Negative emotional stimuli enhance vestibular processing

Recent studies have shown that vestibular stimulation can influence affective processes. In the present study, we examined whether emotional information can also modulate vestibular perception. Participants performed a vestibular discrimination task on a motion platform while viewing emotional pictures. Six different picture categories were taken from the International Affective Picture System: mutilation, threat, snakes, neutral objects, sports and erotic pictures. Using a Bayesian hierarchical approach we were able to show that vestibular discrimination improved when participants viewed emotionally negative pictures (mutilation, threat, snake) when compared to neutral objects. There was no difference in vestibular discrimination while viewing emotionally positive compared to neutral pictures. We conclude that some of the mechanisms involved in the processing of vestibular information are also sensitive to emotional content. Emotional information signals importance and mobilizes the body for action. In case of danger, a successful motor response requires precise vestibular processing. Therefore, negative emotional information improves processing of vestibular information.

Negative emotional stimuli enhance vestibular processing

Recent studies have shown that vestibular stimulation can influence affective processes. In the present study, we examined whether emotional information can also modulate vestibular perception. Participants performed a vestibular discrimination task on a motion platform while viewing emotional pictures. Six different picture categories were taken from the International Affective Picture System: mutilation, threat, snakes, neutral objects, sports and erotic pictures. Using a Bayesian hierarchical approach we were able to show that vestibular discrimination improved when participants viewed emotionally negative pictures (mutilation, threat, snake) when compared to neutral objects. There was no difference in vestibular discrimination while viewing emotionally positive compared to neutral pictures. We conclude that some of the mechanisms involved in the processing of vestibular information are also sensitive to emotional content. Emotional information signals importance and mobilizes the body for action. In case of danger, a successful motor response requires precise vestibular processing. Therefore, negative emotional information improves processing of vestibular information.

Subclinical thyroid dysfunction and the risk of stroke: a systematic review and meta-analysis

Subclinical thyroid dysfunction has been associated with coronary heart disease, but the risk of stroke is unclear. Our aim is to combine the evidence on the association between subclinical thyroid dysfunction and the risk of stroke in prospective cohort studies. We searched Medline (OvidSP), Embase, Web-of-Science, Pubmed Publisher, Cochrane and Google Scholar from inception to November 2013 using a cohort filter, but without language restriction or other limitations. Reference lists of articles were searched. Two independent reviewers screened articles according to pre-specified criteria and selected prospective cohort studies with baseline thyroid function measurements and assessment of stroke outcomes. Data were derived using a standardized data extraction form. Quality was assessed according to previously defined quality indicators by two independent reviewers. We pooled the outcomes using a random-effects model. Of 2,274 articles screened, six cohort studies, including 11,309 participants with 665 stroke events, met the criteria. Four of six studies provided information on subclinical hyperthyroidism including a total of 6,029 participants and five on subclinical hypothyroidism (n = 10,118). The pooled hazard ratio (HR) was 1.08 (95 % CI 0.87-1.34) for subclinical hypothyroidism (I (2) of 0 %) and 1.17 (95 % CI 0.54-2.56) for subclinical hyperthyroidism (I (2) of 67 %) compared to euthyroidism. Subgroup analyses yielded similar results. Our systematic review provides no evidence supporting an increased risk for stroke associated with subclinical thyroid dysfunction. However, the available literature is insufficient and larger datasets are needed to perform extended analyses. Also, there were insufficient events to exclude clinically significant risk from subclinical hyperthyroidism, and more data are required for subgroup analyses.

