Developmental trajectories of spatial-sequential and spatial-simultaneous working memory in Down syndrome.

BACKGROUND: Working memory (WM) is generally considered an area of weakness in the cognitive profile associated with Down syndrome (DS). The great majority of studies explored WM in this population through a comparison with typical development (TD) on the basis of mental age or developmental level. However, it is also relevant to understand how these skills develop and whether such development could be more related to chronological or developmental level. In the present study, we explored cross-sectional developmental trajectories of spatial-sequential and spatial-simultaneous WM in individuals with DS across chronological age and developmental level. Typically developing children (TD) of similar mental age were also included as a comparison group. METHODS: Eighty-four individuals with DS (aged between 7 and 30 years) and 327 children with TD (aged between 4 and 8 years) were administered with tasks to assess spatial-sequential and spatial-simultaneous WM, together with tasks to assess both general verbal and spatial developmental levels. RESULTS AND CONCLUSION: Performance in spatial-simultaneous WM task was lower compared with spatial-sequential WM task in both groups. In the case of individuals with DS, the developmental trajectories of chronological age are better described through a segmented model showing increased performance until approximately 13 years of age, followed by a rather flat progress. In the case of TD children, developmental trajectories are better described through a linear model in the spatial-simultaneous WM task when chronological age is considered; in the spatial-sequential WM, the increase in performance with age was however characterised by a discontinuity at age 6. The increase in performance followed a linear pattern in both groups (DS and TD) without substantial differences between the types of measure used (verbal vs. spatial) when the developmental level is considered.

The Role of the Subthalamic Nucleus in Sequential Working Memory in De Novo Parkinson's Disease.

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 investigate neural markers of sequential working memory deficits in patients with de novo Parkinson's disease. METHODS: A total of 50 patients with de novo Parkinson's disease and 50 healthy controls completed a digit ordering task during functional magnetic resonance imaging scanning. The task separated the maintenance ("pure recall") and manipulation of sequences ("reorder & recall" vs "pure recall"). RESULTS: In healthy controls, individual participants' task accuracy was predicted by the regional activation and functional connectivity of the subthalamic nucleus. Healthy participants who showed lower subthalamic nucleus activation and stronger subthalamic nucleus connectivity with the putamen performed more accurately in maintaining sequences ("pure recall"). Healthy participants who showed greater ordering-related subthalamic nucleus activation change exhibited smaller accuracy costs in manipulating sequences ("reorder & recall" vs "pure recall"). Patients performed less accurately than healthy controls, especially in "reorder & recall" trials, accompanied by an overactivation in the subthalamic nucleus and a loss of synchrony between the subthalamic nucleus and putamen. Individual patients' task accuracy was predicted only by the subthalamic nucleus connectivity. The contribution of the subthalamic nucleus activation or activation change was absent. We observed no change in the lateral prefrontal cortex. CONCLUSIONS: The overactivation and weakened functional connectivity of the subthalamic nucleus are the neural markers of sequential working memory deficits in de novo Parkinson's disease. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Theta Oscillations Support Prefrontal-hippocampal Interactions in Sequential Working Memory.

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 women, age 27.6 ± 8.2 years) completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus. Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise (random trials) than to maintain ordered lines (ordered trials) before recalling the orientation of a particular line. First, the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC (3-10 Hz). In particular, the hippocampal theta power increase correlated with the memory precision of line orientation. Second, theta phase coherences between the DLPFC and hippocampus were enhanced for ordering, especially for more precisely memorized lines. Third, the theta band DLPFC → hippocampus influence was selectively enhanced for ordering, especially for more precisely memorized lines. This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.

Impaired sequence manipulation in non-demented patients with progressive supranuclear palsy.

