Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness

Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.     

Intentional mis-reporting of food consumption and its relationship with body mass index and psychological scores in women

BACKGROUND: The reasons for mis-reporting food consumption warrant investigation. OBJECTIVE: To document intention to mis-report food consumption and its associations with psychological measures in women. DESIGN: A total of 184 female volunteers aged 18-65 years, comprising 50 seeking help in primary care to lose weight with a body mass index (BMI) >/=30 kg m(-2) (obese-clinical group) and 134 nurses (nonclinical groups) (BMI <25 kg m(-2), n = 52; BMI 25-29.9 kg m(-2), n = 45; BMI >/=30 kg m(-2), n = 37) were studied. A questionnaire was administered containing three psychological tests (self-esteem, psychological well-being and Stunkard's three-factor eating questionnaire) and new items to address food intake mis-reporting. RESULTS: Overall, 68% of participants declared an inclination to mis-report (64% nonclinical, 78% clinical). Inclination to under-report was 29, 33 and 51% in the three nonclinical groups; and 46% among the obese clinical patients. Among the same groups, inclination to over-report were 39, 29, 11 and 32%. After adjusting for social deprivation and BMI, women inclined to mis-report had higher hunger (P = 0.008) and disinhibition (P = 0.005) scores than those intending to report accurately. These variables were associated with current dieting, frequency of dieting, self-reported bingeing and dissatisfaction with body weight. CONCLUSIONS: These findings indicate that intentional under-reporting and over-reporting of food consumption are common in women of all BMI categories and are associated with eating behaviour. Current dieting, frequency of dieting in the past, self-reported bingeing and dissatisfaction with body weight seem to mediate this relationship.     

Pathological laughter and crying in patients with multiple system atrophy-cerebellar type.

In the cerebellar type of multiple system atrophy (MSA-C), the burden of pathological changes involves the cerebellum and its associated brainstem structures in the basis pontis and the inferior olivary nucleus, and as a result, the clinical phenotype is dominated early on by the cerebellar dysfunction. We report our clinical and post mortem findings in a patient with MSA-C who exhibited pathological laughter in the absence of any congruent changes of mood. A review of the clinical notes of 27 other patients with MSA-C revealed a problem with pathological laughter, or crying, or both in 9 more patients. Our finding of about 36% occurrence suggests that the problem of dysregulation of emotional expression is more prevalent in MSA-C than the paucity of reports in the literature suggests. Our findings are consistent with the view that the cerebellum and its interconnected structures may be involved in the regulation of emotional expression.     

Central serotonin depletion impairs both the acquisition and performance of a symmetrically reinforced go/no-go conditional visual discrimination

The involvement of central serotonin systems in behavioural disinhibition in the rat was assessed using a symmetrically reinforced go/no-go conditional visual discrimination task. Selective central 5-HT depletion (generally averaging more than 90% in neocortex, hippocampus and striatum) was induced by intracerebroventricular administration of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) following pretreatment with both a noradrenergic and dopaminergic re-uptake inhibitor. The lesioned animals failed to acquire the conditional visual discrimination. This deficit was due to an inability to withhold responding and thus correctly complete the no-go trials. The lesioned animals responded faster both correctly, during go trials, and incorrectly during no-go trials. Impulsive early responding during the initial 1.2 s of the stimulus presentation was also increased by 5-HT depletion. Subjects that were lesioned after stable performance of the task had been acquired showed a similar, but smaller effect. These animals displayed more accurate performance of the go trials, but poorer performance of the no-go trials. Once again, go trial response latencies were faster and early responses during the no-go trials were increased by the lesion. The results suggest that previous accounts of impulsive responding induced by 5-HT depletion fail to recognise the pervasive nature of this effect, which affects multiple behavioural indices of response disinhibition and can impede the acquisition and performance of discrimination tasks depending on their precise response requirements.     

Prior short-term synaptic disinhibition facilitates long-term potentiation and suppresses long-term depression at CA1 hippocampal synapses

Long-term potentiation (LTP) and long-term depression (LTD) are two main forms of activity-dependent synaptic plasticity that have been extensively studied as the putative mechanisms underlying learning and memory. Current studies have demonstrated that prior synaptic activity can influence the subsequent induction of LTP and LTD at Schaffer collateral-CA1 synapses. Here, we show that prior short-term synaptic disinhibition induced by type A gamma-aminobutyric acid (GABA) receptor antagonist picrotoxin exhibited a facilitation of LTP induction and an inhibition of LTD induction. This effect lasted between 10 and 30 min after washout of picrotoxin and was specifically inhibited by the L-type voltage-operated Ca2+ channel (VOCC) blocker nimodipine, but not by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphopentanoic acid (D-APV). Moreover, this picrotoxin-induced priming effect was mimicked by forskolin, an activator of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), and was blocked by the adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22536) and the PKA inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS). It was also found that following picrotoxin application, CA1 neurons have a higher probability of synchronous discharge in response to a population of excitatory postsynaptic potential (EPSP) of fixed slope (EPSP/spike potentiation). However, picrotoxin treatment did not significantly affect paired-pulse facilitation (PPF). These findings suggest that a brief of GABAergic disinhibition can act as a priming stimulus for the subsequent induction of LTP and LTD at Schaffer collateral-CA1 synapses. The increase in Ca2+ influx through L-type VOCCs in turn triggering a cAMP/PKA signalling pathway is a possible molecular mechanism underlying this priming effect.     

