Brain Sciences

While repetitive transcranial magnetic stimulation (rTMS) is widely used to treat psychiatric disorders, innovations are needed to improve its efficacy. An important limitation is that while psychiatric disorders are associated with fronto-limbic dysregulation, rTMS does not have sufficient depth penetration to modulate affected subcortical structures. Recent advances in task-related functional connectivity provide a means to better link superficial and deeper cortical sources with the possibility of increasing fronto-limbic modulation to induce stronger therapeutic effects. The objective of this pilot study was to test whether task-related, connectivity-based rTMS could modulate amygdala activation through its connectivity with the medial prefrontal cortex (mPFC). fMRI was collected to identify a node in the mPFC showing the strongest connectivity with the amygdala, as defined by psychophysiological interaction analysis. To promote Hebbian-like plasticity, and potentially stronger modulation, 5 Hz rTMS was applied while participants viewed frightening video-clips that engaged the fronto-limbic network. Significant increases in both the mPFC and amygdala were found for active rTMS compared to sham, offering promising preliminary evidence that functional connectivity-based targeting may provide a useful approach to treat network dysregulation. Further research is needed to better understand connectivity influences on rTMS effects to leverage this information to improve therapeutic applications. Full article

Background: Interoceptive information plays a pivotal role in building higher-order cognitive body representations (BR) that neuropsychological and neuroimaging evidence classifies as action-oriented (i.e., body schema) or non-action-oriented (i.e., visuo-spatial body map). This study aimed to explore the development of BR, considering the association with the interoceptive sensibility throughout the lifespan. Methods: Two hundred thirty-nine healthy participants divided into five age groups (7 to 8 years; 9 to 10 years; 18 to 40 years; 41 to 60 years; over 60 years) completed a self-report measure of interoceptive sensibility (the Self-Awareness Questionnaire; SAQ) and were given tasks assessing the two BR (action-oriented: hand laterality task; non-action-oriented: frontal body evocation task). Results: Both children (7–8 and 9–10 years) and older adults (over 60 years) performed worse than young (18–40 years) and middle-aged adults (41–60 years) in action- and non-action-oriented BR tasks. Moderation analyses showed that the SAQ score significantly moderated the relationship between age and action-oriented BR. Conclusions: The current results are consistent with inverted U-shaped developmental curves for action- and non-action-oriented BR. As an innovative aspect, the ability to mentally represent one’s own body parts in diverse states could be negatively affected by higher interoceptive sensibility levels in childhood and late adulthood. Full article

There are consistent associations between physical activity and self-perceived health. However, it is not clear whether associations between self-perceived health and participation in physical activity could be accounted for by associations with cognitive function. In the present study, we examined whether associations between physical activity and cognitive functioning could explain the variability between physical activity and self-perceived health. A sample of 204 older adults performed three cognitive tests selected from the Vienna test system battery: The Determination, Cognitrone, and Visual Memory tests. These tests measure general processing speed, attention, and visual memory, respectively. Participants also completed the 12-item Short Form Health Questionnaire SF-12 to measure perceived health, and the Physical Activity Survey for the Elderly to measure physical activity. Linear regressions and the PROCESS macro for SPSS were used to test our hypotheses. Consistent with our hypotheses, processing speed accounted for significant variance in the relationship between physical activity and self-perceived health. This suggests that cognitive processing speed might be an indirect path by which physical activity relates to enhanced health perceptions. The results demonstrate that associations between physical activity and self-perceptions of health are related to a fundamental cognitive process. Full article

Within the aphasia literature, it is common to link location of lesioned brain tissue to specific patterns of language impairment. This has provided valuable insight into the relationship between brain structure and function, but it does not capture important underlying alterations in function of regions that remain structurally intact. Research has demonstrated that in the chronic stage of aphasia, variable patterns of reduced cerebral blood flow (CBF; hypoperfusion) in structurally intact regions of the brain contribute to persisting language impairments. However, one consistent issue in this literature is a lack of clear consensus on how to define hypoperfusion, which may lead to over- or underestimation of tissue functionality. In the current study, we conducted an exploratory analysis in six individuals with chronic aphasia (>1 year post-onset) using perfusion imaging to (1) suggest a new, individualized metric for defining hypoperfusion; (2) identify the extent of hypoperfused tissue in perilesional bands; and (3) explore the relationship between hypoperfusion and language impairment. Results indicated that our individualized metric for defining hypoperfusion provided greater precision when identifying functionally impaired tissue and its effects on language function in chronic aphasia. These results have important implications for intervention approaches that target intact (or impaired) brain tissue. Full article

