Zheng Ye

CAS Center for Excellence in Brain Science and Intelligence Technology

Background Dopaminergic drugs remain the mainstay of Parkinson’s disease therapy but often fail to improve cognitive problems such as impulsivity. This may be due to the loss of other neurotransmitters, including noradrenaline which is linked to impulsivity and response inhibition. We therefore examined the effect of the selective noradrenaline reu...

Background Deficits in maintaining and manipulating sequential information online can occur even in patients with mild Parkinson's disease. The subthalamic nucleus may play a modulatory role in the neural system for sequential working memory, which also includes the lateral prefrontal cortex. Objectives The objective of this study was to investiga...

Maintaining and manipulating sequences online is essential for daily activities such as scheduling a day. In Parkinson's disease (PD), sequential working memory deficits have been associated with altered regional activation and functional connectivity in the basal ganglia. This study demonstrates that the substantia nigra (SN) integrity correlated...

Background Maintaining and manipulating sequences online is essential for language and memory. In Parkinson’s disease (PD), poor performance in sequencing tasks has been associated with basal ganglia dysfunction, especially subthalamic hyperactivity. Objective This study is aimed to investigate the impact of high-frequency subthalamic nucleus (STN...

Brain dopamine may regulate the ability to maintain and manipulate sequential information online. However, the precise role of dopamine remains unclear. This pharmacological fMRI study examined whether and how the dopamine D2/3 receptor agonist pramipexole modulates fronto-subthalamic or fronto-striatal pathways during sequential working memory. Th...

Background Sequential working memory refers to the cognitive ability to maintain and/or manipulate a set of ordered representations within a short period. It remains unclear whether sequential working memory is impaired in patients with young onset Parkinson's disease (YOPD). Objectives The aim of this study is to evaluate the sequential working m...

Graph theory enables a direct quantification of topological properties of any arbitrary network. Its application in neuroscience has unveiled topological changes of brain networks associated with various neurodegenerative diseases. This study used the graph theory to understand speech deficits in patients with Parkinson’s disease (PD). In particula...

The ability to maintain and manipulate sequential information in working memory, referred to as sequential working memory, plays a vital role in our daily life. While research has shown that methamphetamine abuse affects the neural substrates and the overall functioning of working memory, its specific impact on sequential working memory remains unc...

Introduction Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic knowledge, working memory, and executive function. Similar to patients with Parkinson's disease (PD), patients with progressive supranuclear palsy (PSP) scored lower than healthy adults in the well‐established semantic fl...

Purpose Sequential working memory is the ability to maintain and manipulate sequential information at a second time scale. Patients with progressive supranuclear palsy (PSP) or Parkinson's disease (PD) perform poorly in tests that require the flexible arrangement of thoughts or actions. This study investigated whether sequential working memory is d...

Background Theory of mind (ToM), the ability to infer others' mental state, is essential for social interaction among human beings. It has been widely reported that both cognitive (inference of knowledge) and affective (inference of emotion) components of ToM are disrupted in Parkinson's disease (PD). Previous studies usually focused on the involve...

The human brain is distinguished by its ability to perform explicit logical reasoning like transitive inference. This study investigated the functional role of the inferior parietal cortex in transitive inference with functional MRI. Participants viewed premises describing abstract relations among items. They accurately recalled the relationship be...

Explicit logical reasoning, like transitive inference, is a hallmark of human intelligence. This study investigated cortical oscillations and their interactions in transitive inference with EEG. Participants viewed premises describing abstract relations among items. They accurately recalled the relationship between old pairs of items, effectively i...

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation. This stereoelectroencephalography (SEEG) study investigated how the dorsolateral prefrontal cortex (DLPFC) interacts with the hippocampus in the online processing of sequential information. Twenty patients with epilepsy (eight...

The well-established semantic fluency test measures the ability to produce a sequence of spoken words from a particular category within a limited period of time. Like patients with Parkinson’s disease (PD), patients with progressive supranuclear palsy (PSP) tend to produce fewer correct words than age-matched healthy adults. This study further exam...

Parkinson’s disease (PD), a progressive and incurable neurodegenerative disease, has taken a huge economic toll and medical burden on our society. Increasing evidence has shown a strong link between PD and the gut microbiome, but studies on the relationship between the gut microbiome and the severity of PD are limited. In this study, 90 fecal sampl...

