Altered Allocation of Vertical Attention in Individuals With Autism Spectrum Disorder.

BACKGROUND: Typical adults most frequently orient their attention to other people's eyes, whereas individuals with autism spectrum disorder (ASD) orient their attention to other people's mouths. Typical adults also reveal visuospatial biases on tasks such as vertical and horizontal line bisections. Therefore, the difference in face viewing might be related to a more general group difference in the allocation of vertical attention. OBJECTIVE: To use vertical line bisection and quadrisection tasks to evaluate whether individuals with ASD have a more downward-oriented vertical attentional bias than do typical individuals. METHOD: We recruited 20 individuals with ASD and 20 control participants matched for age (6-23 years), IQ, and sex. We asked the individuals to bisect and quadrisect lines on the top and bottom when the vertical lines were placed at the intersection of their right, left, and center egocentric sagittal planes and their coronal plane. The distances from the true midpoint and quadripoint were measured, and between-group performances were compared. RESULTS: No significant difference was found between the ASD and control groups for vertical line bisections or lower line quadrisections. However, when the ASD group was compared with the control group for higher line quadrisections, the ASD group exhibited a greater upward deviation. CONCLUSION: There is no downward vertical attentional spatial bias associated with ASD that could help to explain these individuals' attentional bias toward the mouth. However, additional studies are required to learn if this atypical upward vertical attentional bias might account for some of the symptoms and signs associated with ASD.

The Effects of Transcutaneous Vagus Nerve Stimulation on Functional Connectivity Within Semantic and Hippocampal Networks in Mild Cognitive Impairment.

Better treatments are needed to improve cognition and brain health in people with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Transcutaneous vagus nerve stimulation (tVNS) may impact brain networks relevant to AD through multiple mechanisms including, but not limited to, projection to the locus coeruleus, the brain's primary source of norepinephrine, and reduction in inflammation. Neuropathological data suggest that the locus coeruleus may be an early site of tau pathology in AD. Thus, tVNS may modify the activity of networks that are impaired and progressively deteriorate in patients with MCI and AD. Fifty patients with MCI (28 women) confirmed via diagnostic consensus conference prior to MRI (sources of info: Montreal Cognitive Assessment Test (MOCA), Clinical Dementia Rating scale (CDR), Functional Activities Questionnaire (FAQ), Hopkins Verbal Learning Test - Revised (HVLT-R) and medical record review) underwent resting state functional magnetic resonance imaging (fMRI) on a Siemens 3 T scanner during tVNS (left tragus, n = 25) or sham control conditions (left ear lobe, n = 25). During unilateral left tVNS, compared with ear lobe stimulation, patients with MCI showed alterations in functional connectivity between regions of the brain that are important in semantic and salience functions including regions of the temporal and parietal lobes. Furthermore, connectivity from hippocampi to several cortical and subcortical clusters of ROIs also demonstrated change with tVNS compared with ear lobe stimulation. In conclusion, tVNS modified the activity of brain networks in which disruption correlates with deterioration in AD. These findings suggest afferent target engagement of tVNS, which carries implications for the development of noninvasive therapeutic intervention in the MCI population.

The functional connectivity and neuropsychology underlying mental planning operations: data from the digital clock drawing test.

We examined the construct of mental planning by quantifying digital clock drawing digit placement accuracy in command and copy conditions, and by investigating its underlying neuropsychological correlates and functional connectivity. We hypothesized greater digit misplacement would associate with attention, abstract reasoning, and visuospatial function, as well as functional connectivity from a major source of acetylcholine throughout the brain: the basal nucleus of Meynert (BNM). Participants (n = 201) included non-demented older adults who completed all metrics within 24 h of one another. A participant subset met research criteria for mild cognitive impairment (MCI; n = 28) and was compared to non-MCI participants on digit misplacement accuracy and expected functional connectivity differences. Digit misplacement and a comparison dissociate variable of total completion time were acquired for command and copy conditions. a priori fMRI seeds were the bilateral BNM. Command digit misplacement is negatively associated with semantics, visuospatial, visuoconstructional, and reasoning (p's < 0.01) and negatively associated with connectivity from the BNM to the anterior cingulate cortex (ACC; p = 0.001). Individuals with MCI had more misplacement and less BNM-ACC connectivity (p = 0.007). Total completion time involved posterior and cerebellar associations only. Findings suggest clock drawing digit placement accuracy may be a unique metric of mental planning and provide insight into neurodegenerative disease.

