In Older Patients Treated for Dizziness and Vertigo in Multimodal Rehabilitation Somatic Deficits Prevail While Anxiety Plays a Minor Role Compared to Young and Middle Aged Patients.

Objective: Many patients with dizziness and vertigo are of older age. It is still unclear which age-associated factors play a role in the treatment of dizziness and vertigo. Therefore, age-associated characteristics of patients subjected to an interdisciplinary day care approach for chronic vertigo and dizziness were analyzed. Subjects and Methods: 650 patients with chronic dizziness/vertigo subjected to a multimodal vestibular rehabilitation day care program were analyzed. Information concerning age, gender, medical diagnosis, medical consultations, technical diagnostics performed and therapy achieved before attending the clinic were collected. Furthermore, data were gathered using the Vertigo Severity Scale (VSS), Hospital Anxiety and Depression Scale (HADS), Mobility Inventory (MI), as well as the intensity of and the distress due to vertigo/dizziness using visual analog scales. As a follow-up, the VSS, HADS, MI, and the visual analog scales were collected again 6 months after attending the therapy program. Three age groups were compared to each other (<41, 41-65, and >65 years of age). Results: One-third of the patients were older than 65 years. This group had typical diagnoses with mainly organic deficits. In contrast to the dominance of mainly multifactorial, organic deficits the older patients reported less medical consultations, fewer technical diagnostics and even fewer treatments than the younger patients. The elderly scored significantly lower in total VSS, in VSS-V (vestibular-balance subscale), in VSS-A (autonomic-anxiety subscale) and in HADS-anxiety. Psychological diagnoses were clearly associated to the younger patients. 424 patients (65.2%) completed the follow-up questionnaire 6 months after attending the therapy week. The older patients revealed improvements of VSS-V and the Avoidance Alone scale of MI as well as decreased distress due to vertigo/dizziness. Conclusion: In the older patients, who took part in our vestibular rehabilitation program, mainly somatic deficits prevail while anxiety plays a minor role compared to young and middle aged patients. Older patients profited from vestibular rehabilitation especially in mobility and vestibular-balance. Therefore, vestibular rehabilitation programs for the elderly with a focus on physio- and occupational therapeutic interventions and less cognitive behavioral therapy may be reasonable.

Bilateral vestibulopathy with positive Tullio phenomenon.

We describe the case of a 34-year-old patient presenting with the unique combination of bilateral vestibulopathy in combination with noise- and pressure-induced nystagmus. Bilateral vestibular dysfunction was demonstrated by pathological results in video-based head impulse testing as well as in caloric testing. In contrast, cervical vestibular-evoked myogenic potentials were normal, demonstrating normal sacculus function. Due to the positive Tullio phenomenon, semicircular dehiscence syndrome was excluded. Recently, this symptom combination was related to the histopathological finding of vestibular atelectasis. LEVEL OF EVIDENCE: NA.Laryngoscope, 128:1223-1225, 2018.

Hippocampal metabolism and prefrontal brain structure: A combined 1H-MR spectroscopy, neuropsychological, and voxel-based morphometry (VBM) study.

Hippocampal structural and functional integrity impacts on multiple remote areas of the brain, and this connectivity is central to multiple cognitive functions in healthy and disease. We studied associations of hippocampal metabolic markers N-acetyl aspartate (NAA) and glutamate (Glu and Glx; assessed with 1H magnetic resonance spectroscopy) and brain grey matter (studied with voxel-based morphometry, VBM) in 20 healthy subjects. We found a significant correlation between right hippocampal NAA and left ventrolateral prefrontal cortical grey matter (TFCE, p<0.05, FWE-corrected), as well as verbal fluency markers, and right hippocampal Glx (glutamate/glutamine) and left cerebellar volume. Our studies demonstrate a structure-function correlation that might underlie the interaction of the hippocampus with prefrontal cortex and cerebellum, which might be central to several neurological and psychiatric disorders, including schizophrenia or depression.

Diffusion tensor imaging of cingulum bundle and corpus callosum in schizophrenia vs. bipolar disorder.

