Beyond the efficacy of transcranial magnetic stimulation in peripartum depression: A systematic review exploring perinatal safety for newborns.

OBJECTIVE: Peripartum depression is defined as the onset of depressive symptoms during pregnancy or within 12 months postpartum and affects 11.9% of women. Currently, its treatment often involves psychotherapy and antidepressants, though only one medication has been specifically approved to treat it. In this context, novel, safe non-pharmacological treatment options have gained growing interest. The present review aims to assess current literature on possible side effects on the developing fetus/newborn of Transcranial Magnetic Stimulation (TMS) use in women with peripartum depression. METHOD: A systematic search was performed using the PubMed, Scopus and Web of Science databases. PRISMA and PROSPERO guidelines were applied. The risk of bias assessment was performed using the Cochrane risk of bias tool version 2.0. RESULTS: Twenty-three studies were included in our systematic review, two were randomized controlled trials. Eleven studies reported mothers experienced mild side effects; none of the included studies reported major side effects for newborns. CONCLUSION: The present systematic review demonstrated that TMS use in women with peripartum depression is safe, feasible and well-tolerated by the developing fetus/newborn, with a good safety and tolerability profile even during breastfeeding.

Impact of sleep disorders and disease duration on neurotrophins levels in cocaine use disorder.

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) and its precursor proBDNF contribute to brain plasticity and neuronal remodeling. Recently, the ratio between proBDNF and BDNF (RpB) has been proposed as a possible marker in major psychiatric disorders. Convergent lines of evidence suggest neurotrophins alterations could be involved into the pathophysiology of Cocaine Use Disorder (CUD) and insomnia. The aims of the present study are to evaluate the correlations between neurotrophins levels, insomnia and clinical features among CUD patients. MATERIALS AND METHODS: Subjects with a moderate to severe CUD were recruited. ProBDNF, BDNF and consequently RpB values were analyzed using ELISA technique. Insomnia severity index (ISI) scale was used to assess the severity of insomnia. Sociodemographic characteristics and CUD habits (e.g., years of cocaine use) were also collected. RESULTS: Twenty-four subjects (mean age 39.3 ± 6.7 years) were recruited. Correlation analysis showed that lower values of RpB were associated with higher ISI score (r = -0.469; p = 0.021), longer history of cocaine use (r = -0.584, p = 0.022) and higher amount of cocaine used (r = -0.655, p = 0.004). DISCUSSION: These preliminary findings may offer a novel insight on neurobiological alterations sustaining cocaine use. Lower RpB, as observed both in high insomnia levels and in chronic cocaine use, could induce a neuroprotective state as a synaptic homeostatic response to chronic damage. These findings also highlight the important role of neurotrophins balance on neurobiological alterations induced by cocaine misuse and insomnia, suggesting that RpB could be considered as a marker of neurotrophic and metabolic state of neural tissue.

High γ-Aminobutyric Acid Content Within the Medial Prefrontal Cortex Is a Functional Signature of Somatic Symptoms Disorder in Patients With Parkinson's Disease.

BACKGROUND: The dysfunctional activity of the medial prefrontal cortex has been associated with the appearance of the somatic symptom disorder, a key feature of the Parkinson's disease (PD) psychosis complex. OBJECTIVES: The objectives of this study were to investigate whether the basal contents of inhibitory γ-aminobutyric acid and excitatory glutamate plus glutamine neurotransmitter levels are changed in the medial prefrontal cortex of patients with PD with somatic symptom disorder and whether this alteration represents a marker of susceptibility of PD to somatic symptom disorder, thus representing a signature of psychosis complex of PD. METHODS: Levels of the γ-aminobutyric acid and glutamate plus glutamine were investigated, at rest, with proton magnetic resonance spectroscopy. Total creatine was used as an internal reference. The study cohort included 23 patients with somatic symptom disorder plus PD, 19 patients with PD without somatic symptom disorder, 19 healthy control subjects, and 14 individuals with somatic symptom disorder who did not show other psychiatric or neurological disorders. RESULTS: We found that, compared with patients with PD without somatic symptom disorder or healthy control individuals, patients with somatic symptom disorder, with or without PD, show increased γ-aminobutyric acid/total creatine levels in the medial prefrontal cortex. The medial prefrontal cortex contents of glutamate plus glutamine/total creatine levels or γ-aminobutyric acid/glutamate plus glutamine were not different among groups. CONCLUSIONS: Our findings highlight a crucial pathophysiologic role played by high γ-aminobutyric acid within the medial prefrontal cortex in the production of somatic symptom disorder. This phenomenon represents a signature of psychosis complex in patients with PD. © 2020 International Parkinson and Movement Disorder Society.

