Sequence Learning Performance Research Articles

Impaired executive functioning mediates the association between aging and deterministic sequence learning

ABSTRACT Sensitivity to the fixed ordering of actions and events, or deterministic sequence learning, is an important skill throughout adulthood. Yet, it remains unclear whether age deficits in sequencing exist, and we lack a firm understanding of which factors might contribute to age-related impairments when they arise. Though debated, executive functioning, governed by the frontal lobe, may underlie age-related sequence learning deficits in older adults. The present study asked if age predicts errors in deterministic sequence learning across the older adult lifespan (ages 55–89), and whether executive functioning accounts for any age-related declines. Healthy older adults completed a comprehensive measure of frontal-based executive abilities as well as a deterministic sequence learning task that required the step-by-step acquisition of associations through trial-and-error feedback. Among those who met a performance-based criterion, increasing age was positively correlated with higher sequencing errors; however, this relationship was no longer significant after controlling for executive functioning. Moreover, frontal-based executive abilities mediated the relationship between age and sequence learning performance. These findings suggest that executive or frontal functioning may underlie age deficits in learning judgment-based, deterministic serial operations.

Deep brain stimulation of the ventrointermediate nucleus of the thalamus to treat essential tremor improves motor sequence learning.

The network of brain structures engaged in motor sequence learning comprises the same structures as those involved in tremor, including basal ganglia, cerebellum, thalamus, and motor cortex. Deep brain stimulation (DBS) of the ventrointermediate nucleus of the thalamus (VIM) reduces tremor, but the effects on motor sequence learning are unknown. We investigated whether VIM stimulation has an impact on motor sequence learning and hypothesized that stimulation effects depend on the laterality of electrode location. Twenty patients (age: 38–81 years; 12 female) with VIM electrodes implanted to treat essential tremor (ET) successfully performed a serial reaction time task, varying whether the stimuli followed a repeating pattern or were selected at random, during which VIM‐DBS was either on or off. Analyses of variance were applied to evaluate motor sequence learning performance according to reaction times (RTs) and accuracy. An interaction was observed between whether the sequence was repeated or random and whether VIM‐DBS was on or off (F[1,18] = 7.89, p = .012). Motor sequence learning, reflected by reduced RTs for repeated sequences, was greater with DBS on than off (T[19] = 2.34, p = .031). Stimulation location correlated with the degree of motor learning, with greater motor learning when stimulation targeted the lateral VIM (n = 23, ρ = 0.46; p = .027). These results demonstrate the beneficial effects of VIM‐DBS on motor sequence learning in ET patients, particularly with lateral VIM electrode location, and provide evidence for a role for the VIM in motor sequence learning.

Sequence learning, prediction, and replay in networks of spiking neurons

Sequence learning, prediction and replay have been proposed to constitute the universal computations performed by the neocortex. The Hierarchical Temporal Memory (HTM) algorithm realizes these forms of computation. It learns sequences in an unsupervised and continuous manner using local learning rules, permits a context specific prediction of future sequence elements, and generates mismatch signals in case the predictions are not met. While the HTM algorithm accounts for a number of biological features such as topographic receptive fields, nonlinear dendritic processing, and sparse connectivity, it is based on abstract discrete-time neuron and synapse dynamics, as well as on plasticity mechanisms that can only partly be related to known biological mechanisms. Here, we devise a continuous-time implementation of the temporal-memory (TM) component of the HTM algorithm, which is based on a recurrent network of spiking neurons with biophysically interpretable variables and parameters. The model learns high-order sequences by means of a structural Hebbian synaptic plasticity mechanism supplemented with a rate-based homeostatic control. In combination with nonlinear dendritic input integration and local inhibitory feedback, this type of plasticity leads to the dynamic self-organization of narrow sequence-specific subnetworks. These subnetworks provide the substrate for a faithful propagation of sparse, synchronous activity, and, thereby, for a robust, context specific prediction of future sequence elements as well as for the autonomous replay of previously learned sequences. By strengthening the link to biology, our implementation facilitates the evaluation of the TM hypothesis based on experimentally accessible quantities. The continuous-time implementation of the TM algorithm permits, in particular, an investigation of the role of sequence timing for sequence learning, prediction and replay. We demonstrate this aspect by studying the effect of the sequence speed on the sequence learning performance and on the speed of autonomous sequence replay.

