Home About us Contact
|
Home About us Contact | ||
|
|
||
Disinhibition
Kinds of Disinhibition Selected AbstractsCriminal cognitions and personality: what does the PICTS really measure?CRIMINAL BEHAVIOUR AND MENTAL HEALTH, Issue 3 2000Dr Vincent Egan Introduction The Psychological Inventory of Criminal Thinking Styles (PICTS) is a measure of the criminal cognitions and thinking styles that maintain offending. The scale comprises 8 a priori thinking styles and two validation scales, the validation scales having been found to be unreliable. Owing to the large amount of apparently shared variance in the original validation study, this data matrix needs re-analysis. Results from the PICTS were examined in relation to general measures of individual differences, in order to link the PICTS to the broader literature on the characteristics of offenders. Method The original PICTS data-matrix was re-analysed using a more parsimonious method of analysis. The PICYS was also given to 54 detained, mentally disordered offenders along with the NEO-Five Factor Inventory, the Sensation-Seeking Scale (SSS), the Attention Deficit Scales for Adults (ADSA) and, as a measure of general intelligence, the Standard Progressive Matrices. Results Principal components analysis suggested that the PICTS really comprised two factors: a lack of thoughtfulness (i.e. lack of attention to one's experience), and wilful hostility, with the first factor being most well defined. Intelligence was not associated with any factor of criminal thinking style. High scores on the ADSA and Disinhibition and Boredom Susceptibility subscales of the SSS were associated with much greater endorsement of criminal sentiments; high Neuroticism, low Extroversion, and low Agreeableness were slightly lower correlates. Discussion The issues involved in criminogenic cognitions need clarification and to be linked to the broader literature on cognitive distortions and personality. Interventions targeted at dismantling impulsive destructive behaviour, whether it be thoughtlessness or wilful hostility, may be effected by increasing thinking skills, so breaking down the cognitions that maintain criminal behaviour. Copyright © 2000 Whurr Publishers Ltd. [source] Evidence for a Role of the Parafascicular Nucleus of the Thalamus in the Control of Epileptic Seizures by the Superior ColliculusEPILEPSIA, Issue 1 2005Karine Nail-Boucherie Summary:,Purpose: The aim of this study was to investigate whether the nucleus parafascicularis (Pf) of the thalamus could be a relay of the control of epileptic seizures by the superior colliculus (SC). The Pf is one of the main ascending projections of the SC, the disinhibition of which has been shown to suppress seizures in different animal models and has been proposed as the main relay of the nigral control of epilepsy. Methods: Rats with genetic absence seizures (generalized absence epilepsy rat from Strasbourg or GAERS) were used in this study. The effect of bilateral microinjection of picrotoxin, a ,-aminobutyric acid (GABA) antagonist, in the SC on the glutamate and GABA extracellular concentration within the Pf was first investigated by using microdialysis. In a second experiment, the effect of direct activation of Pf neurons on the occurrence of absence seizures was examined with microinjection of low doses of kainate, a glutamate agonist. Results: Bilateral injection of picrotoxin (33 pmol/side) in the SC suppressed spike-and-wave discharges for 20 min. This treatment resulted in an increase of glutamate but not GABA levels in the Pf during the same time course. Bilateral injection of kainate (35 pmol/side) into the Pf significantly suppressed spike-and-wave discharges for 20 min, whereas such injections were without effects when at least one site was located outside the Pf. Conclusions: These data suggest that glutamatergic projections to the Pf could be involved in the control of seizures by the SC. Disinhibition of these neurons could lead to seizure suppression and may be involved in the nigral control of epilepsy. [source] A Self-Regulatory Model of Behavioral Disinhibition in Late Adolescence: Integrating Personality Traits, Externalizing Psychopathology, and Cognitive CapacityJOURNAL OF PERSONALITY, Issue 2 2010Tim Bogg ABSTRACT Two samples with heterogeneous prevalence of externalizing psychopathology were used to investigate the structure of self-regulatory models of behavioral disinhibition and cognitive capacity. Consistent with expectations, structural equation modeling in the first sample (N=541) showed a hierarchical model with 3 lower order factors of impulsive sensation seeking, antisociality/unconventionality, and lifetime externalizing problem counts, with a behavioral disinhibition superfactor best accounted for the pattern of covariation among 6 disinhibited personality trait indicators and 4 externalizing problem indicators. The structure was replicated in a second sample (N=463) and showed that the behavioral disinhibition superfactor, and not the lower order impulsive sensation seeking, antisociality/unconventionality, and externalizing problem factors, was associated with lower IQ, reduced short-term memory capacity, and reduced working memory capacity. The results provide a systemic and meaningful integration of major self-regulatory influences during a developmentally important stage of life. [source] Continuity and Change in Personality Traits From Adolescence to Midlife: A 25-Year Longitudinal Study Comparing Representative and Adjudicated MenJOURNAL OF PERSONALITY, Issue 5 2003Julien Morizot The second study examined structural, rank-order, and mean-level continuity. Partial structural continuity was demonstrated through confirmatory factor analysis. Regarding rank-order continuity, the correlations were stronger as age increased, particularly for the adjudicated men. For mean-level continuity, the adjudicated men displayed higher scores from adolescence to midlife for nearly every personality trait related to Disinhibition and Negative Emotionality. Significant decreases were observed in these traits for both samples, supporting the hypothesis of a normative psychological maturation. Although both samples showed this maturation, the adjudicated men displayed a lower rate of change during adolescence and early adulthood. The two samples did not differ in Extraversion and this trait remained more stable, particularly for adjudicated men. [source] Serotonin Transporter Promoter Polymorphism Genotype Is Associated With Behavioral Disinhibition and Negative Affect in Children of AlcoholicsALCOHOLISM, Issue 7 2001Geoffrey R. Twitchell Background : Serotonergic (5-HT) dysfunction has been implicated in the etiology of both behavioral disinhibition (BD) and negative affect (NA). This work extends our previous finding of relationships between whole blood 5-HT and both BD and NA in pubescent, but not prepubescent, children of alcoholics and continues examination of a hypothesized role of 5-HT dysfunction in alcoholism risk. The long and short (L and S) variants of the 5-HT transporter gene-linked polymorphic region (5-HTTLPR) are responsible for differing transcriptional efficiencies in 5-HT uptake. Although associations have been found between the SS 5-HTTLPR genotype and severe alcoholism and neuroticism, recent reports describe relationships between the LL genotype and both low level of response to alcohol and alcoholism diagnosis and a predominance of the LL genotype in early-onset alcoholics. Methods: This report is from an ongoing prospective study of the development of risk for alcoholism and other problematic outcomes in a sample of families classified by father's alcoholism subtype. This study examines relationships between 5-HTTLPR genotype and both child BD (Child Behavior Checklist Aggressive Behavior) and NA (Child Behavior Checklist Anxious/Depressed) in offspring from 47 families. Results: Results showed significantly higher levels of BD and NA in the 16 children with the LL genotype than the 46 SS or SL children. Conclusions: Behaviors of undercontrol, which occur at increased rates in children of alcoholics, may be genetically influenced through the regulation of the 5-HT transporter. Due to the small sample size and the preliminary nature of our findings, replication is necessary. [source] Searching for a developmental typology of personality and its relations to antisocial behaviour: a longitudinal study of an adjudicated men sampleCRIMINAL BEHAVIOUR AND MENTAL HEALTH, Issue 4 2003Julien Morizot The search for an empirically based personality typology has regained the interest of researchers. To date, however, empirical inquiries have mainly been cross-sectional. In this study, an empirically based developmental typology of personality was identified using data from a prospective longitudinal study of a sample of men adjudicated during their adolescence and assessed on four occasions until midlife. Cluster analyses were performed on measures of disinhibition, negative emotionality, and extraversion. Four developmental types of personality were identified. The first was characterized by average scores in the three traits in adolescence that decreased linearly until midlife (39%). The second type displayed very high scores in disinhibition and negative emotionality in adolescence that decreased rapidly during early adulthood (24%). The third type was characterized by very high scores in disinhibition and negative emotionality that remained stable until midlife, while extraversion was average during adolescence and then decreased rapidly until midlife (17%). The fourth type was characterized by high scores in disinhibition and negative emotionality in adolescence that was followed by cycles of decreases and increases until midlife (20%). These four developmental types of personality seemed to be related to known antisocial behaviour trajectories. Copyright © 2003 Whurr Publishers Ltd. [source] Personality traits as prospective predictors of suicide attemptsACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2009S. Yen Objective:, To examine higher order personality factors of negative affectivity (NA) and disinhibition (DIS), as well as lower order facets of impulsivity, as prospective predictors of suicide attempts in a predominantly personality disordered sample. Method:, Data were analyzed from 701 participants of the Collaborative Longitudinal Personality Disorders Study with available follow-up data for up to 7 years. Cox proportional hazards regression analyses was used to examine NA and DIS, and facets of impulsivity (e.g. urgency, lack of perseverance, lack of premeditation and sensation seeking), as prospective predictors of suicide attempts. Results:, NA, DIS and all facets of impulsivity except for sensation seeking were significant in univariate analyses. In multivariate models which included sex, childhood sexual abuse, course of major depressive disorder and substance use disorders, only NA and lack of premeditation remained significant in predicting suicide attempts. DIS and the remaining impulsivity facets were not significant. Conclusion:, NA emerged as a stronger and more robust predictor of suicide attempts than DIS and impulsivity, and warrants greater attention in suicide risk assessment. Distinguishing between facets of impulsivity is important for clinical risk assessment. [source] Parental alcohol dependence and the transmission of adolescent behavioral disinhibition: a study of adoptive and non-adoptive familiesADDICTION, Issue 4 2009Serena M. King ABSTRACT Aim To examine the genetic and environmental influences of parental alcoholism on offspring disinhibited behavior. Design We compared the effect of parental alcoholism history on offspring in adoptive and non-adoptive families. In families with a history of parental alcohol dependence, we examined the effect of exposure to parental alcoholism symptoms during the life-time of the adolescent. Setting Assessments occurred at the University of Minnesota from 1998 to 2004. Participants Adolescents adopted in infancy were ascertained systematically from records of three private Minnesota adoption agencies; non-adopted adolescents were ascertained from Minnesota birth records. Adolescents and their rearing parents participated in in-person assessments. Measurements For adolescents, measures included self- reports of delinquency, deviant peers, substance use, antisocial attitudes and personality. For parents, we conducted DSM-IV clinical assessments of alcohol abuse and dependence. Findings A history of parental alcohol dependence was associated with higher levels of disinhibition only when adolescents were related biologically to their rearing parents. Within families with a history of parental alcoholism, exposure to parental alcohol misuse during the life-time of the adolescent was associated with increased odds of using alcohol in adopted adolescents only. Conclusions These findings suggest that the association between a history of parental alcohol dependence and adolescent offspring behavioral disinhibition is attributable largely to genetic rather than environmental transmission. We also obtained some evidence for parental alcohol misuse as a shared environmental risk factor in adoptive families. [source] Area-Specific