As the second-largest neurodegenerative disease in the world, Parkinson’s disease (PD) has brought a severe economic and medical burden to our society. Growing evidence in recent years suggests that the gut microbiome may influence PD, but the exact pathogenesis of PD remains unclear. In addition, the current diagnosis of PD could be inaccurate and...

A long-running debate concerns whether dopamine or noradrenaline deficiency drives response disinhibition in Parkinson’s disease (PD). This study aimed to investigate whether damage to the locus coeruleus (LC) or substantia nigra (SN) might impact inhibitory functions of the fronto-subthalamic hyperdirect or fronto-striatal indirect pathway. Patien...

Parkinson’s disease (PD) is the second most common neurodegenerative disease with mixed motor and non-motor symptoms. Dopaminergic drugs remain the mainstay of therapy for PD. However, some motor symptoms (e.g., gait problems) and a broad range of non-motor symptoms (e.g., cognitive impairment and depression) are often unresponsive to dopaminergic...

Cognitive impairment is a common non-motor symptom in Parkinson's disease (PD), with executive dysfunction being an initial manifestation. We aimed to investigate whether and how longitudinal changes in the prefrontal perfusion correlate with mild cognitive impairment (MCI) in patients with PD. We recruited 49 patients with PD with normal cognition...

Recent evidence has shown potential cognitive benefits in Parkinson’s disease from restoring neuro- transmitter deficits including noradrenergic and serotonergic transmission. Here, we study global and regional brain network organization using task-free imaging, which minimizes performance confounds and the bias towards predetermined networks. Thir...

Idiopathic normal pressure hydrocephalus (iNPH) is a significant cause of the severe cognitive decline in the elderly population. There is no cure for iNPH, but cognitive symptoms can be partially alleviated through cerebrospinal fluid (CSF) diversion. In the early stages of iNPH, cognitive deficits occur primarily in the executive functions and wo...

Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic memory, working memory, and executive function. Semantic disfluency is a common problem in Parkinson’s disease (PD) and Alzheimer’s disease (AD). We demonstrated a graph theoretical analysis of semantic fluency in patients with PD ( N...

Daily activities like preparing a meal rely on the ability to arrange thoughts and actions in the right order. Patients with Parkinson’s disease have difficulties in sequencing tasks. Their deficits in sequential working memory have been associated with basal ganglia dysfunction. Here we demonstrate that altered parietal alpha and theta oscillation...

The ability to follow instructions is critical for learning new skills and may support successful aging. Recent evidence indicates a close link between following instructions and working memory, and that action-based processing at encoding and retrieval can improve this ability. In this study, we examined the ability to follow instructions and the...

The ability to sequence thoughts and actions is impaired in Parkinson’s disease (PD). In PD, a distinct error pattern has been found in the offline performance of sequential working memory. This study examined how PD’s performance of sequential working memory unfolds over time using mouse tracking techniques. Non-demented patients with mild PD (N =...

Pauses, disfluencies and language problems in Alzheimer’s disease can be naturally modeled by fine-tuning Transformer-based pre-trained language models such as BERT and ERNIE. Using this method with pause-encoded transcripts, we achieved 89.6% accuracy on the test set of the ADReSS ( A lzheimer’s D ementia Re cognition through S pontaneous S peech)...

We as humans do not value lives consistently. While we are willing to act for one victim, we often become numb as the number of victims increases. The empathic ability to adopt others’ perspectives is essential for motivating help. However, the perspective-taking ability in our brains seems limited. Using functional MRI, we demonstrated that the co...

MECP2 gain- and loss-of-function in genetically-engineered monkeys recapitulates typical phenotypes in autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remains unknown. Here we report a combination of gene-circuit-behavior analyses including MECP2 co-expression network, locomotive and cognitiv...

Mitochondrial chronic progressive external ophthalmoplegia (CPEO) is a major manifestation of human mitochondrial encephalomyopathies. Previous studies have shown cognitive deficits in patients with mitochondrial diseases. However, these studies often included patients with heterogeneous subtypes of mitochondrial diseases. Here, we aimed to provide...

Maintaining the ability to arrange thoughts and actions in an appropriate serial order is crucial for complex behavior. We aimed to investigate age differences in the fronto-striato-parietal network underlying serial ordering using functional magnetic resonance imaging. We exposed 25 young and 27 older healthy adults to a digit ordering task, where...