Both schizophrenia and bipolar disorder show abnormalities of white matter, as seen in diffusion tensor imaging (DTI) analyses of major brain fibre bundles. While studies in each of the two conditions have indicated possible overlap in anatomical location, there are few direct comparisons between the disorders. Also, it is unclear whether phenotypically similar subgroups (e.g. patients with bipolar disorder and psychotic features) might share white matter pathologies or be rather similar. Using region-of-interest (ROI) analysis of white matter with diffusion tensor imaging (DTI) at 3 T, we analysed fractional anisotropy (FA), radial diffusivity (RD), and apparent diffusion coefficient (ADC) of the corpus callosum and cingulum bundle in 33 schizophrenia patients, 17 euthymic (previously psychotic) bipolar disorder patients, and 36 healthy controls. ANOVA analysis showed significant main effects of group for RD and ADC (both elevated in schizophrenia). Across the corpus callosum ROIs, there was not group effect on FA, but for RD (elevated in schizophrenia, lower in bipolar disorder) and ADC (higher in schizophrenia, intermediate in bipolar disorder). Our findings show similarities and difference (some gradual) across regions of the two major fibre tracts implicated in these disorders, which would be consistent with a neurobiological overlap of similar clinical phenotypes.

BrainAGE score indicates accelerated brain aging in schizophrenia, but not bipolar disorder.

BrainAGE (brain age gap estimation) is a novel morphometric parameter providing a univariate score derived from multivariate voxel-wise analyses. It uses a machine learning approach and can be used to analyse deviation from physiological developmental or aging-related trajectories. Using structural MRI data and BrainAGE quantification of acceleration or deceleration of in individual aging, we analysed data from 45 schizophrenia patients, 22 bipolar I disorder patients (mostly with previous psychotic symptoms / episodes), and 70 healthy controls. We found significantly higher BrainAGE scores in schizophrenia, but not bipolar disorder patients. Our findings indicate significantly accelerated brain structural aging in schizophrenia. This suggests, that despite the conceptualisation of schizophrenia as a neurodevelopmental disorder, there might be an additional progressive pathogenic component.

Cortical complexity in bipolar disorder applying a spherical harmonics approach.

Recent studies using surface-based morphometry of structural magnetic resonance imaging data have suggested that some changes in bipolar disorder (BP) might be neurodevelopmental in origin. We applied a novel analysis of cortical complexity based on fractal dimensions in high-resolution structural MRI scans of 18 bipolar disorder patients and 26 healthy controls. Our region-of-interest based analysis revealed increases in fractal dimensions (in patients relative to controls) in left lateral orbitofrontal cortex and right precuneus, and decreases in right caudal middle frontal, entorhinal cortex, and right pars orbitalis, and left fusiform and posterior cingulate cortices. While our analysis is preliminary, it suggests that early neurodevelopmental pathologies might contribute to bipolar disorder, possibly through genetic mechanisms.

Effects of subclinical depression, anxiety and somatization on brain structure in healthy subjects.

BACKGROUND: Dimensional approaches in highly prevalent psychiatric disorders like depression or anxiety could lead to a better understanding of pathogenesis and advantages in early detection and prevention. In an effort to better understand associations of brain structural variation across the depression/anxiety spectra, we investigated minor subclinical symptoms in a non-clinical healthy population. METHODS: We studied 177 healthy subjects from the community, who underwent high-resolution T1-weighted 3T MRI and completed the symptom-checklist-90 (SCL-90-R). Using voxel-based morphometry (VBM) analysis with CAT12 software, we correlated SCL-90-R-subscales for depression, anxiety, and somatization with gray matter across the brain. RESULTS: Significant positive gray matter correlations emerged across all three scales in different areas: the depression subscale correlated positively with gray matter in the Rolandic operculum, superior temporal gyrus (left) and postcentral gyrus (bilateral), the anxiety subscale correlated positively with middle temporal gyrus, Rolandic operculum, middle cingular gyrus and precuneus bilaterally, and the somatization subscale with left inferior prefrontal cortex. Somatization also showed negative correlations with cerebellar vermis and right supplementary motor area. LIMITATIONS: Our study is limited to VBM and does not include surface-based measures. It also only contains subjects with very small psychological distress by partly overlapping symptoms. CONCLUSION: Our findings are consistent with a non-linear relationship between symptom severity and cortical volume in several brain areas involved in both emotion regulation as well as altered in clinically manifest depressive/anxiety disorders.

Cognitive function in euthymic bipolar disorder (BP I) patients with a history of psychotic symptoms vs. schizophrenia.