Resonance of Excitatory Networks in Neocortex: Control by Outward CurrentsEPILEPSIA, Issue 8 2007Manuel A. Castro-Alamancos Summary:, During disinhibition or low [Mg++]o buffer, 7,14 Hz (,10 Hz) oscillations are generated by excitatory networks of interconnected pyramidal cells in motor (agranular) cortex but are absent in barrel (granular) cortex. Here we studied if the inability of barrel cortex to produce ,10 Hz oscillations during these conditions is because barrel cortex networks lack the necessary cellular mechanisms or, alternatively, because those mechanisms are inhibited by outward currents. The results show that blockers of slowly inactivating voltage-dependent K+ currents unmask ,10 Hz oscillations in barrel cortex, and this occurs in unison with the unmasking of intrinsic inward Ca++ currents that are kept suppressed by the outward currents. Moreover, the ,10 Hz oscillations unmasked in barrel cortex occur independently in upper and lower layers indicating that the ,10 Hz oscillation mechanisms are kept suppressed in multiple networks. The results reveal that the propensity of distinct excitatory networks of neocortex to generate epileptiform oscillatory activities is controlled by outward currents. [source] Evidence for a Role of the Parafascicular Nucleus of the Thalamus in the Control of Epileptic Seizures by the Superior ColliculusEPILEPSIA, Issue 1 2005Karine Nail-Boucherie Summary:,Purpose: The aim of this study was to investigate whether the nucleus parafascicularis (Pf) of the thalamus could be a relay of the control of epileptic seizures by the superior colliculus (SC). The Pf is one of the main ascending projections of the SC, the disinhibition of which has been shown to suppress seizures in different animal models and has been proposed as the main relay of the nigral control of epilepsy. Methods: Rats with genetic absence seizures (generalized absence epilepsy rat from Strasbourg or GAERS) were used in this study. The effect of bilateral microinjection of picrotoxin, a ,-aminobutyric acid (GABA) antagonist, in the SC on the glutamate and GABA extracellular concentration within the Pf was first investigated by using microdialysis. In a second experiment, the effect of direct activation of Pf neurons on the occurrence of absence seizures was examined with microinjection of low doses of kainate, a glutamate agonist. Results: Bilateral injection of picrotoxin (33 pmol/side) in the SC suppressed spike-and-wave discharges for 20 min. This treatment resulted in an increase of glutamate but not GABA levels in the Pf during the same time course. Bilateral injection of kainate (35 pmol/side) into the Pf significantly suppressed spike-and-wave discharges for 20 min, whereas such injections were without effects when at least one site was located outside the Pf. Conclusions: These data suggest that glutamatergic projections to the Pf could be involved in the control of seizures by the SC. Disinhibition of these neurons could lead to seizure suppression and may be involved in the nigral control of epilepsy. [source] Characterization of Neuronal Migration Disorders in Neocortical Structures: Loss or Preservation of Inhibitory Interneurons?EPILEPSIA, Issue 7 2000Petra Schwarz Summary: Purpose: Neuronal migration disorders (NMD) are often associated with therapy-resistant epilepsy. In human cerebral cortex, this hyperexcitability has been correlated with a loss of inhibitory interneurons. We used a rat model of focal cortical NMD (microgyria) to determine whether the expression of epileptiform activity in this model coincides with a decrease in inhibitory interneurons. Methods: In 2- to 4-month-old rats, the density of interneurons immunoreactive for ,-aminobutyric acid (GABA), cal-bindin, and parvalbumin was determined in fronto-parietal cortex in nine 200-,m-wide sectors located up to 2.5 mm lateral and 2.0 mm medial from the lesion center in primary parietal cortex (Par 1). Quantitative measurements in homotopic areas of age-matched sham-operated rats served as controls. Results: The freeze lesion performed in newborn rat cortex resulted in adult rats with a microgyrus extending in a rostro-caudal direction from frontal to occipital cortex. The density of GABA- and parvalbumin-positive neurons in fronto-parietal cortex was not significantly different between lesioned and control animals. Only the density of calbindin-immunoreactive neurons located 1.0 mm lateral and 0.5 mm medial from the lesion was significantly (Student t test, p > 0.05) larger in freeze-lesioned rats (5.817 ± 562 and 6,400 ± 795 cells per mm3, respectively; n = 12) compared with measurements in homotopic regions in Parl cortex of controls (4,507 ± 281 and 4,061 ± 319 cells per mm3, respectively; n = 5). Conclusions: The previously reported widespread functional changes in this model of cortical NMD are not related to a general loss of inhibitory interneurons. Other factors, such as a decrease in GABA receptor density, modifications in GABAA receptor subunit composition, or alterations in the excitatory network, e.g., an increase in the density of calbindin-immunoreactive pyramidal cells, more likely contribute to the global disinhibition and widespread expression of pathophysiological activity in this model of cortical NMD. [source] Growth hormone and changes in energy balance in growth hormone deficient adultsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2008D. Deepak ABSTRACT Background, Adults with growth hormone deficiency (AGHD) have an adverse body composition with an increased prevalence of obesity. It is not known whether growth hormone replacement (GHR) results in alterations in energy intake (EI) and/or energy expenditure (EE). The aim of the study was to investigate the effects of GHR on EI and EE. Materials and methods, Nineteen hypopituitary adults (14 males, 5 females, mean age 46·2 years) with severe GHD (peak GH response to glucagon , 9 mU L,1) were studied. All patients self-injected recombinant human GH starting with 0·3 mg s.c. daily. The following were measured before and following 6 months of stable maintenance of GHR: food intake during a test meal, appetite ratings, resting EE (indirect calorimetry) and voluntary physical activity (accelerometry). Results, GHR nearly doubled voluntary physical activity (mean activity units 3319 vs. 1881, P = 0·007) and improved quality of life score (mean score 9·1 vs. 16·5, P < 0·0001). Subjects reported higher fasting hunger ratings (mean 64·8 vs. 49·6, P = 0·02) but ad libitum energy intake remained unchanged. Eating behavioural traits were favourably altered with lower disinhibition (mean 6·0 vs. 