Schizophrenia is a severe psychiatric disease characterized by a high heritability and a complex genetic architecture. Recent reports based on exome sequencing analyses have highlighted a significant increase of potentially deleterious de novo mutations in different genes in individuals with schizophrenia.
This report presents the mutation screening results of four candidate genes for which such de novo mutations were previously reported (LRP1, KPNA1, ALS2CL and ZNF480). We have not identified any excess of rare variants in the additional SCZ cases we have screened.
This supports the notion that de novo mutations in these four genes are extremely rare in schizophrenia and further highlights the high degree of genetic heterogeneity of this disease.
Schizophrenia; De novo mutation; LRP1; ALS2CL; KPNA1; ZNF480
Recent data support the beneficial role of gesturing during mental practice. The present study examined whether coupling motor imagery (MI) with some movement sequences (dynamic imagery condition) impacted motor performance to a greater extent than performing MI while remaining motionless.
A group of active high jumpers imagined their jump both with and without associated arm movement. Three outcome variables were measured: the number of successful attempts, the temporal congruence between MI and actual jump performance, and the technical quality of the jump.
Data revealed that dynamic imagery enhanced both MI quality and temporal congruence between MI and motor performance, and further improved the technical efficacy of the jump. Athletes also reported more vivid representation while coupling MI with actual movement.
These data support the hypothesis that performing dynamic imagery might contribute to enhance MI quality and efficacy, and sketch potentially fruitful new directions for MI practice.
Movement imagery; Dynamic imagery; Motor cognition; Motor performance; Mental imagery
We report on a 6-year-old Turkish boy with profound sensorineural deafness, balance disorder, severe disorder of oral motor function, and mild developmental delay. Further findings included scaphocephaly, plagiocephaly, long palpebral fissures, high narrow palate, low-set posteriorly rotated ears, torticollis, hypoplastic genitalia and faulty foot posture. Parents were consanguineous.
Methods and results
Computed tomography and magnetic resonance imaging showed bilateral single widened cochlear turn, narrowing of the internal auditory canal, and bilateral truncation of the vestibulo-cochlear nerve. Microarray analysis and next generation sequencing showed a homozygous deletion of chromosome 5q31.1 spanning 115.3 kb and including three genes: NEUROG1 (encoding neurogenin 1), DCNP1 (dendritic cell nuclear protein 1, C5ORF20) and TIFAB (TIFA-related protein). The inability to chew and swallow, deafness and balance disorder represented congenital palsies of cranial nerves V (trigeminal nerve) and VIII (vestibulo-cochlear nerve) and thus a congenital cranial dysinnervation disorder.
Based on reported phenotypes of neurog1 null mutant mice and other vertebrates, we strongly propose NEUROG1 as the causative gene in this boy. The human NEUROG1 resides within the DFNB60 locus for non-syndromic autosomal recessive deafness on chromosome 5q22-q31, but linkage data have excluded it from being causative in the DFNB60 patients. Given its large size (35 Mb, >100 genes), the 5q22-q31 area could harbor more than one deafness gene. We propose NEUROG1 as a new gene for syndromic autosomal recessive hearing loss and congenital cranial dysinnervation disorder including cranial nerves V and VIII.
Congenital cranial dysinnervation disorder; Moebius syndrome variant; Mondini dysplasia; Sensorineural deafness; Disorder of oral motor function; Aplasia/hypoplasia of cranial sensory ganglia; Aplasia/hypoplasia of cranial nerves V and VIII; NEUROG1; Homozygous deletion; Autosomal recessive
Tryptophan hydroxylase-2 (TPH2) is a potential candidate gene for screening tic disorder (TD).
A case–control study was performed to examine the association between the TPH2 gene and TD. The Sequenom® Mass ARRAY iPLEX GOLD System was used to genotype two single nucleotide polymorphisms (SNPs) of the TPH2 gene in 149 TD children and in 125 normal controls.
For rs4565946, individuals with the TT genotype showed a significantly higher risk of TD than those with TC plus CC genotypes [odds ratio (OR) =3.077, 95% confidence interval (CI): 1.273–7.437; P = 0.009], as did male TD children with the TT genotype (OR = 3.228, 95% CI: 1.153–9.040; P = 0.020). The G allele of rs4570625 was significantly more frequent in TD children with higher levels of tic symptoms (Yale Global Tic Severity Scale, YGTSS) than those in controls among the male children (OR = 1.684, 95%: 1.097–2.583; P = 0.017]. TD children with severe tic symptoms had significantly higher frequencies of rs4546946 TT genotype than did normal controls in boys (OR = 3.292, 95% CI: 1.139–9.513; P = 0.022). We also found that genotype distributions of both SNPs were different between the Asian and European populations.