Psychoactive drugs play a significant role in suicidality when used for intentional overdose or, more frequently, when the intoxication leads to disinhibition and alterations in judgment, thereby making suicide more likely. In this study, we investigated suicidality prevalence among drug users and evaluated the differences in suicide ideation, taking into account the substance categories and the association of suicide ideation intensity with other psychiatric symptoms. Subjects admitted to the Can Misses Hospital’s psychiatry ward in Ibiza were recruited during summer openings of local nightclubs for four consecutive years starting in 2015. The main inclusion criterium was an intake of psychoactive substances during the previous 24 h. The Columbia Suicide Severity Rating Scale (C-SSRS) was used to assess the suicide risk. Suicidality was present in 39% of the study cohort. Suicide Ideation Intensity overall and in the previous month was higher in users of opioids and in general of psychodepressors compared to psychostimulants or psychodysleptics. Suicidality was not correlated with alterations in any of the major psychopathological scales employed to assess the psychiatric background of the study subjects. The presence of high levels of suicidality did not specifically correlate with any major symptom indicative of previous or ongoing psychopathological alterations. These findings suggest that impulsivity and loss of self-control may be determinants of the increased suicidality irrespectively of any major ongoing psychiatric background. Full article

Stress-related sleep disturbances are distressing clinical symptoms in posttraumatic stress disorder patients. Intensely stressful events and their memories change rapid eye movement (REM) sleep in animal models. REM sleep varies with individual differences of stress resilience or vulnerability. The basolateral amygdala (BLA) is a primary mediator of the effects of stress and fear memories on sleep. However, the molecular mechanisms in BLA regulating the effects of fear conditioning, shock training (ST) and context re-exposure (CTX) on REM sleep are not well known. MicroRNAs (miRNAs) are small, non-coding RNAs and posttranscriptional gene regulators of diverse biological processes. The aim of this study is to investigate ST- and CTX-altered miRNAs in the BLA of resilience and vulnerable animals and on REM sleep regulation. MiRNAs expression profiles in BLA were generated following ST and CTX using the Taqman Low Density rodent microRNA array. The altered BLA miRNAs expression and REM sleep reduction observed in ST and CTX vulnerable animals. AntagomiR-221 microinjection into BLA for one of the upregulated miRNAs, miR-221 in BLA, attenuated the REM sleep reduction. This study suggests that miRNAs in the BLA may play a significant role in mediating the effects of stress and fear memories on REM sleep. Full article

Introduction: The petroclival region is among the most challenging anatomical areas to deal with in skull base surgery. Drilling of the anterior part of the petrous bone during the anterior transpetrosal approach involves the risk of injury of the cochlea, superior semicircular canal, internal carotid artery, and internal auditory canal. A thorough understanding of the microneurosurgical anatomy of this region is mandatory to execute the transpetrosal approaches, decreasing the risk of complications. The aim of this study is to describe the anatomical structures of the petroclival region, highlighting the importance of neuronavigation for safe performance of the anterior transpetrosal approach. Methods: Three adult cadaveric human heads were formalin-fixed and injected with colored silicone. They underwent an axial 1 mm slab CT scan, which was used for neuronavigation during the surgical approaches. The anterior petrosectomy was performed with the aid of neuronavigation during the drilling of the petrous bone. The surgical management of a patient harboring a petroclival meningioma, operated on using an anterior transpetrosal approach, was reported as an illustrative case. Results: The anterior petrosectomy was completed accurately with wide exposure of the surgical target without injuring the cochlea and other structures in all three cadaveric specimens. In the surgical case, no approach-related complications occurred, and a gross total resection of the tumor was achieved. Conclusions: Deep knowledge of the location and relationships of the vital elements located within the temporal bone, along with the use of neuronavigation, are the key aspects to perform the anterior transpetrosal approach safely, reducing the risk of complications. Full article

Propagation of brain rhythms among cortical regions is a relevant aspect of cognitive neuroscience, which is often investigated using functional connectivity (FC) estimation techniques. The aim of this work is to assess the relationship between rhythm propagation, FC and brain functioning using data generated from neural mass models of connected Regions of Interest (ROIs). We simulated networks of four interconnected ROIs, each with a different intrinsic rhythm (in θ, α, β and γ ranges). Connectivity was estimated using eight estimators and the relationship between structural connectivity and FC was assessed as a function of the connectivity strength and of the inputs to the ROIs. Results show that the Granger estimation provides the best accuracy, with a good capacity to evaluate the connectivity strength. However, the estimated values strongly depend on the input to the ROIs and hence on nonlinear phenomena. When a population works in the linear region, its capacity to transmit a rhythm increases drastically. Conversely, when it saturates, oscillatory activity becomes strongly affected by rhythms incoming from other regions. Changes in functional connectivity do not always reflect a physical change in the synapses. A unique connectivity network can propagate rhythms in very different ways depending on the specific working conditions. Full article

