Vestibular migraine and persistent postural perceptual dizziness.

Dizziness is a common symptom among patients in primary care, general neurology, and headache clinic practices. Vestibular migraine is conceptualized as a condition of recurrent attacks of vestibular symptoms attributed to migraine. It is now considered the most common cause of spontaneous episodic vertigo. Persistent postural-perceptual dizziness (PPPD) has more recently been defined based on four previous clinical entities as a syndrome of chronic daily dizziness, unsteadiness, or nonspinning vertigo that fluctuates and is exacerbated by postural, motion, or visual factors. Although PPPD is more often precipitated by other conditions causing vertigo, unsteadiness, or dizziness, it is discussed at length in this chapter because vestibular migraine is among the most common triggers for development of PPPD. Pathophysiology of each is incompletely understood, and with lack of biomarkers, the diagnosis of each rests on consensus-derived, symptom-based criteria. Areas of uncertainty exist regarding some overlapping symptoms that may create potential diagnostic confusion between the conditions. This chapter provides a comprehensive review of the current state of vestibular migraine and PPPD, including diagnostic and management guidance for when they occur separately, together, or along with other common comorbidities.

Clinical Characterization, Course, and Treatment of Othello Syndrome: A Case Series and Systematic Review of the Literature.

BACKGROUND: Othello syndrome (OS) is a condition characterized by a delusion of jealousy that one's spouse is having extramarital affairs. As in the eponymous Shakespearean tragedy, there is an unfortunate risk of violence. For patients with these symptoms, consultation-liaison psychiatrists may be asked to assist with evaluating the differential diagnosis, assessing safety, and developing treatment options. OBJECTIVE: This study's objective was to solidify current knowledge of the clinical presentations and management of OS through a systematic review of the literature and description of 2 new cases. METHODS: We conducted a literature search from the start of relevant databases through August 2023 to identify English language case reports of adults (≥18 years) with OS that described clinical evaluations, biological treatments, and outcomes. We extracted demographics, proposed etiologies, treatment choices and responses, duration of delusions, comorbid psychiatric symptoms, neuro-radiographic findings, and presence of physical violence. We reported clinical findings for 2 new cases. RESULTS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we screened 705 abstracts and conducted full-text reviews of 118 articles to identify 73 cases published from 1983 to 2023 meeting inclusion criteria. The mean age was 58.2 years with male predominance (M:F = 1.88). Etiologies included primary psychiatric disorders (16, 22%), other medical conditions (38, 52%), and medications or other substances (19, 26%). Delusional disorder, cerebrovascular accident, and dopaminergic agonists were the most common etiologies, respectively, in these groups. Antipsychotics were the most common treatment (57, 78%). Symptom remission was reported in 51 (70%) cases. The average duration of OS was 39.5 months. Of 32 cases reporting brain imaging insults, 12 of 20 (60%) showed right-sided lesions, and 8 of 20 (40%) showed left-sided lesions, with 9 of 32 (28%) located in the frontal lobes. The most commonly co-existing psychiatric symptom was depression (14, 19%). Violence was reported in 25 cases (34%). Our 2 new cases were consistent with these findings. CONCLUSIONS: OS may be a manifestation of several neuropsychiatric conditions, primarily delusional disorder, cerebrovascular accident, Alzheimer's dementia, and the use of dopaminergic agonists. One-third of cases include violent behaviors. It appears to respond to antipsychotic medications, but treatment is delayed more than 3 years on average. Available data have not localized OS to a specific brain region.

Most patients with disorders of gut-brain interaction receive pharmacotherapy with major or moderate drug-gene interactions.