Our results indicated that the TT genotype of rs4565946 is a potential genetic risk factor for TD, and the allele G of rs4570625 might be associated with the severity of tic symptoms in boys. These polymorphisms might be susceptibility loci for TD in the Chinese Han population. Because of the confounding of co-existing attention deficit hyperactivity disorder (ADHD),these findings need to be confirmed by studies in much larger samples.
Tic disorder; Tryptophan hydroxylase 2; Single nucleotide polymorphisms
Recent evidence suggests that neglect patients seem to have particular problems representing relatively smaller numbers corresponding to the left part of the mental number line. However, while this indicates space-based neglect for representational number space little is known about whether and - if so - how object-based neglect influences number processing.
To evaluate influences of object-based neglect in numerical cognition, a group of neglect patients and two control groups had to compare two-digit numbers to an internally represented standard. Conceptualizing two-digit numbers as objects of which the left part (i.e., the tens digit should be specifically neglected) we were able to evaluate object-based neglect for number magnitude processing.
Object-based neglect was indicated by a larger unit-decade compatibility effect actually reflecting impaired processing of the leftward tens digits. Additionally, faster processing of within- as compared to between-decade items provided further evidence suggesting particular difficulties in integrating tens and units into the place-value structure of the Arabic number system.
In summary, the present study indicates that, in addition to the spatial representation of number magnitude, also the processing of place-value information of multi-digit numbers seems specifically impaired in neglect patients.
Number processing; Number magnitude comparison; Object-based neglect; Multi-digit numbers
Fatigue has a multi-factorial nature. We examined the effects of two types of mental fatigue on spontaneous oscillatory brain activity using magnetoencephalography (MEG).
Participants were randomly assigned to two groups in a single-blinded, crossover fashion to perform two types of mental fatigue-inducing experiments. Each experiment consisted of a 30-min fatigue-inducing 0- or 2-back test session and two evaluation sessions performed just before and after the fatigue-inducing mental task session.
After the 0-back test, decreased alpha power was indicated in the right angular gyrus and increased levels in the left middle and superior temporal gyrus, left postcentral gyrus, right superior frontal gyrus, left inferior frontal gyrus, and right medial frontal gyrus. After the 2-back test, decreased alpha power was indicated in the right middle and superior frontal gyrus and increased levels in the left inferior parietal and superior parietal lobules, right parahippocampal gyrus, right uncus, left postcentral gyrus, left middle frontal gyrus, and right inferior frontal gyrus. For beta power, increased power following the 0-back test was indicated in the left middle temporal gyrus, left superior frontal gyrus, left cingulate gyrus, and left precentral gyrus. After the 2-back test, decreased power was suggested in the left superior frontal gyrus and increased levels in the left middle temporal gyrus and left inferior parietal lobule. Some of these brain regions might be associated with task performance during the fatigue-inducing trials.
Two types of mental fatigue may produce different alterations of the spontaneous oscillatory MEG activities. Our findings would provide new perspectives on the neural mechanisms underlying mental fatigue.
Magnetoencephalography (MEG); Mental fatigue; n-back test visual analogue scale (VAS)
The literature on social dilemmas and punishment focuses on the behaviour of the punisher. However, to fully explain the effect of punishment on cooperation, it is important to understand the psychological mechanisms influencing the behaviour of those who expect to be punished. This paper examines whether the expectation of punishment, rather than the implementation of punishment is sufficient to prevent individuals from free riding. Individual differences in the punishment sensitivity have been linked to both threat responses (flight, fight, fear system, or the FFFS) and to the response to the uncertainty of punishment (BIS-anxiety).The paper, therefore, examines if individual differences in BIS-anxiety and FFFS can explain some of the variability in free riding in the face of implemented and non-implemented punishment.
Participants took part in a series of one-shot Public Goods Games (PGGs) facing two punishment conditions (implemented and non-implemented) and two standard non-punishment PGGs. The punishment was implemented as a centralized authority punishment (i.e., if one participant contributed less than their group members, they were automatically fined). Individual contribution levels and presence/absence of zero contributions indexed free riding. Individual differences in behavioural inhibition were assessed.