Patients with bipolar disorder show cognitive deficits including executive function, which appear to be related to social functioning and outcome. However, subgroups within the spectrum as well as psychopathological features, current mood state/euthymia and disease stage might be confounding factors. We analysed data tests from the Wechsler Intelligence Scale (WIE), verbal fluency (COWA) and trail making tests (TMT-A and TMT-B) obtained in a selected subgroup of currently bipolar I disorder patients, who were currently euthymic and had a history of psychotic symptoms, and compared them to patients with schizophrenia (in remission) and healthy controls, all matched for age, gender, and handedness. Schizophrenia patients showed more severe cognitive impairment, including digit symbol and arithmetic tests, as well as TMT-B (compared to healthy controls), but bipolar patients had stronger impairment on the letter number sequencing test, an indicator of working memory and processing speed. There were no group effects on most verbal fluency tasks (except impairment of schizophrenia patients on one subscale of category fluency). Within the limitations of the study design, our results suggest that even in subgroups of presumably more severely impaired bipolar patients, some cognitive dimensions might achieve remission, possibly related to considerable state effects at testing.

Brain structural correlates of schizotypy and psychosis proneness in a non-clinical healthy volunteer sample.

Schizotypal traits are phenotypic risk factors for schizophrenia, associated with biological changes across a putative schizophrenia spectrum. In this study, we tested the hypothesis that brain structural changes in key brain areas relevant to this spectrum (esp. medial and lateral prefrontal cortex) would vary across different degrees of schizotypal trait expression and/or phenotypic markers of psychosis proneness in healthy non-clinical volunteers. We analysed high-resolution 3Tesla magnetic resonance images (MRI) of 59 healthy volunteers using voxel-based morphometry (VBM), correlating grey matter values to the positive and negative symptom factors of the schizotypal personality questionnaire (SPQ, German version) and a measure of psychosis proneness (community assessment of psychic experiences, CAPE). We found positive correlations between positive SPQ dimension and bilateral inferior and right superior frontal cortices, and positive CAPE dimension and left inferior frontal cortex, as well as CAPE negative dimension and right supplementary motor area (SMA) and left inferior parietal cortex. However, only the positive correlation of the right precuneus with negative schizotypy scores was significant after FWE correction for multiple comparisons. Our findings confirm an effect of schizotypal traits and psychosis proneness on brain structure in healthy subjects, providing further support to a biological continuum model.

Prefrontal gyrification in psychotic bipolar I disorder vs. schizophrenia.

Bipolar disorder and schizophrenia share phenotypic and genotypic features, but might differ in aspects of abnormal neurodevelopmental trajectories. We studied gyrification, a marker of early developmental pathology, in high-resolution MRI scans of 34 patients with schizophrenia, 17 euthymic bipolar I disorder patients with previous psychotic symptoms, and 34 matched healthy controls in order to test the hypothesis of overlapping and diverging prefrontal gyrification abnormalities. We applied a novel, validated method for measuring local gyrification in each vertex point of the reconstructed cortical surface. Psychotic bipolar I patients had higher gyrification in dorsal anterior and infragenual cingulate cortex compared to either schizophrenia or healthy controls, while schizophrenia patients had higher gyrification than controls in anterior medial (BA 10) and orbitofrontal areas, altogether indicating disease-specific alterations in the prefrontal cortex. Our findings indicate gyrification changes in a specific subgroup of bipolar I disorder to affect an area relevant to emotion regulation, and distinct from changes seen in schizophrenia.

Associations of hippocampal metabolism and regional brain grey matter in neuroleptic-naïve ultra-high-risk subjects and first-episode schizophrenia.

Hippocampal pathology has been shown to be central to the pathophysiology of schizophrenia and a putative risk marker for developing psychosis. We applied both (1)H MRS (proton magnetic resonance spectroscopy) at 3Tesla and voxel-based morphometry (VBM) of high-resolution brain structural images in order to study the association of the metabolites glutamate (Glu) and N-acetyl-aspartate (NAA) in the hippocampus with whole-brain morphometry in 31 persons at ultra-high-risk for psychosis (UHR), 18 first-episode schizophrenia patients (Sz), and 42 healthy controls (all subjects being neuroleptic-naïve). Significantly diverging associations emerged for UHR subjects hippocampal glutamate showed positive correlation with the left superior frontal cortex, not seen in Sz or controls, while in first-episode schizophrenia patients a negative correlation was significant between glutamate and a left prefrontal area. For NAA, we observed different associations for left prefrontal and caudate clusters bilaterally for both high-risk and first-episode schizophrenia subjects, diverging from the pattern seen in healthy subjects. Our results suggest that associations of hippocampal metabolites in key areas of schizophrenia might vary due to liability to or onset of the disorder.

