times in response to a muscarinic cholinergic agonist (pilocarpine 20 mg/kg) if a single systemic dosage of chlorpromazine was injected 24 hours previously. The effect was comparable to injecting an additional 10 mg/kg of pilocarpine. These results strongly suggest that cholinergic rebound from chlorpromazine administrations during lithium treatment could facilitate subclinical electrical lability and very localized neuronal necrosis within the limbic system of clinical patients, resulting in normalization of psychiatric symptoms.     

How brain arousal systems determine different temperament types and the major dimensions of personality

Theory and research is described which led to the hypothesis that the choleric (E+N+) and melancholic (E−N+) temperaments are determined by differences in thalamocortical inhibition of brain-stem processes. An opportunity to test this hypothesis was provided by the recent discovery of 4, 7, and 10 Hz response waves confounded in EEG averaged evoked potentials [Robinson, D. L. (1999b). The technical, neurological, and psychological significance of ‘alpha’ ‘theta’ and ‘delta’ waves confounded in EEG evoked potentials: 1. A study of peak latencies. Electroencephalography and Clinical Neurophysiology, 110, 1427–1434; (2000). The technical neurological, and psychological significance of ‘alpha’, ‘delta’, and ‘theta’ waves confounded in EEG evoked potentials: A study of peak amplitudes. Personality and Individual Differences, 28, 673–693]. These responses are attributed to the brain-stem, limbic, and thalamocortical arousal systems, respectively, and in the cited reports principal components analysis of data obtained from 93 participants confirmed the existence of predicted excitatory and inhibitory relationships. ANOVA was used in the present study to test the further prediction that there should be strong inhibition of the 4 Hz system by the 10 Hz system in melancholics (E−N+) and weak inhibition of the 4 Hz system in cholerics (E+N+), with median inhibition predicted for the other temperament types. There was a large and statistically significant difference between the mean scores on the PCA inhibition factor obtained for the temperament groups, with temperament defined in terms of high and low EPQ extraversion (E) and neuroticism (N) scores. The significance of these results is discussed with reference to fundamental questions raised by Pavlov's pioneering research but left unanswered for the best part of a century. Implications for the future conduct of personality research are also considered.     

The “nootropic” approach to the pharmacology of the integrative activity of the brain 1, 2

The integrative activity of the brain is particularly related to the telencephalic level of CNS. Drugs affecting learning and memory usually interfere with the reticular or limbic system, and are either stimulants or sedatives. In contrast, Piracetam (U C B 6215) is an atoxic compound which, up to dosages such as g/kg, does not interfere with autonomic functions, general behavior, level of wakefulness, the limbic system, etc. Yet, in dosages such as mg/kg it improves several learning and memory abilities, protects against experimental amnesic agents, facilitates EEG recovery after severe hypoxia and also facilitates interhemispheric transfer (transcallosal evoked potential and learned behavior). Discussion is made on the basis of the particular neuropharmacology as well as on the available biochemical and human clinical correlations to emphasize the selectivity of this compound on telencephalic integrative mechanisms. Piracetam is presented as the first-comer of a new psychotropic class for which the termnootropic is proposed.     

Neuroimaging and Depression: Current Status and Unresolved Issues

ABSTRACT— Major depression is among the most debilitating, prevalent, and recurrent of all psychiatric disorders. Over the past decade, investigators have examined the neural mechanisms associated with this disorder. In this article we present an overview of neuroimaging research that has assessed the structure and functioning of the amygdala, subgenual anterior cingulate cortex, and dorsolateral prefrontal cortex in major depression. We then describe results of studies that have attempted to elucidate the nature of the relations among these brain structures. The picture that emerges from these investigations is one in which heightened activity in limbic structures that underlie the experience and expression of emotion dampens activation in dorsal cortical structures that are involved in affect regulation, reducing their ability to influence limbic activation. We conclude by highlighting unresolved issues concerning the roles of these structures in depression and their relation to specific symptoms of this disorder.     

Limbic system dysfunction and inventoried psychopathology among incarcerated pedophiles

This study explored relationships between “highly probable” neuropathology in the limbic system (as gauged by clinically elevated scores on the Limbic System Check-list-33, or LSCL-33, a screening index for limbic system dysfunction developed by medical researchers at Harvard and Dartmouth) and inventoried psychopathology (as gauged through scores on the MMPI) among a group of adjudicated pedophiles incarcerated for treatment in a specialized prison for criminal sexual psychopaths in a mid-Atlantic state. Principal findings: Only 33 percent of this sample of incarcerated pedophiles exhibits scores on the LSCL-33 at a level high enough to warrant a medical conclusion of “probable” limbic system dysfunction. When scores on the MMPI are grouped according to critical values for clinically relevant scores on the LSCL-33, significant F ratios in one-way analyses of variance are observed on L, F, K, Hs, D, Hy, Pa, Pt, Sc, and Ma. Mean T scores for “probable” dysfunctionals simultaneously reach elevations at or above the threshold of clinical significance for Pd, Pa, and Sc. On that basis, the categorization psychopathic paranoid schizophrenia readily applies to limbic system dysfunctional child sexual abusers studied in this inquiry, but not to their nondysfunctional counterparts. But significant F ratios are observed neither for the age of the victim(s) in the instant offense(s), for the number of prior arrests for sex offenses, for the number of prior arrests for any and all felony offenses, including sex offenses, nor for the offender's current age. However, a stepwise multiple regression between gross number of prior arrests for any and all offenses (including sex offenses) as the most robust of the indices of past criminal activity and both LSCL-33 and MMPI scores across all offenders represented in this inquiry (i.e., the limbic system dysfunctional, the nondysfunctional, and a mid-range group) proceeds to four steps, achieving a multiple R of .575 and encompassing Pd, Mf, Pa, and LSCL-33 scores as the most efficient interactive post-dictive set. Stepwise multiple regression analyses of past arrest record computed independently for limbic system dysfunctionals and nondysfunctionals progresses among dysfunctionals to seven steps, achieving a multiple R of .867 and encompassing Pd, Hy, Ma, Mf, Si, Pa, and Sc scores as the most efficient interactive post-dictive set; and among nondysfunctionals, to six steps, achieving a multiple R of .797 and encompassing Mf, D, Pt, Hy, Pa, and over-controlled hostility scores as the most efficient interactive post-dictive set. The latter results are interpreted as suggesting that neuropathology and psychopathology interact with and potentiate each other in post-dicting criminal behavior among the pedophiles studied in this inquiry. This study was supported in part by the Fund for Correctional and Forensic Psychology, Rutgers University Foundation. The investigators express deep appreciation to Charles Albino for assis-tance in data collection.