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 differently impaired in patients with PSP versus PD. METHOD: Twenty-nine patients with PSP Richardson's syndrome (PSP-RS), 36 patients with PD, and 36 healthy controls (HC) completed 3 well-established neuropsychological tests, including digit span forward (DST-F), digit span backward (DST-B), and adaptive digit ordering tests (DOT-A). The DST-F required maintaining digit sequences, and the DST-B and DOT-A required maintaining and manipulating digit sequences. FINDING: The PSP-RS group scored lower than the PD and HC groups in the DST-B and DOT-A but not in the DST-F, indicating that the ability to manipulate sequences was impaired, but the maintenance ability was preserved in PSP-RS patients. Moreover, in PSP-RS, the DST-B score negatively correlated with the severity of motor symptoms. The actual levodopa dose positively correlated with the DST-B ordering cost (DST-F score vs. DST-B score). The PSP patients who took a greater dose of levodopa tended to have higher DST-B ordering cost. There was no effect of levodopa on DST-B or DOT-A in PD. CONCLUSION: These results suggested that the ability to manipulate sequence was already reduced in patients with PSP-RS and was worse than in patients with PD.

The synaptic correlates of serial position effects in sequential working memory.

Sequential working memory (SWM), referring to the temporary storage and manipulation of information in order, plays a fundamental role in brain cognitive functions. The serial position effect refers to the phenomena that recall accuracy of an item is associated to the order of the item being presented. The neural mechanism underpinning the serial position effect remains unclear. The synaptic mechanism of working memory proposes that information is stored as hidden states in the form of facilitated neuronal synapse connections. Here, we build a continuous attractor neural network with synaptic short-term plasticity (STP) to explore the neural mechanism of the serial position effect. Using a delay recall task, our model reproduces the the experimental finding that as the maintenance period extends, the serial position effect transitions from the primacy to the recency effect. Using both numerical simulation and theoretical analysis, we show that the transition moment is determined by the parameters of STP and the interval between presented stimulus items. Our results highlight the pivotal role of STP in processing the order information in SWM.

Altered alpha and theta oscillations correlate with sequential working memory in Parkinson's disease.

Daily activities such as 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 oscillations correlate with sequential working memory in Parkinson's disease. We included 15 patients with Parkinson's disease (6 women, mean age: 66.0 years), 24 healthy young (14 women, mean age: 24.1 years), and 16 older participants (7 women, mean age: 68.6 years). All participants completed a picture ordering task with scalp electroencephalogram (EEG) recording, where they arranged five pictures in a specific order and memorized them over a delay. When encoding and maintaining picture sequences, patients with Parkinson's disease showed a lower baseline alpha peak frequency with higher alpha power than healthy young and older participants. Patients with a higher baseline alpha power responded more slowly for ordered trials. When manipulating picture sequences, patients with Parkinson's disease showed a lower frequency of maximal power change for random versus ordered trials than healthy young and older participants. Healthy older participants showed a higher frequency of maximal power change than healthy young participants. Compared with patients with frequency of maximal power change in the alpha band (8-15 Hz), patients with frequency of maximal power change in the theta band (4-7 Hz) showed a higher ordering-related accuracy cost (random versus ordered) in the main task and tended to respond more slowly and less accurately in an independent working memory test. In conclusion, altered baseline alpha oscillations and task-dependent modulation of alpha and theta oscillations may be neural markers of poor sequential working memory in Parkinson's disease.

Subthalamic Nucleus Stimulation Impairs Sequence Processing in Patients with Parkinson's Disease.

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) deep brain stimulation (DBS) on sequence processing in PD. METHODS: Twenty-nine patients with PD (17 women) completed a 'before/after' sentence task and a digit ordering task with STN DBS ON and OFF. In the sentence task, patients read a sequence of events expressed in the actual order of occurrence ('after' sentences) or reversed order ('before' sentences) for comprehension. In the digit task, patients recalled a sequence of ordered digits (ordered trials) or reordered and recalled random digits in ascending order (random trials). Volumes of tissue activated (VTAs) were estimated for the motor and associative STN. RESULTS: Patients were slower with STN DBS ON versus OFF in both tasks, although their motor symptoms were significantly improved under DBS. In the sentence task, patients showed higher ordering-related reaction time costs ('before' > 'after') with DBS ON versus OFF. Moreover, patients with larger left associative VTAs, smaller total motor VTAs, and more daily exposure to dopaminergic drugs tended to show larger reaction time cost increases under DBS. In the digit ordering task, patients with too large or too small right associative VTAs tended to show larger reaction time cost increases under DBS. CONCLUSION: Stimulating the STN, especially its associative part, might impair sequence processing in language and memory.

