This work was supported by matching and donation funds (Cerebrovascular Research Fund, SHAC Matching Grant, UGC Matching Grant, and Dr. William Mong Research Fund in Neurology awarded to Professor R.T.F. Cheung).

The study protocol was approved by the Institutional Review Board of the University of Hong Kong / Hospital Authority Hong Kong West Cluster (HKU/HA HKW IRB) for human research.
1. Participants
<ol>
	<li>Recruit otherwise healthy elderly Chinese subjects (from 65 to 99 years old, mean age 72) with a history of hypertension for at least 5 years.</li>
	<li>Exclude participants with any disease affecting the cognitive function and/or with any disability hindering the completion of the required assessment, including but not limited to stroke, dementia, encephalitis, depression, diabetes mellitus and coronary heart diseases.</li>
	<li>Inform the participant of the scope of the study before obtaining the written consent.</li>
</ol>
2. Neuropsychological assessment
<ol>
	<li>Arrange an interview for each participant to administer a battery of neuropsychological tests focusing on six cognitive domains (Table 1) and to collect the demographic and clinical data. Review the participant&#39;s medical records to ensure the reliability of relevant information.</li>
	<li>Forward/Backward digit span tests
	<ol>
		<li>Prepare groups of random digit sequences of increasing length (Figure 1A). Start with a three-digit sequence. Read out the digit sequence aloud at a rate of one digit per second. Ask the participant to immediately recall the digit sequence verbally in the Forward digit span test10.</li>
		<li>Have the participant recall progressively longer digit sequences with one more digit each time the participant has successfully recalled the digit sequence without any error.</li>
		<li>Give a different digit sequence of the same length if the participant has failed in the first trial of a specific length. End the test if the participant has failed again. Discontinue the test also when the participant has failed up to three times in total.</li>
		<li>Record the longest length of the digit sequence the participant has successfully recalled without any error.</li>
		<li>Start with a three-digit sequence and ask the participant to recall the digit sequence in a reverse order in the Backward digit span test. Follow the steps of Forward digit span test otherwise.</li>
	</ol>
	</li>
	<li>MoCA
	<ol>
		<li>Administer MoCA using the validated version. Use the Cantonese version to measure global cognitive function in our protocol and to construct compound domain scores11,12.</li>
		<li>MoCA verbal learning task: Read five words from different categories (<img align="center" alt="Equation" src="/files/ftp_upload/61017/61017char1.jpg" /> as Chinese characters for face, cloth, church, daisy and red color in our protocol, respectively) to the participant. Ask the participant to immediately recall the words. Repeat the reading and immediate recall a second time. Remind the participant about a delayed recall 5 minutes later. Assign one point to each correct word during the delayed recall.</li>
		<li>MoCA naming task: Show pictures of three animals (lion, rhinoceros and camel in our protocol) and ask the participant to tell their names. Assign one point to each correct name.</li>
		<li>MoCA repetition task: Read a simple sentence to the participant and ask the participant to immediately repeat it. Repeat the procedure with a more complex sentence. Assign one point to each correct repetition.</li>
		<li>MoCA drawing a cube task: Ask the participant to copy a cube printed on a sheet of paper in nearby blank space. Assign one point if the cube is copied correctly.</li>
		<li>MoCA drawing a clock task: Ask the participant to draw a clock face with time at 11:10. Assign one point each for accurate completion of the clock face, numbers and pointers, respectively.</li>
	</ol>
	</li>
	<li>Stroop test
	<ol>
		<li>Use the Chinese Translated Victoria Version of the Stroop test in our protocol13.</li>
		<li>Inform the participant to finish three sessions each with 24 stimuli printed in four different colors in 6 rows within a sheet of paper (Figure 1B). Start with dots (color naming subtask), next with four Chinese characters (of meaning not related to any color; neutral color subtask), and finally with four Chinese characters (of meaning related to a color but in another color different from their meaning, e.g., <img align="center" alt="Equation" src="/files/ftp_upload/61017/61017char2.jpg" /> as a Chinese character for &#34;red&#34; printed in green; interference subtask). Remind the participant to name the color of the printed stimuli (i.e., green, blue, yellow or red) and disregard their meaning.</li>
		<li>Allow the participant to use the first 4 stimuli in each session as a practice to ensure a full understanding of the rules. Point out any error during the practice stage and encourage the participant to correctly name the color.</li>