Individuals contributed more under the threat of punishment (both implemented and non-implemented). However, individuals contributed less when the punishment was not implemented compared to when it was. Those scoring high in BIS-anxiety contributed more when the punishment expectations were not implemented. This effect was not observed for FFFS.
Supporting previous research, punishment had a powerful effect in increasing contribution levels in the PGGs. However, when expected punishment was not implemented, individual differences in punishment sensitivity, specifically in BIS-anxiety, were related to fewer contributions (increased free riding) as compared to the situation when punishment was not implemented. This has implications for our understanding of why some people cannot resist the temptation to free ride, even when facing possible punishment for their actions. Our findings suggest that the diminished functioning of mechanisms, associated with trait behavioural inhibition, can partly explain such behaviours.
Cooperation; Free riding; Punishment risk; Behavioural inhibition; Individual differences
The pig is emerging as a model species that bridges the gap between rodents and humans in research. In particular, the miniature pig (referred to hereafter as the minipig) is increasingly being used as non-rodent species in pharmacological and toxicological studies. However, there is as yet a lack of validated behavioral tests for pigs, although there is evidence that the spatial holeboard task can be used to assess the working and reference memory of pigs. In the present study, we compared the learning performance of commercial pigs and Göttingen minipigs in a holeboard task.
Biperiden, a muscarinic M1 receptor blocker, is used to induce impairments in cognitive function in animal research. The two groups of pigs were treated orally with increasing doses of biperiden (0.05 – 20 mg.kg-1) after they had reached asymptotic performance in the holeboard task.
Both the conventional pigs and the Göttingen minipigs learned the holeboard task, reaching nearly errorless asymptotic working and reference memory performance within approximately 100 acquisition trials. Biperiden treatment affected reference, but not working, memory, increasing trial duration and the latency to first hole visit at doses ≥ 5 mg.kg-1.
Both pig breeds learned the holeboard task and had a comparable performance. Biperiden had only a minor effect on holeboard performance overall, and mainly on reference memory performance. The effectiveness needs to be evaluated further before definitive conclusions can be drawn about the ability of this potential cognition impairer in pigs.
Working memory; Reference memory; Animal model; Holeboard task; Spatial learning task; Biperiden
The present study represents an initial attempt to assess the role of apathy in motivated decision making on the Iowa Gambling Task. Clinical descriptions of patients with apathy highlight deficits in the cognitive, emotional and behavioural aspects of goal directed activity, yet standard neurocognitive tests of these measures fail to demonstrate reliable sensitivity to the disorder. Available research suggests the Iowa Gambling Task is a robust test of complex emotional socio-executive processes involved in motivational decision making, which can analogue real-world goal-directed behaviour.
We ask whether performance on the Iowa Gambling Task can distinguish brain damaged patients with apathy symptoms from 1) brain damaged patients without apathy and 2) neurologically intact controls. Overall, 22 healthy adults and 29 brain damaged patients took part in this study.
Brain damaged patients with apathy were distinctively impaired on the Iowa Gambling Task compared to both non-apathetic brain damaged patients and neurologically intact healthy controls. On the other hand, standard measures for the cognitive control of behaviour failed to show this sensitivity.
Our results demonstrated that the Iowa Gambling Task is sensitive to the presence of apathy symptoms. We discuss these findings in terms of neurocognition deficits in apathy and the related implications for rehabilitation and clinical intervention.
Apathy; Motivational decision making; Iowa gambling task
Neuropsychiatric symptoms such as psychosis are prevalent in patients with probable Alzheimer’s disease (AD) and are associated with increased morbidity and mortality. Because these disabling symptoms are generally not well tolerated by caregivers, patients with these symptoms tend to be institutionalized earlier than patients without them. The identification of protective and risk factors for neuropsychiatric symptoms in AD would facilitate the development of more specific treatments for these symptoms and thereby decrease morbidity and mortality in AD. The E4 allele of the apolipoprotein E (APOE) gene is a well-documented risk factor for the development of AD. However, genetic association studies of the APOE 4 allele and BPS in AD have produced conflicting findings.
This study investigates the association between APOE and neuropsychiatric symptoms in a large sample of clinically well-characterized subjects with probable AD (n=790) who were systematically evaluated using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Behavioral Rating Scale for Dementia (BRSD).
