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1.
J Neurol ; 270(11): 5408-5417, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37462754

ABSTRACT

BACKGROUND: Progressive cognitive decline is an inevitable feature of Huntington's disease (HD) but specific criteria and instruments are still insufficiently developed to reliably classify patients into categories of cognitive severity and to monitor the progression of cognitive impairment. METHODS: We collected data from a cohort of 180 positive gene-carriers: 33 with premanifest HD and 147 with manifest HD. Using a specifically developed gold-standard for cognitive status we classified participants into those with normal cognition, those with mild cognitive impairment, and those with dementia. We administered the Parkinson's Disease-Cognitive Rating Scale (PD-CRS), the MMSE and the UHDRS cogscore at baseline, and at 6-month and 12-month follow-up visits. Cutoff scores discriminating between the three cognitive categories were calculated for each instrument. For each cognitive group and instrument we addressed cognitive progression, sensitivity to change, and the minimally clinical important difference corresponding to conversion from one category to another. RESULTS: The PD-CRS cutoff scores for MCI and dementia showed excellent sensitivity and specificity ratios that were not achieved with the other instruments. Throughout follow-up, in all cognitive groups, PD-CRS captured the rate of conversion from one cognitive category to another and also the different patterns in terms of cognitive trajectories. CONCLUSION: The PD-CRS is a valid and reliable instrument to capture MCI and dementia syndromes in HD. It captures the different trajectories of cognitive progression as a function of cognitive status and shows sensitivity to change in MCI and dementia.


Subject(s)
Cognitive Dysfunction , Huntington Disease , Parkinson Disease , Humans , Huntington Disease/complications , Huntington Disease/diagnosis , Huntington Disease/genetics , Neuropsychological Tests , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Cognitive Dysfunction/psychology , Cognition , Parkinson Disease/complications , Parkinson Disease/diagnosis
2.
J Huntingtons Dis ; 10(4): 459-468, 2021.
Article in English | MEDLINE | ID: mdl-34602494

ABSTRACT

BACKGROUND: Arithmetic word-problem solving depends on the interaction of several cognitive processes that may be affected early in the disease in gene-mutation carriers for Huntington's disease (HD). OBJECTIVE: Our goal was to examine the pattern of performance of arithmetic tasks in premanifest and manifest HD, and to examine correlations between arithmetic task performance and other neuropsychological tasks. METHODS: We collected data from a multicenter cohort of 165 HD gene-mutation carriers. The sample consisted of 31 premanifest participants: 16 far-from (>12 years estimated time to diagnosis; preHD-A) and 15 close-to (≤12 years estimated time to diagnosis; preHD-B), 134 symptomatic patients (early-mild HD), and 37 healthy controls (HC). We compared performance between groups and explored the associations between arithmetic word-problem solving and neuropsychological and clinical variables. RESULTS: Total arithmetic word-problem solving scores were lower in preHD-B patients than in preHD-A (p < 0.05) patients and HC (p < 0.01). Early-mild HD patients had lower scores than preHD patients (p < 0.001) and HC (p < 0.001). Compared to HC, preHD and early-mild HD participants made more errors as trial complexity increased. Moreover, arithmetic word-problem solving scores were significantly associated with measures of global cognition (p < 0.001), frontal-executive functions (p < 0.001), attention (p < 0.001) visual working memory (p < 0.001), mental rotation (p < 0.001), and confrontation naming (p < 0.05). CONCLUSION: Arithmetic word-problem solving is affected early in the course of HD and is related to deficient processes in frontal-executive and mentalizing-related processes.


Subject(s)
Huntington Disease , Biomarkers , Cognition , Disease Progression , Executive Function , Humans , Huntington Disease/genetics , Neuropsychological Tests , Problem Solving
4.
Cortex ; 134: 207-222, 2021 01.
Article in English | MEDLINE | ID: mdl-33291046

ABSTRACT

We present the results of 51 stroke patients with free central visual fields of which about half suffer from clear deficits of midlevel vision undetected by standard clinical tests. These patients yield significantly elevated thresholds for detection and/or discrimination between forms defined by motion, colour, or line orientation ('texture'). As demonstrated by voxel-based lesion-symptom mapping (VLSM) the underlying lesions involve mainly area human V4 (hV4) located in the posterior third of the fusiform gyrus and extending into the lingual gyrus. Patient's detection thresholds correlate only very weakly between the submodalities tested, indicating partly separate neural networks on mid-level vision for colour, motion, and texture detection. Correlations are far stronger for form discrimination tasks, indicating partly shared mechanisms for even simple form discrimination of distinct visual submodalities. We conclude that deficits of visual perception are far more common after strokes in visual brain areas than is apparent in clinical practice. Our results further clarify the functional organization of midlevel visual cortical areas.


