Vertical pseudoneglect: Sensory-attentional versus action-intentional.

INTRODUCTION: Healthy persons demonstrate an upward bias on the vertical-line bisection test (vertical or "altitudinal" pseudoneglect). This bias might be sensory-attentional or action-intentional in origin. To test the action-intention hypothesis, we analyze whether the direction of action has an effect on altitudinal pseudoneglect. METHODS: Twenty-four healthy right-handed adults performed vertical-line bisection on an apparatus designed to distinguish the effects of sensory-attention and action-intention. Depending on hand placement, participants estimated line midpoints with a marker that moved in the same (congruent) or opposite (incongruent) direction as their hand movements. Two binary factors - hand movement in the upward versus downward direction and congruent vs incongruent hand movements - produced four conditions. RESULTS: There was upward deviation from the midline across all conditions. Bisections in the incongruent condition were higher than in the congruent condition. Bisections were also higher with upward hand movements than with downward hand movements. There was not a significant interaction between these factors. CONCLUSIONS: These results suggest that vertical pseudoneglect is primarily influenced by the allocation of allocentric attention, rather than action-intention. However, action-perceptual spatial incongruence increased this deviation. Perhaps the incongruent condition requires greater allocation of attention, but further exploration is needed. Additionally, these results suggest that visual attention follows the direction of motor action. Future studies of visual attention should consider the potential influence of this factor.

Relationships between respiratory sinus arrhythmia and stress in college students.

The purpose of this study was to examine the relationships between university students' respiratory sinus arrhythmia (RSA) profiles and both retrospective and momentary ratings of stress. Participants were undergraduate students enrolled in an introductory health science course (N = 64). Participants provided RSA data at rest (tonic) and following an orthostatic challenge (phasic), completed the 10-item Perceived Stress Scale (PSS), and completed 6 daily ecological momentary assessments (EMA) of stress for 1 week. Higher tonic RSA was associated with lower perceived stress assessed via PSS and average EMA responses. Those with higher tonic RSA did not differ in their experience of stress across the week, whereas those with lower tonic RSA experienced increased stress across the week, and these trajectories varied as a function of phasic responses. These findings suggest a need for greater emphasis on behavioral strategies for maintaining and enhancing autonomic nervous system health among college students.

Unilateral Apraxic Agraphia without Ideomotor Apraxia from a callosal lesion in a patient with Marchiafava-Bignami disease.

Apraxic agraphia can be caused by left hemispheric cerebral lesions in the area that contains the spatial representations of the movements required to write, from a lesion in, or connections to, the frontal premotor cortex that converts these spatial representations to motor programs (Exner's area).  A right-handed woman with Marchiafava Bignami disease and lesions of the genu and splenium of her corpus callosum had apraxic agraphia without ideomotor apraxia of her left. A disconnection of Exner's area in the left hemisphere from the right hemisphere's premotor and motor areas may have led to her inability to write with her left hand.

The visual kinetic depth effect is altered with Parkinson's disease.

BACKGROUND: People with Parkinson's disease (PD) often have visual-perceptual disorders. The goal of this study was to learn if they can develop a three dimensional (3D) percept that depends on the kinetic depth effect; that is, the viewer's ability to spatially integrate over time images that are moving along many trajectories. METHODS: Sixteen patients with PD and 12 healthy matched controls were presented with stimuli that were comprised of a circular region of randomly placed dots that moved as orthographic projections of a sphere. With a normal kinetic depth effect, the Training stimuli appear as an opaque rotating ball and the Test stimuli appear as a rotating transparent ball. RESULTS: Whereas all controls and all PD patients reported seeing the Training stimuli as a rotating ball, the patients with PD were significantly less likely to report the Test stimuli appearing as a 3D "ball" than were the healthy participants. Instead, seven PD patients often reported these bidirectional stimuli appeared "flat." CONCLUSIONS: This study has revealed that some patients with PD have impaired spatio-temporal integration of bidirectional visual motions, but the mechanism accounting for this loss, as well as why only some patients had this deficit, needs further study. When the driver of a moving vehicle fixates upon a stationary target in the surroundings, bidirectional retinal image motions may occur. Failure to perceive 3D structure in such moving scenes can be plausibly suspected to contribute to adverse events such as auto accidents.