7·2, P = 0·02) and lower susceptibility to hunger ratings (4·6 vs. 6·8, P = 0·001) after GHR. Additionally, GHR did not result in significant changes in resting EE, body weight and body mass index. Conclusions, GHR in AGHD significantly improves voluntary physical activity and quality of life. Following GHR, subjects experience greater ,state' (physiological) hunger, reductions in eating disinhibition and hunger susceptibility, but no effects on calorie intake or macronutrient choice were detected. [source] Frontal-lobe mediated behavioral dysfunction in amyotrophic lateral sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2010M. Witgert Background:, Cognitive impairment secondary to frontal lobe atrophy exists in 40,60% of Amyotrophic Lateral Sclerosis (ALS) cases. We aimed to determine the prevalence of frontal-lobe mediated behavioral impairment in (ALS) and to ascertain its relationship to cognitive impairment. Methods:, Two-hundred and twenty five patients diagnosed with sporadic ALS were evaluated for behavioral dysfunction using the Frontal Systems Behavior Scale (FrSBe), a validated measure used to examine frontal-lobe mediated behaviors, specifically apathy, executive dysfunction and disinhibition; a total behavior score is also provided. Additionally, a subset of patients also underwent a comprehensive neuropsychological evaluation. Results:, Changes in the total FrSBe scores were observed in 24.4% of the patients and 39.6% of the patients had impairment in at least one behavioral domain with symptoms of Apathy being the most common (31.1%). Cognitively impaired ALS patients had worse total (P = 0.05) and apathy scores (P < 0.01); however, behavioral dysfunction was also present in 16% of the cognitively intact patients. Half of the behaviorally intact patients exhibited cognitive impairment. Significant correlations were observed for performance on certain neuropsychological tests (Animal fluency, Block Design, Logical Memory I and Verbal Series Attention Test) and severity of behavioral dysfunction on certain FrSBe sub scores. Conclusions:, Frontal-lobe mediated behavioral dysfunction appears to be common in ALS. Cognitively impaired ALS patients had greater behavioral dysfunction. Recognition of behavioral and cognitive dysfunction may assist health-care providers and care-givers recognize changes in decision-making capacity and treatment compliance of patients with ALS. [source] The pathophysiology of spasticityEUROPEAN JOURNAL OF NEUROLOGY, Issue 2002G. Sheean Spasticity is only one of several components of the upper motor neurone (UMN) syndrome, known collectively as the `positive' phenomena, that are characterized by muscle overactivity. Other components include tendon hyper-reflexia, clonus, the clasp-knife phenomenon, flexor and extensor spasms, a Babinski sign, and spastic dystonia. Spasticity is a form of hypertonia due to hyperexcitable tonic stretch reflexes. It is distinguished from rigidity by its dependence upon the speed of the muscle stretch and by the presence of other positive UMN signs. Hyperactive spinal reflexes mediate most of these positive phenomena, while others are due to disordered control of voluntary movement or abnormal efferent drive. An UMN lesion disturbs the balance of supraspinal inhibitory and excitatory inputs, producing a state of net disinhibition of the spinal reflexes. These include proprioceptive (stretch) and nociceptive (flexor withdrawal and extensor) reflexes. The clinical syndrome resulting from an UMN lesion depends more upon its location and extent, and the time since it occurred, than on the pathology of the lesion. However, the change in spinal reflex excitability cannot simply be due to an imbalance in supraspinal control. The delayed onset after the lesion and the frequent reduction in reflex excitability over time, suggests plasticity in the central nervous system. Knowledge of the electrophysiology and neurochemistry of spinal reflexes, together with the action of antispasticity drugs, helps us to understand the pathophysiology of spasticity. [source] Neuronal disinhibition in the trigeminal nucleus caudalis in a model of chronic neuropathic painEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2010Yasmina B. Martin Abstract The mechanisms underlying neuropathic facial pain syndromes are incompletely understood. We used a unilateral chronic constriction injury of the rat infraorbital nerve (CCI-IoN) as a facial neuropathic model. Pain-related behavior of the CCI-IoN animals was tested at 8, 15 and 26 days after surgery (dps). The response threshold to mechanical stimulation with von Frey hairs on the injured side was reduced at 15 and 26 dps, indicating the presence of allodynia. We performed unitary recordings in the caudalis division of the spinal trigeminal nucleus (Sp5C) at 8 or 26 dps, and examined spontaneous activity and responses to mechanical and thermal stimulation of the vibrissal pad. Neurons were identified as wide dynamic range (WDR) or low-threshold mechanoreceptive (LTM) according to their response to tactile and/or noxious stimulation. Following CCI-IoN, WDR neurons, but not LTM neurons, increased their spontaneous activity at 8 and 26 dps, and both types of Sp5C neurons increased their responses to tactile stimuli. In addition, the on,off tactile response in neurons recorded after CCI-IoN was followed by afterdischarges that were not observed in control cases. Compared with controls, the response inhibition observed during paired-pulse stimulation was reduced after CCI-IoN. Immunohistochemical studies showed an overall decrease in GAD65 immunoreactivity in Sp5C at 26 dps, most marked in laminae I and II, suggesting that following CCI-IoN the inhibitory circuits in the sensory trigeminal nuclei are depressed. Consequently, our results strongly suggest that disinhibition of Sp5C neurons plays a relevant role in the appearance of allodynia after CCI-IoN. [source] Long-range oscillatory Ca2+ waves in rat spinal dorsal hornEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2005Ruth Ruscheweyh Abstract Synchronous activity of large populations of neurons shapes neuronal networks during development. However, re-emergence of such activity at later stages of development could severely disrupt the orderly processing of sensory information, e.g. in the spinal dorsal horn. We used Ca2+ imaging in spinal cord slices of neonatal and young rats to assess under which conditions synchronous activity occurs in dorsal horn. No spontaneous synchronous Ca2+ transients were detected. However, increasing neuronal excitability by application of 4-aminopyridine after pretreatment