BACKGROUND: How variations predicted by pharmacogenomic testing to alter drug metabolism and therapeutic response affect outcomes for patients with disorders of gut- brain interaction is unclear. AIMS: To assess the prevalence of pharmacogenomics-predicted drug-gene interactions and symptom outcomes for patients with disorders of gut-brain interaction. METHODS: Patients who were treated in our clinical practice for functional dyspepsia/bowel disorder underwent pharmacogenomic testing. The change in symptoms from baseline to 6 months was compared for patients with variations in CYP2D6 and CYP2C19, which metabolize neuromodulators, and SLC6A4, which encodes the sodium- dependent serotonin transporter. RESULTS: At baseline, 79 of 94 participants (84%) had at least one predicted major drug- gene interaction, and all 94 (100%) had at least one predicted moderate interaction. For the 44 participants who completed a survey of their symptoms at 6 months, the mean (SD) irritable bowel syndrome-symptom severity score decreased from 284 (71) at baseline to 231 (95) at 6 months (p < 0.001). Among patients taking selective serotonin reuptake inhibitors, the decrease in symptom severity (p = 0.03) and pain (p = 0.002) scores from baseline to 6 months was greater for patients with a homozygous SLC6A4 long/long genotype (n = 30) (ie, increased serotonin transporter activity) than for patients with homozygous short/short or heterozygous long/short genotypes (n = 64). Symptom outcomes were not affected by CYP2D6 or CYP2C19 variations. CONCLUSIONS: The homozygous SLC6A4 long/long genotype confers better symptom resolution for patients with disorders of gut-brain interaction who take selective serotonin reuptake inhibitors than do the homozygous short/short or heterozygous long/short genotypes.

Persistent Postural-Perceptual Dizziness: Review and Update on Key Mechanisms of the Most Common Functional Neuro-otologic Disorder.

Persistent postural-perceptual dizziness (PPPD) is a functional neuro-otologic (vestibular) disorder manifesting dizziness, unsteadiness, or nonspinning vertigo lasting 3 months or more and exacerbated by upright posture, active or passive motion, and complex visual stimuli. PPPD is the most common cause of chronic vestibular symptoms. Early pathophysiologic models of PPPD emphasized the adverse effects of anxiety on postural control and spatial orientation. More recent concepts added predictive processing of sensory inputs and alterations in motion perception. Herein, a third-generation model incorporates prioritization of postural stability over fluid locomotion to explain symptoms, physiologic and neuroimaging data, and effects of current treatments.

Functional neurological seizures and migraine: A systematic review and case series.

BACKGROUND: The seizure subtype of functional neurological disorder (FND-seizures) is a common neuropsychiatric condition manifesting with episodic epilepsy-like events. Despite the common belief that FND-seizures are precipitated by psychological stressors, neurological disorders may also be triggers. In 1890, Babinski described four cases of FND symptoms associated with migraine attacks. Despite the passing of more than 130 years since this first clinical observation, the relationship between FND-seizures and migraine is not fully elucidated. OBJECTIVES: (1) To complete a systematic review of the literature that investigated potential associations between FND-seizures and migraine and the response of FND seizures to treatment with migraine prophylactic medications (2). To undertake a retrospective study of patients with FND-seizures and migraine, including response to migraine prophylaxis. METHODS: (1) Using PRISMA methods, we completed a systematic review of EMBASE and Scopus databases from inception to March 31, 2021, for literature on FND-seizures and migraine. (2) Our multi-disciplinary team, including subspecialists in psychosomatic medicine, epilepsy, and headache disorders, reviewed consecutive patients diagnosed with FND-seizures and migraine to assess potential causal associations and responses to standard migraine prophylactic medications. RESULTS: (1) The search yielded seven studies from 126 screened manuscripts (N = 1,186 patients with FND-seizures; mean age 38.7 years; 72.6% female). They varied substantially in design, population, diagnostic measures, and outcomes. Nevertheless, all studies found associations between FND-seizures and migraine, which were stronger than those between epileptic seizures and migraine in comparative investigations, but provided limited information on treatment response. (2) In our case series, investigators reached unanimous consensus that migraine attacks triggered FND-seizures in 28/43 (65.1%) patients reviewed (mean age, 38.8 years; 74% female). In 19/26 (73%) patients with adequate follow-up data, treatment with migraine prophylactic medications alone (no behavioral interventions) concomitantly reduced FND-seizure and headache frequency by >50%. CONCLUSION: Our systematic review and case series indicate that migraine attacks may trigger FND-seizures, perhaps more often that currently understood, and suggest that migraine prophylaxis may reduce FND-seizure frequency in such cases. To validate these observations, fully powered prospective investigations are required.

Outpatient Motor Retraining for Functional Movement Disorder: Predictors of a Favorable Short-Term Response.