Subject(s)
Stroke , Visual Cortex , Brain Mapping , Humans , Orientation , Stroke/complications , Stroke/diagnostic imaging , Visual Cortex/diagnostic imaging , Visual Fields , Visual Perception
5.
J Neurol ; 267(5): 1527-1535, 2020 May.
Article in English | MEDLINE | ID: mdl-32030521

ABSTRACT

BACKGROUND: Cognitive impairment is an essential feature of Huntington's disease (HD) and dementia is a predictable outcome in all patients. However, validated instruments to assess global cognitive performance in the field of HD are lacking. OBJECTIVES: We aimed to explore the utility of the Parkinson's disease-Cognitive Rating Scale (PD-CRS) for the screening of global cognition in HD. METHODS: A multicenter cohort of 132 HD patients at different disease stages and 33 matched healthy controls were classified as having preserved cognition, mild cognitive impairment (HD-MCI) or dementia (HD-Dem) according to the Clinical Dementia Rating and Functional Independence Score. The PD-CRS and the Mini-Mental State Examination were administered. Receiver operating characteristic curve analysis was used to determine optimal cutoffs to differentiate patients according to their cognitive status. RESULTS: A PD-CRS cutoff score ≤ 81/82 was optimal to detect HD-MCI (sensitivity = 93%; specificity = 80%; area under the curve (AUC) = 0.940), and ≤ 63/64 was optimal to detect HD-Dem (sensitivity = 90%; specificity = 87%; AUC = 0.933). MMSE scores failed to show robust psychometric properties in this context. DISCUSSION: The PD-CRS is a valid and reliable instrument to assess global cognition in HD in routine clinical care and clinical trials.


Subject(s)
Cognitive Dysfunction/diagnosis , Dementia/diagnosis , Huntington Disease/diagnosis , Neuropsychological Tests/standards , Adult , Cognitive Dysfunction/etiology , Cohort Studies , Dementia/etiology , Female , Humans , Huntington Disease/complications , Huntington Disease/genetics , Male , Middle Aged , Reproducibility of Results
6.
Cortex ; 64: 327-42, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25597524

ABSTRACT

Thalamic nuclei act as sensory, motor and cognitive relays between multiple subcortical areas and the cerebral cortex. They play a crucial role in cognitive functions such as executive functioning, memory and attention. In the acute period after thalamic stroke attentional deficits are common. The precise functional relevance of specific nuclei or vascular sub regions of the thalamus for attentional sub functions is still unclear. The theory of visual attention (TVA) allows the measurement of four independent attentional parameters (visual short term memory storage capacity (VSTM), visual perceptual processing speed, selective control and spatial weighting). We combined parameter-based assessment based on TVA with lesion symptom mapping in standard stereotactic space in sixteen patients (mean age 41.2 ± 11.0 SD, 6 females), with focal thalamic lesions in the medial (N = 9), lateral (N = 5), anterior (N = 1) or posterior (N = 1) vascular territories of the thalamus. Compared with an age-matched control group of 52 subjects (mean age 40.1 ± 6.4, 35 females), the patients with thalamic lesions were, on the group level, mildly impaired in visual processing speed and VSTM. Patients with lateral thalamic lesions showed a deficit in processing speed while all other TVA parameters were within the normal range. Medial thalamic lesions can be associated with a spatial bias and extinction of targets either in the ipsilesional or the contralesional field. A posterior case with a thalamic lesion of the pulvinar replicated a finding of Habekost and Rostrup (2006), demonstrating a spatial bias to the ipsilesional field, as suggested by the neural theory of visual attention (NTVA) (Bundesen, Habekost, & Kyllingsbæk, 2011). A case with an anterior-medial thalamic lesion showed reduced selective attentional control. We conclude that lesions in distinct vascular sub regions of the thalamus are associated with distinct attentional syndromes (medial = spatial bias, lateral = processing speed).