Corrigendum: Effects of Second Language Learning on the Plastic Aging Brain: Functional Connectivity, Cognitive Decline, and Reorganization.

[This corrects the article DOI: 10.3389/fnins.2019.00423.].

Subjective Cognitive Decline and Nighttime Sleep Alterations, a Longitudinal Analysis.

Objective: The aim of this study was to analyze quantitative sleep changes and their implication on subjective cognitive decline (SCD). Objective sleep patterns were investigated by an actigraph and recorded at the baseline and 2-year after in order to examine specific sleep alterations in SCD. Background: Sleep disorders are very common among average elderly adults and an altered sleep pattern is known to be a risk factor for future development of mild cognitive impairment (MCI) and dementia. Recent studies have shown how sleep is objectively altered in average senior adults with SCD, without any other significant change in cognition and behavior or brain structure. Considering that both SCD and disrupted sleep are risk factors for future MCI and dementia, with sleep only as a modifiable risk factor, further research is required to deeply investigate the interaction between sleep and SCD. Methods: Among 70 community-dwelling elderly individuals who had been enrolled at baseline, 35 (64.6 ± 5.6 years, 15 M/20 F) underwent a complete neuropsychological battery and 1-week wrist actigraphy recording 2 years later during the follow-up stage. Individuals were divided into two groups according to their SCD Questionnaire (SCD-Q) score. Sleep hours, sleep efficiency and onset latency, napping and time awake after sleep onset (WASO) were collected. All individuals underwent structural magnetic resonance imaging (MRI) examination to exclude brain disorders. Data collection was performed at baseline and after 2 years at the follow-up phase. Results: A significantly different night sleep time between the two groups was observed: SCD showed a lower total sleep time (TST) than non-SCD subjects. Moreover, a total time spent in bed (TIB) was significantly lower in SCD subjects over 2 years of observation. Conclusions: Objective changes over time of the sleep pattern, specifically TIB and TST, are present in SCD individuals. The results of the study show that sleep alterations are common in SCD and underline the clinical importance of screening in order to assess sleep alterations as well as improve sleep in average adults with SCD complaints.

Effects of Second Language Learning on the Plastic Aging Brain: Functional Connectivity, Cognitive Decline, and Reorganization.

Learning a new language requires the use of extensive neural networks and can represent a powerful tool to reorganize brain neuroplasticity. In this study, we analyze how a 4 months long second language learning program (16, 2 h sessions) can lead to functional changes in the brain of healthy elderly individuals. A large number of studies point out a decline of brain-skills with age; here it is analyzed how cognition together with functional brain organization can be improved later in life. Twenty-six older adults (59-79 years old) were enrolled in the present study. A complete neuropsychological examination was administered before and after the intervention to measure global cognition levels, short- and long-term memory, attention, language access and executive functions. At the end of the program, in the intervention group, the results showed a significant improvement in global cognition together with an increased functional connectivity in the right inferior frontal gyrus (rIFG), right superior frontal gyrus (rSFG) and left superior parietal lobule (lSPL). These findings can be added to the current neurobiological breakthroughs of reshaping brain networks with a short language learning practice in healthy elderly subjects. Therefore, learning a foreign-language may represent a potentially helpful cognitive intervention for promoting healthy aging.

Reduced Dynamic Coupling Between Spontaneous BOLD-CBF Fluctuations in Older Adults: A Dual-Echo pCASL Study.

Measurement of the dynamic coupling between spontaneous Blood Oxygenation Level Dependent (BOLD) and cerebral blood flow (CBF) fluctuations has been recently proposed as a method to probe resting-state brain physiology. Here we investigated how the dynamic BOLD-CBF coupling during resting-state is affected by aging. Fifteen young subjects and 17 healthy elderlies were studied using a dual-echo pCASL sequence. We found that the dynamic BOLD-CBF coupling was markedly reduced in elderlies, in particular in the left supramarginal gyrus, an area known to be involved in verbal working memory and episodic memory. Moreover, correcting for temporal shift between BOLD and CBF timecourses resulted in an increased correlation of the two signals for both groups, but with a larger increase for elderlies. However, even after temporal shift correction, a significantly decreased correlation was still observed for elderlies in the left supramarginal gyrus, indicating that the age-related dynamic BOLD-CBF uncoupling in this region is more pronounced and can be only partially explained with a simple time-shift between the two signals. Interestingly, these results were observed in a group of elderlies with normal cognitive functions, suggesting that the study of dynamic BOLD-CBF coupling during resting-state is a promising technique, potentially able to provide early biomarkers of functional changes in the aging brain.