Background: Treating functional movement disorder (FMD) with motor retraining is effective but resource intensive. Objectives: Identify patient, disease, and program variables associated with favorable treatment outcomes. Methods: Retrospective review of the 1 week intensive outpatient FMD program at Mayo Clinic in Minnesota from February 2019 to August 2021. Outcomes included patient-reported measures (Canadian Occupational Performance Measure-Performance and Satisfaction subscales [COPM-P and COPM-S, range 0-10] and Global Rating of Change [GROC, -7 to +7]) and a retrospective investigator-rated scale (0-3, worse/not improved to significantly improved/resolved). Linear regression models identified variables predicting favorable outcomes. Results: Participants (n = 201, 74% female, mean age = 46) had median FMD duration of 24 months. The commonest FMD subtypes were gait disorder (65%), tremor (41%) and weakness (17%); 53% had ≥2 subtypes. Most patients (88%) completed a therapeutic screening process before program entry. Patient-reported outcomes at the end of the week improved substantially (COPM-P average change 3.8 ± 1.9; GROC post-program average 5.5 ± 1.7). Available investigator-rated outcomes from short-term follow-up were also positive (102/122 [84%] moderately to significantly improved/resolved). Factors predicting greater improvement in COPM-P were completing therapeutic screening, higher number of non-motor symptoms, shorter FMD duration, earlier program entry, lower baseline COPM scores, and (among screened patients) higher GROC between therapeutic screening and program start. Conclusion: Patients with diverse FMD subtypes improved substantially over a 1 week period. Utilization of therapeutic screening and greater improvement between therapeutic screening and program start were novel predictors of favorable outcomes. Non-motor symptoms did not preclude positive responses, although patients with predominant non-motor burden were excluded.

Trends in Stimulant and Sedative/Hypnotic Dispensing: An Exploratory Study.

OBJECTIVE: To investigate patterns and trends of co-prescriptions of stimulants and sedatives within the last 6 years at a tertiary care center. METHOD: Patients 18 years of age and older who were dispensed at least one stimulant prescription from an institutional pharmacy between 1/1/2015 and 7/1/2021 were included. Prescription data for any co-prescribed sedative/hypnotic were collected. RESULTS: Both the number of stimulant dispenses and the number of patients with stimulant dispenses increased significantly with yearly incidence rate ratios of 1.115 (95% CI [1.110, 1.119]) and 1.090 (95% CI [1.084, 1.096]), respectively. The number of patients with a stimulant dispensed who also had a benzodiazepine or "Z-drug" sedative-hypnotic dispensed at any point in the search timeframe increased significantly with incidence rate ratios of 1.077 and 1.092, respectively. The number of stimulant dispenses, number of patients with stimulant dispenses, and number of patients with a stimulant dispensed who also had both a benzodiazepine and Z-drug dispensed at any point in the search timeframe increased significantly more in Non-White than in White patients. CONCLUSIONS: The results confirm previous findings of increases in dispensing of stimulants over the past 6 years and report increased polypharmacy of stimulants and sedative-hypnotics.

The Psychometric Properties of the 9-Item Vestibular Activities Avoidance Instrument.

OBJECTIVE: The purpose of this study was to establish the psychometric properties of the 9-Item Vestibular Activities Avoidance Instrument (VAAI-9), a patient-reported outcome measure developed to identify fear avoidance beliefs in persons with vestibular disorders. METHODS: This prospective cohort study included 100 participants 18 years and older seeking care at a balance disorders clinic for dizziness. Participants completed the VAAI-9, the Dizziness Handicap Inventory (DHI), and other patient-reported outcomes at the initial visit and the 3-month follow-up. To measure test-retest reliability, the VAAI-9 was completed again 5 days after the initial visit and was analyzed using a 2-way mixed ICC for absolute agreement. Internal consistency was determined using the Cronbach alpha. The Spearman correlation coefficient was used to assess convergent validity of the VAAI-9 with other outcomes. Receiver operating characteristic curves were used to identify baseline VAAI-9 cutoff scores for those who reported mild (DHI ≤ 30) or moderate or severe (DHI > 30) perceived disability at the 3-month follow-up. RESULTS: The mean age of the study cohort was 49 (SD = 16) years; 73 (73%) were women. Seventy-one participants completed the 5-day follow-up, and 68 completed the 3-month follow-up. The VAAI-9 demonstrated excellent internal consistency (α = 0.91) and test-retest reliability (ICC = 0.90). Baseline VAAI-9 scores had moderate to strong associations with other outcome measures at baseline and 3 months. A baseline VAAI-9 score of 26 or higher had a sensitivity of 80.6% and a specificity of 78.4% for identifying a DHI score of >30 at 3 months (area under the curve = 0.86). CONCLUSIONS: The results provide evidence of excellent reliability and validity for the 9-item VAAI in persons with vestibular disorders. A baseline VAAI-9 score of ≥26 identified individuals at risk of persistent moderate to severe disability due to dizziness. IMPACT: Initial levels of fear avoidance beliefs measured using the VAAI-9 provided important prognostic information about outcomes for persons with vestibular symptoms.