Our study found that hallucinations were significantly more likely to occur in subjects with no APOΕ4 alleles than in subjects with two Ε4 alleles (15% of subjects and 5% of subjects, respectively; p=.0066), whereas there was no association between the occurrence of delusions, aberrant motor behavior, or agitation and the number of Ε4 alleles. However, 94% of the subjects with hallucinations also had delusions (D+H).
These findings suggest that in AD the Ε4 allele is differentially associated with D+H but not delusions alone. This is consistent with the hypothesis that distinct psychotic subphenotypes may be associated with the APOE allele.
Alzheimer’s disease; Apolipoprotein E; Genetics; Behavior; Hallucinations
Neurosteroids are synthesized in the brain and modulate brain excitability. There is increasing evidence of their sedative, anesthetic and antiseizure properties, as well as their influence on mood. Currently neurosteroids are classified as pregnane neurosteroids (allopregnanolone and allotetrahydrodeoxycorticosterone), androstane neurosteroids (androstanediol and etiocholanone) or sulfated neurosteroids (pregnenolone sulfate and dehydroepiandrosterone sulfate). Both preclinical and clinical findings indicate that progesterone derivative neurosteroids such as allopregnanolone and allotetrahydrodeoxycorticosterone play a role in mood disorders. Clozapine and olanzapine, which were shown to be effective in stabilizing bipolar disorder, elevate pregnenolone levels in rat hippocampus, cerebral cortex, and serum. In lithium-treated mice, the blood levels of allopregnanolone and pregnenolone were elevated compared to control levels. Women diagnosed with bipolar disorder typically show symptomatic exacerbation in relation to the menstrual cycle, and show vulnerability to the onset or recurrence of mood disorders immediately after giving birth, when the levels of neurosteroid derivatives of progesterone drop. Whereas in women who had recovered from bipolar disorder, the plasma concentration of allopregnanolone was elevated compared to either healthy controls or women with major depressive disorder during the premenstrual period. During depressive episodes, blood level of allopregnanolone is low. Treatment with fluoxetine tends to stabilize the levels of neurosteroids in depression. These findings converge to suggest that these steroids have significant mood-stabilizing effect. This hypothesis is consistent with the observation that a number of anticonvulsants are effective therapies for bipolar disorder, a finding also consistent with the antiseizure properties of neurosteroids. Further exploration of action of neuroactive steroids is likely to open new frontiers in the investigation of the etiology and treatment of mood disorders, particularly bipolar disorders.
Among the most robust neural abnormalities differentiating individuals with Attention-Deficit/Hyperactivity Disorder (ADHD) from typically developing controls are elevated levels of slow oscillatory activity (e.g., theta) and reduced fast oscillatory activity (e.g., alpha and beta) during resting-state electroencephalography (EEG). However, studies of resting state EEG in adults with ADHD are scarce and yield inconsistent findings.
EEG profiles, recorded during a resting-state with eyes-open and eyes-closed conditions, were compared for college students with ADHD (n = 18) and a nonclinical comparison group (n = 17).
The ADHD group showed decreased power for fast frequencies, especially alpha. This group also showed increased power in the slow frequency bands, however, these effects were strongest using relative power computations. Furthermore, the theta/beta ratio measure was reliably higher for the ADHD group. All effects were more pronounced for the eyes-closed compared to the eyes-open condition. Measures of intra-individual variability suggested that brains of the ADHD group were less variable than those of controls.
The findings of this pilot study reveal that college students with ADHD show a distinct neural pattern during resting state, suggesting that oscillatory power, especially alpha, is a useful index for reflecting differences in neural communication of ADHD in early adulthood.
Quantitative Electroencephalography (EEG); Adults; Power; Attention-deficit/hyperactivity disorder (ADHD); Resting state; Alpha; Beta; Theta; Intra-individual variability; Eyes open; Eyes closed
Different models of cortical lesion lead to different effects on plasticity of connections and loss of function. In opposition to ischemia, cortical lesion made by ablation does not induce significant adaptive plasticity of corticocortical and corticostriatal projections and leads to functional alterations other than those observed after ischemia. We have demonstrated sensorimotor recovery after treatment with bone marrow-derived mesenchymal stem cells (MSCs) or bone marrow mononuclear cells (BMMCs) in a model of focal cortical ischemia. Here, we extended this analysis evaluating the effect of these cells on sensorimotor recovery after focal cortical ablation, reproducing the same size and location of previous ischemic lesion.