Subject(s)
Attention/physiology , Perceptual Disorders/physiopathology , Space Perception/physiology , Stroke/physiopathology , Thalamus/physiopathology , Female , Functional Laterality/physiology , Humans , Male , Middle Aged , Neuropsychological Tests , Perceptual Disorders/etiology , Reaction Time/physiology , Stroke/complications , Visual Perception/physiology
7.
Neuropsychologia ; 74: 30-6, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25448855

ABSTRACT

The posterior parietal cortex (PPC) and the dorsolateral prefrontal cortex (DLPFC) are known to be part of a cortical network involved in visual spatial attention. Top-down control can modulate processing at target and distractor positions over a sequence of trials, leading to positive priming at prior target positions and negative priming at prior distractor positions. In order to elucidate the exact time course of this top-down mechanism we here propose a transcranial magnetic stimulation (TMS) protocol. Single-pulses were applied over the right PPC, the right DLPFC or over the vertex (sham stimulation) at five time intervals (50, 100, 150, 200, 250 ms) after onset of a probe display during a spatial negative priming paradigm. Both suppression of the negative priming effect at a previous distractor position and enhancement of positive priming at a previous target position was found if a TMS pulse was applied 100 ms after the probe display onset either over the right DLPFC or the right PPC. We suggest that top-down mechanisms within the right fronto-parietal attention network are compromised during TMS interference in this time window.


Subject(s)
Attention/physiology , Frontal Lobe/physiology , Parietal Lobe/physiology , Space Perception/physiology , Transcranial Magnetic Stimulation , Adult , Analysis of Variance , Brain Mapping , Female , Functional Laterality/physiology , Humans , Male , Nerve Net/physiology , Photic Stimulation , Reaction Time/physiology , Time Factors , Young Adult
8.
J Neurol ; 262(2): 316-25, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25381457

ABSTRACT

Homonymous hemianopia (HH) is a frequent deficit resulting from lesions to post-chiasmal brain structures with a significant negative impact on activities of daily living. To address the question how patients with HH may compensate their visual field defect in a naturalistic environment, we performed a driving simulation experiment and quantitatively analyzed both eye and head movements using a head-mounted pupil camera. 14 patients with HH and 14 matched healthy control subjects participated in the study. Based on the detection performance of dynamically moving obstacles, which appeared unexpectedly along the sides of the road track, we divided the patient group into a high- and a low-performance group. Then, we compared parameters of eye and head movements between the two patient groups and the matched healthy control group to identify those which mediate successful detection of potentially hazardous objects. Differences in detection rates could not be explained by demographic variables or the extent of the visual field defect. Instead, high performance of patients with HH in the naturalistic setting of our driving simulation depended on an adapted visual exploratory behavior characterized by a relative increase in the amplitude and a corresponding increase in the peak velocity of saccades, widening horizontally the distribution of eye movements, and by a shift of the overall distribution of saccades into the blind hemifield. The result of the group comparison analyses was confirmed by a subsequent stepwise regression analysis which identified the horizontal spread of eye movements as single factor predicting the detection of hazardous objects.


Subject(s)
Automobile Driving , Eye Movements/physiology , Head Movements/physiology , Hemianopsia/complications , Psychomotor Performance/physiology , Activities of Daily Living , Computer Simulation , Female , Humans , Male , Middle Aged , Reaction Time/physiology
9.
Brain Stimul ; 8(2): 216-23, 2015.
Article in English | MEDLINE | ID: mdl-25481073

ABSTRACT

BACKGROUND: Several studies have demonstrated a bilateral field advantage (BFA) in early visual attentional processing, that is, enhanced visual processing when stimuli are spread across both visual hemifields. The results are reminiscent of a hemispheric resource model of parallel visual attentional processing, suggesting more attentional resources on an early level of visual processing for bilateral displays [e.g. Sereno AB, Kosslyn SM. Discrimination within and between hemifields: a new constraint on theories of attention. Neuropsychologia 1991;29(7):659-75.]. Several studies have shown that the BFA extends beyond early stages of visual attentional processing, demonstrating that visual short term memory (VSTM) capacity is higher when stimuli are distributed bilaterally rather than unilaterally. OBJECTIVE/HYPOTHESIS: Here we examine whether hemisphere-specific resources are also evident on later stages of visual attentional processing. METHODS: Based on the Theory of Visual Attention (TVA) [Bundesen C. A theory of visual attention. Psychol Rev 1990;97(4):523-47.] we used a whole report paradigm that allows investigating visual attention capacity variability in unilateral and bilateral displays during navigated repetitive transcranial magnetic stimulation (rTMS) of the precuneus region. RESULTS: A robust BFA in VSTM storage capacity was apparent after rTMS over the left precuneus and in the control condition without rTMS. In contrast, the BFA diminished with rTMS over the right precuneus. CONCLUSION: This finding indicates that the right precuneus plays a causal role in VSTM capacity, particularly in bilateral visual displays.