A relationship between obstructive sleep apnea (OSA) and abnormalities in 24-h electrocardiogram (ECG) Holter monitoring has not been sufficiently documented. The aim of this study was to analyze the relation between the occurrence and the severity of OSA and the parameters of ECG Holter monitoring in a group of patients with diagnosed OSA. Ninety-four patients with clinical suspicion of OSA were qualified for the study (mean age 53.7). All participants underwent a medical history, laboratory tests, 24-h ECG Holter monitoring, and single-night video-polysomnography (vPSG) using the American Academy of Sleep Medicine recommendations. A group of patients with diagnosed OSA was characterized by more frequent occurrence of supraventricular tachycardia (SVT) and ventricular arrhythmias (VPC). A statistically significant positive correlation was shown between the apnea-hypopnea index (AHI) and average heart rate, supraventricular arrhythmias (SVPC) pairs, SVT, and pauses >2.5 s. In regression analysis, higher AHI constituted an independent predicator for the increased number of pauses >2.5 s, SVT, and SVPC pairs in 24-h ECG Holter monitoring. In summary, patients with OSA are characterized by the increased number of abnormalities in 24-h ECG Holter monitoring. Full article

Background: Disorders of the hip and lumbar spine can create similar patterns of pain and dysfunction. It is unknown whether all surgeons, regardless of orthopedic or neurosurgery training, investigate and diagnose concurrent hip and spine pathology at the same rate. Methods: Data were retrieved from Taiwan’s National Health Insurance Research Database (NHIRD). Enrolled patients were stratified into hip and spine surgery at the same admission (Both), hip surgery before spine surgery (HS), or spine surgery before hip surgery (SH). The SH group was further subdivided based on whether spine surgery was performed by an orthopedic surgeon (OS) or neurosurgeon (NS), and differences in preoperative radiographic examinations and diagnoses were collected and analyzed. Results: In total, 1824 patients received lumbar spine surgery within 1 year before or after hip replacement surgery. Of these, 103 patients had spine and hip surgery in the same admission (Both), 1290 patients had spine surgery before hip surgery (SH), and 431 patients had hip surgery before spine surgery (HS). In the SH group, patients were categorized into spine surgery by orthopedic surgeons (OS) (n = 679) or neurosurgeons (NS) (n = 522). In the SH group, orthopedic surgeons investigated hip pathology with X-rays more often (52.6% vs. 38.1%, p < 0.001) and diagnosed more cases of hip disease (43.6% vs. 28.9%, p < 0.001) than neurosurgeons. Conclusions: Of patients in Taiwan’s NHIRD who had concurrent surgical degenerative hip and lumbar spine disorders who had spine surgery before hip surgery, orthopedic surgeons obtained hip images and made hip-related diagnoses more frequently than did neurosurgeons. Full article

The relationship between sensory profile and repetitive behaviours in autism spectrum disorder (ASD) has long been known. However, there is no consensus on the type of relationship that exists between them. This monocentric retrospective–prospective observational study aimed (a) to detect a clinical correlation between the severity of repetitive behaviours and the alterations of sensory profile in a sample of 50 children diagnosed with ASD; (b) to evaluate how different patterns of stereotypies and sensory alterations correlate with each other and with the main clinical–instrumental variables in the same sample. We enrolled 29 children in the retrospective phase of the study and 21 in the prospective phase. The Repetitive Behaviour Scale-Revised (RBS-R) and the Short Sensory Profile (SSP) were administered to the caregivers, and clinical–instrumental data were collected. SSP and RBS-R total scores directly correlated with a high significance rate. Among the subscales, the strongest correlations involved “Visual/Auditory Sensitivity”, related to “Stereotyped Behaviour” and “Sameness Behaviour”. “Under-Responsive/Seeks Sensation” related to “Stereotyped Behaviour”. Sex and intellectual disability significantly influenced both the stereotypies and the sensory alterations of the examined population. In conclusion, this study provides new insights into the relationship between sensory alterations and repetitive behaviours in ASD children by using direct medical observation and parent observation. Full article