Focal cerebral aspiration of the six cortical layers in left frontoparietal cortex was performed in male Wistar rats. One day later, MSCs or BMMCs were administrated (i.v.) in the ablated animals. Vehicle was administrated in the control group. Sensorimotor tests were performed before and after injury followed by i.v. injection. The monitoring of functional recovery was performed weekly during three post-ablation months. The results showed significant sensorimotor recovery with both treatments, whereas control groups had no recovery. Moreover, both cell types induced the same level of recovery.
Bone marrow cells showed therapeutic efficacy in a model of brain injury known to promote low structural plasticity. Thus, the results support the idea of BMMCs as better candidates to treat acute CNS injuries than MSCs, since they have the same therapeutic potential, but its obtainment for autologous transplantation has been shown to be faster and easier.
Motor cortex; Cell therapy; Stem cell; Functional recovery; Structural plasticity
Deficient operant extinction has been hypothesized to be constitutive of ADHD dysfunction. In order to elucidate the behavioral mechanisms underlying this deficit, the performance of an animal model of ADHD, the spontaneously hypertensive rat (SHR), was compared against the performance of a control strain, the Wistar-Kyoto rat (WKY) during extinction.
Following extensive training of lever pressing under variable interval schedules of food reinforcement (reported previously), SHR and WKY rats were exposed to two sessions of extinction training. Extinction data was analyzed using the Dynamic Bi-Exponential Refractory Model (DBERM) of operant performance. DBERM assumes that operant responses are organized in bouts separated by pauses; during extinction, bouts may decline across multiple dimensions, including frequency and length. DBERM parameters were estimated using hierarchical Bayesian modeling.
SHR responded more than WKY during the first extinction session. DBERM parameter estimates revealed that, at the onset of extinction, SHR produced more response bouts than WKY. Over the course of extinction, response bouts progressively shortened for WKY but not for SHR.
Based on prior findings on the sensitivity of DBERM parameters to motivational and schedule manipulations, present data suggests that (1) more frequent response bouts in SHR are likely related to greater incentive motivation, and (2) the persistent length of bouts in SHR are likely related to a slower updating of the response-outcome association. Overall, these findings suggest specific motivational and learning deficits that may explain ADHD-related impairments in operant performance.
Variable interval; Bout; Extinction; SHR; ADHD; Hierarchical model; Learning; Motivation; Response-outcome association; Dynamic Bi-Exponential Refractory Model (DBERM)
Mutations of the glucocerebrosidase (GBA) gene have reportedly been associated with Parkinson disease (PD) in various ethnic populations such as Singaporean, Japanese, Formosan, Canadian, American, Portuguese, Greek, Brazilian, British, Italian, Ashkenazi Jewish, southern and southwestern Chinese. The purpose of this study is to determine in central China whether or not the reported GBA mutations remain associated with PD.
In this project, we conducted a controlled study in a cohort of 208 central Chinese PD patients and 298 controls for three known GBA mutations (L444P, N370S and R120W).
Our data reveals a significantly higher frequency of L444P mutation in GBA gene of PD cases (3.4%) compared with the controls (0.3%) (P = 0.007, OR = 10.34, 95% CI = 1.26 - 84.71). Specifically, the frequency of L444P mutation was higher in the late onset PD (LOPD) cases compared with that in control subjects. The N370S and R120W mutations were detected in neither the PD group nor the control subjects.
Our observations demonstrated that the GBA L444P mutation confers genetic risk for PD, especially LOPD, among the population in the central China area.
Parkinson’s disease; Glucocerebrosidase; L444P; N370S; R120W; Central China
Previous reports suggest that omega-3 (n-3) polyunsaturated fatty acids (PUFA) supplements may reduce ADHD-like behaviour. Our aim was to investigate potential effects of n-3 PUFA supplementation in an animal model of ADHD.
We used spontaneously hypertensive rats (SHR). SHR dams were given n-3 PUFA (EPA and DHA)-enriched feed (n-6/n-3 of 1:2.7) during pregnancy, with their offspring continuing on this diet until sacrificed. The SHR controls and Wistar Kyoto (WKY) control rats were given control-feed (n-6/n-3 of 7:1). During postnatal days (PND) 25–50, offspring were tested for reinforcement-dependent attention, impulsivity and hyperactivity as well as spontaneous locomotion. The animals were then sacrificed at PND 55–60 and their neostriata were analysed for monoamine and amino acid neurotransmitters with high performance liquid chromatography.
n-3 PUFA supplementation significantly enhanced reinforcement-controlled attention and reduced lever-directed hyperactivity and impulsiveness in SHR males whereas the opposite or no effects were observed in females. Analysis of neostriata from the same animals showed significantly enhanced dopamine and serotonin turnover ratios in the male SHRs, whereas female SHRs showed no change, except for an intermediate increase in serotonin catabolism. In contrast, both male and female SHRs showed n-3 PUFA-induced reduction in non-reinforced spontaneous locomotion, and sex-independent changes in glycine levels and glutamate turnover.