Brain structure in schizophrenia vs. psychotic bipolar I disorder: A VBM study.

While schizophrenia and bipolar disorder have been assumed to share phenotypic and genotypic features, there is also evidence for overlapping brain structural correlates, although it is unclear whether these relate to shared psychotic features. In this study, we used voxel-based morphometry (VBM8) in 34 schizophrenia patients, 17 euthymic bipolar I disorder patients (with a history of psychotic symptoms), and 34 healthy controls. Our results indicate that compared to healthy controls schizophrenia patients show grey matter deficits (p<0.05, FDR corrected) in medial and right dorsolateral prefrontal, as well as bilaterally in ventrolateral prefrontal and insular cortical areas, thalamus (bilaterally), left superior temporal cortex, and minor medial parietal and parietooccipital areas. Comparing schizophrenia vs. bipolar I patients (p<0.05, FDR corrected) yielded a similar pattern, however, there was an additional significant reduction in schizophrenia patients in the (posterior) hippocampus bilaterally, left dorsolateral prefrontal cortex, and left cerebellum. Compared to healthy controls, the deficits in bipolar I patients only reached significance at p<0.001 (uncorr.) for a minor parietal cluster, but not for prefrontal areas. Our results suggest that the more extensive prefrontal, thalamic, and hippocampal deficits that might set apart schizophrenia and bipolar disorder might not be related to mere appearance of psychotic symptoms at some stage of the disorders.

Brain structure in people at ultra-high risk of psychosis, patients with first-episode schizophrenia, and healthy controls: a VBM study.

Early intervention research in schizophrenia has suggested that brain structural alterations might be present in subjects at high risk of developing psychosis. The heterogeneity of regional effects of these changes, which is established in schizophrenia, however, has not been explored in prodromal or high-risk populations. We used high-resolution MRI and voxel-based morphometry (VBM8) to analyze grey matter differences in 43 ultra high-risk subjects for psychosis (meeting ARMS criteria, identified through CAARMS interviews), 24 antipsychotic-naïve first-episode schizophrenia patients and 49 healthy controls (groups matched for age and gender). Compared to healthy controls, resp., first-episode schizophrenia patients had reduced regional grey matter in left prefrontal, insula, right parietal and left temporal cortices, while the high-risk group showed reductions in right middle temporal and left anterior frontal cortices. When dividing the ultra-high-risk group in those with a genetic risk vs. those with attenuated psychotic symptoms, the former showed left anterior frontal, right caudate, as well as a smaller right hippocampus, and amygdala reduction, while the latter subgroup showed right middle temporal cortical reductions (each compared to healthy controls). Our findings in a clinical psychosis high-risk cohort demonstrate variability of brain structural changes according to subgroup and background of elevated risk, suggesting frontal and possibly also hippocampal/amygdala changes in individuals with genetic susceptibility. Heterogeneity of structural brain changes (as seen in schizophrenia) appears evident even at high-risk stage, prior to potential onset of psychosis.

Brain structure in narcissistic personality disorder: a VBM and DTI pilot study.

We analysed T1-weighted MRI scans using voxel-based morphometry (VBM) and tract-based spatial statistics (TBBS) on diffusion tensor images (DTI) in narcissistic personality disorder (NaPD) patients and healthy controls. Grey matter deficits include right prefrontal and bilateral medial prefrontal/anterior cingulate cortices, and decreased fractional anisotropy in right frontal lobe white matter.

Superior temporal metabolic changes related to auditory hallucinations: a (31)P-MR spectroscopy study in antipsychotic-free schizophrenia patients.