Differences in B7 and CD28 family gene expression in the peripheral blood between newly diagnosed young-onset and adult-onset type 1 diabetes patients.

Type-1 diabetes (T1D) is a heterogeneous autoimmune disease, and there are pathogenetic differences between young- and adult-onset T1D patients. We hypothesized that the expressions of genes involved in costimulatory immune system pathways in peripheral blood are differently regulated in young- and adult-onset T1D. Study group I consisted of 80 children, adolescents, and young adults (age range 1.4-21.4 y; 31 controls and 49 T1D patients). Study group II consisted of 48 adults (age range 22.0-78.4 y; 30 controls and 18 T1D patients). The mRNA expression levels of CD86, CD28, CD25, CD226, CD40, BTLA, GITR, PDCD1, FoxP3, TGF-ß, ICOS, sCTLA4, flCTLA4, and CD80 were measured in peripheral blood. Genetic polymorphisms (HLA haplotypes; rs231806, rs231775, and rs3087243 in CTLA4; rs763361 in CD226; and rs706778 in CD25) and T1D-associated autoantibodies were analyzed. In group I, there was significantly lower expression of CD226 in T1D patients than in the controls. In group II, there were significantly higher expression levels of CD86 and TGF-ß in T1D patients than in the controls. In the T1D patients in group I, the upregulated CD80 expression correlated with the expression of both CTLA4 splice variants (sCTLA4 and flCTLA4). In contrast, in group II, upregulated CD86 correlated with TGF-ß and CD25. In group I, the inhibitory CD80-CTLA4 pathway was activated, whereas, in group II, the activation CD86-CD28 pathway and TGF-ß production were activated. These results emphasize the differences between young-onset and adult-onset T1D in the regulation of costimulatory pathways. These differences should be considered when developing novel treatments for T1D.

A full-brain, bootstrapped analysis of diffusion tensor imaging robustly differentiates Parkinson disease from healthy controls.

There is a compelling need for early, accurate diagnosis of Parkinson's disease (PD). Various magnetic resonance imaging modalities are being explored as an adjunct to diagnosis. A significant challenge in using MR imaging for diagnosis is developing appropriate algorithms for extracting diagnostically relevant information from brain images. In previous work, we have demonstrated that individual subject variability can have a substantial effect on identifying and determining the borders of regions of analysis, and that this variability may impact on prediction accuracy. In this paper we evaluate a new statistical algorithm to determine if we can improve accuracy of prediction using a subjects left-out validation of a DTI analysis. Twenty subjects with PD and 22 healthy controls were imaged to evaluate if a full brain diffusion tensor imaging-fractional anisotropy (DTI-FA) map might be capable of segregating PD from controls. In this paper, we present a new statistical algorithm based on bootstrapping. We compare the capacity of this algorithm to classify the identity of subjects left out of the analysis with the accuracy of other statistical techniques, including standard cluster-thresholding. The bootstrapped analysis approach was able to correctly discriminate the 20 subjects with PD from the 22 healthy controls (area under the receiver operator curve or AUROC 0.90); however the sensitivity and specificity of standard cluster-thresholding techniques at various voxel-specific thresholds were less effective (AUROC 0.72-0.75). Based on these results sufficient information to generate diagnostically relevant statistical maps may already be collected by current MRI scanners. We present one statistical technique that might be used to extract diagnostically relevant information from a full brain analysis.

Interferon and interferon-inducible gene activation in patients with type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease that is thought to be triggered by environmental factors in genetically susceptible individuals. Enteroviruses have been mentioned as the most probable induction component of the disease. Nevertheless, the literature is controversial regarding the association of T1D with viral infection and first-line antiviral defence components, for example type I interferons (IFNs). Our aim was to test the hypothesis that an abnormality in IFN-stimulated gene patterns may cause a failure in immunological tolerance and, thereby, initiate T1D as an autoimmune disorder. We studied material from 64 T1D and 36 control subjects, divided into two age groups: <10 years and ≥10 years old. Using a relative gene expression method, we observed a lower expression of interferon-induced helicase 1 (IFIH1) and other type I IFN-induced genes in the blood cells of T1D subjects, especially subjects under 10 years old, in spite of their higher IFN levels as measured by the pSTAT1-inducing capacity of their sera. Likewise, freshly purified CpG-stimulated cells from T1D patients showed significantly lower upregulation of IFN-induced genes, that is IFIH1 and CXCL10, compared to cells from the control group. The identified dysregulation in the IFN-α-induced antiviral response in T1D patients, especially in early childhood, could be one of the factors affecting T1D development.