Real-World Implementation of Best-Evidence Cancer Distress Management: Truly Comprehensive Cancer Care.

BACKGROUND: Cancer distress management is an evidence-based component of comprehensive cancer care. Group-delivered cognitive behavioral therapy for cancer distress (CBT-C) is the first distress treatment associated with replicated survival advantages in randomized clinical trials. Despite research supporting patient satisfaction, improved outcomes, and reduced costs, CBT-C has not been tested sufficiently within billable clinical settings, profoundly reducing patient access to best-evidence care. This study aimed to adapt and implement manualized CBT-C as a billable clinical service. PATIENTS AND METHODS: A stakeholder-engaged, mixed-methods, hybrid implementation study design was used, and the study was conducted in 3 phases: (1) stakeholder engagement and adaptation of CBT-C delivery, (2) patient and therapist user testing and adaptation of CBT-C content, and (3) implementation of practice-adapted CBT-C as a billable clinical service focused on evaluation of reach, acceptability, and feasibility across stakeholder perspectives. RESULTS: A total of 40 individuals and 7 interdisciplinary group stakeholders collectively identified 7 primary barriers (eg, number of sessions, workflow concerns, patient geographic distance from center) and 9 facilitators (eg, favorable financial model, emergence of oncology champions). CBT-C adaptations made before implementation included expanding eligibility criteria beyond breast cancer, reducing number of sessions to 5 (10 total hours), eliminating and adding content, and revising language and images. During implementation, 252 patients were eligible; 100 (40%) enrolled in CBT-C (99% covered by insurance). The primary reason for declining enrollment was geographic distance. Of enrollees, 60 (60%) consented to research participation (75% women; 92% white). All research participants completed at least 60% of content (6 of 10 hours), with 98% reporting they would recommend CBT-C to family and friends. CONCLUSIONS: CBT-C implementation as a billable clinical service was acceptable and feasible across cancer care stakeholder measures. Future research is needed to replicate acceptability and feasibility results in more diverse patient groups, test effectiveness in clinical settings, and reduce barriers to access via remote delivery platforms.

Predictors of persistent postural-perceptual dizziness (PPPD) and similar forms of chronic dizziness precipitated by peripheral vestibular disorders: a systematic review.

BACKGROUND: The literature on predictors of persistent postural-perceptual dizziness (PPPD) following peripheral vestibular insults has not been systematically reviewed. METHODS: We systematically reviewed studies on predictors of PPPD and its four predecessors (phobic postural vertigo, space-motion discomfort, chronic subjective dizziness and visual vertigo). Investigations focused on new onset chronic dizziness following peripheral vestibular insults, with a minimum follow-up of 3 months. Precipitating events, promoting factors, initial symptoms, physical and psychological comorbidities and results of vestibular testing and neuroimaging were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: We identified 13 studies examining predictors of PPPD or PPPD-like chronic dizziness. Anxiety following vestibular injury, dependent personality traits, autonomic arousal and increased body vigilance following precipitating events and visual dependence, but not the severity of initial or subsequent structural vestibular deficits or compensation status, were the most important predictors of chronic dizziness. Disease-related abnormalities of the otolithic organs and semi-circular canals and age-related brain changes seem to be important only in a minority of patients. Data on pre-existing anxiety were mixed. CONCLUSIONS: After acute vestibular events, psychological and behavioural responses and brain maladaptation are the most likely predictors of PPPD, rather than the severity of changes on vestibular testing. Age-related brain changes appear to have a smaller role and require further study. Premorbid psychiatric comorbidities, other than dependent personality traits, are not relevant for the development of PPPD.

Case Report: Right Insular Stroke Causing Simultaneous Onset of a Functional Vestibular Disorder and Psychiatric Disorder-Persistent Postural-Perceptual Dizziness and Post-stroke Depression.