		<li>Remind and encourage the participant to complete the remaining 20 stimuli as quickly and accurately as possible. Record the time used by the participant to complete each session (excluding the practice stage).</li>
	</ol>
	</li>
	<li>SDMT
	<ol>
		<li>Pair 1 to 9 digits in the numeric order with nine unassociated symbols14.</li>
		<li>Print a list of the nine symbols in a random order without the corresponding digits (Figure 1C). Ask the participant to fill in the blank with the correctly paired digit below each symbol. Allow the participant to check back and forth the printed pairs for reference at any time of the test.</li>
		<li>Allow the participant to try filling the first 10 blanks as a practice to ensure a full understanding of the rules. Point out any error during the practice stage and encourage the participant to be correct.</li>
		<li>Remind and encourage the participant to fill in the blank as quickly and accurately as possible in the next 90 seconds. Record the number of correct responses in the written-SDMT.</li>
		<li>Continue the test but ask the participant to provide the correctly paired digit verbally. Record the number of correct responses in the oral-SDMT.</li>
	</ol>
	</li>
	<li>Verbal fluency
	<ol>
		<li>Ask the participant to provide a verbal list of names belonged to each of the three categories (i.e., animals, vegetables and fruits) separately in one minute for each category15.</li>
		<li>Record the total number of names for each category.</li>
	</ol>
	</li>
</ol>
3. MRI acquisition and Visual rating of SCLs on MRI
<ol>
	<li>Perform a multi-sequence 3-Tesla MRI scanning for the participant using the parameters and including the sequences summarized in Table 2. Complete the MRI scanning within one month of the neuropsychological assessment.</li>
	<li>Identify and visually rate SCLs on MRI according to standard criteria by experienced raters in an anonymous manner. Ensure good intra- and inter-rater reliability.</li>
	<li>Use T1-weighted and fluid-attenuated inversion recovery (FLAIR) images to identify SLs (as hypointense foci of 2-15 mm diameter on both sequences, usually with a hyperintence rim on FLAIR images) and their locations (Figure 2A). Re-confirm the SLs on T2-weighted images (as hyperintense foci at the same locations).
	<ol>
		<li>Search all brain regions in a pre-specified order from anterior to posterior and from one side to the other to avoid any omission (i.e., starting from frontal lobe, island lobe, basal ganglion, thalamus, temporal lobe, parietal lobe, occipital lobe, cerebellum and finally to brain stem, and starting from the left side and then to the right side).</li>
	</ol>
	</li>
	<li>Use susceptibility-weighted imaging (SWI) to identify CMBs (as punctuate or small round/oval hypointense foci of 2-10 mm diameter) and their locations (Figure 2B). Divide the whole brain region into 7 anatomical locations (i.e., cortex and grey-white junction, subcortical white matter, basal ganglia grey matter, internal and external capsule, thalamus, brain stem and cerebellum) according to the Brain Observer MicroBleed Scale (BOMBS)16.</li>
	<li>Label SLs and CMBs as strictly lobar SLs and CMBs, respectively, when they are confined to the lobar white matter. Label them as deep SLs and CMBs, respectively, when deep or infratentorial lesions are observed with and without additional lobar lesions17,18.</li>
	<li>Use T2-weighted and FLAIR images to identify WMHs (bilateral, almost symmetrical hyperintense areas) (Figure 2C). Re-confirm WMHs on T1-weighted images (as isointense or hypointense areas at the same locations). Recognize PVHs and DWMHs separately. Use the Fazekas scale to rate the severity of WMHs19.</li>
	<li>Rate PVHs appearing as &#34;caps&#34; or pencil-thin lining, smooth &#34;halo&#34; and irregular signal extending into the deep white matter as grade 1, 2 and 3, respectively. Rate DWMHs appearing as punctate foci, small confluent areas and large confluent areas as grade 1, 2 and 3, respectively.</li>
</ol>
4. Statistical analysis
<ol>
	<li>Perform all analyses using the statistical package SPSS 22.0 for MacBook.</li>
	<li>Transform the participant&#39;s score for each test using z transformation: 
	<img alt="Equation" src="/files/ftp_upload/61017/61017eq1.jpg" /></li>
	<li>Invert the Stroop test scores so that a higher score represents better performance.</li>
	<li>Calculate a compound score for each cognitive domain by averaging the mean z score of all component tests under the same domain8,9: 
	The compound score for executive function = (z score of backward digit span + z score of Stroop interference + z score of verbal fluency) / 3</li>
	<li>Use linear regression models to explore the association between each type of SCLs and cognitive function, adjusting for age, sex, and educational level. Perform further analyses after adjusting for vascular risk factors if significant associations are identified.</li>
	<li>Conduct additional analyses after further adjustment for the other types of SCLs in order to assess the independence of the association between the load of a specific type of SCLs and cognition.</li>
</ol>