Subject(s)
Memory, Short-Term/physiology , Parietal Lobe/physiology , Transcranial Magnetic Stimulation , Visual Perception/physiology , Adult , Attention/physiology , Female , Functional Laterality/physiology , Humans , Male , Photic Stimulation , Young Adult
10.
Neurosci Biobehav Rev ; 46 Pt 1: 58-70, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25003803

ABSTRACT

Cognitive control can be reactive or proactive in nature. Reactive control mechanisms, which support the resolution of interference, start after its onset. Conversely, proactive control involves the anticipation and prevention of interference prior to its occurrence. The interrelation of both types of cognitive control is currently under debate: Are they mediated by different neuronal networks? Or are there neuronal structures that have the potential to act in a proactive as well as in a reactive manner? This review illustrates the way in which integrating knowledge gathered from behavioral studies, functional imaging, and human electroencephalography proves useful in answering these questions. We focus on studies that investigate interference resolution at the level of working memory representations. In summary, different mechanisms are instrumental in supporting reactive and proactive control. Distinct neuronal networks are involved, though some brain regions, especially pre-SMA, possess functions that are relevant to both control modes. Therefore, activation of these brain areas could be observed in reactive, as well as proactive control, but at different times during information processing.


Subject(s)
Brain/physiology , Cognition/physiology , Memory, Short-Term/physiology , Mental Processes/physiology , Nerve Net/physiology , Brain Mapping , Humans
11.
Cortex ; 56: 38-50, 2014 Jul.
Article in English | MEDLINE | ID: mdl-23206528

ABSTRACT

Neuropsychological deficits after occipital infarction are most often described in case studies and only a small sample of studies has attempted to exactly correlate the anatomical localization of lesions with associated neuropsychological symptoms. The present study investigated a large number of patients (N = 128) in order to provide an overview of neurological and neuropsychological deficits after occipital, occipito-temporal and occipito-parietal infarction. A particular approach of the study was to define exact anatomical correlates of neuropsychological dysfunction by using voxel-based lesion-symptom mapping (VLSM) in 61 patients. In addition to a visual field defect and phosphenes, patients often reported anomia, difficulties in reading and memory deficits. Visual disorders, such as achromatopsia, akinetopsia or prosopagnosia, were rarely reported by the patients. Memory and visual disorders were diagnosed efficiently using simple clinical screening tests, such as the Rey-Osterrieth Complex Figure Test for immediate recall, the Demtect and the Lang Stereo Test. Visual field defects, reading disorders and the perception of phosphenes were associated primarily with lesions of the calcarine sulcus. Anomia and memory deficits were related to lesions of the occipital inferior gyrus, the lingual gyrus and hippocampus, as well as to lesions of principal white matter tracts.


Subject(s)
Cerebral Infarction/physiopathology , Memory Disorders/physiopathology , Occipital Lobe/pathology , Parietal Lobe/pathology , Temporal Lobe/pathology , Vision Disorders/physiopathology , Adult , Aged , Aged, 80 and over , Cerebral Infarction/complications , Cerebral Infarction/pathology , Female , Humans , Magnetic Resonance Imaging , Male , Memory Disorders/etiology , Memory Disorders/pathology , Middle Aged , Neuropsychological Tests , Occipital Lobe/physiopathology , Parietal Lobe/physiopathology , Temporal Lobe/physiopathology , Vision Disorders/etiology , Vision Disorders/pathology , Visual Fields/physiology , Young Adult
12.
Front Psychol ; 4: 47, 2013.
Article in English | MEDLINE | ID: mdl-23408377

ABSTRACT

With the present study we investigated cue-induced preparation in a Simon task and measured electroencephalogram and functional magnetic resonance imaging (fMRI) data in two within-subjects sessions. Cues informed either about the upcoming (1) spatial stimulus-response compatibility (rule cues), or (2) the stimulus location (position cues), or (3) were non-informative. Only rule cues allowed anticipating the upcoming compatibility condition. Position cues allowed anticipation of the upcoming location of the Simon stimulus but not its compatibility condition. Rule cues elicited fastest and most accurate performance for both compatible and incompatible trials. The contingent negative variation (CNV) in the event-related potential (ERP) of the cue-target interval is an index of anticipatory preparation and was magnified after rule cues. The N2 in the post-target ERP as a measure of online action control was reduced in Simon trials after rule cues. Although compatible trials were faster than incompatible trials in all cue conditions only non-informative cues revealed a compatibility effect in additional indicators of Simon task conflict like accuracy and the N2. We thus conclude that rule cues induced anticipatory re-coding of the Simon task that did not involve cognitive conflict anymore. fMRI revealed that rule cues yielded more activation of the left rostral, dorsal, and ventral prefrontal cortex as well as the pre-SMA as compared to POS and NON-cues. Pre-SMA and ventrolateral prefrontal activation after rule cues correlated with the effective use of rule cues in behavioral performance. Position cues induced a smaller CNV effect and exhibited less prefrontal and pre-SMA contributions in fMRI. Our data point to the importance to disentangle different anticipatory adjustments that might also include the prevention of upcoming conflict via task re-coding.