of the slice with blockers of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate, ,-aminobutyric acid (GABA)A and glycine receptors evoked repetitive Ca2+ waves in dorsal horn. These waves spread mediolaterally with a speed of 1.0 ± 0.1 mm/s and affected virtually every dorsal horn neuron. The Ca2+ waves were associated with large depolarizing shifts of the membrane potential of participating neurons and were most likely synaptically mediated because they were abolished by blockade of action potentials or N -methyl- d -aspartate (NMDA) receptors. They were most pronounced in the superficial dorsal horn and absent from the ventral horn. A significant proportion of the Ca2+ waves spread to the contralateral dorsal horn. This seemed to be enabled by disinhibition as primary afferent-induced dorsal horn excitation crossed the midline only when GABAA and glycine receptors were blocked. Interestingly, the Ca2+ waves occurred under conditions where AMPA/kainate receptors were blocked. Thus, superficial dorsal horn NMDA receptors are able to sustain synchronous neuronal excitation in the absence of functional AMPA/kainate receptors. [source] Lesions to the subthalamic nucleus decrease impulsive choice but impair autoshaping in rats: the importance of the basal ganglia in Pavlovian conditioning and impulse controlEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2005Catharine A. Winstanley Abstract Although the subthalamic nucleus (STN) is involved in regulating motor function, and inactivation of this structure relieves the motor symptoms in Parkinsonian patients, recent data indicate that corticosubthalamic connections are involved in both the regulation of attention and the ability to withhold from responding. Considerable evidence suggests that the neural circuitry underlying such behavioural disinhibition or impulsive action can be at least partially dissociated from that implicated in impulsive decision-making and it has been suggested that the tendency to choose impulsively is related to the ability to form and use Pavlovian associations. To explore these hypotheses further, STN-lesioned rats were tested on the delay-discounting model of impulsive choice, where impulsivity is defined as the selection of a small immediate over a larger delayed reward, as well as in a rodent autoshaping paradigm. In contrast to previous reports of increased impulsive action, STN lesions decreased impulsive choice but dramatically impaired the acquisition of the autoshaping response. When the STN was lesioned after the establishment of autoshaping behaviour, lesioned subjects were more sensitive to the omission of reward, indicative of a reduction in the use of Pavlovian associations to control autoshaping performance. These results emphasize the importance of the STN in permitting conditioned stimulus,unconditioned stimulus associations to regulate goal-seeking, a function which may relate to the alterations in impulsive choice observed in the delay-discounting task. These data bear a striking similarity to those observed after lesions of the orbitofrontal cortex and are suggestive of an important role for corticosubthalamic connections in complex cognitive behaviour. [source] Rapid functional plasticity in the primary somatomotor cortex and perceptual changes after nerve blockEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2004Thomas Weiss Abstract The mature human primary somatosensory cortex displays a striking plastic capacity to reorganize itself in response to changes in sensory input. Following the elimination of afferent return, produced by either amputation, deafferentation by dorsal rhizotomy, or nerve block, there is a well-known but little-understood ,invasion' of the deafferented region of the brain by the cortical representation zones of still-intact portions of the brain adjacent to it. We report here that within an hour of abolishing sensation from the radial and medial three-quarters of the hand by pharmacological blockade of the radial and median nerves, magnetic source imaging showed that the cortical representation of the little finger and the skin beneath the lower lip, whose intact cortical representation zones are adjacent to the deafferented region, had moved closer together, presumably because of their expansion across the deafferented area. A paired-pulse transcranial magnetic stimulation procedure revealed a motor cortex disinhibition for two muscles supplied by the unaffected ulnar nerve. In addition, two notable perceptual changes were observed: increased two-point discrimination ability near the lip and mislocalization of touch of the intact ulnar portion of the fourth finger to the neighbouring third finger whose nerve supply was blocked. We suggest that disinhibition within the somatosensory system as a functional correlate for the known enlargement of cortical representation zones might account for not only the ,invasion' phenomenon, but also for the observed behavioural correlates of the nerve block. [source] Intravenous heroin self-administration decreases GABA efflux in the ventral pallidum: an in vivo microdialysis study in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2004Stéphanie Caillé Abstract Several lines of evidence suggest that opiate-induced disinhibition of the ventral pallidum participates in the mediation of opiate reward, though direct in vivo evidence to support this hypothesis has been lacking. The present experiment tested this hypothesis by investigating alterations in ventral pallidal amino acid efflux using in vivo microdialysis during ongoing intravenous heroin self-administration in rats. Concentrations of the inhibitory amino acid GABA in ventral pallidal dialysates were significantly reduced within the first 10 min of heroin self-administration (0.02 mg per infusion; FR-1), and remained ,,65% of presession baseline levels for the remainder of the 3-h self-administration session. Dialysate glutamate levels were unaltered during the first hour of heroin intake but significantly increased to a stable level of ,,120% presession values during the subsequent 2 h of self-administration. Thus, heroin self-administration is associated with both decreased GABA efflux and a late phase increase in glutamate efflux in the ventral pallidum. These observations are consistent with the hypothesis that heroin self-administration results in a disinhibition and/or excitation of the ventral pallidum. [source] The generation of rhythmic activity in dissociated cultures of rat spinal cordEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2001Jürg Streit Abstract Locomotion in vertebrates is controlled by central