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K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Atrophy+of+the+left+dorsolateral+prefrontal+cortex+is+associated+with+poor+performance+in+verbal+fluency+in+elderly+poststroke+women.">Atrophy of the left dorsolateral prefrontal cortex is associated with poor performance in verbal fluency in elderly poststroke women.</a> Neural Regeneration Research. 8 (4), 346-356 (2013).</li><li>Dufouil, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Severe+cerebral+white+matter+hyperintensities+predict+severe+cognitive+decline+in+patients+with+cerebrovascular+disease+history.">Severe cerebral white matter hyperintensities predict severe cognitive decline in patients with cerebrovascular disease history.</a> Stroke. 40 (6), 2219-2221 (2009).</li><li>Mungas, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Longitudinal+volumetric+MRI+change+and+rate+of+cognitive+decline.">Longitudinal volumetric MRI change and rate of cognitive decline.</a> Neurology. 65 (4), 565-571 (2005).</li><li>Benjamin, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lacunar+Infarcts,+but+Not+Perivascular+Spaces,+Are+Predictors+of+Cognitive+Decline+in+Cerebral+Small-Vessel+Disease.">Lacunar Infarcts, but Not Perivascular Spaces, Are Predictors of Cognitive Decline in Cerebral Small-Vessel Disease.</a> Stroke. 49 (3), 586-593 (2018).</li><li>Carey, C. 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The authors have no conflict of interest to declare.

In the study, we have combined the results of a battery of neuropsychological assessment and findings of a multi-sequence MRI examination to evaluate the impact of different types of SCLs on various cognitive functions. The major types of SCLs were examined (i.e., CMBs, SLs and WMHs). As previous studies have revealed that SCLs in different locations may represent different pathology and lead to different consequences, we categorized CMBs and SLs into strictly lobar (i.e., lobar only without deep ones) and deep ones (wit...

Silent lacunes (SLs), cerebral microbleeds (CMBs) and white matter hyperintensities (WMHs) are referred to as silent cerebrovascular lesions (SCLs). Two types of WMHs are recognized: periventricular WMHs (PVHs) and deep WMHs (DWMHs). SCLs were once regarded as benign lesions without clinical significance. After decades of research, SCLs are now confirmed to be linked to varying functional impairment and cognitive deficits1,2. Nevertheless, consistent evidence is still limited in the spectrum and magnitude of cognitive effects of different types of SCLs. Moreover, the underlying mechanisms are elusive.
Most previous studies either recruited hospital patients with severe medical conditions3,4,5 or included participants with advanced cerebral small vessel diseases6,7. The heterogeneity of the participants among different studies has partly contributed to the inconsistent results. To exclude these confounding factors, we conducted the current one-centered&#160;study as an attempt to provide a clear picture through assessment of a relatively large, pure cohort recruited from a primary care setting. Furthermore, previous studies have predominantly focused on one or two types of SCLs and did not fully evaluate the independent associations between individual SCLs and specific cognitive functions. Therefore, we assessed various types of SCLs in the current study.
Neuropsychological tests are widely used to assess cognitive function of specific domains. They are useful in differentiation between normal aging and early cognitive impairment. Results of properly conducted neuropsychological assessment are sensitive in discerning behavioral and functional deficits. A battery of structured neuropsychological tests was chosen, including forward and backward digit span tests, symbol digit modalities test (SDMT), Stroop test, verbal fluency test and Montreal Cognitive Assessment (MoCA). Scores from these tests were grouped and combined to represent performance in different cognitive domains8,9. Such a method is widely used and is time efficient. A major drawback is that different neuropsychological tests may partly overlap in their tested domains. A more specific alternative is to use computer-based assessment with well-designed modules constructed using the E-Prime system, which is time-consuming and may not be suitable for screening purposes.
In conclusion, we aimed to assess the associations between the burden of different SCLs and impairment of various cognitive domains. Furthermore, vascular risk factors and other types of SCLs were controlled for to determine the distinct and independent profile&#160;of cognitive impairment of each type of SCLs.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>3T MRI</td>
			<td>Philips Medical Systems</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

evaluation of the cognitive performance of hypertensive patients with silent cerebrovascular lesions

