Lowered Delta Activity in Post-COVID-19 Patients with Fatigue and Cognitive Impairment.

In post-COVID-19 syndrome (PCS), neurocognitive symptoms and fatigue are often associated with alterations in electroencephalographic (EEG) activity. The present study investigates the brain source activity at rest in PCS patients (PCS-pts) perceiving cognitive deficits and fatigue. A total of 18 PCS-pts and 18 healthy controls (HCs) were enrolled. A Montreal Cognitive Assessment (MoCA), Perceived Cognitive Difficulties Scale (PDCS) and Fatigue Severity Scale (FSS) were administered for assessing the symptoms' severity. Brain activity at rest, both with open (OE) and closed eyes (CE), was recorded by high-density EEG (Hd-EEG) and localized by source estimation. Compared to HCs, PCS-pts exhibited worse performance in executive functions, language and memory, and reported higher levels of fatigue. At resting OE state, PCS-pts showed lower delta source activity over brain regions known to be associated with executive processes, and these changes were negatively associated with PDCS scores. Consistent with recent literature data, our findings could indicate a dysfunction in the neuronal networks involved in executive functions in PCS-pts complaining of fatigue and cognitive impairment.

Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome.

OBJECTIVE: Transcranial magnetic stimulation (TMS) studies showed that patients with cognitive dysfunction and fatigue after COVID-19 exhibit impaired cortical GABAB-ergic activity, as revealed by reduced long-interval intracortical inhibition (LICI). Aim of this study was to test the effects of co-ultramicronized palmitoylethanolamide/luteolin (PEA-LUT), an endocannabinoid-like mediator able to enhance GABA-ergic transmission and to reduce neuroinflammation, on LICI. METHODS: Thirty-nine patients (26 females, mean age 49.9 ± 11.4 years, mean time from infection 296.7 ± 112.3 days) suffering from persistent cognitive difficulties and fatigue after mild COVID-19 were randomly assigned to receive either PEA-LUT 700 mg + 70 mg or PLACEBO, administered orally bid for eight weeks. The day before (PRE) and at the end of the treatment (POST), they underwent TMS protocols to assess LICI. We further evaluate short-latency afferent inhibition (SAI) and long-term potentiation (LTP)-like cortical plasticity. RESULTS: Patients treated with PEA-LUT but not with PLACEBO showed a significant increase of LICI and LTP-like cortical plasticity. SAI remained unaffected. CONCLUSIONS: Eight weeks of treatment with PEA-LUT restore GABAB activity and cortical plasticity in long Covid patients. SIGNIFICANCE: This study confirms altered physiology of the motor cortex in long COVID-19 syndrome and indicates PEA-LUT as a candidate for the treatment of this post-viral condition.

Conscious agency vs. pre-conscious sensory filtering: Disparate suppression of trigeminal blink reflex by self-stimulation and by prepulses.

Modulation of the blink reflex (BR) to supraorbital nerve (SON) stimulation by a weak somatosensory prepulse (sPP) consists of inhibition of R2 and facilitation of R1. Similar BR changes occur with self-stimulation. Our aim was to compare neurophysiological processes underlying both effects. We assessed BR parameters in 18 healthy participants following right SON stimulation either performed by an experimenter (experiment 1A) or following self-stimulation (experiments 1B, 1C). In experiments 1A and 1C, sPPs to digit 2 preceded SON stimuli by 40, 100, 200 and 500 ms. In experiment 1B: self-stimulation was delayed by 40, 100, 200, and 500 ms. In experiment 2, BRs were elicited by an experimenter randomly during a 2-s period before participants applied self-stimulation. In experiment 1, as expected, sPPs caused facilitation of R1 and inhibition of R2, which peaked at 100 ms ISI, similarly in experiments 1A and 1C. Self-stimulation caused a decrease of R2, which was evident in a broad range of time intervals. In experiment 2, R2 was already inhibited at the onset of the 2-s period, while R1 began to rise significantly 1.4 s before self-stimulation. Both effects progressively increased until self-triggering. The results concur with a time-locked gating mechanism of prepulses at brainstem level, whereas self-stimulation modulates BR in a tonic manner, reflecting a cognitive influence due to self-agency.

Altered motor cortex physiology and dysexecutive syndrome in patients with fatigue and cognitive difficulties after mild COVID-19.

BACKGROUND AND PURPOSE: Fatigue and cognitive difficulties are reported as the most frequently persistent symptoms in patients after mild SARS-CoV-2 infection. An extensive neurophysiological and neuropsychological assessment of such patients was performed focusing on motor cortex physiology and executive cognitive functions. METHODS: Sixty-seven patients complaining of fatigue and/or cognitive difficulties after resolution of mild SARS-CoV-2 infection were enrolled together with 22 healthy controls (HCs). Persistent clinical symptoms were investigated by means of a 16-item questionnaire. Fatigue, exertion, cognitive difficulties, mood and 'well-being' were evaluated through self-administered tools. Utilizing transcranial magnetic stimulation of the primary motor cortex (M1) resting motor threshold, motor evoked potential amplitude, cortical silent period duration, short-interval intracortical inhibition, intracortical facilitation, long-interval intracortical inhibition and short-latency afferent inhibition were evaluated. Global cognition and executive functions were assessed with screening tests. Attention was measured with computerized tasks. RESULTS: Post COVID-19 patients reported a mean of 4.9 persistent symptoms, high levels of fatigue, exertion, cognitive difficulties, low levels of well-being and reduced mental well-being. Compared to HCs, patients presented higher resting motor thresholds, lower motor evoked potential amplitudes and longer cortical silent periods, concurring with reduced M1 excitability. Long-interval intracortical inhibition and short-latency afferent inhibition were also impaired, indicating altered GABAB -ergic and cholinergic neurotransmission. Short-interval intracortical inhibition and intracortical facilitation were not affected. Patients also showed poorer global cognition and executive functions compared to HCs and a clear impairment in sustained and executive attention. CONCLUSIONS: Patients with fatigue and cognitive difficulties following mild COVID-19 present altered excitability and neurotransmission within M1 and deficits in executive functions and attention.