pattern generators in the spinal cord. The roles of specific network architecture and neuronal properties in rhythm generation by such spinal networks are not fully understood. We have used multisite recording from dissociated cultures of embryonic rat spinal cord grown on multielectrode arrays to investigate the patterns of spontaneous activity in randomised spinal networks. We were able to induce similar patterns of rhythmic activity in dissociated cultures as in slice cultures, although not with the same reliability and not always with the same protocols. The most reliable rhythmic activity was induced when a partial disinhibition of the network was combined with an increase in neuronal excitability, suggesting that both recurrent synaptic excitation and neuronal excitability contribute to rhythmogenesis. During rhythmic activity, bursts started at several sites and propagated in variable ways. However, the predominant propagation patterns were independent of the protocol used to induce rhythmic activity. When synaptic transmission was blocked by CNQX, APV, strychnine and bicuculline, asynchronous low-rate activity persisted at ,,50% of the electrodes and ,,70% of the sites of burst initiation. Following the bursts, the activity in the interval was transiently suppressed below the level of intrinsic activity. The degree of suppression was proportional to the amount of activity in the preceding burst. From these findings we conclude that rhythmic activity in spinal cultures is controlled by the interplay of intrinsic neuronal activity and recurrent excitation in neuronal networks without the need for a specific architecture. [source] Facial nerve injury-induced disinhibition in the primary motor cortices of both hemispheresEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2000Tamás Farkas Abstract Unilateral facial nerve transection induces plastic reorganization of the somatotopic order in the primary motor cortex area (MI). This process is biphasic and starts with a transient disinhibition of connections between cortical areas in both hemispheres. Little is known about the underlying mechanisms. Here, cortical excitability has been studied by paired pulse electrical stimulation, applied either within the MI or peripherally to the trigeminal nerve, while the responses were recorded bilaterally in the MI. The ratios between the amplitudes of the second and first evoked potentials (EPs or fEPSPs) were taken as measures of the inhibitory capacity in the MI ipsilateral or contralateral to the nerve injury. A skin wound or unilateral facial nerve exposure immediately caused a transient facilitation, which was followed by a reset to some level of inhibition in the MI on both sides. After facial nerve transection, the first relatively mild reduction of inhibition started shortly (within 10 min) after denervation. This was followed by a second step, involving a stronger decrease in inhibition, 40,45 min later. Previous publications have proved that sensory nerve injury (deafferentation) induces disinhibition in corresponding areas of the sensory cortex. It is now demonstrated that sham operation and, to an even greater extent, unilateral transection of the purely motoric facial nerve (deefferentation), each induce extended disinhibition in the MIs on both sides. [source] Role of GABAergic neurones in the nucleus tractus solitarii in modulation of cardiovascular activityEXPERIMENTAL PHYSIOLOGY, Issue 9 2010Jasenka Zubcevic GABAergic neurones are interspersed throughout the nucleus tractus solitarii (NTS), and their tonic activity is crucial to the maintenance of cardiorespiratory homeostasis. However, the mechanisms that regulate the magnitiude of GABAergic inhibition in the NTS remain unknown. We hypothesized that the level of GABAergic inhibition is proportionally regulated by the level of excitatory synaptic input to the NTS from baroreceptors. Using the in situ working heart,brainstem preparation in normotensive and spontaneously hypertensive rats, we blocked GABAA receptor-mediated neurotransmission in the NTS with gabazine (a specific GABAA receptor antagonist) at two levels of perfusion pressure (low PP, 60,70 mmHg; and high PP, 105,125 mmHg) while monitoring the immediate changes in cardiorespiratory variables. In normotensive rats, gabazine produced an immediate bradycardia consistent with disinhibition of NTS circuit neurones that regulate heart rate (HR) which was proportional to the level of arterial pressure (,HR at low PP, ,57 ± 9 beats min,1; at high PP, ,177 ± 9 beats min,1; P < 0.001), suggesting that GABAergic circuitry in the NTS modulating heart rate was arterial pressure dependent. In contrast, there was no significant difference in the magnitude of gabazine-induced bradycardia in spontaneously hypertensive rats at low or high PP (,HR at low PP, ,45 ± 10 beats min,1; at high PP, ,58 ± 7 beats min,1). With regard to thoracic sympathetic nerve activity (tSNA), at high PP there was a significant reduction in tSNA during the inspiratory (I) phase of the respiratory cycle, but only in the normotensive rat (,,tSNA =,18.7 ± 10%). At low PP, gabazine caused an elevation of the postinspiration phase of tSNA in both normotensive (,,tSNA = 23.7 ± 2.9%) and hypertensive rats (,,tSNA = 44.2 ± 14%). At low PP, gabazine produced no change in tSNA during the mid-expiration phase in either rat strain, but at high PP we observed a significant reduction in the mid-expiration phase tSNA, but only in the spontaneously hypertensive rat (,,tSNA =,25.2 ± 8%). Gabazine at both low and high PP produced a reduction in the late expiration phase of tSNA in the hypertensive rat (low PP, ,,tSNA =,29.4 ± 4.4%; high PP, ,tSNA =,22.8 ± 3%), whereas in the normotensive rat this was only significant at high PP (,,tSNA =,42.5 ± 6.1%). Therefore, in the spontaneously hypertensive rat, contrary to the GABAA receptor-mediated control of HR, it appears that GABAA receptor-mediated control of tSNA in the NTS is arterial pressure dependent. This study provides new insight into the origin of GABAergic inhibition in NTS circuitry affecting heart rate and sympathetic activity. [source] Impaired spatial reference memory and increased exploratory behavior in P301L tau transgenic miceGENES, BRAIN AND BEHAVIOR, Issue 5 2006L. Pennanen The neuropathological hallmark shared between Alzheimer's disease (AD) and familial frontotemporal dementia (FTDP-17) are neurofibrillary tangles (NFT) which are composed of filamentous aggregates of the microtubule-associated protein tau. Their formation has been reproduced in transgenic mice, which express the FTDP-17-associated mutation P301L