Evidence accumulated from the last decade has proven that silent cerebrovascular lesions (SCLs) and their underlying pathogenic processes contribute to cognitive decline in the elderly. However, the distinct effects of each type of the lesions on cognitive performance remain unclear. Moreover, research data from Chinese elderly with SCLs is scarce. In this study, 398 otherwise healthy hypertensive elderly subjects (median age 72 years) were included and assessed. All participates were required to complete a battery of structured neuropsychological assessment, including forward and backward digit span tests, symbol digit modalities test, Stroop test, verbal fluency test and Montreal Cognitive Assessment. These tests were used to assess attention, executive function, information processing speed, language, memory and visuospatial function. A multi-sequence 3T MRI scanning was arranged within one month of the neuropsychological assessment to evaluate the burden of SCLs. SCLs were rated visually. Cerebral microbleeds (CMBs) and silent lacunes (SLs) were identified as strictly lobar CMBs and SLs or deep CMBs and SLs according to their locations, respectively. Similarly, white matter hyperintensities (WMHs) were separated into periventricular WMHs (PVHs) and deep WMHs (DWMHs). A series of linear regression models were used to assess the correlation between each type of SCLs and individual cognitive function domain. The results showed that CMBs tend to impair language-related cognition. Deep SLs affect executive function, but this association disappeared after controlling for other types of SCLs. PVHs, rather than DWMHs, are associated with cognitive decline, especially in executive function and processing speed. It is concluded that different aspects of SCLs have differential impact on cognitive performance in hypertensive elderly Chinese.

The mean age of the 398 participants was 72.0 (from 65 to 99, SD = 5.1) years, and there were 213 men (53. 5%; Table 3). Table 4 summarizes the neuropsychological assessment results. Only 5 participants had all four types of SCLs. One or more types of SCLs were found in 169 (42.5%) participants, and 35 (8.8%) and 17 (4.3%) participants had 2 and 3 types of SCLs, respectively (Table 5).
<p class="jove_content" fo:keep-together.within-p...

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Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions

Here, we present a protocol to assess whether various types of silent cerebrovascular lesions are differentially associated with deficits in certain cognitive domains in a cohort of 398 hypertensive elderly Chinese, using a combination of neuropsychological tests and multi-sequence 3T MRI scanning.

Evidence accumulated from the last decade has proven that silent cerebrovascular lesions (SCLs) and their underlying pathogenic processes contribute to ...

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2.9K Views.  The First Affiliated Hospital of Wenzhou Medical University. Here, we present a protocol to assess whether various types of silent cerebrovascular lesions are differentially associated with deficits in certain cognitive domains in a cohort of 398 hypertensive elderly Chinese, using a combination of neuropsychological tests and multi-sequence 3T MRI scanning.

Video: Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions

A Method for Investigating Age-related Differences in the Functional Connectivity of Cognitive Control Networks Associated with Dimensional Change Card Sort Performance

The ability to adjust behavior to sudden changes in the environment develops gradually in childhood and adolescence. For example, in the Dimensional Change Card Sort task, participants switch from sorting cards one way, such as shape, to sorting them a different way, such as color. Adjusting behavior in this way exacts a small performance cost, or switch cost, such that responses are typically slower and more error-prone on switch trials in which the sorting rule changes as compared to repeat trials in which the sorting rule remains the same. The ability to flexibly adjust behavior is often said to develop gradually, in part because behavioral costs such as switch costs typically decrease with increasing age. Why aspects of higher-order cognition, such as behavioral flexibility, develop so gradually remains an open question. One hypothesis is that these changes occur in association with functional changes in broad-scale cognitive control networks. On this view, complex mental operations, such as switching, involve rapid interactions between several distributed brain regions, including those that update and maintain task rules, re-orient attention, and select behaviors. With development, functional connections between these regions strengthen, leading to faster and more efficient switching operations. The current video describes a method of testing this hypothesis through the collection and multivariate analysis of fMRI data from participants of different ages.