Feeding n-3 PUFAs to the ADHD model rats induced sex-specific changes in reinforcement-motivated behaviour and a sex-independent change in non-reinforcement-associated behaviour, which correlated with changes in presynaptic striatal monoamine and amino acid signalling, respectively. Thus, dietary n-3 PUFAs may partly ameliorate ADHD-like behaviour by reinforcement-induced mechanisms in males and partly via reinforcement-insensitive mechanisms in both sexes.
Omega-3; ADHD; Behaviour; Dopamine; Serotonin; Glutamate; Neostriatum
The question whether Developmental Dyscalculia (DD; a deficit in the ability to process numerical information) is the result of deficiencies in the non symbolic numerical representation system (e.g., a group of dots) or in the symbolic numerical representation system (e.g., Arabic numerals) has been debated in scientific literature. It is accepted that the non symbolic system is divided into two different ranges, the subitizing range (i.e., quantities from 1-4) which is processed automatically and quickly, and the counting range (i.e., quantities larger than 4) which is an attention demanding procedure and is therefore processed serially and slowly. However, so far no study has tested the automaticity of symbolic and non symbolic representation in DD participants separately for the subitizing and the counting ranges.
DD and control participants undergo a novel version of the Stroop task, i.e., the Enumeration Stroop. They were presented with a random series of between one and nine written digits, and were asked to name either the relevant written digit (in the symbolic task) or the relevant quantity of digits (in the non symbolic task) while ignoring the irrelevant aspect.
DD participants, unlike the control group, didn't show any congruency effect in the subitizing range of the non symbolic task.
These findings suggest that DD may be impaired in the ability to process symbolic numerical information or in the ability to automatically associate the two systems (i.e., the symbolic vs. the non symbolic). Additionally DD have deficiencies in the non symbolic counting range.
Possible interactions between nervous and immune systems in neuro-psychiatric disorders remain elusive. Levels of brain dopamine transporter (DAT) have been implicated in several impulse-control disorders, like attention deficit / hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Here, we assessed the interplay between DAT auto-immunity and behavioural / neurochemical phenotype.
Male CD-1 mice were immunized with DAT peptide fragments (DAT-i), or vehicle alone (VEH), to generate elevated circulating levels of DAT auto-antibodies (aAbs). Using an operant delay-of-reward task (20 min daily sessions; timeout 25 sec), mice had a choice between either an immediate small amount of food (SS), or a larger amount of food after a delay (LL), which increased progressively across sessions (from 0 to 150 sec).
DAT-i mice exhibited spontaneous hyperactivity (2 h-longer wake-up peak; a wake-up attempt during rest). Two sub-populations differing in behavioural flexibility were identified in the VEH control group: they showed either a clear-cut decision to select LL or clear-cut shifting towards SS, as expected. Compared to VEH controls, choice-behaviour profile of DAT-i mice was markedly disturbed, together with long-lasting alterations of the striatal monoamines. Enhanced levels of DA metabolite HVA in DAT-i mice came along with slower acquisition of basal preferences and with impaired shifting; elevation also in DOPAC levels was associated with incapacity to change a rigid selection strategy. This scarce flexibility of performance is indicative of a poor adaptation to task contingencies.
Hyperactivity and reduced cognitive flexibility are patterns of behaviour consistent with enduring functional impairment of striatal regions. It is yet unclear how anti-DAT antibodies could enter or otherwise affect these brain areas, and which alterations in DAT activity exactly occurred after immunization. Present neuro-behavioural alterations, coming along with an experimentally-induced rise of circulating DAT-directed aAbs, open the issue of a potential role for auto-immunity in vulnerability to impulse-control disorders.