of tau. In these mice, tau aggregates are found in many brain areas including the hippocampus and the amygdala, both of which are characterized by NFT formation in AD. Previous studies using an amygdala-specific test battery revealed an increase in exploratory behavior and an accelerated extinction of conditioned taste aversion in these mice. Here, we assessed P301L mice in behavioral tests known to depend on an intact hippocampus. Morris water maze and Y-maze revealed intact spatial working memory but impairment in spatial reference memory at 6 and 11 months of age. In addition, a modest disinhibition of exploratory behavior at 6 months of age was confirmed in the open field and the elevated O-maze and was more pronounced during aging. [source] Developmental change in the relation between executive functions and symptoms of ADHD and co-occurring behaviour problemsINFANT AND CHILD DEVELOPMENT, Issue 1 2006Karin C. Brocki Abstract In a sample of 92 children aged 6,13 years this study investigates the normal developmental change in the relation between executive functioning (EF) and the core behavioural symptoms associated with attention deficit hyperactivity disorder (ADHD) (hyperactivity/impulsivity and inattention) as well as symptoms often co-occurring with childhood hyperactivity (conduct- and internalizing problems). EF was assessed by using multiple tests grouped through prior factor analysis, resulting in cognitive measures relating to disinhibition, speed/arousal, verbal working memory, non-verbal working memory, and fluency. The results showed that although disinhibition was positively related to hyperactivity/impulsivity and inattention mainly for the youngest age group, there were no significant age effects for these relations. Instead, age effects were found for the relations between speed/arousal and inattention as well as for the relations between verbal working memory/fluency and inattention. In the oldest age group poor performance on these cognitive measures was associated with high ratings of inattention. For the total sample a relation was obtained between disinhibition and hyperactivity/impulsivity as well as between both working memory measures and internalizing problems. In conclusion, the results from this study suggest that poor inhibition is most clearly associated with ADHD symptoms for younger children, whereas poor functioning with regard to later developing and more complex executive functions such as working memory and fluency is associated with ADHD symptoms for older children. Copyright © 2006 John Wiley & Sons, Ltd. [source] Restraint, hunger, and disinhibition following treatment for binge-eating disorderINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 6 2009Kristina A. Downe MS Abstract Objective: To examine changes in total, flexible and rigid restraint, hunger, and disinhibition in obese individuals with Binge-Eating Disorder (BED), and assess whether these variables are associated with binge abstinence at post-treatment and during two-year follow-up. Method: A total of 116 obese individuals with BED were randomized to a 20-week treatment trial plus two-year follow-up. Using the Eating Inventory (EI), we assessed these factors at pretreatment, post-treatment, and follow-up time-points and examined their relationship to binge abstinence at post-treatment, 12- and 24-month follow-up. Results: Low disinhibition and high-total restraint are associated with post-treatment binge abstinence. There are no significant relationships between post-treatment EI variables and binge abstinence at 12- and 24-month follow-up. Discussion: Reducing disinhibition as well as increasing EI dietary restraint during BED treatment may be important for short-term success. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2009 [source] Improvement in behavioural symptoms in patients with moderate to severe Alzheimer's disease by memantine: a pooled data analysisINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2008S. Gauthier Abstract Introduction Behavioural disturbances are a common and distressing aspect of Alzheimer's disease (AD). This pooled analysis evaluated the specific benefits of memantine on behavioural disturbances in patients with moderate to severe AD. Methods Data were pooled from six 24/28-week, randomised, placebo-controlled, double-blind studies. Of the 2,311 patients included in these studies, 1,826 patients with moderate to severe AD (MMSE <20) were included in this analysis, corresponding to the extended indication for memantine in Europe. In this subgroup, 959 patients received memantine 20,mg/day and 867 received placebo. Behavioural symptoms were rated using the Neuropsychiatric Inventory (NPI) total and single-item scores at weeks 12 and 24/28. Results At weeks 12 and 24/28, ITT analysis demonstrated that memantine treatment produced statistically significant benefits over placebo treatment in NPI total score (p,=,0.001 and p,=,0.008), and in NPI single items: delusions (p,=,0.007,week 12, p,=,0.001,week 24/28), hallucinations (p,=,0.037,week 12), agitation/aggression (p,=,0.001,week 12, p,=,0.001,week 24/28), and irritability/lability (p,=,0.005,week 24/28), LOCF population. Analysis of the patients without symptoms at baseline indicated reduced emergence of agitation/aggression (p,=,0.002), delusions (p,=,0.047), and disinhibition (p,=,0.011), at week 12, and of agitation/aggression (p,=,0.002), irritability/lability (p,=,0.004), and night-time behaviour (p,=,0.050) at week 24/28 in those receiving memantine. OC analyses yielded similar results. Conclusions The data suggest that memantine is effective in treating and preventing the behavioural symptoms of moderate to severe AD. Specific persistent benefits were observed on the symptoms of delusions and agitation/aggression, which are known to be associated with rapid disease progression, increased caregiver burden, early institutionalisation, and increased costs of care. Copyright © 2007 John Wiley & Sons, Ltd. [source] Risk factors for neuropsychiatric symptoms in dementia: the Cache County StudyINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 9 2006M. Steinberg Abstract Objective To investigate the probability of individual neuropsychiatric symptoms in dementia patients as a function of eight risk factors. Methods In the Cache County Study, we administered the Neuropsychiatric Inventory (NPI) to 328 dementia patients at baseline. Approximately 18 months later, we re-administered the NPI to 184 participants available for follow-up. Generalized estimating equation methods were used to model the probability of individual neuropsychiatric symptoms