Introduction: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder that can be precipitated by acquired brain injuries. Poststroke depression (PSD) is the most common psychiatric sequela of stroke, affecting 33% of stroke survivors. Pathophysiologic mechanisms of PPPD and PSD are not fully understood. Case Report: A 40-year-old woman developed new, debilitating chronic dizziness exacerbated by her own motion and exposure to visual motion stimuli plus prolonged depressive symptoms, both beginning within days after a localized right insular stroke. A collaborative evaluation by specialists in neurology, otorhinolaryngology, optometry, and psychiatry concluded that the insular stroke caused simultaneous onset of PPPD and PSD. Discussion: Prior case reports described short-lived vertigo following insular strokes, but no long-term vestibular symptoms without ongoing nystagmus or gait ataxia. In this case, chronic dizziness and motion sensitivity continued in the absence of focal neurologic deficits, invoking the possibility that changes in functioning of brain networks subserving spatial orientation persisted despite otherwise adequate recovery from the stroke, a mechanism previously proposed for PPPD. This case also reinforced prior work implicating pathways through the insula in PSD. Co-occurrence of PPPD and PSD offers insights into simultaneous functions of the insula in multiple networks in human brain.

Functional neurological disorder: new subtypes and shared mechanisms.

Functional neurological disorder is common in neurological practice. A new approach to the positive diagnosis of this disorder focuses on recognisable patterns of genuinely experienced symptoms and signs that show variability within the same task and between different tasks over time. Psychological stressors are common risk factors for functional neurological disorder, but are often absent. Four entities-functional seizures, functional movement disorders, persistent perceptual postural dizziness, and functional cognitive disorder-show similarities in aetiology and pathophysiology and are variants of a disorder at the interface between neurology and psychiatry. All four entities have distinctive features and can be diagnosed with the support of clinical neurophysiological studies and other biomarkers. The pathophysiology of functional neurological disorder includes overactivity of the limbic system, the development of an internal symptom model as part of a predictive coding framework, and dysfunction of brain networks that gives movement the sense of voluntariness. Evidence supports tailored multidisciplinary treatment that can involve physical and psychological therapy approaches.

Structural connectivity of autonomic, pain, limbic, and sensory brainstem nuclei in living humans based on 7 Tesla and 3 Tesla MRI.

Autonomic, pain, limbic, and sensory processes are mainly governed by the central nervous system, with brainstem nuclei as relay centers for these crucial functions. Yet, the structural connectivity of brainstem nuclei in living humans remains understudied. These tiny structures are difficult to locate using conventional in vivo MRI, and ex vivo brainstem nuclei atlases lack precise and automatic transformability to in vivo images. To fill this gap, we mapped our recently developed probabilistic brainstem nuclei atlas developed in living humans to high-spatial resolution (1.7 mm isotropic) and diffusion weighted imaging (DWI) at 7 Tesla in 20 healthy participants. To demonstrate clinical translatability, we also acquired 3 Tesla DWI with conventional resolution (2.5 mm isotropic) in the same participants. Results showed the structural connectome of 15 autonomic, pain, limbic, and sensory (including vestibular) brainstem nuclei/nuclei complex (superior/inferior colliculi, ventral tegmental area-parabrachial pigmented, microcellular tegmental-parabigeminal, lateral/medial parabrachial, vestibular, superior olivary, superior/inferior medullary reticular formation, viscerosensory motor, raphe magnus/pallidus/obscurus, parvicellular reticular nucleus-alpha part), derived from probabilistic tractography computation. Through graph measure analysis, we identified network hubs and demonstrated high intercommunity communication in these nuclei. We found good (r = .5) translational capability of the 7 Tesla connectome to clinical (i.e., 3 Tesla) datasets. Furthermore, we validated the structural connectome by building diagrams of autonomic/pain/limbic connectivity, vestibular connectivity, and their interactions, and by inspecting the presence of specific links based on human and animal literature. These findings offer a baseline for studies of these brainstem nuclei and their functions in health and disease, including autonomic dysfunction, chronic pain, psychiatric, and vestibular disorders.

Electrical stimulation of the cochlea for treatment of chronic disabling tinnitus: an open-label trial towards the development of an implantable device.