Resting-state functional brain connectivity is related to subsequent procedural learning skills in school-aged children

This magnetoencephalography (MEG) study investigates how procedural sequence learning performance is related to prior brain resting-state functional connectivity (rsFC), and to what extent sequence learning induces rapid changes in brain rsFC in school-aged children.Procedural learning was assessed in 30 typically developing children (mean age ± SD: 9.99 years ± 1.35) using a serial reaction time task (SRTT). During SRTT, participants touched as quickly and accurately as possible a stimulus sequentially or randomly appearing in one of the quadrants of a touchscreen. Band-limited power envelope correlation (brain rsFC) was applied to MEG data acquired at rest pre- and post-learning. Correlation analyses were performed between brain rsFC and sequence-specific learning or response time indices.Stronger pre-learning interhemispheric rsFC between inferior parietal and primary somatosensory/motor areas correlated with better subsequent sequence learning performance and faster visuomotor response time. Faster response time was associated with post-learning decreased rsFC within the dorsal extra-striate visual stream and increased rsFC between temporo-cerebellar regions.In school-aged children, variations in functional brain architecture at rest within the sensorimotor network account for interindividual differences in sequence learning and visuomotor performance. After learning, rapid adjustments in functional brain architecture are associated with visuomotor performance but not sequence learning skills.

Examining implicit procedural learning in tetraplegia using an oculomotor serial reaction time task.

Clinical observations indicate that implicit procedural learning, a central component of physical and psychosocial rehabilitation, is impeded following spinal cord injury. In accordance, previous research has revealed a specific deficit in implicit sequence learning among individuals with paraplegia using a standard, manual version of the serial reaction time task. To extend these findings and shed light on the underlying sources of potential spinal cord injury-related deficits in sequence learning, we used an ocular activated serial reaction time task to compare sequence learning performance between individuals with tetraplegia and healthy controls. Twelve participants with spinal cord injury in C5-T1 were compared to 12 matched control participants on measures derived from an ocular activated serial reaction time task. Depression and additional cognitive measures were assessed to explore the source and specificity of potential sequence learning deficits. Like controls, and in contrast with previous findings in paraplegia, the spinal cord injury group showed intact implicit sequence learning, evidenced by declining reaction times and improved anticipation over the first six blocks of the serial reaction time task, and an advantage for the initial learning sequence over a novel interference sequence. The ocular activated serial reaction time task elicited a performance pattern similar to standard motor versions, such that participants with tetraplegia demonstrated unimpaired sequence learning. This suggests that previously reported implicit sequence learning deficits in spinal cord injury directly involved motor functioning rather than cognitive aspects of the task, and that the ocular activated sequence learning task could be a valid alternative for assessing implicit sequence learning in populations that cannot perform spinal-cord dependent motor tasks. Implications for post-spinal cord injury rehabilitation and adjustment are discussed.

Focused-attention meditation increases cognitive control during motor sequence performance: Evidence from the N2 cortical evoked potential