Callosal disconnection and limb-kinetic apraxia.

According to Liepmann, patients with limb-kinetic apraxia (LKA) have a loss of upper limb deftness-dexterity. Prior studies have revealed in right-handed patients that, whereas injury of the left hemisphere induces an ipsilesional LKA, injury to the right hemisphere does not induce an ipsilesional LKA. There are at least two possible means by which the left hemisphere may influence the deftness of the left hand, either by callosal connections or by ipsilesional corticospinal projections. The purpose of this study was to learn whether a patient with a focal lesion of the corpus callosum had a callosal disconnection LKA. This 57-year-old right-handed man had a memory impairment, and upon brain imaging, was found to have a septum pellucidum cyst, which was causing mild ventricular obstruction to the occipital and temporal horns. He underwent an endoscopic-assisted fenestration of the septum pellucidum. Postoperative imaging revealed a lesion of the mesial portion of his corpus callosum and an assessment of praxis revealed that he had both a limb-kinetic and ideomotor apraxia of his left but not his right hand. The observation that this man had a callosal disconnection LKA of his left hand suggests that in some people it is the left hemisphere's premotor or motor cortex that enables the right hemisphere's motor system to program deft movements of the left hand.

Affective communication deficits associated with cerebellar degeneration.

The cerebellum has extensive connections with the frontal lobes. Cerebellar injury has been reported to induce frontal-executive cognitive dysfunction and blunting of affect. We examined a patient with idiopathic cerebellar degeneration with impaired family relationships attributed to an "emotional disconnection." Examination revealed ataxia, dysmetria, and adiadochokinesia more severe on the left and frontal-executive dysfunction; memory and cognitive functions were otherwise normal. Testing of emotional communication included assessments of emotional semantic knowledge, emotional prosody, and emotional facial expressions. Comprehension was normal but expression was severely impaired. Cerebellar dysfunction can cause a defect in facial and prosodic emotional communication.

Atypical autonomic regulation, auditory processing, and affect recognition in women with HIV.

This study examined the effect of HIV on visceromotor (i.e., heart rate and heart rate variability) and somatomotor (i.e., auditory processing and affect recognition) components of a Social Engagement System defined by the Polyvagal Theory (Porges, 1995) that links vagal regulation of the heart with brainstem regulation of the striated muscles of the face and head. Relative to at risk HIV-seronegative women, HIV-seropositive women had less heart rate variability (i.e., respiratory sinus arrhythmia) and had poorer performance on auditory processing and affect recognition tasks. CD4 was negatively correlated with the accuracy to detect specific emotions. The observed indices of atypical autonomic and behavioral regulation may contribute to greater difficulties in social behavior and social communication between HIV-infected women and other individuals in their social network.

Reliability analysis of the resting state can sensitively and specifically identify the presence of Parkinson disease.

Parkinson disease (PD) is characterized by a number of motor and behavioral abnormalities that could be considered deficits of a "no task" or "resting" state, including resting motor findings and defects in emerging from a resting state (e.g., resting tremor, elevated resting tone, abulia, akinesia, apathy). PET imaging, and recently, the MRI technique of continuous arterial spin labeling (CASL) have shown evidence of changes in metabolic patterns in individuals with PD. The purpose of this study was to learn if the presence of PD could be "predicted" based on resting fluctuations of the BOLD signal. Participants were 15 healthy controls, 14 subjects with PD, and 1 subject who presented as a control but later developed PD. The amplitude of the low frequency fluctuation (ALFF) was used as an index of brain activity level in the resting state. Participants with PD using this index showed a reliable decrease in activity in a number of regions, including the supplementary motor cortex, the mesial prefrontal cortex, the right middle frontal gyrus, and the left cerebellum (lobule VII/VIII) as well as increased activity in the right cerebellum (lobule IV/V). Using a cross validation approach we term "Reliability Mapping of Regional Differences" (RMRD) to analyze our sample, we were able to reliably distinguish participants with PD from controls with 92% sensitivity and 87% specificity. Our "pre-diagnostic" subject segregated in our analysis with the PD group. These results suggest that resting fMRI should be considered for development as a biomarker and analytical tool for evaluation of PD.