Hemodialyzed Individuals' Left Spatial Attentional Bias Is Normalized Following Successful Kidney Transplantation.

BACKGROUND: Healthy people have a leftward spatial attentional bias, called pseudoneglect. Individuals with end-stage renal disease (ESRD) who are receiving hemodialysis often demonstrate an increase in their leftward spatial attentional bias. Whereas a successful kidney transplant often improves the cognitive functions of individuals who previously received hemodialysis, the effect of a kidney transplant on this abnormal allocation of spatial attention has not been investigated. OBJECTIVE: To investigate the effects of kidney transplant on individuals who were being treated with dialysis and had an increase in their left spatial attentional bias. METHOD: The performance of 20 hemodialyzed individuals with ESRD on the line bisection test was compared to that of 17 demographically matched individuals with ESRD, who had received a kidney transplant, and 23 demographically matched healthy controls (HC). RESULTS: All of the participants exhibited a left spatial bias on the line bisection task. When compared with the HC, the hemodialyzed individuals demonstrated a significantly greater left spatial bias. There was, however, no difference in spatial bias between the HC and the individuals who had received a kidney transplant. CONCLUSION: A successful kidney transplant can improve patients' abnormal leftward allocation of spatial attention. However, future studies are needed to better understand the mechanisms of this spatial attentional bias in hemodialyzed individuals and the normalization of bias following transplantation.

Emotional and Neuropsychiatric Disorders Associated with Alzheimer's Disease.

Alzheimer's disease is associated with impairments in emotional communication including comprehension and production of facial emotional expressions, comprehension of affective prosody, and alexithymia. It is also associated with disorders of emotional experience including mood disorders (depression and anxiety), agitation/aggression, and psychosis. Agitation/aggression and psychosis are particularly disruptive, are associated with earlier institutionalization, and pose a major challenge to institutional management. Treatment of disorders of emotional experience has been primarily pharmacologic (reviewed here in detail) and has relied heavily on antipsychotic medications despite the small effect sizes demonstrated in a large number of randomized controlled trials and the prevalence of serious side effects associated with these drugs. Recent studies suggest that treatment with pimavanserin, an antipsychotic without activity at dopamine receptors, may represent an important advance for treatment of psychotic manifestations, even as the drug appears to pose significant risk. Dextromethorphan/quinidine may represent an important advance in the treatment of agitation/aggression. There is also compelling evidence that sleep disorders, which are common among patients with Alzheimer's disease and are readily treatable, may potentiate psychotic manifestations and agitation/aggression, but further studies are needed.

Spatial artistic displays of emotional valence.

Background: While right-left hemispheric valence dichotomies have been demosntrated in various lesion stidues, it not entirely known if these dichotomies are portrayed in art. Methods: We examined 192 paintings to learn if there is an association between paintings that portray happy-positive or sad-negative scenes and the agent looking to the right or left side relative to their head's midsagittal plane. Results: There were 38 paintings with a positive valence and 32 with a negative valence in which the eyes were turned rightward or leftward. Of 38 positive valence paintings, 28 had the agent looking rightward, and 10 looking leftward. Of 32 negative valence paintings, 15 had the agent looking rightward and 17 leftward. Discussion: Hemisphere activation is associated with contralateral deviation of the eyes. Whereas the right hemisphere mediates negative emotions allocates spatial attention to both left and right hemispace, the left hemisphere primarily allocates attention to the right. Since the left hemisphere appears to mediate positive emotions and the right hemisphere negative emotions, results from this study are consistent with hemispheric emotional valence attentional hypotheses. However, the relationship between artist knowledge about gaze and the utilization of gaze direction to portray emotional experiences is not known.

Upper Limb Apraxia.

