Time cognition is an essential function of human life, and the impairment affects a variety of behavioral patterns. Neuropsychological approaches have been widely demonstrated that Parkinson's ...disease (PD) impairs time cognitive processing. Many researchers believe that time cognitive deficits are due to the basal ganglia, including the striatum or subthalamic nucleus, which is the pathomechanism of PD, and are considered to produce only transient recovery due to medication effects. In this perspective, we focus on a compensatory property of brain function based on the improved time cognition independent of basal ganglia recovery and an overlapping structure on the neural network based on an improved inhibitory system by time cognitive training, in patients with PD. This perspective may lead to restoring multiple functions through single function training.
Noncoding repeat expansions cause various neuromuscular diseases, including myotonic dystrophies, fragile X tremor/ataxia syndrome, some spinocerebellar ataxias, amyotrophic lateral sclerosis and ...benign adult familial myoclonic epilepsies. Inspired by the striking similarities in the clinical and neuroimaging findings between neuronal intranuclear inclusion disease (NIID) and fragile X tremor/ataxia syndrome caused by noncoding CGG repeat expansions in FMR1, we directly searched for repeat expansion mutations and identified noncoding CGG repeat expansions in NBPF19 (NOTCH2NLC) as the causative mutations for NIID. Further prompted by the similarities in the clinical and neuroimaging findings with NIID, we identified similar noncoding CGG repeat expansions in two other diseases: oculopharyngeal myopathy with leukoencephalopathy and oculopharyngodistal myopathy, in LOC642361/NUTM2B-AS1 and LRP12, respectively. These findings expand our knowledge of the clinical spectra of diseases caused by expansions of the same repeat motif, and further highlight how directly searching for expanded repeats can help identify mutations underlying diseases.
Highlights ► We review the pathophysiology of basal ganglia (BG) dysfunction in Parkinson’s disease (PD) based on saccade performance. ► Saccade abnormalities in PD may be caused by the excessive ...inhibition of the superior colliculus (SC) due to the increased BG output and decreased activity of the frontal cortex-BG circuit, as well as impaired suppression of reflexive saccades that may be explained by the “leaky” suppression of the SC. ► Treatment of PD, such as L-dopa therapy and deep brain stimulation, works by normalizing these abnormal BG functions, but in different ways.
Non-invasive and readily implemented in the clinical setting, eye movement studies have been conducted extensively not only in healthy human subjects but also in patients with neurological disorders. ...The purpose of saccade studies is to “read out” the pathophysiology underlying neurological disorders from the saccade records, referring to known primate physiology. In the current review, we provide an overview of studies in which we attempted to elucidate the patterns of saccade abnormalities in over 250 patients with neurological disorders, including cerebellar ataxia and brainstem pathology due to neurodegenerative disorders, and what they tell about the pathophysiology of patients with neurological disorders. We also discuss how interventions, such as deep brain stimulation, affect saccade performance and provide further insights into the workings of the oculomotor system in humans. Finally, we argue that it is important to understand the functional significance and behavioral correlate of saccade abnormalities in daily life, which could require eye tracking methodologies to be performed in settings similar to daily life.
Epilepsy is a common neurological disorder, and mutations in genes encoding ion channels or neurotransmitter receptors are frequent causes of monogenic forms of epilepsy. Here we show that abnormal ...expansions of TTTCA and TTTTA repeats in intron 4 of SAMD12 cause benign adult familial myoclonic epilepsy (BAFME). Single-molecule, real-time sequencing of BAC clones and nanopore sequencing of genomic DNA identified two repeat configurations in SAMD12. Intriguingly, in two families with a clinical diagnosis of BAFME in which no repeat expansions in SAMD12 were observed, we identified similar expansions of TTTCA and TTTTA repeats in introns of TNRC6A and RAPGEF2, indicating that expansions of the same repeat motifs are involved in the pathogenesis of BAFME regardless of the genes in which the expanded repeats are located. This discovery that expansions of noncoding repeats lead to neuronal dysfunction responsible for myoclonic tremor and epilepsy extends the understanding of diseases with such repeat expansion.