Cognitive dysfunction in children with brain tumors at diagnosis

Background: Survivors of brain tumors have a high risk for a wide range of cognitive problems. These dysfunctions are caused by the lesion itself and its surgical removal, as well as subsequent treatments (chemo- and/or radiation therapy). Multiple recent studies have indicated that children with brain tumors (BT) might already exhibit cognitive problems at diagnosis, i.e., before the start of any medical treatment. The aim of the present study was to investigate the baseline neuropsychological profile in children with BT compared to children with an oncological diagnosis not involving the central nervous system (CNS). Methods: Twenty children with BT and 27 children with an oncological disease without involvement of the CNS (age range: 6.1 to 16.9 years) were evaluated with an extensive battery of neuropsychological tests tailored to the patient’s age. Furthermore, the child and his/her parent(s) completed self-report questionnaires about emotional functioning and quality of life. In both groups, tests were administered before any therapeutic intervention such as surgery, chemotherapy or irradiation. Groups were comparable with regard to age, gender and socioeconomic status. Results: Compared to the control group, patients with BTs performed significantly worse in tests of working memory, verbal memory and attention (effect sizes between 0.28 and 0.47). In contrast, the areas of perceptual reasoning, processing speed and verbal comprehension were preserved at the time of measurement. Conclusion: Our results highlight the need for cognitive interventions early in the treatment process in order to minimize or prevent academic difficulties as patients return to school.

The mitochondrial ADP/ATP carrier (SLC25 family): pathological implications of its dysfunction.

In aerobic eukaryotic cells, the high energy metabolite ATP is generated mainly within the mitochondria following the process of oxidative phosphorylation. The mitochondrial ATP is exported to the cytoplasm using a specialized transport protein, the ADP/ATP carrier, to provide energy to the cell. Any deficiency or dysfunction of this membrane protein leads to serious consequences on cell metabolism and can cause various diseases such as muscular dystrophy. Described as a decisive player in the programmed cell death, it was recently shown to play a role in cancer. The objective of this review is to summarize the current knowledge of the involvement of the ADP/ATP carrier, encoded by the SLC25A4, SLC25A5, SLC25A6 and SLC25A31 genes, in human diseases and of the efforts made at designing different model systems to study this carrier and the associated pathologies through biochemical, genetic, and structural approaches.

Dysfunction of Cortical Dendritic Integration in Neuropathic Pain Reversed by Serotoninergic Neuromodulation

Neuropathic pain is caused by long-term modifications of neuronal function in the peripheral nervous system, the spinal cord, and supraspinal areas. Although functional changes in the forebrain are thought to contribute to the development of persistent pain, their significance and precise subcellular nature remain unexplored. Using somatic and dendritic whole-cell patch-clamp recordings from neurons in the anterior cingulate cortex, we discovered that sciatic nerve injury caused an activity-dependent dysfunction of hyperpolarization-activated cyclic nucleotide-regulated (HCN) channels in the dendrites of layer 5 pyramidal neurons resulting in enhanced integration of excitatory postsynaptic inputs and increased neuronal firing. Specific activation of the serotonin receptor type 7 (5-HT7R) alleviated the lesion-induced pathology by increasing HCN channel function, restoring normal dendritic integration, and reducing mechanical pain hypersensitivity in nerve-injured animals in vivo. Thus, serotoninergic neuromodulation at the forebrain level can reverse the dendritic dysfunction induced by neuropathic pain and may represent a potential therapeutical target.

Do executive dysfunction and freezing of gait in Parkinson's disease share the same neuroanatomical correlates?

Current hypotheses postulate a relationship between executive dysfunction and freezing of gait (FOG) in Parkinson's disease (PD). Hitherto, most evidence comes from entirely clinical approaches, while knowledge about this relationship on the morphological level is sparse. The aim of this study was therefore to assess the overlap of gray matter atrophy associated with FOG and executive dysfunction in PD. We included 18 PD patients with FOG and 20 without FOG in our analysis. A voxel-based morphometry approach was used to reveal voxel clusters in the gray matter which were associated with FOG and executive dysfunction as measured by the Frontal Assessment Battery, respectively. Conjunction analysis was applied to detect overlaps of the associated patterns. FOG correlated with different cortical clusters in the frontal and parietal lobes, whereas those associated with the FAB scores were, although widespread, widely confined to the frontal lobe. Conjunction analysis revealed a significant cluster of gray matter loss in the right dorsolateral prefrontal cortex. We could show that the patterns of neurodegeneration associated with FOG and executive dysfunction (as measured by the FAB) share atrophic changes in the same cortical areas. However, there is also a considerable number of cortical areas where neurodegenerative changes are only unique for either sign. Particularly, the involvement of parietal lobe areas seems to be more specific for FOG.