GABA content within medial prefrontal cortex predicts the variability of fronto-limbic effective connectivity.

The amygdala-medial prefrontal cortex (mPFC) circuit plays a key role in social behavior. The amygdala and mPFC are bidirectionally connected, functionally and anatomically, via the uncinate fasciculus. Recent evidence suggests that GABA-ergic neurotransmission within the mPFC could be central to the regulation of amygdala activity related to emotions and anxiety processing. However, the functional and neurochemical interactions within amygdala-mPFC circuits are unclear. In the current study, multimodal magnetic resonance imaging techniques were combined to investigate effective connectivity within the amygdala-mPFC network and its relationship with mPFC neurotransmission in 22 healthy subjects aged between 41 and 88 years. Effective connectivity in the amygdala-mPFC circuit was assessed on resting-state functional magnetic resonance imaging data using spectral dynamic causal modelling. State and trait anxiety were also assessed. The mPFC was shown to be the target of incoming outputs from the amygdalae and the source of exciting inputs to the limbic system. The amygdalae were reciprocally connected by excitatory projections. About half of the variance relating to the strength of top-down endogenous connection between right amygdala and mPFC was explained by mPFC GABA levels. State anxiety was correlated with the strength of the endogenous connections between right amygdala and mPFC. We suggest that mPFC GABA content predicts variability in the effective connectivity within the mPFC-amygdala circuit, providing new insights on emotional physiology and the underlying functional and neurochemical interactions.

Functional and neurochemical interactions within the amygdala-medial prefrontal cortex circuit and their relevance to emotional processing.

The amygdala-medial prefrontal cortex (mPFC) circuit plays a key role in emotional processing. GABA-ergic inhibition within the mPFC has been suggested to play a role in the shaping of amygdala activity. However, the functional and neurochemical interactions within the amygdala-mPFC circuits and their relevance to emotional processing remain unclear. To investigate this circuit, we obtained resting-state functional magnetic resonance imaging (rs-fMRI) and proton MR spectroscopy in 21 healthy subjects to assess the potential relationship between GABA levels within mPFC and the amygdala-mPFC functional connectivity. Trait anxiety was assessed using the State-Trait Anxiety Inventory (STAI-Y2). Partial correlations were used to measure the relationships among the functional connectivity outcomes, mPFC GABA levels and STAI-Y2 scores. Age, educational level and amount of the gray and white matters within 1H-MRS volume of interest were included as nuisance variables. The rs-fMRI signals of the amygdala and the vmPFC were significantly anti-correlated. This negative functional coupling between the two regions was inversely correlated with the GABA+/tCr level within the mPFC and the STAI-Y2 scores. We suggest a close relationship between mPFC GABA levels and functional interactions within the amygdala-vmPFC circuit, providing new insights in the physiology of emotion.

Atrophy of hippocampal subfields and adjacent extrahippocampal structures in dementia with Lewy bodies and Alzheimer's disease.

The hippocampus and adjacent extrahippocampal structures are organized in distinct and specialized regions which process heterogeneous functions, including memory, and visuospatial functions. Specific alterations of the different hippocampal subfields and adjacent extrahippocampal structures could differently contribute to the pathophysiology of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Based on visual symptoms which characterize DLB patients, the hippocampal subfields and the adjacent extrahippocampal structures which are mainly involved in the visual functions could be impaired in DLB and preserved in AD. To test this hypothesis, we performed structural magnetic resonance imaging on 19 DLB, 15 AD, and 19 age-matched healthy controls. FreeSurfer's pipelines were used to perform parcellation of hippocampus and adjacent extrahippocampal structures and to assess the structural changes within each region. The cornu ammonis and subiculum were bilaterally damaged in AD and preserved in DLB. The perirhinal cortex and parahippocampus were damaged in DLB but not in AD. Our findings demonstrate that the hippocampal subfields and adjacent extrahippocampal structures were differently altered in AD and DLB. Particularly, DLB patients showed a more focused alteration of the extrahippocampal structures linked to visual functions.

GABA content within the ventromedial prefrontal cortex is related to trait anxiety.