Tracking Response Dynamics of Sequential Working Memory in Patients With Mild Parkinson's Disease.

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 = 40) and healthy controls (N = 40) completed a computerized digit ordering task with a computer mouse. We measured response dynamics in terms of the initiation time, ordering time, movement time, and area under the movement trajectory curve. This approach allowed us to distinguish between the cognitive processes related to sequence processing before the actual movement (initiation time and ordering time) and the execution processes of the actual movement (movement time and area under the curve). PD patients showed longer initiation times, longer movement times, and more constrained movement trajectories than healthy controls. The initiation time and ordering time negatively correlated with the daily exposure to levodopa and D2/3 receptor agonists, respectively. The movement time positively correlated with the severity of motor symptoms. We demonstrated an altered temporal profile of sequential working memory in PD. Stimulating D1 and D2/3 receptors might speed up the maintenance and manipulation of sequences, respectively.

Age differences in the fronto-striato-parietal network underlying serial ordering.

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 they had to reorder and recall sequential digits or simply to recall them. We detected a network comprising of the lateral and medial prefrontal, posterior parietal, and striatal regions. In young adults, the prefrontal and parietal regions were more activated and more strongly connected with the supplementary motor area for "reorder & recall" than "pure recall" trials (psychophysiological interaction, PPI). In older adults, the prefrontal and parietal activations were elevated, but the PPI was attenuated. Individual adults who had a stronger PPI performed more accurately in "reorder & recall" trials. The decreased PPI appeared to be compensated by increased physiological correlations between the prefrontal/parietal cortex and the striatum, and by that between the striatum and the supplementary motor area.

Theta Oscillations Support Prefrontal-hippocampal Interactions in Sequential Working Memory / 神经科学通报·英文版

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 women, age 27.6 ± 8.2 years) completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus. Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise (random trials) than to maintain ordered lines (ordered trials) before recalling the orientation of a particular line. First, the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC (3-10 Hz). In particular, the hippocampal theta power increase correlated with the memory precision of line orientation. Second, theta phase coherences between the DLPFC and hippocampus were enhanced for ordering, especially for more precisely memorized lines. Third, the theta band DLPFC → hippocampus influence was selectively enhanced for ordering, especially for more precisely memorized lines. This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.

Spatial-Sequential Working Memory in Younger and Older Adults: Age Predicts Backward Recall Performance within Both Age Groups.

Working memory is vulnerable to age-related decline, but there is debate regarding the age-sensitivity of different forms of spatial-sequential working memory task, depending on their passive or active nature. The functional architecture of spatial working memory was therefore explored in younger (18-40 years) and older (64-85 years) adults, using passive and active recall tasks. Spatial working memory was assessed using a modified version of the Spatial Span subtest of the Wechsler Memory Scale - Third Edition (WMS-III; Wechsler, 1998). Across both age groups, the effects of interference (control, visual, or spatial), and recall type (forward and backward), were investigated. There was a clear effect of age group, with younger adults demonstrating a larger spatial working memory capacity than the older adults overall. There was also a specific effect of interference, with the spatial interference task (spatial tapping) reliably reducing performance relative to both the control and visual interference (dynamic visual noise) conditions in both age groups and both recall types. This suggests that younger and older adults have similar dependence upon active spatial rehearsal, and that both forward and backward recall require this processing capacity. Linear regression analyses were then carried out within each age group, to assess the predictors of performance in each recall format (forward and backward). Specifically the backward recall task was significantly predicted by age, within both the younger and older adult groups. This finding supports previous literature showing lifespan linear declines in spatial-sequential working memory, and in working memory tasks from other domains, but contrasts with previous evidence that backward spatial span is no more sensitive to aging than forward span. The study suggests that backward spatial span is indeed more processing-intensive than forward span, even when both tasks include a retention period, and that age predicts backward spatial span performance across the adult lifespan, within both younger and older adulthood.