Negative Emotional Stimuli Enhance Vestibular Processing

Recent studies have shown that vestibular stimulation can influence affective processes. In the present study, we examined whether emotional information can also modulate vestibular perception. Participants performed a vestibular discrimination task on a motion platform while viewing emotional pictures. Six different picture categories were taken from the International Affective Picture System: mutilation, threat, snakes, neutral objects, sports, and erotic pictures. Using a Bayesian hierarchical approach, we were able to show that vestibular discrimination improved when participants viewed emotionally negative pictures (mutilation, threat, snake) when compared to neutral/positive objects. We conclude that some of the mechanisms involved in the processing of vestibular information are also sensitive to emotional content. Emotional information signals importance and mobilizes the body for action. In case of danger, a successful motor response requires precise vestibular processing. Therefore, negative emotional information improves processing of vestibular information.

Subclinical thyroid dysfunction and fracture risk: a meta-analysis.

IMPORTANCE Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. DATA EXTRACTION Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations. MAIN OUTCOME AND MEASURES The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. RESULTS Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. CONCLUSIONS AND RELEVANCE Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.

Compensatory saccades benefit from prediction during head impulse testing in early recovery from vestibular deafferentation

The head impulse test (HIT) can identify a deficient vestibulo-ocular reflex (VOR) by the compensatory saccade (CS) generated once the head stops moving. The inward HIT is considered safer than the outward HIT, yet might have an oculomotor advantage given that the subject would presumably know the direction of head rotation. Here, we compare CS latencies following inward (presumed predictable) and outward (more unpredictable) HITs after acute unilateral vestibular nerve deafferentation. Seven patients received inward and outward HITs delivered at six consecutive postoperative days (POD) and again at POD 30. All head impulses were recorded by portable video-oculography. CS included those occurring during (covert) or after (overt) head rotation. Inward HITs included mean CS latencies (183.48 ms ± 4.47 SE) that were consistently shorter than those generated during outward HITs in the first 6 POD (p = 0.0033). Inward HITs induced more covert saccades compared to outward HITs, acutely. However, by POD 30 there were no longer any differences in latencies or proportions of CS and direction of head rotation. Patients with acute unilateral vestibular loss likely use predictive cues of head direction to elicit early CS to keep the image centered on the fovea. In acute vestibular hypofunction, inwardly applied HITs may risk a preponderance of covert saccades, yet this difference largely disappears within 30 days. Advantages of inwardly applied HITs are discussed and must be balanced against the risk of a false-negative HIT interpretation.

An unusual stroke-like clinical presentation of Creutzfeldt-Jakob disease: acute vestibular syndrome

INTRODUCTION Vertigo and dizziness are common neurological symptoms in general practice. Most patients have benign peripheral vestibular disorders, but some have dangerous central causes. Recent research has shown that bedside oculomotor examinations accurately discriminate central from peripheral lesions in those with new, acute, continuous vertigo/dizziness with nausea/vomiting, gait unsteadiness, and nystagmus, known as the acute vestibular syndrome. CASE REPORT A 56-year-old man presented to the emergency department with acute vestibular syndrome for 1 week. The patient had no focal neurological symptoms or signs. The presence of direction-fixed, horizontal nystagmus suppressed by visual fixation without vertical ocular misalignment (skew deviation) was consistent with an acute peripheral vestibulopathy, but bilaterally normal vestibuloocular reflexes, confirmed by quantitative horizontal head impulse testing, strongly indicated a central localization. Because of a long delay in care, the patient left the emergency department without treatment. He returned 1 week later with progressive gait disturbance, limb ataxia, myoclonus, and new cognitive deficits. His subsequent course included a rapid neurological decline culminating in home hospice placement and death within 1 month. Magnetic resonance imaging revealed restricted diffusion involving the basal ganglia and cerebral cortex. Spinal fluid 14-3-3 protein was elevated. The rapidly progressive clinical course with dementia, ataxia, and myoclonus plus corroborative neuroimaging and spinal fluid findings confirmed a clinicoradiographic diagnosis of Creutzfeldt-Jacob disease. CONCLUSIONS To our knowledge, this is the first report of an initial presentation of Creutzfeldt-Jacob disease closely mimicking vestibular neuritis, expanding the known clinical spectrum of prion disease presentations. Despite the initial absence of neurological signs, the central lesion location was differentiated from a benign peripheral vestibulopathy at the first visit using simple bedside vestibular tests. Familiarity with these tests could help providers prevent initial misdiagnosis of important central disorders in patients presenting vertigo or dizziness.