Apathy, depression, and motor symptoms have distinct and separable resting activity patterns in idiopathic Parkinson disease.

Apathy and depression are heterogeneous syndromes with symptoms that overlap clinically. This clinical overlap leads to problems with classification and diagnosis in clinical populations. No functional imaging study has attempted to separate brain regions altered in apathy from those altered in depression in a clinical population. Parkinson disease (PD) is a disorder in which apathy and depression co-exist in a single population. We evaluate the relationship between apathy, depression, and motor severity of disease in PD, focusing on the relationship between these factors and the amplitude of the low frequency fluctuation (ALFF) in the resting state. We first evaluated if the resting ALFF signal is a reliable measure for our clinical question. For this, we develop and introduce a cross validation approach we term the "Regional Mapping of Reliable Differences" (RMRD) method to evaluate reliability of regions of interest deemed "significant" by standard voxel-wise techniques. Using this approach, we show that the apathy score in this sample is best predicted by ALFF signal in the left supplementary motor cortex, the right orbitofrontal cortex, and the right middle frontal cortex, whereas depression score is best predicted by ALFF signal in the right subgenual cingulate. Disease severity was best predicted by ALFF signal in the right putamen. A number of additional regions are also statistically (but not reliably) correlated with our neuropsychological measures and disease severity. Our results support the use of resting fMRI as a means to evaluate neuropsychiatric states and motor disease progression in Parkinson disease, and the clinical and epidemiologic observation that apathy and depression are distinct pathological entities. Our finding that "significance" and "reliability" are dissociated properties of regions of interest identified as significant using standard voxel-wise techniques suggests that including reliability analyses may add useful scientific information in neurobehavioral research.

The effects of cerebral white matter changes on cardiovascular responses to cognitive and physical activity in a stroke population.

Autonomic nervous system (ANS) control may be disrupted by cerebrovascular disease. We investigated the relationship between alterations in white matter integrity and regulation of the ANS in 23 participants who sustained a stroke within 5 years. These participants underwent diffusion tensor imaging, and fractional anisotropy values were calculated (DTI-FA) for each hemisphere and lobe. Cognitive and physical exertion tasks were performed while recording an electrocardiogram. Respiratory sinus arrhythmia (RSA) decreased more during a verbal fluency task with lower left hemisphere DTI-FA. Further, the physical stressor yielded decreases in RSA with lower frontal DTI-FA and higher temporal lobe DTI-FA, p < .05 (perhaps a release effect on the central autonomic network). Decrements in ANS regulation may have functional consequences that alter behavior, as well as potentially increasing the risk for further vascular disease.

Emotional indifference in Alzheimer's disease.

One of the most common and disabling symptoms of Alzheimer's disease is apathy. Patients with Alzheimer's disease might appear apathetic for several reasons, including deficits in emotional communication, presence of depression, perceptual-semantic-cognitive deficits, and a degeneration of areas of the brain important in experiencing emotions. The purpose of this study was to learn if patients with Alzheimer's disease have a reduction in the depth of their emotional experiences. Participants with Alzheimer's disease and healthy comparison subjects were asked to view pleasant and unpleasant pictures and to rate these pictures by making a mark on pieces of paper that had a happy face on one end (proximal or distal) and a sad face at the other end. The more pleasant they found this picture, the closer their mark should be to the happy face and vice versa. Patients with Alzheimer's disease judged these pictures' emotional valence as less intense than did the comparison subjects and also made more valence-inconsistent responses. These results might have been induced by impaired picture comprehension or a reduction of emotional experiences induced by degeneration of the limbic-cortical-reticular networks.

Graphesthesia: a test of graphemic movement representations or tactile imagery?