This video presents a method of examining age-related changes in functional connectivity of cognitive control networks engaged by targeted tasks/processes. The technique is based on multi-variate analysis of fMRI data.

The ability to adjust behavior to sudden changes in the environment develops gradually in childhood and adolescence. For example, in the Dimensional ...

Assessing Functional Performance in the Mdx Mouse Model

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder for which no cure is available. Nevertheless, several potential pharmaceutical compounds and gene therapy approaches have progressed into clinical trials. With improvement in muscle function being the most important end point in these trials, a lot of emphasis has been placed on setting up reliable, reproducible, and easy to perform functional tests to pre clinically assess muscle function, strength, condition, and coordination in the mdx mouse model for DMD. Both invasive and noninvasive tests are available. Tests that do not exacerbate the disease can be used to determine the natural history of the disease and the effects of therapeutic interventions (e.g. forelimb grip strength test, two different hanging tests using either a wire or a grid and rotarod running). Alternatively, forced treadmill running can be used to enhance disease progression and/or assess protective effects of therapeutic interventions on disease pathology. We here describe how to perform these most commonly used functional tests in a reliable and reproducible manner. Using these protocols based on standard operating procedures enables comparison of data between different laboratories.

Assessing Functional Performance in the Mdx Mouse Model

The primary outcome measure in clinical trials for neuromuscular disorders is generally improved muscle function. Therefore, assessing the effect of potential therapeutic compounds on muscle performance pre clinically in mouse models is of great importance. We here describe several functional tests to address this.

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder for which no cure is available. Nevertheless, several potential ...

Irrelevant Stimuli and Action Control: Analyzing the Influence of Ignored Stimuli via the Distractor-Response Binding Paradigm

Selection tasks in which simple stimuli (e.g. letters) are presented and a target stimulus has to be selected against one or more distractor stimuli are frequently used in the research on human action control. One important question in these settings is how distractor stimuli, competing with the target stimulus for a response, influence actions. The distractor-response binding paradigm can be used to investigate this influence. It is particular useful to separately analyze response retrieval and distractor inhibition effects. Computer-based experiments are used to collect the data (reaction times and error rates). In a number of sequentially presented pairs of stimulus arrays (prime-probe design), participants respond to targets while ignoring distractor stimuli. Importantly, the factors response relation in the arrays of each pair (repetition vs. change) and distractor relation (repetition vs. change) are varied orthogonally. The repetition of the same distractor then has a different effect depending on response relation (repetition vs. change) between arrays. This result pattern can be explained by response retrieval due to distractor repetition. In addition, distractor inhibition effects are indicated by a general advantage due to distractor repetition. The described paradigm has proven useful to determine relevant parameters for response retrieval effects on human action.

The distractor-response binding paradigm is described. It can be used to shed light on the influence irrelevant stimuli, competing with targets for a response, can have on human action. Both response retrieval effects and distractor inhibition effects can be analyzed within the paradigm.

Selection tasks in which simple stimuli (e.g. letters) are presented and a target stimulus has to be selected against one or more distractor stimuli are ...

The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice

Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many neuropsychiatric and neurodevelopmental disorders, including depression, post-traumatic stress disorder, schizophrenia and autism spectrum disorder. Deficits in cognitive function also represent the most difficult symptom domain&#160;to successfully treat, as serotonin reuptake inhibitors and tricyclic antidepressants have only modest effects. Functional neuroimaging studies and postmortem analysis of human brain tissue implicate the PFC as being a primary region of dysregulation in patients with these disorders. However, preclinical behavioral assays used to assess these deficits in mouse models which can be readily manipulated genetically and could provide the basis for studies of new treatment avenues have been underutilized. Here we describe the adaptation of a behavioral assay, the attentional set shifting task (AST), to be performed in mice to assess prefrontal cortex mediated cognitive deficits. The neural circuits underlying behavior during the AST are highly conserved across humans, nonhuman primates and rodents, providing excellent face, construct and predictive validity.

The goal of this protocol is to perform a behavioral assay such as the attentional set shifting task (AST) to assess prefrontal cortex-mediated cognitive flexibility in mice.

Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many ...

The Emotional Stroop Task: Assessing Cognitive Performance under Exposure to Emotional Content

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than to ink colors of neutral words. The difference shows that people are affected by the emotional content conveyed by the carrier words even though they are irrelevant to the color-naming task at hand. The ESE has been widely deployed with patient populations, as well as with non-selected populations, because the emotion words can be selected to match the tested pathology. The ESE is a powerful tool, yet it is vulnerable to various threats to its validity. This report refers to potential sources of confounding and includes a modal experiment that provides the means to control for them. The most prevalent threat to the validity of existing ESE studies is sustained effects and habituation wrought about by repeated exposure to emotion stimuli. Consequently, the order of exposure to emotion and neutral stimuli is of utmost importance. We show that in the standard design, only one specific order produces the ESE.

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than those of neutral words. This report refers to potential sources of confounding and includes a modal experiment that provides the means to control for them.

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than to ink colors of neutral words. The ...

A Pressure Injection System for Investigating the Neuropharmacology of Information Processing in Awake Behaving Macaque Monkey Cortex

The top-down modulation of feed-forward cortical information processing is functionally important for many cognitive processes, including the modulation of sensory information processing by attention. However, little is known about which neurotransmitter systems are involved in such modulations. A practical way to address this question is to combine single-cell recording with local and temporary neuropharmacological manipulation in a suitable animal model. Here we demonstrate a technique combining acute single-cell recordings with the injection of neuropharmacological agents in the direct vicinity of the recording electrode. The video shows the preparation of the pressure injection/recording system, including preparation of the substance to be injected. We show a rhesus monkey performing a visual attention task and the procedure of single-unit recording with block-wise pharmacological manipulations.

Here, we show the pressure injection of neuropharmacological substances during single-cell recording in an awake, behaving macaque monkey. This procedure allows pharmacological manipulation in the direct vicinity of a cortical recording site.

The top-down modulation of feed-forward cortical information processing is functionally important for many cognitive processes, including the modulation ...

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease

This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of four mountains within a computer-generated landscape is tested using a delayed match-to-sample paradigm. Allocentric spatial memory is assessed by altering the viewpoint, colors and textures between the initially presented and target images.
Allocentric spatial memory is a key function of the hippocampus, one of the earliest brain regions to be affected in Alzheimer&#39;s disease (AD) and impairment of hippocampal function predates the onset of dementia. It was hypothesized that performance on the 4MT would aid the diagnosis of predementia AD, which manifests clinically as Mild Cognitive Impairment (MCI).
The 4MT was applied to patients with MCI, stratified further based on cerebrospinal fluid (CSF) AD biomarker status (10 MCI biomarker positive, 9 MCI biomarker negative), and with mild AD dementia, as well as healthy controls. Comparator tests included tests of episodic memory and attention widely accepted as sensitive measures of early AD. Behavioral data were correlated with quantitative MRI measures of the hippocampus, precuneus and posterior cingulate gyrus.
4MT scores were significantly different between the two MCI groups (p = 0.001), with a test score of &#8804;8/15 associated with 100% sensitivity and 78% specificity for the classification of MCI with positive AD biomarkers, i.e., predementia AD. 4MT test scores correlated with hippocampal volume (r = 0.42) and cortical thickness of the precuneus (r = 0.55).
In conclusion, the 4MT is effective in identifying the early stages of AD. The short duration, easy application and scoring, and favorable psychometric properties of the 4MT fulfil the need for a simple but accurate diagnostic test for predementia AD.

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer&#039;s Disease

This article describes the 4 Mountains Test (4MT), a hippocampus-dependent test of working allocentric spatial memory. The hippocampus is affected early in Alzheimer's disease (AD) and this article outlines the 4MT methodology and results of patient testing, which demonstrates the value of the 4MT in the diagnosis of pre-dementia AD.

This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of ...

