Assessment of Cortical Plasticity in Schizophrenia by Transcranial Magnetic Stimulation

Neural plasticity refers to the capability of the brain to modify its structure and/or function and organization in response to a changing environment. Evidence shows that disruption of neuronal plasticity and altered functional connectivity between distinct brain networks contribute significantly to the pathophysiological mechanisms of schizophrenia. Transcranial magnetic stimulation has emerged as a noninvasive brain stimulation tool that can be utilized to investigate cortical excitability with the aim of probing neural plasticity mechanisms. In particular, in pathological disorders, such as schizophrenia, cortical dysfunction, such as an aberrant excitatory-inhibitory balance in cortical networks, altered cortical connectivity, and impairment of critical period timing are very important to be studied using different TMS paradigms. Studying such neurophysiological characteristics and plastic changes would help in elucidating different aspects of the pathophysiological mechanisms underlying schizophrenia. This review attempts to summarize the findings of available TMS studies with diagnostic and characterization aims, but not with therapeutic purposes, in schizophrenia. Findings provide further evidence of aberrant excitatory-inhibitory balance in cortical networks, mediated by neurotransmitter pathways such as the glutamate and GABA systems. Future studies with combining techniques, for instance, TMS with brain imaging or molecular genetic typing, would shed light on the characteristics and predictors of schizophrenia.

Utility of Transcranial Magnetic Simulation in Studying Upper Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is characterised by progressive dysfunction of the upper and lower motor neurons. The disease can evolve over time from focal limb or bulbar onset to involvement of other regions. There is some clinical heterogeneity in ALS with various phenotypes of the disease described, from primary lateral sclerosis, progressive muscular atrophy and flail arm/leg phenotypes. Whilst the majority of ALS patients are sporadic in nature, recent advances have highlighted genetic forms of the disease. Given the close relationship between ALS and frontotemporal dementia, the importance of cortical dysfunction has gained prominence. Transcranial magnetic stimulation (TMS) is a noninvasive neurophysiological tool to explore the function of the motor cortex and thereby cortical excitability. In this review, we highlight the utility of TMS and explore cortical excitability in ALS diagnosis, pathogenesis and insights gained from genetic and variant forms of the disease.

Intravenous methadone causes acute toxic and delayed inflammatory encephalopathy with persistent neurocognitive impairments

Background The mu-opioid agonist methadone is administered orally and used in opioid detoxification and in the treatment of moderate-to-severe pain. Acute oral methadone–use and –abuse have been associated with inflammatory and toxic central nervous system (CNS) damage in some cases and cognitive deficits can develop in long-term methadone users. In contrast, reports of intravenous methadone adverse effects are rare. Case presentation Here, we report a patient who developed acute bilateral hearing loss, ataxia and paraparesis subsequently to intravenous methadone-abuse. While the patient gradually recovered from these deficits, widespread magnetic resonance imaging changes progressed and delayed-onset encephalopathy with signs of cortical dysfunction persisted. This was associated with changes in the composition of monocyte and natural killer cell subsets in the cerebrospinal fluid. Conclusion This case suggests a potential bi-phasic primary toxic and secondary inflammatory CNS damage induced by intravenous methadone.