Previous work found that single-session focused attention meditation (FAM) enhanced motor sequence learning through increased cognitive control as a mechanistic action, although electrophysiological correlates of sequence learning performance following FAM were not investigated. We measured the persistent frontal N2 event-related potential (ERP) that is closely related to cognitive control processes and its ability to predict behavioural measures. Twenty-nine participants were randomised to one of three conditions reflecting the level of FAM experienced prior to a serial reaction time task (SRTT): 21 sessions of FAM (FAM21, N = 12), a single FAM session (FAM1, N = 9) or no preceding FAM control (Control, N = 8). Continuous 64-channel EEG were recorded during SRTT and N2 amplitudes for correct trials were extracted. Component amplitude, regions of interests, and behavioural outcomes were compared using mixed effects regression models between groups. FAM21 exhibited faster reaction time performances in majority of the learning blocks compared to FAM1 and Control. FAM21 also demonstrated a significantly more pronounced N2 over majority of anterior and central regions of interests during SRTT compared to the other groups. When N2 amplitudes were modelled against general learning performance, FAM21 showed the greatest rate of amplitude decline over anterior and central regions. The combined results suggest that FAM training provided greater cognitive control enhancement for improved general performance, and less pronounced effects for sequence-specific learning performance compared to the other groups. Importantly, FAM training facilitates dynamic modulation of cognitive control: lower levels of general learning performance was supported by greater levels of activation, whilst higher levels of general learning exhibited less activation.

Plasticity induction in the pre-supplementary motor area (pre-SMA) and SMA-proper differentially affects visuomotor sequence learning

BackgroundBoth pre-supplementary motor area (pre-SMA) and SMA-proper (SMA) must play important roles in visuomotor sequence learning. However, functional differences between the pre-SMA and SMA have not been well studied in humans. ObjectiveTo elucidate the functional differences between the pre-SMA and SMA in sequence learning in humans. MethodsTo induce LTP/LTD, we administered quadripulse transcranial magnetic stimulation (QPS) with an inter-stimulus interval of 5 or 50 ms (QPS-5/50) over the pre-SMA or SMA in healthy volunteers. The sham stimulation was also done as a control. We studied the effects of LTP/LTD in the pre-SMA/SMA on a new sequence learning and the performance of well-learned sequence by using sequence learning task called the “2 × 10 task”. Effects on the simple choice reaction time task were also studied for comparison. ResultsQPS-5 over the pre-SMA increased the error rate without any changes in movement speed. When administered over the SMA, QPS-5 decreased, and QPS-50 increased the rate of reaction time reduction across trials without changes in the error rate. QPS over neither the pre-SMA nor SMA affected the performances of a well-learned sequence or a simple choice reaction time task. ConclusionsOur findings that QPS over the pre-SMA correlated with sequence learning performance and that over the SMA with execution speed are consistent with the previous results in animals and humans. Our results lend further support to the utility of QPS for modulating motor learning in humans.

Deconstructing Procedural Memory: Different Learning Trajectories and Consolidation of Sequence and Statistical Learning.

Procedural learning is a fundamental cognitive function that facilitates efficient processing of and automatic responses to complex environmental stimuli. Here, we examined training-dependent and off-line changes of two sub-processes of procedural learning: namely, sequence learning and statistical learning. Whereas sequence learning requires the acquisition of order-based relationships between the elements of a sequence, statistical learning is based on the acquisition of probabilistic associations between elements. Seventy-eight healthy young adults (58 females and 20 males) completed the modified version of the Alternating Serial Reaction Time task that was designed to measure Sequence and Statistical Learning simultaneously. After training, participants were randomly assigned to one of three conditions: active wakefulness, quiet rest, or daytime sleep. We examined off-line changes in Sequence and Statistical Learning as well as further improvements after extended practice. Performance in Sequence Learning increased during training, while Statistical Learning plateaued relatively rapidly. After the off-line period, both the acquired sequence and statistical knowledge was preserved, irrespective of the vigilance state (awake, quiet rest or sleep). Sequence Learning further improved during extended practice, while Statistical Learning did not. Moreover, within the sleep group, cortical oscillations and sleep spindle parameters showed differential associations with Sequence and Statistical Learning. Our findings can contribute to a deeper understanding of the dynamic changes of multiple parallel learning and consolidation processes that occur during procedural memory formation.

Is the Hebb repetition task a reliable measure of individual differences in sequence learning?

