PSYCHIATRY

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Oscillatory neural signatures of visual perception across developmental stages in individuals with 22q11.2 deletion syndrome

Background: Numerous behavioral studies have highlighted the contribution of visual perceptual deficits to the nonverbal cognitive profile of individuals with 22q11.2 deletion syndrome. However, the neurobiological processes underlying these widespread behavioral alterations are yet to be fully understood. Thus, in this paper, we investigated the role of neural oscillations toward visuoperceptual deficits to elucidate the neurobiology of sensory impairments in deletion carriers. Methods: We acquired 125 high-density electroencephalography recordings during a visual grating task in a group of 62 deletion carriers and 63 control subjects. Stimulus-elicited oscillatory responses were analyzed with 1) time-frequency analysis using wavelets decomposition at sensor and source level, 2) intertrial phase coherence, and 3) Granger causality connectivity in source space. Additional analyses examined the development of neural oscillations across age bins. Results: Deletion carriers had decreased theta-band (4–8 Hz) and gamma-band (58–68 Hz) spectral power compared with control subjects in response to the visual stimuli, with an absence of age-related increase of theta- and gamma-band responses. Moreover, adult deletion carriers had decreased gamma- and theta-band responses but increased alpha/beta desynchronization (10–25 Hz) that correlated with behavioral performance. Granger causality estimates reflected an increased frontal-occipital connectivity in the beta range (22–40 Hz). Conclusions: Deletion carriers exhibited decreased theta- and gamma-band responses to visual stimuli, while alpha/beta desynchronization was preserved. Overall, the lack of age-related changes in deletion carriers implicates developmental impairments in circuit mechanisms underlying neural oscillations. The dissociation between the maturation of theta/gamma- and alpha/beta-band responses may indicate a selective impairment in supragranular cortical layers, leading to compensatory top-down connectivity

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex affects divided attention immediately after cessation of stimulation

Transcranial magnetic stimulation has evolved into a powerful neuroscientific tool allowing to interfere transiently with specific brain functions. In addition, repetitive TMS (rTMS) has long-term effects (e.g. on mood), probably mediated by neurochemical alterations. While long-term safety of rTMS with regard to cognitive functioning is well established from trials exploring its therapeutic efficacy, little is known on whether rTMS can induce changes in cognitive functioning in a time window ranging from minutes to hours, a time in which neurochemical effects correlated with stimulation have been demonstrated. This study examined effects of rTMS on three measures of executive function in healthy subjects who received one single rTMS session (40 trains of 2 s duration 20 Hz stimuli) at the left dorsolateral prefrontal cortex (DLPFC). Compared to a sham condition one week apart, divided attention performance was significantly impaired about 30-60 min after rTMS, while Stroop-interference and performance in the Wisconsin Card Sorting Test was unaffected after rTMS. Repetitive TMS of the left DLPFC, at stimulation parameters used in therapeutic studies, does not lead to a clinically relevant impairment of executive function after stimulation. However, the significant effect on divided attention suggests that cognitive effects of rTMS are not limited to the of acute stimulation, and may possibly reflect known neurochemical alterations induced by rTMS. Sensitive cognitive measures may be useful to trace those short-term effects of rTMS non-invasively in humans

Dysfunctional gaze processing in bipolar disorder

Gaze conveys emotional information, and humans present sensitivity to its direction from the earliest days of life. Bipolar disorder is a disease characterized by fluctuating states of emotional and cognitive dysregulation. To explore the role of attentional control on face processing in bipolar patients (BP) we used gaze direction as an emotion modulation parameter in a two-back Working Memory (WM) task while high-density EEG data were acquired. Since gaze direction influences emotional attributions to faces with neutral expressions as well, we presented neutral faces with direct and averted gaze. Nineteen euthymic BP and a sample of age- and gender-matched controls were examined.In BP we observed diminished P200 and augmented P300 evoked responses, differentially modulated by non-repeated or repeated faces, as well as by gaze direction. BP showed a reduced P200 amplitude, significantly stronger for faces with direct gaze than averted gaze. Source localization of P200 indicated decreased activity in sensory-motor regions and frontal areas suggestive of abnormal affective processing of neutral faces.The present study provides neurophysiological evidence for abnormal gaze processing in BP and suggests dysfunctional processing of direct eye contact as a prominent characteristic of bipolar disorder. Keywords: Bipolar disorder, Gaze processing, Face recognition, Memory, ERP, EEG source imagin