Structural deficits in the superior temporal cortex and transverse temporal gyri appear to be related to auditory hallucinations in schizophrenia, which are a key symptom of this disorder. However, the cellular and neurochemical underpinnings are poorly understood and hardly studied in vivo. We used (31)P-MRS (magnetic resonance spectroscopy) with chemical shift imaging to assess the association between left superior temporal cortex metabolism and severity of auditory hallucinations in 29 schizophrenia patients off antipsychotics. Hallucinations scores derived from the Scale for the Assessment of Positive Symptoms showed significant positive correlations with both measures of phospholipids (phosphomonoesters and phosphodiesters), and energy (inorganic phosphate and phosphocreatine, but not adenosine tri-phosphate) metabolism in left superior temporal gyrus/Heschl gyrus voxels. There was no correlation of metabolites in these regions with formal thought disorder, a symptom also linked to superior temporal pathology, thus suggesting symptom specificity. Our findings provide a link between established structural deficits and neurochemical pathology related to membrane pathology and markers of general metabolic turnover.

Thalamocortical connectivity during resting state in schizophrenia.

Schizophrenia has been linked to disturbed connectivity between large-scale brain networks. Altered thalamocortical connectivity might be a major mechanism mediating regionally distributed dysfunction, yet it is only incompletely understood. We analysed functional magnetic resonance imaging data obtained during resting state from 22 DSM-IV schizophrenia patients and 22 matched healthy controls to directly assess the differences in thalamocortical functional connectivity. We identified significantly higher overall thalamocortical functional connectivity in patients, which was mostly accounted for by difference in thalamic connections to right ventrolateral prefrontal and bilateral secondary motor and sensory (superior temporal and lateral occipital) cortical areas. Voxelwise analysis showed group differences at the thalamic level to be mostly in medial and anterior thalamic nuclei and arising thalamocortical changes to be mostly due to higher positive correlations in prefrontal and superior temporal correlations, as well as absent negative correlations to sensory areas in patients. Our findings demonstrate that different types of thalamocortical dysfunction contribute to network alterations, including lack of inhibitory interaction attributed to the lack of significant negative thalamic/sensory cortical connections. These results emphasize the functional importance of the thalamus in the pathophysiology of schizophrenia.

Frequency domains of resting state default mode network activity in schizophrenia.

Probabilistic independent component analysis was applied to identify the default mode network (DMN) in resting state data obtained with functional magnetic resonance imaging from 25 DSM-IV schizophrenia and 25 matched healthy subjects. Power spectrum analysis showed a significant diagnosis × frequency interaction and higher power in one frequency band, indicating an alteration of DMN frequency spectrum in schizophrenia.

Effects of olanzapine on 31P MRS metabolic markers in schizophrenia.

Antipsychotic drug action might include mechanisms related to normalising phospholipid and high-energy metabolism. We applied brain metabolic imaging with (31)P magnetic resonance spectroscopy ((31)P MRS) and two-dimensional chemical shift imaging to assess changes of metabolism of phospholipids and high-energy phosphates in schizophrenia patients at baseline (four antipsychotic-naïve and three off antipsychotics) and at follow-up, after 6 weeks of treatment with olanzapine. Results indicate a significant increase of adenosine-triphosphate (ATP) in the right inferior temporal cortex and a trend towards ATP decrease in the left cerebellum. This suggests a shift in high-energy phosphates (rather than phospholipids), possibly related to normalisation of functioning in these areas.

Default mode network activity in schizophrenia studied at resting state using probabilistic ICA.

Alterations in brain function in schizophrenia and other neuropsychiatric disorders are evident not only during specific cognitive challenges, but also from functional MRI data obtained during a resting state. Here we apply probabilistic independent component analysis (pICA) to resting state fMRI series in 25 schizophrenia patients and 25 matched healthy controls. We use an automated algorithm to extract the ICA component representing the default mode network (DMN) as defined by a DMN-specific set of 14 brain regions, resulting in z-scores for each voxel of the (whole-brain) statistical map. While goodness of fit was found to be similar between the groups, the region of interest (ROI) as well as voxel-wise analysis of the DMN showed significant differences between groups. Healthy controls revealed stronger effects of pICA-derived connectivity measures in right and left dorsolateral prefrontal cortices, bilateral medial frontal cortex, left precuneus and left posterior lateral parietal cortex, while stronger effects in schizophrenia patients were found in the right amygdala, left orbitofrontal cortex, right anterior cingulate and bilateral inferior temporal cortices. In patients, we also found an inverse correlation of negative symptoms with right anterior prefrontal cortex activity at rest and negative symptoms. These findings suggest that aberrant default mode network connectivity contributes to regional functional pathology in schizophrenia and bears significance for core symptoms.