Patients with corticobasal degeneration (CBG) often demonstrate agraphesthesia in the same hand they demonstrate apraxia. To recognize letters written in their hand subjects can develop a spatial representation and access graphemic representations. Alternatively, people can use movement working memory and match movement patterns to stored letter movement representations. To learn the method normally used without vision, normal subjects (12) had letters written on their palm either in the normal manner or in a reverse direction. If letters written on the hand are recognized by their spatial features (as when visually reading) direction should not influence letter recognition, but if letters written on the hand are recognized by movement patterns, then in the reverse condition recognition should be impaired. When letters were written normally there were no differences in error between the tactile and visual modality. When letters were written in reverse, however, normal subjects made more errors in the tactile than visual condition. Normally, people identify letters written on their hand by covertly copying (mirroring) the examiner and then access letter movement representations. This might explain why patients with CBG often have agraphesthesia associated with apraxia.

Bilateral restless legs affecting a phantom limb, treated with dopamine agonists.

BACKGROUND: Restless legs syndrome (RLS) is a common condition characterised by unpleasant sensations deep inside the legs, which usually occurs at rest and especially at night. These sensations are accompanied by an urge to move the limb, and movements result in a temporary relief of the symptoms. The pathophysiology of RLS is not completely known, especially the role of afferent feedback. An individual with a below the knee amputation who developed restless legs in his real and phantom limbs is reported. METHODS AND RESULTS: A 54-year-old man with a left leg amputation 22 years ago developed RLS, primarily at night, that met the International RLS Study Group's criteria for RLS. This RLS, however, involved both his real and phantom lower limbs. Movement and phantom movements, as well as treatment with dopamine agonists, relieved this symptom in both the real and amputated limbs. However, creating an image of the limb moving without "moving" the limb did not improve the uncomfortable sensations in either limb. CONCLUSIONS: That restless legs can occur simultaneously in a phantom as well as a real limb and that the perception of movement in a phantom limb as well as dopaminergic treatment improved the symptoms provides further support for the important role of central nervous system dysfunction in the development of this disorder.

Turning off artistic ability: the influence of left DBS in art production.

BACKGROUND: The influence of Parkinson's disease (PD) as well as deep brain stimulation (DBS) on visual-artistic production of people who have been artists is unclear. We systematically assessed the artistic-creative productions of a patient with PD who was referred to us for management of a left subthalamic region (STN) DBS. The patient was an artist before her disease started, permitting us to analyze changes in her artistic-creative production over the course of the illness and during her treatment with DBS. METHODS: We collected her paintings from four time periods: Time 1 (Early Pre-Presymptomatic), Time 2 (Later Presymptomatic), Time 3 (Symptomatic), and Time 4 (DBS Symptomatic). A total of 59 paintings were submitted to a panel of judges, who rated the paintings on 6 different artistic qualities including: aesthetics, closure, evocative impact, novelty, representation, technique. RESULTS: Aesthetics and evocative impact significantly declined from Time 2 to Time 4. Representation and technique indicated a curvilinear relationship, with initial improvement from Time 1 to Time 2 followed by a decline from Time 2 to Time 4. CONCLUSIONS: These results suggest that left STN/SNR-DBS impacted artistic performances in our patient. The reason for these alterations is not known, but it might be that alterations of left hemisphere functions induce a hemispheric bias reducing the influence the right hemisphere which is important for artistic creativity. The left hemisphere itself plays a critical role in artistic creativity and DBS might have altered left hemisphere functions or altered the mesolimbic system which might have also influenced creativity. Future studies will be required to learn how PD and DBS influence creativity.

Creativity in Parkinson's disease as a function of right versus left hemibody onset.

