Impaired gamma-band activity during perceptual organization in adults with autism spectrum disorders: evidence for dysfunctional network activity in frontal-posterior cortices

Current theories of the pathophysiology of autism spectrum disorders (ASD) have focused on abnormal temporal coordination of neural activity in cortical circuits as a core impairment of the disorder. In the current study, we examined the possibility that gamma-band activity may be crucially involved in aberrant brain functioning in ASD. Magneto-encephalographic (MEG) data were recorded from 13 adult human participants with ASD and 16 controls during the presentation of Mooney faces. MEG data were analyzed in the 25-150 Hz frequency range and a beamforming approach was used to identify the sources of spectral power. Participants with ASD showed elevated reaction times and reduced detection rates during the perception of upright Mooney faces, while responses to inverted stimuli were in the normal range. Impaired perceptual organization in the ASD group was accompanied by a reduction in both the amplitude and phase locking of gamma-band activity. A beamforming approach identified distinct networks during perceptual organization in controls and participants with ASD. In controls, perceptual organization of Mooney faces involved increased 60-120 Hz activity in a frontoparietal network, while in the ASD group stronger activation was found in visual regions. These findings highlight the contribution of impaired gamma-band activity toward complex visual processing in ASD, suggesting atypical modulation of high-frequency power in frontoposterior networks.     

Dopaminergic receptor blockade changes a functional connectivity network centred on the amygdala

Resting‐state connectivity has become an increasingly important measure in characterizing the functional integrity of brain circuits in neuro‐psychiatric conditions. One approach that has recently gained prominence in this regard—and which we use in this study—is to investigate how resting‐state connectivity depends on the integrity of certain neuromodulator systems. Here, we use a pharmacological challenge in combination with functional magnetic resonance imaging to investigate the impact of dopaminergic receptor blockade on whole brain functional connectivity in twenty healthy human subjects. Administration of the D2‐receptor antagonist haloperidol led to a profound change in functional integration in network nodes linked to the amygdala. Compared to placebo and baseline measurements, network‐based statistics and pairwise connectivity analyses revealed reduced connectivity and decreased link strength between the amygdala and the bilateral posterior cingulate cortex and other cortical areas. This was complemented by less extensive but very circumscribed enhanced connectivity between the amygdala and the right putamen during D2‐receptor blockade. It will be interesting to investigate whether these pharmacologically induced shifts in resting‐state connectivity will similarly be evident in clinical conditions that involve a dysfunction of the dopaminergic system. Our findings might also aid in interpreting alterations in more complex states, such as those seen psychiatric conditions and their treatment. Hum Brain Mapp 37:4148–4157, 2016. © 2016 Wiley Periodicals, Inc.     

Hemodynamic and oxygenation profiles in the early period after hyperbaric oxygen therapy: an observational study of intensive-care patients

BACKGROUND: We studied whether hemodynamic and oxygenation profiles are altered in critically ill patients after exposure to hyperbaric oxygen (HBO). METHODS: Ten intensive-care patients (two females, eight males) undergoing HBO treatment after major abdominal surgery, after burn injury and after CO poisoning were included. All subjects were put on mechanical ventilation and received continuous sedation, and had HBO treatment at 2.2 absolute atmospheres for 50 min. DESIGN: Observational prospective study, and repeated measure design. RESULTS: Hemodynamic and oxygen transport patterns were determined before (C0), 1 h (C1) and 2 h (C2) after HBO therapy with continuous cardiac output dual oximetry pulmonary arterial catheter, a central venous and radial arterial line. Data were analyzed with non-parametric repeated measure analysis. Key results are expressed as a percentage of baseline (C0 values correspond to 100%) at C1 and C2 (median values, lower and upper limit of confidence interval): cardiac index [C1: 105% (98-135), C2: 99% (91-117), P = 0.19], systemic (P = 0.62) and pulmonary vascular (P = 0.76) resistance indices were unchanged, but pulmonary venous admixture (Qs/Qt) increased [C1: 173% (112-298), C2: 140% (92-241), P = 0.00002)] and arterial oxygen tension decreased [C1: 76% (67-94), C2: 82% (72-112), P = 0.010]. CONCLUSION: The hemodynamic profile remained unaffected. The increase in Qs/Qt and the decrease in PaO2 may be attributed to the inhalation of HBO, and both are reversible.     