Auto-antibodies to neuro-receptors; DAT; Delay of reward; Flexibility of choice behaviour; ADHD; OCD
Subjects were tested for their ability to identify objects that were represented by an array of dots that marked the major contours, usually only the outer boundary. Each dot was briefly flashed to make its position known, and a major variable was the time interval that was required to flash all the dots for a given shape. Recognition declined as the total time for display of the dot inventory was increased. Each shape was shown to a given subject only once and it was either recognized -- named – or not. Although the recorded response was binary, a large number of subjects was tested, which made it possible to derive regression functions and thus specify an intercept and slope for each shape. Shapes differed substantially in their slopes, which is likely due to the amount of redundant information provided by neighboring dots. Indices of shape attributes were also derived, specifically Attneave’s indices of complexity, mean curvature, inflection count, and symmetry. Three of the four shape attributes were significantly related to intercept and slope levels, but none made a substantial contribution. This suggests that these attributes are not essential properties that define shapes and allow for recognition.
Shape recognition; Contour attributes; Shape encoding
Fear conditioning-induced changes in cerebellar Purkinje cell responses to a conditioned stimulus have been reported in rabbits. It has been suggested that synaptic long-term potentiation and the resulting increases in firing rates of Purkinje cells are related to the acquisition of conditioned fear in mammals. However, Purkinje cell activities during acquisition of conditioned fear have not been analysed, and changes in Purkinje cell activities throughout the development of conditioned fear have not yet been investigated. In the present study, we tracked Purkinje cell activities throughout a fear conditioning procedure and aimed to elucidate further how cerebellar circuits function during the acquisition and expression of conditioned fear.
Activities of single Purkinje cells in the corpus cerebelli were tracked throughout a classical fear conditioning procedure in goldfish. A delayed conditioning paradigm was used with cardiac deceleration as the conditioned response. Conditioning-related changes of Purkinje cell responses to a conditioned stimulus and unconditioned stimulus were examined.
The majority of Purkinje cells sampled responded to the conditioned stimulus by either increasing or decreasing their firing rates before training. Although there were various types of conditioning-related changes in Purkinje cells, more than half of the cells showed suppressed activities in response to the conditioned stimulus after acquisition of conditioned fear. Purkinje cells that showed unconditioned stimulus-coupled complex-spike firings also exhibited conditioning-related suppression of simple-spike responses to the conditioned stimulus. A small number of Purkinje cells showed increased excitatory responses in the acquisition sessions. We found that the magnitudes of changes in the firing frequencies of some Purkinje cells in response to the conditioned stimulus correlated with the magnitudes of the conditioned responses on a trial-to-trial basis.
These results demonstrate that Purkinje cells in the corpus cerebelli of goldfish show fear conditioning-related changes in response to a stimulus that had been emotionally neutral prior to conditioning. Unconditioned stimulus-induced climbing fibre inputs to the Purkinje cells may be involved in mediating these plastic changes.
Cerebellum; Fear conditioning; Goldfish; Purkinje cell
Recent clinical studies revealed emotional and cognitive impairments associated with absence epilepsy. Preclinical research with genetic models of absence epilepsy however have primarily focused on dysfunctional emotional processes and paid relatively less attention to cognitive impairment. In order to bridge this gap, we investigated age-dependent changes in learning and memory performance, anxiety-like behavior, and locomotor activity of WAG/Rij rats (a valid model of generalized absence epilepsy) using passive avoidance, Morris water maze, elevated plus maze, and locomotor activity cage. We tested 5 month-old and 13 month-old WAG/Rij rats and compared their performance to age-matched Wistar rats. Results revealed a decline in emotional and spatial memory of WAG/Rij rats compared to age-matched Wistar rats only at 13 months of age. Importantly, there were no significant differences between WAG/Rij and Wistar rats in terms of anxiety-like behavior and locomotor activity at either age. Results pointed at age-dependent learning and memory deficits in the WAG/Rij rat model of absence epilepsy.
Anxiety; Learning; Locomotor Activity; Memory; Rats; WAG/Rij; Wistar
Human time perception is influenced by various factors such as attention and drowsiness. Nevertheless, the impact of cerebral vigilance fluctuations on temporal perception has not been sufficiently explored. We assumed that the state of vigilance ascertained by electroencephalography (EEG) during the perception of a given auditory rhythm would influence its reproduction. Thus, we hypothesised that the re-tapping interval length and the accuracy of reproduction performance would vary depending on the state of vigilance determined by EEG.
12 female and 9 male subjects ranging from 21 to 38 years (M = 25.52, SD = 3.75) participated in a test paradigm comprising a) a resting EEG for the determination of vigilance while an auditory rhythm was presented, b) a short activity of the proband to be sure of sufficient alertness, and c) a tapping task to reproduce the presented rhythm. Vigilance states of three consecutive 1-sec-EEG-segments of the resting EEG before the reproduction phase were classified using the Vigilance Algorithm Leipzig (VIGALL).