Relationship between personality change and the onset and course of alcohol dependence in young adulthood

Aims To examine the reciprocal effects between the onset and course of alcohol use disorder (AUD) and normative changes in personality traits of behavioral disinhibition and negative emotionality during the transition between adolescence and young adulthood. Design Longitudinal–epidemiological study assessing AUD and personality at ages 17 and 24 years. Setting Participants were recruited from the community and took part in a day‐long, in‐person assessment. Participants Male (n = 1161) and female (n = 1022) twins participating in the Minnesota Twin Family Study. Measurements The effects of onset (adolescent versus young adult) and course (persistent versus desistent) of AUD on change in personality traits of behavioral disinhibition and negative emotionality from ages 17 to 24 years. Findings Onset and course of AUD moderated personality change from ages 17 to 24 years. Adolescent onset AUD was associated with greater decreases in behavioral disinhibition. Those with an adolescent onset and persistent course failed to exhibit normative declines in negative emotionality. Desistence was associated with a ‘recovery’ towards psychological maturity in young adulthood, while persistence was associated with continued personality dysfunction. Personality traits at age 11 predicted onset and course of AUD, indicating personality differences were not due to active substance abuse. Conclusions Personality differences present prior to initiation of alcohol use increase risk for alcohol use disorder, but the course of alcohol use disorder affects the rate of personality change during emerging adulthood. Examining the reciprocal effects of personality and alcohol use disorder within a developmental context is necessary to improve understanding for theory and intervention.     

Group II metabotropic glutamate receptors reduce excitatory but not inhibitory neurotransmission in rat barrel cortex in vivo

Group II metabotropic (mGlu) receptors are known to play an important role in regulating the release of excitatory transmitter in a number of brain areas. Previous experiments demonstrated that (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) depressed excitatory transmission in the adult rat barrel cortex. Here we show, using in vivo extracellular single unit recordings and iontophoretic application of drugs, that selective activation of Group II mGlu receptors depresses excitatory but not inhibitory transmission. The selective Group II receptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) had similar depressant effects to 1S,3R-ACPD on tactile evoked responses of rapidly adapting neurons. The depressant effects were seen on shorter latency (<12 ms) responses, were most pronounced in layers 3-4 (and 5b for 2R,4R-APDC only), and were reversibly antagonized by the Group II receptor antagonist (2S)-alpha-ethylglutamic acid (EGLU) relative to depressions produced by iontophoretic GABA. Where 1S,3R-ACPD and 2R,4R-APDC depressed excitatory transmission, there was little or no effect on postsynaptic excitations produced by iontophoretic AMPA--a result that supports a presynaptic location of Group II receptors on excitatory terminals. To assess the possible involvement of Group II mGlu receptors in the modulation of inhibition, we studied the effect of iontophoretic 1S,3R-ACPD in a condition-test protocol. The results contrasted markedly from those previously observed using the Group III agonist L(+)-2-amino-4-phosphonobutyric acid in that activation of Group II receptors using 1S,3R-ACPD did not modulate inhibition. Therefore our results show that Group II mGlu receptors play an important role in modulating excitatory, but not inhibitory, transmission. We propose that the Group II mGlu receptors are located on excitatory terminals, and act as autoreceptors. Their role appears to be important in the early stages of cortical processing, by keeping excitatory inputs within specified physiological limits, and possibly by mediating depression evidenced during synaptic plasticity.     

The role of the cerebellum in the pathogenesis of cortical myoclonus

The putative involvement of the cerebellum in the pathogenesis of cortical myoclonic syndromes has been long hypothesized, as neuropathological changes in patients with cortical myoclonus have most commonly been found in the cerebellum rather than in the suspected culprit, the primary somatosensory cortex. A model of increased cortical excitability due to loss of cerebellar inhibitory control via cerebello‐thalamo‐cortical connections has been proposed, but evidence remains equivocal. Here, we explore this hypothesis by examining syndromes that present with cortical myoclonus and ataxia. We first describe common clinical characteristics and underlying neuropathology. We critically view information on cerebellar physiology with regard to motorcortical output and compare findings between hypothesized and reported neurophysiological changes in conditions with cortical myoclonus and ataxia. We synthesize knowledge and focus on neurochemical changes in these conditions. Finally, we propose that the combination of alterations in inhibitory neurotransmission and the presence of cerebellar pathology are important elements in the pathogenesis of cortical myoclonus. © 2014 Movement Disorder Society     

Electrocortical measures of performance monitoring from go/no-go and flanker tasks: Differential relations with trait dimensions of the triarchic model of psychopathy

This study examined associations of performance-monitoring event-related potentials (ERPs) from go/no-go and flanker tasks with one another, and with psychopathy-related traits of disinhibition, meanness, and boldness. A task-dependent relationship was evident between the error-related negativity (ERN) and trait disinhibition, with high-disinhibited participants showing reduced no-go ERN but not flanker ERN. Disinhibition was also inversely related to variants of the P3 and the error positivity (Pe) from these two tasks. A factor analysis of the ERPs revealed two distinct factors, one reflecting shared variance among the P3 and Pe measures from the two tasks, and the other covariance among the N2 and ERN measures. Scores on the P3/Pe factor, but not the N2/ERN factor, were inversely related to disinhibition, and accounted for associations of this trait with variants of the P3 and Pe across tasks. The implication is that high trait disinhibition relates mainly to reductions in brain responses associated with later elaborative stages in the processing of motivationally significant events across different tasks. Importantly, no-go ERN predicted disinhibition scores beyond N2/ERN factor scores, indicating that high disinhibition is not generally related to diminished early preresponse conflict and error processing, but rather to processing impairments in conditions calling for inhibition of prepotent response tendencies.