Japanese kanji (morphograms) have two ways of reading:
on
-reading (Chinese-style pronunciation) and
kun
-reading (native Japanese pronunciation). It is known that some Japanese patients with ...semantic dementia read kanji with
on
-reading but not with
kun
-reading. To characterize further reading impairments of patients with semantic dementia, we analyzed data from a total of 9 patients who underwent reading and writing tests of kanji and kana (Japanese phonetic writing) and
on
-
kun
reading tests containing two-character kanji words with
on
-
on
reading,
kun
-
kun
reading, and specific (so-called Jukujikun or irregular
kun
) reading. The results showed that
on
-reading preceding (pronouncing first with
on
-reading) and
kun
-reading deletion (inability to recall
kun
-reading) were observed in nearly all patients. In the
on
-
kun
reading test,
on
-reading (57.6% correct),
kun
-reading (46.6% correct), and specific-reading (30.0% correct) were more preserved in this decreasing order (phonology-to-semantics gradient), although
on
-reading and
kun
-reading did not significantly differ in performance, according to a more rigorous analysis after adjusting for word frequency (and familiarity). Furthermore,
on
-substitution (changing to
on
-reading) errors in
kun
-reading words (27.0%) were more frequent than
kun
-substitution (changing to
kun
-reading) errors in
on
-reading words (4.0%). These results suggest that
kun
-reading is more predominantly disturbed than
on
-reading, probably because
kun
-reading and specific-reading are closely associated with the meaning of words.
At each time in our life, we choose one or few behaviors, while suppressing many other behaviors. This is the basic mechanism in the basal ganglia, which is done by tonic inhibition and selective ...disinhibition. Dysfunctions of the basal ganglia then cause 2 types of disorders (difficulty in initiating necessary actions and difficulty in suppressing unnecessary actions) that occur in Parkinson’s disease. The basal ganglia generate such opposite outcomes through parallel circuits: The direct pathway for initiation and indirect pathway for suppression. Importantly, the direct pathway processes good information and the indirect pathway processes bad information, which enables the choice of good behavior and the rejection of bad behavior. This is mainly enabled by dopaminergic inputs to these circuits. However, the value judgment is complex because the world is complex. Sometimes, the value must be based on recent events, thus is based on short-term memories. Or, the value must be based on historical events, thus is based on long-term memories. Such memory-based value judgment is generated by another parallel circuit originating from the caudate head and caudate tail. These circuit-information mechanisms allow other brain areas (e.g., prefrontal cortex) to contribute to decisions by sending information to these basal ganglia circuits. Moreover, the basal ganglia mechanisms (i.e., what to choose) are associated with cerebellum mechanisms (i.e., when to choose). Overall, multiple levels of parallel circuits in and around the basal ganglia are essential for coordinated behaviors. Understanding these circuits is useful for creating clinical treatments of disorders resulting from the failure of these circuits.
•Velocity saccade profile of progressive supranuclear palsy (PSP) showed reduced peak velocity and prolonged duration.•The change was most prominent in the cerebellar subtype of PSP and correlated ...with disease severity.•The velocity profile can be used as an indicator of not only brainstem but also cerebellar pathology in various PSP subtypes.
To study whether the velocity profile of horizontal saccades could be used as an indicator of brainstem and cerebellar output dysfunction, depending on progressive supranuclear palsy (PSP) subtype.
We compared the velocity profiles in 32 PSP patients of various subtypes with 38 age-matched normal subjects, including Richardson syndrome (RS), PSP-parkinsonism (PSPp), and pure akinesia (PAGF), and cerebellar subtypes of PSP (PSPc).
PSP patients showed reduced peak velocity along with increased duration, especially in the deceleration phase. This alteration was more prominent for larger target eccentricities (20–30 degrees), and correlated with disease severity. The changes were most pronounced in PSPc patients, with irregular increases and decreases in velocity profile, followed by RS patients, whereas the change was smaller in PSPp and normal in PAGF patients.
Saccade velocity profile can be an indicator of brainstem and/or cerebellar output. Altered velocity profile of PSP patients may reflect the pathology in the brainstem, but may also reflect cerebellar dysfunction, most prominently in PSPc.
Saccade velocity profile may be used as an indicator of latent cerebellar/brainstem dysfunction.
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