PURPOSE OF REVIEW: Limb apraxia is one of the most common and most disabling disorders caused by brain damage. However, apraxia is one of the least recognized disorders associated with cerebral disease. This article discusses the signs and symptoms of, means of testing for, the pathophysiology of, and possible management of upper limb apraxia. RECENT FINDINGS: Upper limb apraxia has four major forms: ideomotor, limb-kinetic, conceptual, and ideational. Although recent findings are included in this article, a full understanding of these disorders, including the means of testing, their possible pathophysiology, and the diseases that may cause these disorders, requires that some older literature is also discussed. SUMMARY: This article guides clinicians in testing for and diagnosing the different forms of upper limb apraxia, identifying the underlying diseases that may cause apraxia, managing the different forms of the disorder, and possible forms of rehabilitation.

The Allocation of Vertical Attention in Patients with End-Stage Renal Disease Receiving Dialysis.

Objectives: Alterations of spatial attention can have adverse effects, such a greater probability of accidents. Patients with end-stage renal disease (ESRD) receiving dialysis have stronger left-sided spatial attentional bias, suggesting that this disorder or treatment alters the brain networks that mediate spatial attention. The hemispheric networks that mediate the allocation of horizontal attention may also influence the allocation of vertical attention. However, the allocation of vertical spatial attention has not been studied in ESRD patients. Methods: Twenty-three ESRD patients receiving dialysis and 23 healthy right-handed controls performed line bisections using 24 vertical lines (24 cm long and 2 mm thick) aligned with the intersection of their midsagittal and coronal planes. Results: Hemodialyzed ESRD patients had a significantly greater upward bias than healthy controls. The magnitude of this bias was correlated with the duration of the kidney disease. Conclusions: The reason why upward attentional bias is increased in hemodialyzed ESRD patients is not known. Further research is needed to better understand the brain mechanism that might account for this bias, as well as its treatment. However, hemodialyzed ESRD patients and their families-caregivers should be made aware of this disorder to avoid accidents such as tripping.

Kidney transplantation and action-intentional improvements: Evidence from an ERP study.

Reaction slowing observed in dialyzed patients results from deficits in initiating and sustaining motor response mobilization. The present study aimed at investigating whether these deficits are reversible following successful kidney transplantation. To achieve this goal, behavioral and electrophysiological (EEG) data were assessed from healthy control participants as well as kidney transplant and dialyzed patients performing a series of reaction time tasks. The results demonstrated that in patients who received kidney transplant a normalization of response latencies and brain preparatory activity was observed. At the same time, when compared to healthy individuals, increased attention engagement was observed in both clinical groups of patients. No behavioral and electrophysiological indices of impaired monitoring were observed in any of the clinical groups.

Emotion and mood disorders associated with epilepsy.

Epilepsy is a disorder characterized by recurrent seizures. Epilepsy can alter mood and emotions. Treatments for epilepsy can also alter mood and emotions. This chapter reviews the emotional changes that can occur before, during, and after a seizure, such as fear and anger, the interictal mood disorders associated with epilepsy, such as depression and anxiety, as well as alterations of emotional processing including comprehending and expressing emotional prosody and faces. The possible treatments of these emotional and mood disorders are also reviewed.

Disorders of facial emotional expression and comprehension.

One of the most important means of communicating emotions is by facial expressions. About 30-40 years ago, several studies examined patients with right and left hemisphere strokes for deficits in expressing and comprehending emotional facial expressions. The participants with right- or left-hemispheric strokes attempted to determine if two different actors were displaying the same or different emotions, to name the different emotions being displayed, and to select the face displaying an emotion named by the examiner. Investigators found that the right hemisphere-damaged group was impaired on all these emotional facial tests and that this deficit was not solely related to visuoperceptual processing defects. Further studies revealed that the patients who were impaired at recognizing emotional facial expressions and who had lost these visual representations of emotional faces often had damage to their right parietal lobe and their right somatosensory cortex. Injury to the cerebellum has been reported to impair emotional facial recognition, as have dementing diseases such as Alzheimer's disease and frontotemporal dementia, movement disorders such as Parkinson's disease and Huntington's disease, traumatic brain injuries, and temporal lobe epilepsy. Patients with right hemisphere injury are also more impaired than left-hemisphere-damaged patients when attempting to voluntarily produce facial emotional expressions and in their spontaneous expression of emotions in response to stimuli. This impairment does not appear to be induced by emotional conceptual deficits or an inability to experience emotions. Many of the disorders that cause impairments of comprehension of affective facial expressions also impair facial emotional expression. Treating the underlying disease may help patients with impairments of facial emotion recognition and expression, but unfortunately, there have not been many studies of rehabilitation.