Objective Inhibitory control is a key deficit in patients with schizophrenia. This study aims to test whether emotions can facilitate inhibition in patients with schizophrenia when they increase attention to inhibitory process. Method A total of 36 patients with schizophrenia and 36 healthy controls completed an emotional stop-signal task. The tas...

Parkinson’s disease has multiple detrimental effects on motor and cognitive systems in the brain. In contrast to motor deficits, cognitive impairments in Parkinson’s disease are usually not ameliorated, and can even be worsened, by dopaminergic treatments. Recent evidence has shown potential benefits from restoring other neurotransmitter deficits,...

MECP2 gain- and loss-of-function in genetically-engineered monkeys demonstrably recapitulate typical phenotypes in patients, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remains unknown. Using expression profiles of 13,888 genes in 182 macaque neocortical samples, we first show that MECP2 coexpres...

Introduction: The ability to arrange thoughts and actions in an appropriate serial order is impaired in Parkinson's disease (PD). However, it is unclear how serial order is represented and manipulated and how the representation or manipulation is altered in the early stages of PD. We aimed to analyze the pattern of performance errors in serial ord...

The ability to flexibly retrieve and implement sequences of actions is essential to motor learning and planning. Recent research has indicated that serial memory for instructions is influenced by presentation modality (spoken vs. visual demonstration) and recall modality (verbal vs. enacted recall). The present study extended this work by investiga...

Inhibitory control requires precise regulation of activity and connectivity within multiple brain networks. Previous studies have typically evaluated age-related changes in regional activity or changes in interregional interactions. Instead, we test the hypothesis that activity and connectivity make distinct, complementary contributions to performa...

The ability to arrange thoughts and actions in an appropriate serial order (the problem of serial order) is essential to complex behaviors such as language, reasoning and cognitive planning. Patients with Parkinson’s disease (PD) perform poorly in tasks that rely on the successful rearrangement of working memory representations. We hypothesized tha...

The dopamine (DA) system has been implicated in the mediation of cost/benefi t evaluations involved in the intertemporal choices between immediate and delayed rewards. This involvement was further investigated in two studies of normal participants that had to decide between a smaller immediate and a larger delayed reward in a series of 27 decisions...

Interpersonal and intrapersonal differences in brain responses to sexual stimuli have been linked with individuals’ testosterone levels. However, it remains unclear how hormones modulate brain functions underlying sexual arousal. In order to assess the effects of chronic hormonal treatment, we used functional magnetic resonance imaging in a group o...

Developmental dyslexia is a specific deficit in reading and spelling that often persists into adulthood. In the present study, we used slow event-related fMRI and independent component analysis to identify brain networks involved in perception of audio-visual speech in a group of adult readers with dyslexia (RD) and a group of fluent readers (FR)....

Pramipexole is widely prescribed to treat Parkinson's disease but has been reported to cause impulse control disorders such as pathological gambling. Recent neurocomputational models suggested that D2 agonists may distort functional connections between the striatum and the motor cortex, resulting in impaired reinforcement learning and pathological...

Dyslexia is an impairment of reading and spelling that affects both children and adults even after many years of schooling. Dyslexic readers have deficits in the integration of auditory and visual inputs but the neural mechanisms of the deficits are still unclear. This fMRI study examined the neural processing of auditorily presented German numbers...

Empathy is an essential ability for prosocial behavior. Previous imaging studies identified a number of brain regions implicated in affective and cognitive aspects of empathy. In this study, we investigated the neural correlates of empathy from a network perspective using graph theory and beta-series correlations. Two independent data sets were acq...

Listeners interpret utterances by integrating information from multiple sources including word level semantics and world knowledge. When the semantics of an expression is inconsistent with his or her knowledge about the world, the listener may have to search through the conceptual space for alternative possible world scenarios that can make the exp...

Parkinson's disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connec...

Cognitive impairment is common in Parkinson's disease (PD), but often not improved by dopaminergic treatment. New treatment strategies targeting other neurotransmitter deficits are therefore of growing interest. Imaging the brain at rest ('task-free') provides the opportunity to examine the impact of a candidate drug on many of the brain networks t...