Resting-State Cerebello-Cortical Dysfunction in Parkinson's Disease

Purpose: Recently, the cerebellum's role in Parkinson's disease (PD) has been highlighted. Therefore, this study sought to test the hypothesis that functional connectivity (FC) between cerebellar and cortical nodes of the resting-state networks differentiates PD patients from controls by scanning participants at rest using functional magnetic resonance imaging (fMRI) and investigating connectivity of the cerebellar nodes of the resting-state networks.Materials and Methods: Sixty-two PD participants off medication for at least 12 h and 33 normal controls (NCs) were scanned at rest using blood oxygenation level-dependent fMRI scans. Motor and cognitive functions were assessed with the Movement Disorder Society's Revision of the Unified Parkinson's Disease Rating Scale III and Montreal Cognitive Assessment, respectively. Connectivity was investigated with cerebellar seeds defined by Buckner's 7-network atlas.Results: PD participants had significant differences in FC when compared to NC participants. Most notably, PD patients had higher FC between cerebellar nodes of the somatomotor network (SMN) and the corresponding cortical nodes. Cognitive functioning was differentially associated with connectivity of the cerebellar SMN and dorsal attention network. Further, cerebellar connectivity of frontoparietal and default mode networks correlated with the severity of motor function.Conclusion: Our study demonstrates altered cerebello-cortical FC in PD, as well as an association of this FC with PD-related motor and cognitive disruptions, thus providing additional evidence for the cerebellum's role in PD.

Benefits of post-stroke telerehabilitation

Introduction: Stroke was responsible for 139.4 million cases of global disability in 2019, many of which require rehabilitation. Telerehabilitation has emerged as a promising remote therapy aimed at improving the deficits resulting from stroke. Objective: To compare the benefits of telerehabilitation with the usual methods of rehabilitation in post-stroke patients. Methodology: In April 2021, a literature review including systematic reviews of studies in humans, available in full and published in the last 5 years was executed on MedLine using the descriptors “stroke”, “telerehabilitation” and their MeSH variations. Results: The first selected article revealed that post-stroke telerehabilitation resulted in less expenses and was associated with comparable improvements to the standard treatment group in the recovery of motor deficits, cortical dysfunction and depression. The second review concluded that telerehabilitation was equal to or greater than usual rehabilitation for improvements in daily living and psychological status and restoration of quality of life and motor performance. The third study found that telerehabilitation achieved similar results to face-to-face therapy and usual care on improving daily life. The fourth article reinforced the benefits of telerehabilitation on several outcomes, although current evidence is limited. Conclusion: Telerehabilitation can be an adequate alternative to the care of post-stroke patients, however, further studies are needed to establish the benefits it provides.

Cortical Circuit Dysfunction in a Mouse Model of Alpha-synucleinopathy in Vivo

Considerable fluctuations in cognitive performance and eventual dementia are an important characteristic of alpha-synucleinopathies, such as Parkinson’s disease (PD) and Lewy Body dementia (LBD) and are linked to cortical dysfunction. The presence of misfolded and aggregated alpha-synuclein (a-syn) in the cerebral cortex of patients has been suggested to play a crucial role in this process. However, the consequences of a-syn accumulation on the function of cortical networks at cellular resolution in vivo are largely unknown. Here we used the striatal seeding model in wildtype mice in order to induce robust a-synuclein pathology in the cerebral cortex. 9 months after a single intrastriatal injection of a-syn preformed fibrils, we performed in vivo two-photon calcium imaging in awake mice. We observed profound alterations of the function of layer 2/3 cortical neurons in somatosensory cortex (S1), as witnessed by an enhanced response to whisking and increased synchrony, accompanied by a decrease in baseline Ca2+ levels. Stereological analyses revealed a reduction in GAD67-positive inhibitory cells in S1 in PFF-injected brains. These findings point to a disturbed excitation/inhibition balance as an important driver of circuit dysfunction in alpha-synucleinopathies, which may underly cognitive changes in these diseases.

Transient cortical circuits match spontaneous and sensory-driven activity during development

At the earliest developmental stages, spontaneous activity synchronizes local and large-scale cortical networks. These networks form the functional template for the establishment of global thalamocortical networks and cortical architecture. The earliest connections are established autonomously. However, activity from the sensory periphery reshapes these circuits as soon as afferents reach the cortex. The early-generated, largely transient neurons of the subplate play a key role in integrating spontaneous and sensory-driven activity. Early pathological conditions—such as hypoxia, inflammation, or exposure to pharmacological compounds—alter spontaneous activity patterns, which subsequently induce disturbances in cortical network activity. This cortical dysfunction may lead to local and global miswiring and, at later stages, can be associated with neurological and psychiatric conditions.