Normative References for Graphomotor and Latency Digital Clock Drawing Metrics for Adults Age 55 and Older: Operationalizing the Production of a Normal Appearing Clock.

BACKGROUND: Relative to the abundance of publications on dementia and clock drawing, there is limited literature operationalizing 'normal' clock production. OBJECTIVE: To operationalize subtle behavioral patterns seen in normal digital clock drawing to command and copy conditions. METHODS: From two research cohorts of cognitively-well participants age 55 plus who completed digital clock drawing to command and copy conditions (n = 430), we examined variables operationalizing clock face construction, digit placement, clock hand construction, and a variety of time-based, latency measures. Data are stratified by age, education, handedness, and number anchoring. RESULTS: Normative data are provided in supplementary tables. Typical errors reported in clock research with dementia were largely absent. Adults age 55 plus produce symmetric clock faces with one stroke, with minimal overshoot and digit misplacement, and hands with expected hour hand to minute hand ratio. Data suggest digitally acquired graphomotor and latency differences based on handedness, age, education, and anchoring. CONCLUSION: Data provide useful benchmarks from which to assess digital clock drawing performance in Alzheimer's disease and related dementias.

Proof of concept: digital clock drawing behaviors prior to transcatheter aortic valve replacement may predict length of hospital stay and cost of care.

AIMS: Reduced pre-operative cognitive functioning in older adults is a risk factor for postoperative complications, but it is unknown if preoperative digitally-acquired clock drawing test (CDT) cognitive screening variables, which allow for more nuanced examination of patient performance, may predict lengthier hospital stay and greater cost of hospital care. This issue is particularly relevant for older adults undergoing transcatheter aortic valve replacement (TAVR), as this surgical procedure is chosen for intermediate-risk older adults needing aortic replacement. This proof of concept research explored if specific latency and graphomotor variables indicative of planning from digitally-acquired command and copy clock drawing would predict post-TAVR duration and cost of hospitalization, over and above age, education, American Society of Anesthesiologists (ASA) physical status classification score, and frailty. METHODS: Form January 2018 to December 2019, 162 out of 190 individuals electing TAVR completed digital clock drawing as part of a hospital wide cognitive screening program. Separate hierarchical regressions were computed for the command and copy conditions of the CDT and assessed how a-priori selected clock drawing metrics (total time to completion, ideal digit placement difference, and hour hand distance from center; included within the same block) incrementally predicted outcome, as measured by R2 change significance values. RESULTS: Above and beyond age, education, ASA physical status classification score, and frailty, only digitally-acquired CDT copy performance explained significant variance for length of hospital stay (9.5%) and cost of care (8.9%). CONCLUSIONS: Digital variables from clock copy condition provided predictive value over common demographic and comorbidity variables. We hypothesize this is due to the sensitivity of the copy condition to executive dysfunction, as has been shown in previous studies for subtypes of cognitive impairment. Individuals undergoing TAVR procedures are often frail and executively compromised due to their cerebrovascular disease. We encourage additional research on the value of digitally-acquired clock drawing within different surgery types. Type of cognitive impairment and the value of digitally-acquired CDT command and copy parameters in other surgeries remain unknown.

Right up- left down.

BACKGROUND: When performing the clock-drawing test healthy participants often draw the clock face using a counter clockwise movement. The reason for this circular directional bias is not known. These actions may be related to the development of motor or attentional programs that associate leftward with downward movements, and rightward with upward movements. METHODS: To further examine this down-left, up-right programming hypothesis, we examined the direction of circular movements made during cursive writing by dividing the first curved movements into the following pairs, up versus down, and leftward versus rightward. RESULTS AND CONCLUSIONS: With almost all the letters analyzed, when initially moving upward there was a simultaneous rightward movement and when initially moving downward a leftward movement. The results suggest that there appears to be a relationship between downward and leftward movements as well as between upward and right rightward movements. In addition, there is some evidence to suggest that the right-upward movements may be mediated by the left hemisphere and left-downward movements by the right hemisphere. Although our results suggest motor or spatial attentional programs may account for counter clockwise face drawing, activities such as learned writing direction may influence this spatial bias. Therefore, additional research is needed to better understand if these spatial biases are learned or intrinsic and the neuropsychological mechanisms that might account for these asymmetries.