The Hebb repetition task, an operationalization of long-term sequence learning through repetition, is the focus of renewed interest, as it is taken to provide a laboratory analogue for naturalistic vocabulary acquisition. Indeed, recent studies have consistently related performance in the Hebb repetition task with a range of linguistic (dis)abilities. However, despite the growing interest in the Hebb repetition effect as a theoretical construct, no previous research has ever tested whether the task used to assess Hebb learning offers a stable and reliable measure of individual performance in sequence learning. Since reliability is a necessary condition to predictive validity, in the present work, we tested whether individual ability in visual verbal Hebb repetition learning displays basic test-retest reliability. In a first experiment, Hebrew-English bilinguals performed two verbal Hebb tasks, one with English and one with Hebrew consonant letters. They were retested on the same Hebb tasks after a period of about 6 months. Overall, serial recall performance proved to be a stable and reliable capacity of an individual. By contrast, the test-retest reliability of individual learning performance in our Hebb task was close to zero. A second experiment with French speakers replicated these results and demonstrated that the concurrent learning of two repeated Hebb sequences within the same task minimally improves the reliability scores. Taken together, our results raise concerns regarding the usefulness of at least some current Hebb learning tasks in predicting linguistic (dis)abilities. The theoretical implications are discussed.

Sleep and memory consolidation: Motor performance and proactive interference effects in sequence learning

That post-training sleep supports the consolidation of sequential motor skills remains debated. Performance improvement and sensitivity to proactive interference are both putative measures of long-term memory consolidation. We tested sleep-dependent memory consolidation for visuo-motor sequence learning using a proactive interference paradigm. Thirty-three young adults were trained on sequence A on Day 1, then had Regular Sleep (RS) or were Sleep Deprived (SD) on the night after learning. After two recovery nights, they were tested on the same sequence A, then had to learn a novel, potentially competing sequence B. We hypothesized that proactive interference effects on sequence B due to the prior learning of sequence A would be higher in the RS condition, considering that proactive interference is an indirect marker of the robustness of sequence A, which should be better consolidated over post-training sleep. Results highlighted sleep-dependent improvement for sequence A, with faster RTs overnight for RS participants only. Moreover, the beneficial impact of sleep was specific to the consolidation of motor but not sequential skills. Proactive interference effects on learning a new material at Day 4 were similar between RS and SD participants. These results suggest that post-training sleep contributes to optimizing motor but not sequential components of performance in visuo-motor sequence learning.

Resting state connectivity predicts implicit sequence learning performance: a replication and extension

PARTICIPANTS § 33 young adults ages 18-34 (M±SD = 20.7 ± 2.6) from Washington, DC metro area § 2 participants subsequently eliminated from all analyses due to image artifact or meeting study drug exclusion criteria (final sample: N = 31) fMRI DATA ACQUISITION & PREPROCESSING § Subjects scanned in resting state (eyes open) for 11 minutes in 3T Siemens Trio magnet § 264 whole brain images, gradient EPI acquisition (TR = 2500ms, TE = 30ms, 90oflip angle, FOV = 192 x192mm, voxel size = 3 mm isotropic) § Data preprocessing in SPM8 (Slice Time Correction/Realignment, Normalization to EPI template, Resliced to 3mm, Smoothing {8mm FWHM}, Band-pass filtering, and “scrubbing” (Power et al., 2012) with at least 200 volumes retained per participant BEHAVIORAL TESTING (see top middle panel) § Took place in scanner immediately following the resting scan § 3 sessions (720 trials) of the Triplets Learning Task (TLT; Howard, Howard, Dennis, & Kelly, 2008), modified for fMRI § Computer-based recognition task and interview to assess explicit awareness RESTING STATE FUNCTIONAL CONNECTIVITY CALCULATIONS § Bilateral dorsal caudate (DC) seed created in Marsbar as two spheres (R and L hemispheres) of radius 6mm, centered around coordinates taken from Di Martino et al. (2008) Seed based Voxelwise resting state connectivity: § For each subject, partial correlations computed between timecourse of DC seed and those of every other voxel in brain, controlling for motion (from realignment parameter timecourses) and physiological noise (approximated by timecourses of WM and CSF); resulting r-values converted to Z-scores before statistical analyses of correlation strengths § Produced brain map of intrinsic connectivity strength with the DC for each subject Correlations with SL performance: § Single-subjects’ whole brain connectivity maps entered as the DV in regression models (SPM8) testing for correlations with SL performance within a medial temporal lobe (MTL) region of interest, as well as across the whole brain § Mean framewise displacement included in models as a covariate of no interest § Whole Brain results corrected for multiple comparisons at P 54) Resting State Connectivity Predicts Implicit Sequence Learning Performance: A Replication and Extension