Eye-Tracking Control to Assess Cognitive Functions in Patients with Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with pathological involvement of upper and lower motoneurons, subsequently leading to progressive loss of motor and speech abilities. In addition, cognitive functions are impaired in a subset of patients. To evaluate these potential deficits in severely physically impaired ALS patients, eye-tracking is a promising means to conduct cognitive tests. The present article focuses on how eye movements, an indirect means of communication for physically disabled patients, can be utilized to allow for detailed neuropsychological assessment. The requirements, in terms of oculomotor parameters that have to be met for sufficient eye-tracking in ALS patients are presented. The properties of stimuli, including type of neuropsychological tests and style of presentation, best suited to successfully assess cognitive functioning, are also described. Furthermore, recommendations regarding procedural requirements are provided. Overall, this methodology provides a reliable, easy to administer and fast approach for assessing cognitive deficits in patients who are unable to speak or write such as patients with severe ALS. The only confounding factor might be deficits in voluntary eye movement control in a subset of ALS patients.

Cognitive deficits are common in about one third of patients with amyotrophic lateral sclerosis, a neurological condition leading to progressive impairments in speech and movement abilities. To conduct cognitive tests in patients unable to speak or write a reliable and easy to administer eye-tracking paradigm was developed.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with pathological involvement of upper and lower motoneurons, subsequently leading to ...

The Other End of the Leash: An Experimental Test to Analyze How Owners Interact with Their Pet Dogs

It has been suggested that the way in which owners interact with their dogs can largely vary and influence the dog-owner bond, but very few objective studies, so far, have addressed how the owner interacts with the dog. The goal of the present study was to record dog owners&#39; interaction styles by means of objective observation and coding. The experiment included eight standardized situations in which owners of pet dogs were asked to perform specific tasks including both positive (i.e. playing, teaching a new task, showing a preference towards an object in a food searching task, greeting after separation) and potentially distressing tasks (i.e. physical restriction during DNA sampling, putting a T-shirt onto the dog, giving basic obedience commands while the dog was distracted). The video recordings were coded off-line using a specifically designed coding scheme including scores for communication, social support, warmth, enthusiasm, and play style, as well as frequency of behaviors like petting, praising, commands, and attention sounds. Exploratory Factor Analysis of the 20 variables measured revealed 3 factors, labeled as Owner Warmth, Owner Social Support, and Owner Control, which can be viewed as analogues to parenting style dimensions. The experimental procedure introduced here represents the first standardized measure of interaction styles of dog owners. The methodology presented here is a useful tool to investigate individual variation in the interaction style of pet dog owners that can be used to explain differences in the dog-human relationship, dogs&#39; behavioral outcomes, and dogs stress coping strategies, all crucial elements both from a theoretical and applied point of view.

This article presents eight different experimental tasks, mirroring the everyday life of dogs and owners, used to analyze how owners interact with their dogs in a standardized way. The tasks included both positive (e.g. play) and negative (potentially stressful) situations (e.g. physical restriction).

It has been suggested that the way in which owners interact with their dogs can largely vary and influence the dog-owner bond, but very few objective ...

Virtual Reality Experiments with Physiological Measures

Virtual reality (VR) experiments are increasingly employed because of their internal and external validity compared to real-world observation and laboratory experiments, respectively. VR is especially useful for geographic visualizations and investigations of spatial behavior. In spatial behavior research, VR provides a platform for studying the relationship between navigation and physiological measures (e.g., skin conductance, heart rate, blood pressure). Specifically, physiological measures allow researchers to address novel questions and constrain previous theories of spatial abilities, strategies, and performance. For example, individual differences in navigation performance may be explained by the extent to which changes in arousal mediate the effects of task difficulty. However, the complexities in the design and implementation of VR experiments can distract experimenters from their primary research goals and introduce irregularities in data collection and analysis. To address these challenges, the Experiments in Virtual Environments (EVE) framework includes standardized modules such as participant training with the control interface, data collection using questionnaires, the synchronization of physiological measurements, and data storage. EVE also provides the necessary infrastructure for data management, visualization, and evaluation. The present paper describes a protocol that employs the EVE framework to conduct navigation experiments in VR with physiological sensors. The protocol lists the steps necessary for recruiting participants, attaching the physiological sensors, administering the experiment using EVE, and assessing the collected data with EVE evaluation tools. Overall, this protocol will facilitate future research by streamlining the design and implementation of VR experiments with physiological sensors.

Virtual reality (VR) experiments can be difficult to implement and require meticulous planning. This protocol describes a method for the design and implementation of VR experiments that collect physiological data from human participants. The Experiments in Virtual Environments (EVE) framework is employed to accelerate this process.