VOR gain by head impulse video-oculography differentiates acute vestibular neuritis from stroke

OBJECTIVE Vestibular neuritis is often mimicked by stroke (pseudoneuritis). Vestibular eye movements help discriminate the two conditions. We report vestibulo-ocular reflex (VOR) gain measures in neuritis and stroke presenting acute vestibular syndrome (AVS). METHODS Prospective cross-sectional study of AVS (acute continuous vertigo/dizziness lasting >24 h) at two academic centers. We measured horizontal head impulse test (HIT) VOR gains in 26 AVS patients using a video HIT device (ICS Impulse). All patients were assessed within 1 week of symptom onset. Diagnoses were confirmed by clinical examinations, brain magnetic resonance imaging with diffusion-weighted images, and follow-up. Brainstem and cerebellar strokes were classified by vascular territory-posterior inferior cerebellar artery (PICA) or anterior inferior cerebellar artery (AICA). RESULTS Diagnoses were vestibular neuritis (n = 16) and posterior fossa stroke (PICA, n = 7; AICA, n = 3). Mean HIT VOR gains (ipsilesional [standard error of the mean], contralesional [standard error of the mean]) were as follows: vestibular neuritis (0.52 [0.04], 0.87 [0.04]); PICA stroke (0.94 [0.04], 0.93 [0.04]); AICA stroke (0.84 [0.10], 0.74 [0.10]). VOR gains were asymmetric in neuritis (unilateral vestibulopathy) and symmetric in PICA stroke (bilaterally normal VOR), whereas gains in AICA stroke were heterogeneous (asymmetric, bilaterally low, or normal). In vestibular neuritis, borderline gains ranged from 0.62 to 0.73. Twenty patients (12 neuritis, six PICA strokes, two AICA strokes) had at least five interpretable HIT trials (for both ears), allowing an appropriate classification based on mean VOR gains per ear. Classifying AVS patients with bilateral VOR mean gains of 0.70 or more as suspected strokes yielded a total diagnostic accuracy of 90%, with stroke sensitivity of 88% and specificity of 92%. CONCLUSION Video HIT VOR gains differ between peripheral and central causes of AVS. PICA strokes were readily separated from neuritis using gain measures, but AICA strokes were at risk of being misclassified based on VOR gain alone.

Out-of-Body Experiences and Other Complex Dissociation Experiences in a Patient with Unilateral Peripheral Vestibular Damage and Deficient Multisensory Integration

Out-of-body experiences (OBEs) are illusory perceptions of one's body from an elevated disembodied perspective. Recent theories postulate a double disintegration process in the personal (visual, proprioceptive and tactile disintegration) and extrapersonal (visual and vestibular disintegration) space as the basis of OBEs. Here we describe a case which corroborates and extends this hypothesis. The patient suffered from peripheral vestibular damage and presented with OBEs and lucid dreams. Analysis of the patient's behaviour revealed a failure of visuo-vestibular integration and abnormal sensitivity to visuo-tactile conflicts that have previously been shown to experimentally induce out-of-body illusions (in healthy subjects). In light of these experimental findings and the patient's symptomatology we extend an earlier model of the role of vestibular signals in OBEs. Our results advocate the involvement of subcortical bodily mechanisms in the occurrence of OBEs.