Pilot Investigation: Older Adults With Atrial Fibrillation Demonstrate Greater Brain Leukoaraiosis in Infracortical and Deep Regions Relative to Non-Atrial Fibrillation Peers.

BACKGROUND: This pilot study explored differences in distribution of white matter hyperintensities (called leukoaraiosis; LA) in older adults (mean age = 67 years) with atrial fibrillation (AF) vs. non-AF peers measured by: (1) depth distribution; (2) anterior-posterior distribution; (3) associations between LA and cortical thickness; and (4) presence of lacunae and stroke. METHODS: Participant data (AF n = 17; non-AF peers n = 17) were acquired with the same magnetic resonance imaging protocols. LA volume was quantified by cortical depth (periventricular, deep, infracortical) and in anterior and posterior regions. Cortical thickness by lobe was assessed relative to LA load. RESULTS: Relative to non-AF peers, the AF group had twice the total LA volume (AF = 2.1% vs. Non-AF = 0.9%), over 10 times greater infracortical LA (AF = 0.72% vs. Non-AF = 0.07%), and three times greater deep LA (AF = 2.1% vs. Non-AF = 0.6%). Examinations of the extent of LA in anterior vs. posterior regions revealed a trend for more posterior relative to anterior LA. In the entire sample, total LA and infracortical LA were negatively associated with temporal lobe thickness. Only those with AF presented with lacunae or stroke. CONCLUSION: Aging adults with AF had more total white matter disease than those without AF, particularly near the cortical mantle and deep within the cortex. Total and infracortical white matter disease in the entire sample negatively associated with temporal lobe thickness. Results suggest that those with AF have a distinct pattern of LA relative to those without AF, and that LA severity for all individuals may associate with structural changes in the cortex.

Musical hallucinations with a right frontotemporal stroke.

MUSICAL HALLUCINATIONS: have been reported in association with psychiatric diseases, brain stem strokes, deafness, degenerative diseases, intoxications, pharmacologic agents, and epilepsy. We present a patient who in the absence of these disorders developed musical hallucinations from an infarction of the right hemisphere that primarily injured his right frontal and anterior temporal lobes. This report discusses some of the possible mechanisms for this patient's presentation. Although the mechanism of his musical hallucinations remains unclear, recognition of this uncommon syndrome is important when structuring rehabilitation and management for patients with stroke who have this disorder.

Hugo Liepmann, Parkinson's disease and upper limb apraxia.

It has now been 100 years since Hugo Liepmann, in his classic 1920 paper described limb kinetic, ideomotor, and ideational apraxia. There are now several rating scales used to assess and grade the signs and symptoms associated with Parkinson's disease; however, none of these assesses patients for the presence of these disabling forms of upper limb apraxia. This paper, reviews the four types of apraxia that can be associated with Parkinson's disease, how they can be tested, the disabilities associated with these disorders and possible treatments.

Degenerative dementia with proximal radial and lower vertical spatial neglect.

A 75 year-old man had a two-year history of progressive memory loss, trouble with finances and getting lost. On examination, he scored 16/30 in MoCA test, noticeably impaired on the attentional tasks. His screening bloodtests werenormal. Brain imaging revealed hippocampal atrophy and bilaterallarge areas of leukoaraiosis below posterior parietal lobes. On vertical line bisection he revealed a large upward bias and on radial bisection, a distal bias. Degeneration of his posterior parietal cortex may have caused both the leukoaraiosis and vertical-radial neglect. Unawareness of portions of space can be a source of disability and cause injury. Therefore, patients with degenerative dementia, especially those with similar patterns of leukoaraiosis or parietal degeneration should be tested for vertical and radial forms of spatial neglect.