BACKGROUND: Chronic tinnitus affects millions of people globally and constitutes the most commonly compensated disability among military service members in the United States. Existing treatment options largely surround helping patients cope with their disease as opposed to directly suppressing tinnitus perception. The current study investigated the efficacy of electrical stimulation of the cochlea on chronic disabling tinnitus. METHODS: In this single-arm, open-label clinical trial, 22 adult subjects with severe-range asymmetric or unilateral non-pulsatile tinnitus underwent electrical stimulation of the cochlea through use of an extra-cochlear electrode positioned on the cochlear promontory. Each subject underwent 3 stimulation treatments over 3 weeks at 7-day intervals. Tinnitus severity was determined by Tinnitus Handicap Inventory (THI), Tinnitus Functional Index (TFI), and Tinnitus Visual Analog Scale (VAS). Inclusion criteria required subjects have no worse than moderate sensorineural hearing loss determined by pre-enrollment audiometric testing. The primary outcome was nadir post-treatment THI scores, obtained at seven timepoints following electrical stimulation, with clinically significant improvement defined as a decrease of ≥ 7. RESULTS: All 22 (100%) subjects experienced clinically significant improvement in the THI during the study period with a mean decrease in scores of - 31 (95% CI - 38 to - 25) from a baseline of 48. Twenty (91%) experienced clinically significant improvement detectable on at least two of the three tinnitus survey instruments and 17 (77%) experienced clinically significant improvement detectable on all three survey instruments (i.e., THI, TFI, and VAS). Eight (36%) subjects reported either complete (THI of 0; n = 3) or near-complete (THI 1-4; n = 5) suppression of their tinnitus following a stimulation session. Thirteen (59%) subjects reported a nadir following stimulation at or below the threshold for "no or slight handicap" on the THI (≤ 16). No adverse events were observed. CONCLUSIONS: These findings establish the foundation for the development of an extra-cochlear implantable device that delivers electrical stimulation to the cochlea for the treatment of disabling tinnitus. For patients considering device implantation, trans-tympanic cochlear promontory stimulation can facilitate patient selection. Trial Registration ClinicalTrials.gov Identifier: NCT03759834. URL: https://clinicaltrials.gov/ct2/show/NCT03759834.

Characterization of Postural Sway in Patients With Persistent Postural-Perceptual Dizziness (PPPD) Using Wearable Motion Sensors.

OBJECTIVE: To extend previous investigations of postural control in patients with persistent-postural perceptual dizziness (PPPD). STUDY DESIGN: Case-controlled, cross-sectional, observational investigation. SETTING: Tertiary care center. PATIENTS: Fifteen patients with PPPD, 15 control volunteers. INTERVENTIONS: Measurement of anterior-posterior (AP) and medial-lateral (ML) sway at the waist using wearable accelerometers during posturography; assessment of reach and gait. MAIN OUTCOME MEASURES: Peak-to-peak AP and ML sway displacement on the six conditions of the Sensory Organization Test (SOT); Scores on the SOT, Functional Reach Test (FRT), and Dynamic Gait Index (DGI). RESULTS: Compared to control volunteers, patients with PPPD had significantly greater sway displacement at the waist in the AP direction in SOT conditions 3, 5, and 6 and in the ML direction in SOT conditions 2 and 4, resulting in significantly lower median equilibrium scores on the composite index and all six SOT conditions. Patients with PPPD had significantly lower scores on the FRT and DGI that were not correlated with SOT performance. AP sway in conditions 3 and 6 differentiated patients with PPPD from controls with high sensitivity (≥0.87) and specificity (≥0.87). CONCLUSIONS: This study replicated previous work showing poor SOT performance by patients with PPPD who had greater AP sway associated with visual dependence and greater ML sway in low demand conditions than controls. Patients with PPPD also performed poorer on the FRT and DGI, but lack of correlation with SOT scores suggested different mechanisms of impairment in postural control, reach, and ambulation. AP sway demonstrated potential as a diagnostic marker.

Brain Correlates of Persistent Postural-Perceptual Dizziness: A Review of Neuroimaging Studies.

Persistent postural-perceptual dizziness (PPPD), defined in 2017, is a vestibular disorder characterized by chronic dizziness that is exacerbated by upright posture and exposure to complex visual stimuli. This review focused on recent neuroimaging studies that explored the pathophysiological mechanisms underlying PPPD and three conditions that predated it. The emerging picture is that local activity and functional connectivity in multimodal vestibular cortical areas are decreased in PPPD, which is potentially related to structural abnormalities (e.g., reductions in cortical folding and grey-matter volume). Additionally, connectivity between the prefrontal cortex, which regulates attentional and emotional responses, and primary visual and motor regions appears to be increased in PPPD. These results complement physiological and psychological data identifying hypervigilant postural control and visual dependence in patients with PPPD, supporting the hypothesis that PPPD arises from shifts in interactions among visuo-vestibular, sensorimotor, and emotional networks that overweigh visual over vestibular inputs and increase the effects of anxiety-related mechanisms on locomotor control and spatial orientation.