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Abstract Visual hallucinations (VH) and pareidolia, a type of minor hallucination, share common underlying mechanisms. However, the similarities and differences in their brain regions remain poorly understood in Parkinson’s disease (PD). A total of 104 drug-naïve PD patients underwent structural MRI and were assessed for pareidolia using the Noise Pareidolia Test (NPT) were enrolled. Subcortical gray matter volume and cortical surface volume were analyzed using the FreeSurfer software. Structural analyses revealed associations between NPT scores and atrophy in the right thalamus, right hippocampus, right temporal cortex, and right orbitofrontal cortex in all PD participants. These results were almost the same after adjusting for right-handed 97 patients with PD. It is considered that hallucinations in patients with PD are related to altered integration of sensory input (bottom-up) and prior knowledge (top-down) within the visual system. Our findings indicate that pareidolia in PD involves both bottom-up (thalamus and temporal cortex) and top-down (orbitofrontal cortex) processing disturbances; in contrast, VH predominantly involves bottom-up but not top-down regions. Understanding these distinctions could aid in the development of targeted interventions for hallucinations in patients with PD.

Abstract Amyotrophic lateral sclerosis (ALS) is a disease that affects motor neurons and has a poor prognosis. We focused on TAR DNA-binding protein 43 kDa (TDP-43), which is a common component of neuronal inclusions in many ALS patients. To analyze the contribution of TDP-43 mutations to ALS in human cells, we first introduced TDP-43 mutations into healthy human iPSCs using CRISPR/Cas9 gene editing technology, induced the differentiation of these cells into motor and sensory neurons, and analyzed factors that are assumed to be altered in or associated with ALS (cell morphology, TDP-43 localization and aggregate formation, cell death, TDP-43 splicing function, etc.). We aimed to clarify the pathological alterations caused solely by TDP-43 mutation, i.e., the changes in human iPSC-derived neurons with TDP-43 mutation compared with those with the same genetic background except TDP-43 mutation. Oxidative stress induced by hydrogen peroxide administration caused the death of TDP-43 mutant-expressing motor neurons but not in sensory neurons, indicating the specific vulnerability of human iPSC-derived motor neurons with TDP-43 mutation to oxidative stress. In our model, we observed aggregate formation in a small fraction of TDP-43 mutant-expressing motor neurons, suggesting that aggregate formation seems to be related to ALS pathology but not the direct cause of cell death. This study provides basic knowledge for elucidating the pathogenesis of ALS and developing treatments for the disease.

Drooling is a common and troublesome symptom in Parkinson's disease (PD), but the underlying pathophysiological mechanisms remain unclear. Studies in recent years have suggested each part of the striatum has different functions. Here, we investigated the association between drooling and dopaminergic dysfunction in each part of the striatum among patients with de novo PD. We retrospectively reviewed consecutive enrolled patients who had been diagnosed with de novo PD. Drooling was assessed using the Non-Motor Symptoms Questionnaire item 1. Uptake of 123I-ioflupane in each part of the striatum bilaterally on single positron emission computed tomography was quantitatively evaluated in PD patients with or without drooling. We enrolled 44 PD patients, comprising 12 with drooling and 32 without drooling. Significantly lower uptake of 123I-ioflupane was identified among patients with drooling compared to patients without drooling in the right anterior putamen (median 0.49 vs 0.74, p = 0.004) and right posterior putamen (median 0.23 vs 0.41, p = 0.02). These findings suggest that in PD patients, drooling is associated with dopaminergic dysfunction in the right putamen.

The level of α-synuclein, a component of Lewy bodies, in cerebrospinal fluid (CSF) in Parkinson's disease (PD) has attracted recent attention. Most meta-analyses conclude that CSF levels of α-synuclein are decreased in PD. Patients with PD present with cognitive impairment, including frontal/executive dysfunction in the early phase and later emergence of visuospatial and mnemonic deficits. To examine whether CSF α-synuclein levels reflect the activities of various cognitive domains, we reviewed reports examining the association of these levels with cognitive performance in each domain in PD. Among 13 cross-sectional studies, five showed that a lower CSF α-synuclein level was associated with worse cognitive function. In four of these five reports, frontal/executive function showed this association, suggesting a link of the pathophysiology with Lewy bodies. In three other reports, a higher CSF α-synuclein level was associated with temporal-parieto-occipital cognitive deterioration such as memory. In the other five reports, the CSF α-synuclein level did not correlate with cognitive performance for any domain. In four longitudinal studies, a higher baseline CSF α-synuclein level was associated with a worse cognitive outcome, including cognitive processing speed, visuospatial function and memory in two, but not with any cognitive outcome in the other two. The different associations may reflect the heterogeneous pathophysiology in PD, including different pathogenic proteins, neurotransmitters. Thus, more studies of the association between cognitive domains and CSF levels of pathogenic proteins are warranted.

The intensity and frequency of harmful algal blooms (HABs) have increased, posing a threat to human seafood resources due to massive kills of cultured fish and toxin contamination of bivalves. In recent years, bacteria that inhibit the growth of HAB species were found to be densely populated on the biofilms of some macroalgal species, indicating the possible biological control of HABs by the artificial introduction of macroalgal beds. In this study, an artificially created Ulva pertusa bed using mobile floating cages and a natural macroalgal bed were studied to elucidate the distribution of algal growth-limiting bacteria (GLB). The density of GLB affecting fish-killing raphidophyte Chattonella antiqua, and two harmful dinoflagellates, were detected between 106 and 107 CFU g−1 wet weight on the biofilm of artificially introduced U. pertusa and 10 to 102 CFU mL−1 from adjacent seawater; however, GLB found from natural macroalgal species targeted all tested HAB species (five species), ranging between 105 and 106 CFU g−1 wet weight in density. These findings provide new ecological insights of GLB at macroalgal beds, and concurrently demonstrate the possible biological control of HABs by artificially introduced Ulva beds.