Abnormal development of early auditory processing in 22q11.2 Deletion Syndrome

Abstract The 22q11.2 Deletion Syndrome (22q11.2 DS) is one of the highest genetic risk factors for the development of schizophrenia spectrum disorders. In schizophrenia, reduced amplitude of the frequency mismatch negativity (fMMN) has been proposed as a promising neurophysiological marker for progressive brain pathology. In this longitudinal study in 22q11.2 DS, we investigate the progression of fMMN between childhood and adolescence, a vulnerable period for brain maturation. We measured evoked potentials to auditory oddball stimuli in the same sample of 16 patients with 22q11.2 DS and 14 age-matched controls in childhood and adolescence. In addition, we cross-sectionally compared an increased sample of 51 participants with 22q11.2 DS and 50 controls divided into two groups (8–14 and 14–20 years). The reported results are obtained using the fMMN difference waveforms. In the longitudinal design, the 22q11.2 deletion carriers exhibit a significant reduction in amplitude and a change in topographic patterns of the mismatch negativity response from childhood to adolescence. The same effect, reduced mismatch amplitude in adolescence, while preserved during childhood, is observed in the cross-sectional study. These results point towards functional changes within the brain network responsible for the fMMN. In addition, the adolescents with 22q11.2 DS displayed a significant increase in amplitude over central electrodes during the auditory N1 component. No such differences, reduced mismatch response nor increased N1, were observed in the typically developing group. These findings suggest different developmental trajectories of early auditory sensory processing in 22q11.2 DS and functional changes that emerge during the critical period of increased risk for schizophrenia spectrum disorders

Deviant dynamics of EEG resting state pattern in 22q11.2 deletion syndrome adolescents: A vulnerability marker of schizophrenia?

Previous studies have repeatedly found altered temporal characteristics of EEG microstates in schizophrenia. The aim of the present study was to investigate whether adolescents affected by the 22q11.2 deletion syndrome (22q11DS), known to have a 30 fold increased risk to develop schizophrenia, already show deviant EEG microstates. If this is the case, temporal alterations of EEG microstates in 22q11DS individuals could be considered as potential biomarkers for schizophrenia. We used high-density (204 channel) EEG to explore between-group microstate differences in 30 adolescents with 22q11DS and 28 age-matched controls. We found an increased presence of one microstate class (class C) in the 22q11DS adolescents with respect to controls that was associated with positive prodromal symptoms (hallucinations). A previous across-age study showed that the class C microstate was more present during adolescence and a combined EEG-fMRI study associated the class C microstate with the salience resting state network, a network known to be dysfunctional in schizophrenia. Therefore, the increased class C microstates could be indexing the increased risk of 22q11DS individuals to develop schizophrenia if confirmed by our ongoing longitudinal study comparing both the adult 22q11DS individuals with and without schizophrenia, as well as schizophrenic individuals with and without 22q11DS.status: publishe

Aberrant developmental patterns of gamma-band response and long-range communication disruption in youths with 22q11.2 deletion syndrome

Objective: Brain oscillations play a pivotal role in synchronizing responses of local and global ensembles of neurons. Patients with schizophrenia exhibit impairments in oscillatory response, which are thought to stem from abnormal maturation during critical developmental stages. Studying individuals at genetic risk for psychosis, such as 22q11.2 deletion carriers, from childhood to adulthood may provide insights into developmental abnormalities. Methods: The authors acquired 106 consecutive T1-weighted MR images and 40-Hz auditory steady-state responses (ASSRs) with high-density (256 channel) EEG in a group of 58 22q11.2 deletion carriers and 48 healthy control subjects. ASSRs were analyzed with 1) time-frequency analysis using Morlet wavelet decomposition, 2) intertrial phase coherence (ITPC), and 3) theta-gamma phase-amplitude coupling estimated in the source space between brain regions activated by the ASSRs. Additionally, volumetric analyses were performed with FreeSurfer. Subanalyses were conducted in deletion carriers who endorsed psychotic symptoms and in subgroups with different age bins. Results: Deletion carriers had decreased theta and late-latency 40-Hz ASSRs and phase synchronization compared with control subjects. Deletion carriers with psychotic symptoms displayed a further reduction of gamma-band response, decreased ITPC, and decreased top-down modulation of gamma-band response in the auditory cortex. Reduced gamma-band response was correlated with the atrophy of auditory cortex in individuals with psychotic symptoms. In addition, a linear increase of theta and gamma power from childhood to adulthood was found in control subjects but not in deletion carriers. Conclusions: The results suggest that while all deletion carriers exhibit decreased gamma-band response, more severe local and long-range communication abnormalities are associated with the emergence of psychotic symptoms and gray matter loss. Additionally, the lack of age-related changes in deletion carriers indexes a potential developmental impairment in circuits underlying the maturation of neural oscillations during adolescence. The progressive disruption of gamma-band response in 22q11.2 deletion syndrome supports a developmental perspective toward understanding and treating psychotic disorders

DOI 10.1007/s10548-013-0314-x ORIGINAL PAPER Parieto-Frontal Circuits During Observation of Hidden and Visible Motor Acts in Children. A High-density EEG Source Imaging Study

Abstract Several studies showed that in the human brain specific premotor and parietal areas are activated during the execution and observation of motor acts. The activation of this premotor-parietal network displaying the so-called Mirror Mechanism (MM) was proposed to underpin basic forms of action understanding. However, the functional properties of the MM in children are still largely unknown. In order to address this issue, we recorded high-density EEG from 12 children (6 female, 6 male; average age 10.5, SD ±2.15). Data were collected when children observed video clips showing hands grasping objects in two different experimental conditions: (1) Full Vision, in which the motor act was fully visible; (2) Hidden, in which the interaction between the hand and the object was not visible. Event-related potentials (ERPs) and topographic map analyses were used to investigate the temporal pattern of the ERPs and their brain source of localization, employing a children template of the Montreal Neurological Institute. Results showed that two different parieto-premotor circuit