Caudate Resting Connectivity Predicts Implicit Probabilistic Sequence Learning

Abstract Implicit probabilistic sequence learning (IPSL) involves extracting statistical regularities from sequences of events without awareness, and is thought to underlie learning of language and behavioral repertoires of everyday life. We examined whether resting-state functional connectivity networks of the caudate predicted individual differences in IPSL performance measured on a separate day. Whole-brain connectivity maps of a bilateral dorsal caudate (DC) seed were created for each subject and examined for voxelwise correlations with sequence learning performance, as well as with overall response speed. Higher learning scores (but not overall response speed) were associated with stronger resting-state connectivity between the DC and right medial temporal lobe, as well as with lower resting-state connectivity between the DC and premotor regions involved in motor planning. Thus, how well one learns probabilistic regularities without awareness is predicted by the strength of a striato-cortical network in the resting brain.

Differential working memory correlates for implicit sequence performance in young and older adults

Our recent work has revealed that visuospatial working memory (VSWM) relates to the rate of explicit motor sequence learning (Bo and Seidler in J Neurophysiol 101:3116-3125, 2009) and implicit sequence performance (Bo et al. in Exp Brain Res 214:73-81, 2011a) in young adults (YA). Although aging has a detrimental impact on many cognitive functions, including working memory, older adults (OA) still rely on their declining working memory resources in an effort to optimize explicit motor sequence learning. Here, we evaluated whether age-related differences in VSWM and/or verbal working memory (VWM) performance relates to implicit performance change in the serial reaction time (SRT) sequence task in OA. Participants performed two computerized working memory tasks adapted from change detection working memory assessments (Luck and Vogel in Nature 390:279-281, 1997), an implicit SRT task and several neuropsychological tests. We found that, although OA exhibited an overall reduction in both VSWM and VWM, both OA and YA showed similar performance in the implicit SRT task. Interestingly, while VSWM and VWM were significantly correlated with each other in YA, there was no correlation between these two working memory scores in OA. In YA, the rate of SRT performance change (exponential fit to the performance curve) was significantly correlated with both VSWM and VWM, while in contrast, OA's performance was only correlated with VWM, and not VSWM. These results demonstrate differential reliance on VSWM and VWM for SRT performance between YA and OA. OA may utilize VWM to maintain optimized performance of second-order conditional sequences.

L-DOPA changes ventral striatum recruitment during motor sequence learning in Parkinson's disease

We previously reported a differential effect of dopaminergic medication across the time course of motor sequence learning in early stage Parkinson's (PD) patients [1]. There was a medication-associated impairment specific to the early phase of learning. In the current study, we investigated the BOLD responses associated with this deleterious medication effect on motor sequence learning. We hypothesized that levodopa (l-DOPA) would negatively affect the recruitment of the ventral striatal circuitry during the early phase of learning. Seventeen early stage PD patients ON and OFF l-DOPA and 21 healthy control participants performed an explicit motor sequence learning task inside the MRI scanner. We observed sequence learning-specific activation during the early phase in the ventral putamen for controls and PD OFF but not for PD ON l-DOPA. A comparison of activation between PD OFF and PD ON showed that activation within the ventral putamen was decreased in PD ON compared to PD OFF. The extent of the l-DOPA associated activation decrease in the ventral putamen showed a small, positive correlation with the degree of sequence learning performance decrease in the early phase of learning (r=0.45–0.54 across measures, p<0.05, one-tailed). These findings provide evidence for the negative effects of l-DOPA in PD patients on the ventral putamen circuitry involved in early motor sequence learning, and provide support for a role of this structure in the sequence learning process.