as a function of: gender, age, education, dementia type and severity, APOE status, time of observation, and general medical health. Results Women showed increased tendency toward anxiety, [odds ratio (OR) 2.22, 95% confidence interval (CI) 1.31,3.76] and delusions (OR 2.15, CI 1.22,3.78), but older persons of both sexes showed less tendency toward anxiety. Dementia severity increased the tendency toward hallucinations and agitation (OR 2.42, CI 1.81,3.23) and decreased risk of depression. Positive APOE ,4 status increased the tendency toward aberrant motor behavior (OR 1.84, CI 1.05,3.22). Among dementia diagnoses, those with Alzheimer's disease showed decreased tendency toward agitation (OR 0.58, CI 0.35,0.95), depression (OR 0.56, CI 0.33,0.96) and disinhibition (OR 0.46, CI 0.24,0.88). Later time of observation increased risk of aberrant motor behavior and delusions, and more serious medical comorbidity increased risk of, agitation, irritability, disinhibition, and aberrant motor behavior. Conclusions Gender, age, dementia severity, APOE ,4, dementia diagnosis, time of observation, and general medical health appear to influence the occurrence of individual neuropsychiatric symptoms. Copyright © 2006 John Wiley & Sons, Ltd. [source] Neuropsychiatric symptoms of dementia: cross-sectional analysis from a prospective, longitudinal Belgian studyINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 11 2005Sebastiaan Engelborghs Abstract Objective Given the rather limited knowledge on profiles of neuropsychiatric symptoms (behavioural and psychological signs and symptoms of dementia, BPSD) in several degenerative dementias, we designed a prospective study of which we here present the baseline data. Methods Diagnosed according to strictly applied clinical diagnostic criteria, patients with probable Alzheimer's disease (AD) (n,=,205), frontotemporal dementia (FTD) (n,=,29), mixed dementia (MXD) (n,=,39) and dementia with Lewy bodies (DLB) (n,=,23) were included. All patients underwent a neuropsychological examination and behavioural assessment by means of a battery of scales (Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia). Results In AD and MXD, activity disturbances and aggressiveness occurred in more than 80% of the patients. With a prevalence of 70%, apathy was very common whereas delusions and hallucinations were rare in FTD patients. Frequently used behavioural assessment scales like the Behave-AD systematically underestimated BPSD in FTD whereas the MFS displayed high sensitivity for frontal lobe symptoms. Hallucinations discriminated DLB patients from other dementias. A high prevalence of disinhibition (65%) in DLB pointed to frontal lobe involvement. Conclusions Behavioural assessment may help differentiating between different forms of dementia, further stressing the need for the development of new and more sensitive behavioural assessment scales. By means of the MFS, frontal lobe involvement was frequently observed in DLB. As 70% of FTD patients displayed apathy, prevalence was about two times higher compared to the other disease groups, meanwhile indicating that apathy is frequently observed in dementia, irrespective of its etiology. Copyright © 2005 John Wiley & Sons, Ltd. [source] Behavioural and psychological syndromes in Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 11 2004A. Mirakhur Abstract Objectives The origins of behavioural and psychological symptoms of dementia are still poorly understood. By focusing on piecemeal behaviours as opposed to more robust syndrome change valid biological correlates may be overlooked. Our understanding of BPSD via the identification of neuropsychiatric syndromes. Methods We recruited 435 subjects from old age psychiatry and elderly care memory outpatient clinics fulfilling the criteria for diagnosis of probable Alzheimer's disease. Behavioural and psychological symptoms were assessed using the Neuropsychiatric Inventory. Principal components factor analysis was carried out on the composite scores of the 12 symptom domains to identify behavioural syndromes (factors). Results were confirmed by performing three different rotations: Varimax, Equamax and Quartimax. Results Four factors were identified (which accounted for 57% of the variance): ,affect' factor,depression/dysphoria, anxiety, irritability/lability and agitation/aggression; ,physical behaviour' factor,apathy, aberrant motor behaviour, sleep disturbance and appetite/eating disturbance; ,psychosis' factor,delusions and hallucinations; ,hypomania' factor,disinhibition and elation/euphoria. These groups were unchanged when different methods of rotation were used. Conclusions We report novel observations that agitation/aggression/irritability cluster within a depressive symptom factor and apathy is found within a physical behaviour factor. Copyright © 2004 John Wiley & Sons, Ltd. [source] The persistence of neuropsychiatric symptoms in dementia: the Cache County StudyINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 1 2004Martin Steinberg Abstract Objective To estimate the 18-month persistence of neuropsychiatric symptoms in dementia in a population-based sample, and to compare the severity of neuropsychiatric symptoms at baseline to the severity at 18-month follow-up. Methods A population-based sample of 329 residents of Cache County, Utah, diagnosed with dementia was rated on the Neuropsychiatric Inventory (NPI). Of the 204 participants with neuropsychiatric symptoms at baseline (defined as total NPI score >0), NPI data were obtained approximately 18 months later on 117 who were alive and available for follow-up. Results Eighty-one percent of those with neuropsychiatric symptoms at baseline (defined as total NPI score>0) continued to have at least one symptom at follow-up. Sixty-seven percent of participants with a clinically significant total NPI score (defined as ,;4) at baseline continued to have a clinically significant total NPI score at follow-up. Among the ten neuropsychiatric domains assessed at baseline, delusions persisted in 65.5% of individuals, followed by depression (58.3%), and aberrant motor behavior (55.6%), while hallucinations and disinhibition persisted in only 25.0% and 11.1% respectively. In participants who were symptomatic at both baseline and follow-up, the mean severity scores at the two observation points were comparable in all ten neuropsychiatric domains. Conclusions Neuropsychiatric symptoms in dementia overall were highly persistent. Among those in whom symptoms did persist, symptom severity a year and a half later appeared to be comparable. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||