No evidence for enhanced extinction memory consolidation through noradrenergic reuptake inhibition—delayed memory test and reinstatement in human fMRI

Rationale

One promising approach in the current ambition to maximise treatment benefit for anxiety disorders is the pharmacological enhancement of cognitive–behavioural treatment efficacy, which can be experimentally modelled by pharmacological enhancement of extinction learning/consolidation. Noradrenaline (NA) is involved in memory consolidation, and NAergic innervations are found in brain areas implicated in fear conditioning and extinction.

Objectives

Thus, to enhance extinction memory consolidation through boosted NAergic signalling, we administered 4 mg reboxetine (RBX) immediately after extinction learning (day 2, 24 h after conditioning on day 1) in a randomised, placebo (PLC)-controlled design. At a delayed memory test (day 8), we probed cued and contextual fear and extinction memories before and after a reinstatement manipulation.

Results

After reinstatement, we find significantly enhanced amygdala and posterior hippocampus activation in the RBX group, areas implicated in fear memory expression, while the PLC group exhibited enhanced activation in areas associated with extinction memory expression (vmPFC, anterior hippocampus). No group differences were found in skin conductance responses.

Conclusions

Thus, our data do not support our hypothesis that enhancement of NA signalling may facilitate extinction memory consolidation and provide preliminary evidence that this might rather enhance fear memories on a neural but not physiological (skin conductance responses) level.     

Chronic Administration of Methylphenidate Induced Degeneration of Spermatogenesis in Adult Male Rats

Pharmaceutical Chemistry Journal - Apossible mechanism of methylphenidate (MPH) action upon reproductive system, in particular on the fertility rate of male mice, is discussed.     

Association analysis of the dopamine transporter (DAT1)-67A/T polymorphism in bipolar disorder.

An imbalance in the dopaminergic system in humans has been hypothesized to contribute to the pathogenesis of a number of psychiatric illnesses, including bipolar disorder, schizophrenia, and attention deficit hyperactivity disorder. We performed a case/control study on the DAT1 (HUGO approved symbol SL6A3) gene core promoter polymorphism -67A/T to analyze the possible association of either allele of this polymorphism with bipolar disorder. The allele and genotype frequencies of the polymorphism were studied in 136 patients and 163 controls, which were matched on the basis of sex, age, and ethnicity. The genotype frequencies in the patients group were as follows: AA 30.9%; AT 55.1%; TT 14% versus the genotype frequencies in the control group: AA 49%; AT 41.8%; TT 9.2% [chi2 = 10.3, df = 2, OR = 2.15 (95% CI 1.34-3.47, P < or = 0.006]. The T-allele of the -67A/T polymorphism revealed a approximately 1.4-fold excess in the patients group comparing with the controls (P < or = 0.003). For the first time, these findings provide tentative evidence of the contribution of the DAT1 gene core promoter polymorphism to the etiopathophysiology of bipolar disorder at least in the Iranian population that we have studied. Interestingly, no allelic or genotype association was observed in the female patients (P < or = 0.6 and P < or = 0.7, respectively). Replication studies of independent samples and family-based association studies are necessary to further evaluate the significance of our findings.     

Association of the dopamine transporter gene (DAT1) core promoter polymorphism -67T variant with schizophrenia.

Dysfunction of the central dopaminergic neurotransmission has been suggested to play an important role in the etiology of schizophrenia. The dopamine transporter (DAT1) mediates the active reuptake of dopamine from the synapses and thereby plays a key role in the regulation of the dopaminergic neurotransmission. In this study, we sought to determine the possible association of the DAT1 gene core promoter polymorphism -67A/T with schizophrenia in a case/control study. The allele and genotype frequencies of the polymorphism were studied in 100 patients and 100 controls, which were matched on the basis of sex, age, and ethnicity. The genotype frequencies in the patients group were as follows: AA 29%; AT 59%; TT 12% versus the genotype frequencies in the control group: AA 57%; AT 38%; TT 5% [chi2 = 16.54, df = 2, OR = 2.25 (95% CI 1.46-3.45, P < or = 0.0003]. For the first time, these findings provide tentative evidence for the contribution of the DAT1 gene core promoter polymorphism to the etiopathophysiology of schizophrenia at least in the Iranian male population that we studied. Replication studies of independent samples and family-based association studies are necessary to further evaluate the significance of our findings.