From 'mental fog' to post-acute COVID-19 syndrome's executive function alteration: Implications for clinical approach.

A common symptom of the neuropsychiatric Post-Acute COVID-19 syndrome (neuro-PACS) is the so called 'brain fog'. Patients describe the brain fog as problems with attention, memory and mental fatigue. Brain fog is experienced by 9-55% of people for months after having contracted SARS-CoV-2 virus. Several theories have been proposed to explain PACS's brain fog, including a neuroinflammatory hypothesis, but the hypothesis remains to be proven. Here, we examined inflammatory and immunological blood profile in a cohort of patients with PACS to investigate the association between executive functions and blood inflammatory markers. Executive function was assessed by the Trail Making Test (TMT) Part A and Part B, as well as the Barkley Deficits in Executive Functioning Scale (BDEFS), in 71 patients (36 men), average age of 40 years (range: 15-82, SD: 15.7). Impairment in executive functioning (BDEFS scores and TMT B scores) correlated with increased levels of Interleukin-6 (IL-6), fibrinogen and ferritin. Moreover, elevated levels of Il-6, fibrinogen, ferritin, tumor necrosis factor-alpha and C-reactive protein have been observed in PACS. These findings demonstrate that PACS is characterized by the presence of an immuno-inflammatory process, which is associated with diminished executive functioning. Here, we argue in favour of a shift from the non-descriptive definition of 'mental fog' to a characterization of a subtype of PACS, associated with alteration in executive functioning. Implication for clinical settings and prevention are discussed.

PANDAS/PANS in the COVID-19 Age: Autoimmunity and Epstein-Barr Virus Reactivation as Trigger Agents?

COVID-19 impacted the entire world's population, frequently resulting in long-lasting neuropsychiatric complications. Furthermore, social distancing, lockdowns and fear for one's personal health worsen individual psychological wellbeing, especially in children and adolescents. Herein, we discuss the results of studies that specifically reported data about the impact of the COVID-19 pandemic or infection on children with Pediatric Acute-Onset Neuropsychiatric Disorders (PANS). Furthermore, we present the cases of five adolescents with PANS whose symptomatology increased following SARS-CoV-2 infection. What emerged from this study was that COVID-19 resulted in the exacerbation of obsessions, tics, anxiety and mood symptoms and decreased wellbeing. Moreover, new symptoms, as well as new PANS cases, are reported to have arisen after COVID-19 infection. Here, we hypothesize that the pathogenic mechanisms of silent viruses, such as the Epstein-Barr virus, are related to neuroinflammation, immune responses and reactivation, with additional roles played by social-isolation-related inflammatory processes. The discussion of PANS, which represents a model of immune-mediated neuropsychiatric manifestations, is particularly relevant, with the aim of uncovering the mechanisms that lead to neuropsychiatric Post-Acute COVID-19 Syndrome (PACS). Prospects for future studies and treatment implications are discussed.

Noise in the brain: Transcranial random noise stimulation and perceptual noise act on a stochastic resonance-like mechanism.

Stochastic resonance (SR) is a phenomenon in which a certain amount of random noise added to a weak subthreshold stimulus can enhance signal detectability. It is unknown how external noise interacts with neural noise in producing an SR-like phenomenon and whether this interaction results in a modulation of either network efficiency or the efficiency of single neurons. Using random dot motion stimuli and noninvasive brain stimulation, we attempted to unveil the specific mechanism of action of the SR-like phenomenon in motion perception, if present. We aimed to determine whether signal integration efficiency changes with external noise (random dot numerosity) and how electrical transcranial random noise stimulation (tRNS) can affect the peak performance. The participants performed a coherent motion detection task in which the random dot numerosity varied, whereas the signal-to-noise ratio (SNR) remained constant. We applied placebo or tRNS with an amplitude of either 1 or 2 mA during task execution. We found peaks in participants' performance both in the case of placebo stimulation and in the case of 1-mA tRNS. In the latter case (i.e., with an additional noise source), the peak emerged at lower random dot numerosity levels than when no additional noise was added (placebo). No clear peak was observed with 2-mA tRNS. An equivalent noise (EN) analysis confirmed that SR arises from a modulation of the network efficiency underlying motion signal integration. These results indicate a joint contribution of external and neural noise (modulated by tRNS) in eliciting an SR-like phenomenon.

Vision recovery with perceptual learning and non-invasive brain stimulation: Experimental set-ups and recent results, a review of the literature.

