Parvalbumin is a calcium-binding protein present in inhibitory interneurons that play an essential role in regulating many physiological processes, such as intracellular signaling and synaptic transmission. Changes in parvalbumin expression are deeply related to epilepsy, which is considered one of the most disabling neuropathologies. Epilepsy is a complex multi-factor group of disorders characterized by periods of hypersynchronous activity and hyperexcitability within brain networks. In this scenario, inhibitory neurotransmission dysfunction in modulating excitatory transmission related to the loss of subsets of parvalbumin-expressing inhibitory interneuron may have a prominent role in disrupted excitability. Some studies also reported that parvalbumin-positive interneurons altered function might contribute to psychiatric comorbidities associated with epilepsy, such as depression, anxiety, and psychosis. Understanding the epileptogenic process and comorbidities associated with epilepsy have significantly advanced through preclinical and clinical investigation. In this review, evidence from parvalbumin altered function in epilepsy and associated psychiatric comorbidities were explored with a translational perspective. Some advances in potential therapeutic interventions are highlighted, from current antiepileptic and neuroprotective drugs to cutting edge modulation of parvalbumin subpopulations using optogenetics, designer receptors exclusively activated by designer drugs (DREADD) techniques, transcranial magnetic stimulation, genome engineering, and cell grafting. Creating new perspectives on mechanisms and therapeutic strategies is valuable for understanding the pathophysiology of epilepsy and its psychiatric comorbidities and improving efficiency in clinical intervention.

Cognitive impairments and psychiatric symptoms affect up to half of temporal lobe epilepsy patients and are often more detrimental to their quality of life than the seizures themselves. Evidence indicates that the neurobiology of epileptogenesis shares common pathophysiological mechanisms with psychiatric comorbidities. However, these mechanisms and how they relate to specific behavioral alterations are unclear. We hypothesized that a dysfunctional communication between the hippocampus (HPC) and the prefrontal cortex (PFC), as a consequence of epileptogenesis, would be linked to behavioral and cognitive symptoms observed in the comorbidities of temporal lobe epilepsy. Here, we performed a multilevel study to investigate behavioral, electrophysiological, histopathological, and neurochemical long-term consequences of early-life Status Epilepticus in male rats. We found that adult animals submitted to early-life seizure (ELS) presented behavioral alterations typically found in animal models of psychosis, such as hyperlocomotion, reduction in sensorimotor gating, working memory deficits, and sensitivity to psychostimulants. Noteworthy, ELS rats did not exhibit neuronal loss. Instead, sensorimotor alterations were associated with increased neuroinflammation, as verified by glial fibrillary acidic protein (GFAP) expression, and altered dopamine neurotransmission. Surprisingly, cognitive deficits were linked to an aberrant increase in HPC-PFC long-term potentiation (LTP). Furthermore, ELS rats displayed an abnormal brain state during active behavior characterized by oscillatory dynamics oddly similar to REM sleep. Our results point to impaired hippocampal-prefrontal network dynamics as a possible pathophysiological mechanism by which an epileptogenic insult can cause behavioral changes without neuronal loss. These convergent patterns of dysfunctional activity between epileptogenesis and psychosis bear translational implications for understanding psychiatric and cognitive comorbidities in epilepsy.

This study aimed to explore the impact of anxiety and functional impairment measures on a sample of undergraduate psychology students. Learning performance was evaluated during the emergency remote teaching during the first wave and in the post-vaccination period of the COVID-19 pandemic in Brazil. Data modeling revealed that psychometric indicators of severe anxiety and severe functional impairment predicted students with lower learning performance in pairs of pre- and post-test multiple-choice questions. This is the first study to highlight the association between measures of generalized anxiety and functional impairment having a deleterious impact on students’ learning performance. This manuscript highlights that educational policies should be designed to deal with students’ mental health under stressful situations.

Discerning safety from threat and positive or negative outcomes of adversity are fundamental for mental health. Many brain structures have been implicated in both adaptive and maladaptive stress coping, however, how multiple regions function together as a network in the processing of this information is unclear. Here, we recorded local field potentials from seven regions of the mesolimbic-hippocampal-prefrontal cortical network (MLHFC) of male rats during the conditioning of a stimulus (CS) to the absence (safety) and then to the anticipation (fear) of footshocks, and during an approach-avoidance task. We developed a machine learning pipeline to investigate the relevance of specific features of oscillatory activity in the decoding of fear versus safety and approach versus avoidance. We found that decoding performance increased as a function of the number of brain regions included, reaching the best classification if all regions were considered. In addition, the best decoding was obtained from frequencies within the theta range (4-10 Hz). Remarkably, decoder models showed robust generalization within but not between individuals. Nevertheless, we were also able to identify patterns of MLHFC activity that decoded stress coping states from all rats. These patterns were characterized by increased brain-wide theta synchrony during fear and preceding approach. Our results indicate that stress coping information is encoded at the brain-wide level and highlight individual variability in this neural processing. Our findings also suggest that MLHFC network theta activity underlies active stress coping with both aversive and positive motivational valences.