Age-related modulation in post-movement alpha power increase following motor sequence learning

Age-related modulation in post-movement alpha power increase following motor sequence learning

Dissociating sequence learning performance in Parkinson's disease: Visuomotor sequence acquisition and pattern judgment on a serial reaction time task.

In this study, the sequence learning performance of 16 non-demented patients with Parkinson's disease (PD) was compared with 18 age-matched healthy controls on a verbal version of the serial reaction time (SRT) task intended to encapsulate both visuomotor- and judgment-linked learning processes. Visuomotor sequence performance in PD patients was closely related to baseline response speed, with robust learning demonstrated by patients who responded with comparable speed to controls but severely impaired performance in patients who responded slowly. In contrast, both fast- and slow-responding PD patients were able to successfully categorise patterns according to their sequential status, a performance that was linked to declarative memory for the sequence. The findings highlight the important role of event timing in SRT performance and are in accord with the hypothesis that, despite the important role played by the basal ganglia in motor sequence learning, basal ganglionic dysfunction may not substantially impair sequence order learning so much as the translation of sequence knowledge into rapid motor performance for some PD patients. Intact pattern judgment on the SRT experiment suggests that the integrity of the neostriatum is not essential for learning judgment-linked categorical information about sequences of temporal stimulus movement.

Impairment in explicit visuomotor sequence learning is related to loss of microstructural integrity of the corpus callosum in multiple sclerosis patients with minimal disability

Sequence learning can be investigated by serial reaction-time (SRT) paradigms. Explicit learning occurs when subjects have to recognize a test sequence and has been shown to activate the frontoparietal network in both contralateral and ipsilateral hemispheres. Thus, the left and right superior longitudinal fasciculi (SLF), connecting the intra-hemispheric frontoparietal circuits, could have a role in explicit unimanual visuomotor learning. Also, as both hemispheres are involved, we could hypothesize that the corpus callosum (CC) has a role in this process. Pathological damage in both SLF and CC has been detected in patients with Multiple Sclerosis (PwMS), and microstructural alterations can be quantified by Diffusion Tensor Imaging (DTI). In light of these findings, we inquired whether PwMS with minimal disability showed impairments in explicit visuomotor sequence learning and whether this could be due to loss of white matter integrity in these intra- and inter-hemispheric white matter pathways. Thus, we combined DTI analysis with a modified version of SRT task based on finger opposition movements in a group of PwMS with minimal disability. We found that the performance in explicit sequence learning was significantly reduced in these patients with respect to healthy subjects; the amount of sequence-specific learning was found to be more strongly correlated with fractional anisotropy (FA) in the CC (r=0.93) than in the left (r=0.28) and right SLF (r=0.27) (p for interaction=0.005 and 0.04 respectively). This finding suggests that an inter-hemispheric information exchange between the homologous areas is required to successfully accomplish the task and indirectly supports the role of the right (ipsilateral) hemisphere in explicit visuomotor learning. On the other hand, we found no significant correlation of the FA in the CC and in the SLFs with nonspecific learning (assessed when stimuli are randomly presented), supporting the hypothesis that inter-hemispheric integrity is specifically relevant for explicit sequence learning.