The purpose of this pilot study was to investigate whether transcranial static magnetic field stimulation (tSMS), which can modulate cortical excitability, would influence inhibitory control function when applied over the dorsolateral prefrontal cortex (DLPFC). Young healthy adults (n = 8, mean age ± SD = 24.4 ± 4.1, six females) received the following stimulations for 30 min on different days: (1) tSMS over the left DLPFC, (2) tSMS over the right DLPFC, and (3) sham stimulation over either the left or right DLPFC. The participants performed a Go/NoGo task before, immediately after, and 10 min after the stimulation. They were instructed to extend the right wrist in response to target stimuli. We recorded the electromyogram from the right wrist extensor muscles and analyzed erroneous responses (false alarm and missed target detection) and reaction times. As a result, 50% of the participants made erroneous responses, and there were five erroneous responses in total (0.003%). A series of statistical analyses revealed that tSMS did not affect the reaction time. These preliminary findings suggest the possibility that tSMS over the DLPFC is incapable of modulating inhibitory control and/or that the cognitive load imposed in this study was insufficient to detect the effect. Full article

Objectives: The study aims to assess the impact of the second COVID-19 pandemic wave on migraine characteristics. Methods: This is an observational cross-sectional study conducted on migraine patients previously interviewed during the first Italian pandemic outbreak. A second structured telephone interview was conducted between 20 November 2020 and 18 January 2021. We compared migraine characteristics among T0 (before pandemic), T1 (during the first pandemic phase), and T2 (during the second pandemic phase). Results: Among the 433 patients interviewed during the first pandemic phase, 304 cases were finally considered. One hundred forty-eight patients had a control visit between March 2020 and December 2020, 120 had an in-person visit, 14 by phone, the remainder used telemedicine software provided by the hospital. Frequency of headache, number of symptomatic drugs and headache intensity worsened during T2, compared to T0 and T1, especially in episodic migraine. Headache intensity increased relating to the negative emotional impact of the pandemic. Migraine management during the pandemic did not influence the clinical outcome. Conclusion: The prolongation of the pandemic seems to have a negative impact on migraine evolution. The arousal and negative psychological behavior toward the COVID-19 outbreak seem to worsen migraine. Full article

Cognitive impairment (CI) is a common and disabling symptom of Multiple Sclerosis (MS) with a negative impact on daily living. In this pilot study, we applied magnetoencephalography (MEG) and high density (hd) electroencephalography (EEG) study to evaluate acoustic P300 features in a cohort of early MS. Sixteen MS patients (pwMS) and 19 healthy controls (HCs) matched for age and gender underwent an MEG-/(hd)-EEG-co-recording, using 306-channel Vectorview and 64 scalp electrodes. CI was assessed using Rao’s Brief Repeatable Battery (BRB). Moreover, we performed psychometric tests to assess depression and fatigue. In pwMS, we observed a slight latency prolongation of P300 peak compared to HCs, while P300 amplitude and scalp distribution were similar in the two groups. pwMS did not show an amplitude reduction and different scalp distribution of Event-Related Potentials (ERPs) and Event Related Fields (ERFs) related to an acoustic oddball paradigm. We found an inverse correlation between P300 amplitude and fatigue (r Spearman = −0.4; p = 0.019). In pwMS, phenomena of cortical adaptation to early dysfunction could preserve the cognitive performance of the P300 acoustic task, while the development of fatigue could prospectively lead to amplitude decline of P300, suggesting its possible role as a biomarker. Full article

Individuals with high anxiety preferentially focus attention on emotional information. The autonomic nervous system (ANS) plays an important role in modulating both anxiety and attentional processes. Despite many studies having evaluated attentional bias in anxious people, few of them have investigated the change blindness phenomenon associated with the attentional response toward salient stimuli, considering the role of the ANS. This study aimed to examine the role of heart rate variability (HRV) in trait anxiety and top-down and bottom-up attentional processes toward emotional stimuli. Seventy-five healthy university students were divided into high (N = 39) and low (N = 36) trait anxiety groups and completed a change detection flicker task with neutral, positive, and negative stimuli. The results evidenced a different attentional pattern between people with high and low anxiety considering both the two attentional processes and the valence of the stimuli. Specifically, individuals with high anxiety showed a bias in elaborating emotional stimuli related to their salience (i.e., negative stimuli were faster elaborated than neutral and positive stimuli when top-down attentional mechanisms were involved, while slower performances were highlighted considering bottom-up attentional mechanisms in response to emotional stimuli compared to neutral stimuli). Moreover, an association between HRV, trait anxiety levels, and change blindness phenomenon was confirmed. These results underline the role of HRV as a possible predictor of the alteration of attentional mechanism in anxiety. Full article