The ventromedial prefrontal cortex (vmPFC) plays a key role in emotion processing and regulation. vmPFC dysfunction may lead to disinhibition of amygdala causing high anxiety levels. γ-Aminobutyric acid (GABA) inter-neurons within vmPFC shape the information flow to amygdala. Thus, we hypothesize that GABA content within vmPFC could be relevant to trait anxiety. Forty-three healthy volunteers aged between 20 and 88 years were assessed for trait anxiety with the Subscale-2 of the State-Trait-Anxiety Inventory (STAI-Y2) and were studied with proton magnetic resonance spectroscopy to investigate GABA and Glx (glutamate+glutamine) contents within vmPFC. Total creatine (tCr) was used as internal reference. Partial correlations assessed the association between metabolite levels and STAI-Y2 scores, removing the effect of possible nuisance factors including age, educational level, volumes of gray matter and white matter within magnetic resonance spectroscopy voxel. We observed a positive relationship between GABA/tCr and STAI-Y2 scores. No significant relationships were found between Glx/tCr and STAI-Y2 and between tCr/water and STAI-Y2. No differences were found between males and females as regards to age, STAI-Y2, GABA/tCr, Glx/tCr, tCr/water, gray matter and white matter volumes. We suggest a close relationship between GABA content within vmPFC and trait anxiety providing new insights in the physiology of emotional brain.

Donepezil increases contrast sensitivity for the detection of objects in scenes.

We assessed the effects of donepezil, a drug that stimulates cholinergic transmission, and scopolamine, an antagonist of cholinergic transmission, on contrast sensitivity. 30 young male participants were tested under three treatment conditions: placebo, donepezil, and scopolamine in a random order. Pairs of photographs varying in contrast were displayed left and right of fixation for 50 ms. Participants were asked to locate the scene containing an animal. Accuracy was better under donepezil than under scopolamine, particularly for signals of high intensity (at higher levels of contrast). A control experiment showed that the lower performance under scopolamine did not result from the mydriasis induced by scopolamine. The results suggest that cholinergic stimulation, through donepezil, facilitates signal detection in agreement with studies on animals showing that the pharmacological activation of cholinergic receptors controls the gain in the relationship between the stimulus contrast (intensity of the visual input) and visual response. As Alzheimer disease is associated to depletion in acetylcholine, and there is evidence of deficits in contrast sensitivity in Alzheimer, it might be interesting to integrate such rapid and sensitive visual tasks in the biomarkers at early stage of drug development.

Scene categorization in Alzheimer's disease: a saccadic choice task.

AIMS: We investigated the performance in scene categorization of patients with Alzheimer's disease (AD) using a saccadic choice task. METHOD: 24 patients with mild AD, 28 age-matched controls and 26 young people participated in the study. The participants were presented pairs of coloured photographs and were asked to make a saccadic eye movement to the picture corresponding to the target scene (natural vs. urban, indoor vs. outdoor). RESULTS: The patients' performance did not differ from chance for natural scenes. Differences between young and older controls and patients with AD were found in accuracy but not saccadic latency. CONCLUSIONS: The results are interpreted in terms of cerebral reorganization in the prefrontal and temporo-occipital cortex of patients with AD, but also in terms of impaired processing of visual global properties of scenes.

Animal spotting in Alzheimer's disease: an eye tracking study of object categorization.

We investigated rapid object categorization and, more specifically, the ability to detect a target object within a natural scene in people with mild Alzheimer's disease (AD) using a saccadic choice task. It has been suggested that the anatomical pathway likely used to initiate rapid oculomotor responses in the saccadic choice task could involve the Frontal Eye Field, a structure that is part of the dorsal attentional network, in which connectivity is disrupted in AD. Seventeen patients with mild AD and 23 healthy age-matched controls took part in the study. A group of 24 young healthy observers was included as it has been reported that normal aging affects eye movements. Participants were presented with pairs of colored photographs of natural scenes, one containing an animal (the target) and one containing various objects (distracter), displayed for 1 s left and right of fixation. They were asked to saccade to the scene containing an animal. Neither pathology nor age affected temporal (saccade latencies and durations) and spatial (saccade amplitude) parameters of eye movements. Patients with AD were significantly less accurate than age-matched controls, and older participants were less accurate than young observers. The results are interpreted in terms of noisier sensory information and increased uncertainty in relation to deficits in the magnocellular pathway. The results suggest that, even at a mild stage of the pathology, people exhibit difficulties in selecting relevant objects.