Impaired sequence learning in dystonia mutation carriers: a genotypic effect

Abnormalities in motor sequence learning have been observed in non-manifesting carriers of the DYT1 dystonia mutation. Indeed, motor sequence learning deficits in these subjects have been associated with increased cerebellar activation during task performance. In the current study, we determined whether similar changes are also present in clinically manifesting DYT1 carriers as well as in carriers of other primary dystonia mutations such as DYT6. Additionally, we determined whether sequence learning performance and associated brain activation in these subjects correlate with previously described genotype-related abnormalities of cerebellar pathway integrity and striatal D2 dopamine receptor binding. Nineteen DYT1 carriers (10 non-manifesting DYT1: 51.5±15.1 years; nine manifesting DYT1: 46.1±15.1 years) and 12 healthy control subjects (42.8±15.3 years) were scanned with H2(15)O positron emission tomography while performing controlled sequence learning and reference tasks. Eleven DYT6 carriers (four non-manifesting DYT6: 38.0±22.1; seven manifesting DYT6: 35.3±14.2 years) were evaluated during task performance without concurrent imaging. DYT1 and DYT6 carriers also underwent diffusion tensor magnetic resonance imaging for the assessment of tract integrity and 11C-raclopride positron emission tomography to measure caudate/putamen D2 receptor binding. These imaging measures were correlated with sequence learning performance and associated activation responses. Sequence learning deficits of similar magnitude were observed in manifesting and non-manifesting DYT1 carriers. In contrast, learning deficits were not detected in DYT6 carriers, irrespective of clinical penetrance. Affected DYT1 carriers exhibited significant increases in sequence learning-related activation in the left lateral cerebellar cortex and in the right premotor and inferior parietal regions. Increases in premotor cortical activation observed in the mutation carriers correlated with reductions in cerebellar pathway integrity measured using magnetic resonance diffusion tensor imaging and probabilistic tractography. Additionally, the cerebellar tract changes correlated with reductions in dentate nucleus activation recorded during task performance. Sequence learning performance and task-related activation responses did not correlate with striatal D2 receptor binding. In summary, we found that sequence learning deficits and concomitant increases in cerebellar activation are specific features of the DYT1 genotype. The close relationship between reduced cerebellar pathway integrity and increased learning-related activation of the premotor cortex is compatible with the view of DYT1 dystonia as a neurodevelopmental circuit disorder.

Motor sequence learning performance in Parkinson’s disease patients depends on the stage of disease

It is still unclear, whether patients with Parkinson’s disease (PD) are impaired in the incidental learning of different motor sequences in short succession, although such a deficit might greatly impact their daily life. The aim of this study was thus to clarify the relation between disease parameters of PD and incidental motor learning of two different sequences in short succession. Results revealed that the PD patients were able to acquire two sequences in short succession but needed more time than healthy subjects. However, both the severity of axial manifestations, as assessed on a subsection of the Unified Parkinson’s Disease Rating Scale III (UPDRS III) and the Hoehn and Yahr score, and the levodopa-equivalent dose (LED) were negatively correlated with the sequence learning performance. These findings indicate that, although PD patients are able to learn two sequences in short succession, they need more time and their overall sequence learning performance is strongly correlated with the stage of disease.

Early Parkinson's disease: Longitudinal changes in brain activity during sequence learning

Impairment of sequence learning is common in Parkinson's disease (PD), but the time course of this cognitive abnormality is not known. We assessed longitudinal changes in sequence learning performance and associated task-related cerebral blood flow in 13 early stage PD patients who underwent H 2 15O PET at baseline and again 2 years later. Ten healthy volunteer subjects served as controls. A trend toward decline in learning performance ( p = 0.08) was evident over the 2 years of follow-up. During this interval, significant declines in learning-related activation were detected in parietal and temporo-occipital association areas and in the right dorsolateral prefrontal cortex. Learning-related activation in these regions was normal at baseline, but declined to subnormal levels ( p < 0.01) at 2 years. Significant hippocampal activation ( p < 0.005) was present in the subjects with high learning performance over time. The findings are consistent with a decline in learning-related neural activity in cortical areas with prominent Lewy body formation.