13.
Eur J Neurosci ; 33(12): 2349-58, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21545658

ABSTRACT

Early visual areas (V1, V2, V3/VP, V4v) contain representations of the contralateral hemifield within each hemisphere. Little is known about the role of the visual hemifields along the visuo-spatial attention processing hierarchy. It is hypothesized that attentional information processing is more efficient across the hemifields (known as bilateral field advantage) and that the integration of information is greater within one hemifield as compared with across the hemifields. Using functional magnetic resonance imaging we examined the effect of distance and hemifield on parallel attentional processing in the early visual areas (V1-V4v) at individually mapped retinotopic locations aligned adjacently or separately within or across the hemifields. We found that the bilateral field advantage in parallel attentional processing over separated attended locations can be assigned, at least partly, to differences in distractor position integration in early visual areas. These results provide evidence for a greater integration of locations between two attended locations within one hemifield than across both hemifields. This nicely correlates with behavioral findings of a bilateral field advantage in parallel attentional processing (when distractors in between cannot be excluded) and a unilateral field advantage if attention has to be shifted across separated locations (when locations in between were integrated).


Subject(s)
Attention/physiology , Space Perception/physiology , Visual Cortex/physiology , Visual Fields/physiology , Adult , Brain Mapping/methods , Eye Movements/physiology , Humans , Magnetic Resonance Imaging/methods , Mental Processes/physiology , Photic Stimulation/methods , Psychomotor Performance/physiology
14.
Vision Res ; 50(4): 473-8, 2010 Feb 22.
Article in English | MEDLINE | ID: mdl-20043939

ABSTRACT

Perceptual learning is defined as a long-lasting improvement of perception as a result of experience. Here we examined the role of task on fast perceptual learning for shape localisation either in simple detection or based on form discrimination in different visual submodalities, using identical stimulus position and stimulus types for both tasks. Thresholds for each submodality were identified by four-alternative-forced-choice tasks. Fast perceptual learning occurred for shape detection-based on luminance, motion and color differences but not for texture differences. In contradistinction, fast perceptual learning was not evident in shape localisation based on discrimination. Thresholds of all submodalities were stable across days. Fast perceptual learning seems to differ not only between different visual submodalities, but also across different tasks within the same visual submodality.


Subject(s)
Discrimination, Psychological , Form Perception/physiology , Learning/physiology , Adult , Female , Humans , Male , Photic Stimulation/methods , Sensory Thresholds , Task Performance and Analysis , Young Adult
15.
Psychol Res ; 73(6): 751-61, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19050912

ABSTRACT

Event-related potentials were measured to investigate the role of visual spatial attention mechanisms in conflict processing. We suggested that a more difficult target selection leads to stronger attentional top-down control, thereby reducing the effects of arising conflicts. This hypothesis was tested by varying the selection difficulty in a location negative priming (NP) paradigm. The difficult task resulted in prolonged responses as compared to the easy task. A behavioral NP effect was only evident in the easy task. Psychophysiologically the easy task was associated with reduced parietal N1, enhanced frontocentral N2 and N2pc components and a prolonged P3 latency for the conflict as compared to the control condition. The N2pc effect was also obvious in the difficult task. Additionally frontocentral N2 amplitudes increased and latencies of N2pc and P3 were delayed compared to the easy task. The differences at frontocentral and parietal electrodes are consistent with previous studies ascribing activity in the prefrontal and parietal cortex as the source of top-down attentional control. Thus, we propose that stronger cognitive control is involved in the difficult task, resulting in a reduced behavioral NP conflict.


Subject(s)
Attention/physiology , Cerebral Cortex/physiology , Cognition/physiology , Conflict, Psychological , Electroencephalography , Orientation/physiology , Pattern Recognition, Visual/physiology , Adult , Brain Mapping , Cues , Discrimination, Psychological/physiology , Dominance, Cerebral/physiology , Evoked Potentials/physiology , Female , Frontal Lobe/physiology , Humans , Male , Parietal Lobe/physiology , Reaction Time/physiology , Size Perception/physiology , Young Adult
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