View largeDownload slide Impairments in response inhibition in Parkinson’s disease may reflect loss of noradrenaline and impaired fronto-subcortical connectivity. Rae et al. show that the noradrenaline reuptake inhibitor atomoxetine can restore functional connectivity in the inhibition network. Individual treatment responses depend on disease seve...

Cognitive impairment is common in Parkinson's disease (PD), but often not improved by dopaminergic treatment. New treatment strategies, targeting other neurotransmitter deficits are therefore of growing interest. Imaging the brain at rest ('task-free') provides the opportunity to examine the impact of a candidate drug on many of the brain networks...

Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive mode...

Pathological gambling is thought to result from a shift of balance between two competing neurobiological mechanisms: on the one hand the reward system involved in the regulation of the urge to get rewards and on the other hand the top-down control system. Fifteen pathological gamblers (PG) and fifteen healthy controls (HC) were studied in an event-...

Background / Purpose: Motor inhibition deficits occur in Parkinson’s disease (PD) even in the absence of impulse control disorders. Their aetiology is multifactorial, including the loss of noradrenergic and seroton-ergic projects to the forebrain and structural change in fronto-striatal circuits. Main conclusion: Our study showed that increasi...

Impulsivity is common in Parkinson's disease even in the absence of impulse control disorders. It is likely to be multifactorial, including a dopaminergic 'overdose' and structural changes in the frontostriatal circuits for motor control. In addition, we proposed that changes in serotonergic projections to the forebrain also contribute to response...

A set of cortical and sub-cortical brain structures has been linked with sentence-level semantic processes. However, it remains unclear how these brain regions are organized to support the semantic integration of a word into sentential context. To look into this issue, we conducted a functional magnetic resonance imaging (fMRI) study that required...

Speech comprehension relies on auditory as well as visual information, and is enhanced in healthy subjects, when audiovisual information is present. Patients with schizophrenia have been reported to have problems regarding this audiovisual integration process, but little is known about which underlying neural processes are altered. Functional magne...

Vestibular neuritis (VN) is a sudden peripheral unilateral vestibular failure with often persistent head movement-related dizziness and unsteadiness. Compensation of asymmetrical activity in the primary peripheral vestibular afferents is accomplished by restoration of impaired brainstem vestibulo-ocular and vestibulo-spinal reflexes, but presumably...

Background / Purpose: Impulsivity in Parkinson’s disease (PD) is common even in the absence of impulse control disorders and is likely to be multifactorial. In addition to dopaminergic “overdose” and structural changes in the frontostriatal circuits for motor control, changes in serotonergic projections to the forebrain may also exacerbate the im...

It is estimated that 759 million individuals worldwide are illiterate, i.e. they cannot read or write properly. With 95%, the majority of the illiterate population lives in developing countries. In most cases, these individuals did not attend school and, therefore, did not have the chance to acquire any skills in reading and writing. They are refer...

Introduction Natural speech perception relies on both, auditory and visual information. Both sensory channels provide redundant and complementary information, such that speech perception is enhanced in healthy subjects, when both information channels are present. Objectives Patients with schizophrenia have been reported to have problems regarding...

Women show higher sensitivity than men to emotional and social cues and are therefore better in showing empathy with others and in deciphering other's intentions and mental states. These sex differences have been linked to hormonal levels. However, it remains unclear how hormones modulate neural mechanisms underlying empathic processes. To assess e...

Temporal connectives (before/after) give us the freedom to describe a sequence of events in different orders. Studies have suggested that 'before-initiating' sentences, in which events are expressed in an order inconsistent with their actual order of occurrence, might need additional computation(s) during comprehension. The results of independent c...

Children can learn the meaning of a new word from context during normal reading or listening, without any explicit instruction. It is unclear how such meaning acquisition is supported and achieved in human brain. In this functional magnetic resonance imaging (fMRI) study we investigated neural networks supporting word learning with a functional con...

An initial stage of speech production is conceptual planning, where a speaker determines which information to convey first (the linearization problem). This fMRI study investigated the linearization process during the production of "before" and "after" sentences. In "after" sentences, a series of events is expressed in the order of event occurrence...

Pramipexole is widely prescribed to treat Parkinson's disease. It has been found to cause impulse control disorders such as pathological gambling. To examine how pramipexole modulates the network of reward anticipation, we carried out a pharmacological functional magnetic resonance imaging study with a double-blind, within-subject design. During th...