OBJECTIVE: Creativity is heavily dependent on divergent thinking and divergent thinking appears to be strongly dependent on fontal lobe function. Since patients with Parkinson's disease (PD) often have evidence of frontal lobe dysfunction we wanted to learn if these patients have a reduction of creativity, as well as learning if the side of onset (right versus left) influences the type (verbal versus visuospatial) of decrement in creativity. DESIGN: Participants of this study were patients with right (RHO) or left (LHO) onset PD as well as matched controls. All subjects were given the Abbreviated Torrance Test of Creative Thinking for Adults (ATTA), a widely used test to assess creativity that examines Fluency, Originality, Flexibility and Elaboration. Subjects were also assessed with the Controlled Word Association Test (COWAT). RESULTS/CONCLUSIONS: When compared to controls the patients with RHO, but not LHO, had a decrease of verbal creative fluency. Patients with PD often have a decrease on the COWAT, but performance on the COWAT did not differ between the RHO and the LHO patients. This suggests that patients with PD who have RHO have a decrease in verbal creativity and this decrement does not appear to be related to decreased fluency.

Artistic creativity and DBS: a case report.

BACKGROUND: Deep brain stimulation (DBS) is a treatment for patients with Parkinson's disease (PD) who are not adequately controlled with medications. An artist reported changes in her artistic creativity and art appreciation when treated with left DBS. We sought to study her artistic productions and her appreciation of art while both "on" and "off" left DBS. METHODS: A 69-year-old right-handed woman with an approximate 20-year history of PD was referred to us for management of a left subthalamic region nucleus (STN) DBS placed at another institution 4 years prior. In Experiment 1 we had her rate several dimensions (Evocative Impact, Aesthetics, Novelty, Technique, Closure and Representation) of another artist's paintings. In Experiment 2, we tested her with the Abbreviated Torrance Test (of creativity) for Adults (ATTA). During testing the patient remained on her dopaminergic medication, but was tested on and off left DBS. RESULTS: On the judgment task while "on" left DBS, versus "off" DBS, there were significant reductions in her appreciation of artistic Closure and Technique. When "off" DBS her ATTA creativity index was above average, but when switched "on" her creativity index was below average. CONCLUSIONS: These results suggest the possibility that left ventral STN/SNR DBS reduces creativity as well as appreciation of art. The reason for these alterations is not known, but might be related to enhanced activation of the left hemisphere and reciprocal deactivation of the right hemisphere which mediates both visuospatial skills and global attention, both of which are important in artistic creativity and appreciation.

An ambulatory persistence power curve: motor planning affects ambulatory persistence in Parkinson's disease.

BACKGROUND/OBJECTIVES: When performing activity associated with walking, the amount of walking a person does often will depend on their plans. This study was designed to evaluate the relationship between motor planning and ambulatory persistence in participants with Parkinson's disease (PD) and to see if ambulatory persistence was related to the ability to perform activities of daily living (ADL). METHODS: 20 individuals with idiopathic PD were recruited to perform the Trail making Test (a test of motor planning) and to wear a step activity monitor for 48h. The measurement of persistence of an ambulatory event consisted of the number of steps taken during an event and an ambulatory event was defined as continuous ambulation (taking step) without pausing for 3 or more seconds. The resumption of taking step (ambulation) after 3 or more seconds counted as a new ambulatory event. UPDRS-motor and ADL scale were also obtained. ANALYSIS AND RESULTS: The cumulative percentage of the total ambulatory events at each number of steps was plotted for each subject which when plotted could be described as a sigmoid curve. We found that this sigmoidal curve defined by the equation y=x(n)/(k(n)+x(n)), fit the data well, where k represents a constant specific to each subject, x represents the number of steps during each ambulatory event, and y represents the projected percentage of movement events containing x number of steps or less. (Root Mean Square Error (RMSE)=0.02, R(2)=0.98). Trail making test part A was highly associated with the constant k (R=-0.74, p<0.001). The constant k was also highly associated with the UPDRS ADL subscale (R=-0.81, p=0.0001). A forward bivariate regression model including Part A of the Trail making test, and the UPDRS-ADL subscale predicted 66% of the variability of the constant k. The overall number of steps taken per day, and the UPDRS motor subscale did not contribute to the model. CONCLUSIONS: Defective motor planning in Parkinson's disease as measured by poor performance on a Trail making test is associated with a measurable alteration in ambulatory persistence, and altered ambulatory persistence, quantified by our proposed model parameter, correlates highly with the UPDRS ADL score. Thus, cognitive-motor planning defects might be a major source of disability in PD. We suggest that in future clinical practice gait tests can be used in order to quantify short-term planning ability in neurodegenerative diseases.