Results and discussion
Reproduction accuracy was more precise after high EEG-vigilance stages. Thus, the subjects’ mean deviation from the given rhythm was lower (t(17) = −2.733, p < 0.05) after high vigilance stage A (MW = 0.046, SD = 0.049) than after low vigilance stage B (MW = 0.065, SD = 0.067). The re-tapping-length was significantly shorter (t(17) = −2.190, p < 0.05) for reproduction phases following high EEG-vigilance stage A compared to the lower EEG-vigilance stage B.
These findings support the hypothesis of a varying time perception and of speed alterations of the internal clock after different states of EEG-vigilance, which were automatically classified by VIGALL. Thus, alterations of cognitive processing may be assessable by specific EEG-patterns.
Electroencephalography (EEG); Time perception; Vigilance; Vigilance Algorithm Leipzig (VIGALL)
Limited data from behavioral and brain-imaging studies indicate that personality traits and physical characteristics are processed differently by the brain. Additionally, electrophysiological results of studies comparing the processing of positive and negative words have produced mixed results. It is therefore not clear how physical and personality attributes with emotional valence (i.e., positive and negative valence) are processed. Thus, this study aimed to examine the neural activity associated with words describing personality traits and physical characteristics with positive or negative emotional valence using Event Related Potentials (ERPs).
A sample of 15 healthy adults (7 men, 8 women) participated in a computerized word categorization task. Participants were asked to categorize visual word stimuli as physical characteristics or personality traits, while ERPs were recorded synchronously.
Behavioral reaction times to negative physical stimuli were shorter compared to negative personality words, however reaction times did not significantly differ for positive stimuli. Electrophysiological results showed that personality stimuli elicited larger P2 and LPC (Late Positive Component) amplitudes compared to physical stimuli, regardless of negative or positive valence. Moreover, negative as compared with positive stimuli elicited larger P2 and LPC amplitudes.
Personality and physical stimuli were processed differently regardless of positive or negative valence. These findings suggest that personality traits and physical characteristics are differentially classified and are associated with different motivational significance.
Fibroblast growth factors (FGFs) and their receptors (FGFRs) are necessary for the proper development of gonadotropin-releasing hormone (GnRH) neurons, which are key activators of the hypothalamo-pituitary-gonadal axis. Transgenic mice that have the targeted expression of a dominant negative FGFR (dnFGFR) in GnRH neurons (dnFGFR mice) have a 30% decrease of GnRH neurons. Additionally, only 30–40% of the pups born to the transgenic dams survive to weaning age. These data raised the possibility that FGFR defects in GnRH neurons could adversely affect maternal behavior via novel mechanisms.
We first determined if defective maternal behavior in dnFGFR mothers may contribute to poor pup survival by measuring pup retrieval and a battery of maternal behaviors in primiparous control (n = 10–12) and dnFGFR (n = 13–14) mothers. Other endocrine correlates of maternal behaviors, including plasma estradiol levels and hypothalamic pro-oxyphysin and GnRH transcript levels were also determined using enzyme-linked immunoassay and quantitative reverse transcription polymerase chain reaction, respectively.
Maternal behaviors (% time crouching with pups, time off pups but not feeding, time feeding, and total number of nesting bouts) were not significantly different in dnFGFR mice. However, dnFGFR dams were more likely to leave their pups scattered and took significantly longer to retrieve each pup compared to control dams. Further, dnFGFR mothers had significantly lower GnRH transcripts and circulating E2, but normal pro-oxyphysin transcript levels.
Overall, this study suggests a complex scenario in which a GnRH system compromised by reduced FGF signaling leads to not only suboptimal reproductive physiology, but also suboptimal maternal behavior.
GnRH; Maternal Behavior; Fibroblast Growth Factor; Estradiol; Pup Retrieval
No reliable anatomical or functional alterations have been confirmed in psychiatric neuroimaging; however it can become reliable with translational impact on clinical practice when considering crucial methodological issues. We provide guidelines to authors, editors and reviewers in the implementation/evaluation of neuroimaging studies to bend neuroimaging to be more than basic neuroscience.
Guidelines; Neuroimaging; Magnetic resonance imaging; Region-of-interest; Voxel-based morphometry; Meta-analyses