We examined whether chewing behavior affects the tumor progression-enhancing impact of psychological stress. Human breast cancer cell line (MDA-MB-231) cells were inoculated into the mammary fat pads of athymic nude mice. The mice were assigned randomly to control, stress, and stress+chewing groups. Psychological stress was created by keeping mice in a transparent restraint cylinder for 45 min, three times a day, for 35 days after cell inoculation. Animals in the stress+chewing group were provided with a wooden stick for chewing on during the psychological stress period. Chewing behavior remarkably inhibited the tumor growth accelerated by the psychological stress. Immunohistochemical and Western blot findings revealed that chewing behavior during psychological stress markedly suppressed tumor angiogenesis and cell proliferation. In addition, chewing behavior decreased serum glucocorticoid levels and expressions of glucocorticoid and β2-adrenergic receptors in tumors. Chewing behavior decreased expressions of inducible nitric oxide synthase and 4-hydroxynonenal, and increased expression of superoxide dismutase 2 in tumors. Our findings suggest that chewing behavior could ameliorate the enhancing effects of psychological stress on the progression of breast cancer, at least partially, through modulating stress hormones and their receptors, and the subsequent signaling pathways involving reactive oxygen and nitrogen species. Full article

Response inhibition has been widely explored using the stop signal paradigm in the laboratory setting. However, the mechanism that demarcates attentional capture from the motor inhibition process is still unclear. Error monitoring is also involved in the stop signal task. Error responses that do not complete, i.e., partial errors, may require different error monitoring mechanisms relative to an overt error. Thus, in this study, we included a “continue go” (Cont_Go) condition to the stop signal task to investigate the inhibitory control process. To establish the finer difference in error processing (partial vs. full unsuccessful stop (USST)), a grip-force device was used in tandem with electroencephalographic (EEG), and the time-frequency characteristics were computed with Hilbert–Huang transform (HHT). Relative to Cont_Go, HHT results reveal (1) an increased beta and low gamma power for successful stop trials, indicating an electrophysiological index of inhibitory control, (2) an enhanced theta and alpha power for full USST trials that may mirror error processing. Additionally, the higher theta and alpha power observed in partial over full USST trials around 100 ms before the response onset, indicating the early detection of error and the corresponding correction process. Together, this study extends our understanding of the finer motor inhibition control and its dynamic electrophysiological mechanisms. Full article

The effects of COVID-19 containment measures on the emotional and behavioral development of preschoolers are not clear. We investigated them within an ongoing longitudinal project including typically developing children (TD) and children at high familial risk for neurodevelopmental disorders (HR-NDD) who were potentially more vulnerable. The study included ninety children aged 2–6 years (TD = 48; HR-NDD = 42). Before the emergency phase (T0), all children received a clinical assessment, including the parent questionnaire Child Behavior Checklist for Ages 1.5–5 (CBCL 1.5–5). The same questionnaire was filled out again during the emergency (T1), together with an ad-hoc questionnaire investigating environmental factors characterizing the specific period. Changes in the CBCL profiles between T0 and T1 were evaluated. Overall, irrespective of familial risk, the average T-scores on specific CBCL scales at T1 were higher than at T0. Associations emerged between delta scores reflecting worsening scores on specific CBCL scales and clinical and environmental factors. Our results confirmed the negative impact of the lockdown on preschool children’s emotional/behavioral profiles, and highlight the need for strategic approaches in the age range of 2–6 years, especially for more susceptible children owing to environmental factors and pre-existing emotional problems. Full article

Continuation of experience-dependent neural activity during offline sleep and wakefulness episodes is a critical component of memory consolidation. Using functional magnetic resonance imaging (fMRI), offline consolidation effects have been evidenced probing behavioural and neurophysiological changes during memory retrieval, i.e., in the context of task practice. Resting state fMRI (rsfMRI) further allows investigating the offline evolution of recently learned information without the confounds of online task-related effects. We used rsfMRI to investigate sleep-related changes in seed-based resting functional connectivity (FC) and amplitude of low frequency fluctuations (ALFF) after spatial navigation learning and relearning. On Day 1, offline resting state activity was measured immediately before and after topographical learning in a virtual town. On Day 4, it was measured again before and after relearning in an extended version of the town. Navigation-related activity was also recorded during target retrieval, i.e., online. Participants spent the first post-training night under regular sleep (RS) or sleep deprivation (SD) conditions. Results evidence FC and ALFF changes in task-related neural networks, indicating the continuation of navigation-related activity in the resting state. Although post-training sleep did not modulate behavioural performance, connectivity analyses evidenced increased FC after post-training SD between navigation-related brain structures during relearning in the extended environment. These results suggest that memory traces were less efficiently consolidated after post-learning SD, eventually resulting in the use of compensatory brain resources to link previously stored spatial elements with the newly presented information. Full article