BACKGROUND: Vision is the sense which we rely on the most to interact with the environment and its integrity is fundamental for the quality of our life. However, around the globe, more than 1 billion people are affected by debilitating vision deficits. Therefore, finding a way to treat (or mitigate) them successfully is necessary. OBJECTIVE: This narrative review aims to examine options for innovative treatment of visual disorders (retinitis pigmentosa, macular degeneration, optic neuropathy, refractory disorders, hemianopia, amblyopia), especially with Perceptual Learning (PL) and Electrical Stimulation (ES). METHODS: ES and PL can enhance visual abilities in clinical populations, inducing plastic changes. We describe the experimental set-ups and discuss the results of studies using ES or PL or their combination in order to suggest, based on literature, which treatment is the best option for each clinical condition. RESULTS: Positive results were obtained using ES and PL to enhance visual functions. For example, repetitive transorbital Alternating Current Stimulation (rtACS) appeared as the most effective treatment for pre-chiasmatic disorders such as optic neuropathy. A combination of transcranial Direct Current Stimulation (tDCS) and visual training seems helpful for people with hemianopia, while transcranial Random Noise Stimulation (tRNS) makes visual training more efficient in people with amblyopia and mild myopia. CONCLUSIONS: This narrative review highlights the effect of different ES montages and PL in the treatment of visual disorders. Furthermore, new options for treatment are suggested. It is noteworthy to mention that, in some cases, unclear results emerged and others need to be more deeply investigated.

Transcranial Photobiomodulation for the Treatment of Children with Autism Spectrum Disorder (ASD): A Retrospective Study.

Children with Autism Spectrum Disorder (ASD) face several challenges due to deficits in social function and communication along with restricted patterns of behaviors. Often, they also have difficult-to-manage and disruptive behaviors. At the moment, there are no pharmacological treatments for ASD core features. Recently, there has been a growing interest in non-pharmacological interventions for ASD, such as neuromodulation. In this retrospective study, data are reported and analyzed from 21 patients (13 males, 8 females) with ASD, with an average age of 9.1 (range 5−15), who received six months of transcranial photobiomodulation (tPBM) at home using two protocols (alpha and gamma), which, respectively, modulates the alpha and gamma bands. They were evaluated at baseline, after three and six months of treatment using the Childhood Autism Rating Scale (CARS), the Home Situation Questionnaire-ASD (HSQ-ASD), the Autism Parenting Stress Index (APSI), the Montefiore Einstein Rigidity Scale−Revised (MERS−R), the Pittsburgh Sleep Quality Index (PSQI) and the SDAG, to evaluate attention. Findings show that tPBM was associated with a reduction in ASD severity, as shown by a decrease in CARS scores during the intervention (p < 0.001). A relevant reduction in noncompliant behavior and in parental stress have been found. Moreover, a reduction in behavioral and cognitive rigidity was reported as well as an improvement in attentional functions and in sleep quality. Limitations were discussed as well as future directions for research.

rTMS investigation of resistant Obsessive-Compulsive Related Disorders: Efficacy of targeting the reward system.

Introduction: Repetitive Transcranial Magnetic Stimulation (rTMS) is not only a therapeutic option but also an investigational tool to explore circuits and subjective dimensions in pathological conditions. Obsessive-Compulsive Related Disorders (OCRDs) shared similarities with Substance Use Disorder (SUD), suggesting the involvement of the reward system. This study aimed to verify the efficacy of targeting the reward system with rTMS in OCRDs. Methods: Patients with trichotillomania, hoarding disorder and skin picking disorder were treated with rTMS over the left DorsoLateral PreFrontal Cortex (DLPFC) at 15 Hz, targeting the reward system via the connection with the nucleus accumbens and the ventral tegmental area. All patients were administered with psychometric scales assessing depression symptoms and severity of OCRDs symptoms at the baseline, at the end of the treatment and a 1-month follow-up. Results: Analysis of the results showed a reduction in symptom severity at the end of the treatment in all three groups (p < 0.0001) as well as a reduction in depression symptoms (p < 0.01). Improvements at 1-month follow-up were maintained only in younger patients. Indeed, when changes in scores at the follow-up were analyzed separately for younger (<30 years) and older patients (>60 years), the elderly showed again an increase in symptoms severity, suggesting that the stability of TMS effects over time reduces with age, possibly as an effect of age-related reduction in brain plasticity. Discussion: This study adopted with promising results a protocol (15 Hz over the left DLPFC) targeting the reward system, typically employed in addictions. These results can be in line with the view of OCRDs as behavioral addictions, suggesting the implication of common circuits, such as the reward system, in the mechanisms at the basis of these disorders.