Brain stimulation for cognitive impairments in psychiatric and neurodegenerative disorders

Cognitive impairment is a prevalent symptom in psychiatric and neurodegenerative diseases, leading to significant disability and impairing daily functioning. Psychological disorders with major cognitive impairments include depression, schizophrenia, anxiety, bipolar disorder, and PTSD. In addition, cognitive deficits are also common in neurodegenerative diseases like Alzheimer's (AD), mild cognitive impairment (MCI), Parkinson's (PD), Huntington's (HD), and traumatic brain injury (TBI). Individuals experiencing psychiatric symptoms have a four times higher risk of developing neurodegenerative diseases. 65% of patients with neurodegenerative disorders exhibit affective symptoms during disease
progression. Cognitive impairment and dementia affect millions globally, with numbers expected to rise sharply due to the limited efficacy of current pharmacotherapies. Furthermore, persistent
cognitive decline, even after therapeutic intervention, increases the risk of recurrence and relapse, which further highlights the urgent need for novel therapies.

Brain stimulation-based therapies could help bridge this gap and significantly improve cognition outcomes in psychiatric and neurodegenerative disorders by enhancing progressive plasticity. These therapies include non-invasive and invasive brain stimulation methods. Non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) and direct current stimulation (DCS), promote global plasticity, potentially benefiting cognition. For instance, non-invasive brain stimulations are effective in managing cognitive deficits in treatment-resistant depression, stroke, AD,
MCI, PD, and aging.

Invasive brain stimulation therapies, such as deep brain stimulation (DBS), involve the electrical stimulation of specific brain regions via a pulse generator. DBS uniquely manipulates neuronal circuits to induce progressive plasticity and reverse cognitive decline. The fundamental mechanisms include excitation or inhibition of networks depending on frequency, signal blockage, and synaptic filtering. While these effects are acute, DBS produces long-lasting morphological changes, such as enhanced spine density and dendritic arborization. Targeting areas within the Papez circuit offer robust cognitive enhancement and enduring plasticity. Interestingly, DBS-induced plasticity can be harnessed to promote cognitive remission in various neurological disorders, including depression, AD, epilepsy, PD, and other neurodegenerative disorders. Thus, studies suggest that brain stimulation might have therapeutic potential for managing cognitive impairments in neurological disorders. However, there is a pressing need for more mechanistic studies to understand the molecular underpinnings of cognitive remission following brain stimulation.

This research topic aims to showcase recent findings and summarize the latest advancements in mechanisms of actions of brain stimulation and associated plasticity, as well as their effectiveness in improving cognitive impairments. We welcome the submission of original research, literature reviews, and meta-analyses concerning the impact of brain stimulation on cognitive deficits.

To gain further insights into the mechanisms of actions and beneficial effects of brain stimulation, contributions from a broad spectrum of research disciplines are invited, including:

• Clinical studies or case reports investigating the effects of brain stimulation on cognitive functions
• Animal studies focused on understanding the therapeutic potential of brain stimulation in various psychiatric and neurodegenerative disorders
• Clinical and animal studies exploring mechanistic effects of brain stimulation
• Comprehensive literature reviews and meta-analyses on brain stimulation and cognitive remission

Keywords: Cognitive Impairment, Brain Stimulation Therapy, Neurodegenerative Disorders, Psychiatric Disorders, Neuroplasticity, Transcranial Magnetic Stimulation (TMS)

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