Cognitive deficits and cortical volume loss in COVID-19-related hyposmia.

BACKGROUND AND PURPOSE: Studies have found that up to 73% of COVID-19 patients experience hyposmia. It is unclear if the loss of smell in COVID-19 is due to damage to the peripheral or central mechanisms. This study aimed to explore the impacts of COVID-19-induced hyposmia on brain structure and cognitive functions. METHODS: The study included 36 hyposmic (h-COV) and 21 normosmic (n-COV) participants who had recovered from mild COVID-19 infection, as well as 25 healthy controls (HCs). All participants underwent neurological examination, neuropsychiatric assessment and Sniffin' Sticks tests. High-resolution anatomical images were collected; olfactory bulb (OB) volume and cortical thickness were measured. RESULTS: Addenbrooke's Cognitive Examination-Revised total and language sub-scores were slightly but significantly lower in the h-COV group compared to the HC group (p = 0.04 and p = 0.037). The h-COV group exhibited poorer performance in the Sniffin' Sticks test terms of discrimination score, identification score and the composite score compared to the n-COV and HC groups (p < 0.001, p = 0.001 and p = 0.002 respectively). A decrease in left and right OB volumes was observed in the h-COV group compared to the n-COV and HC groups (p = 0.003 and p = 0.006 respectively). The cortical thickness analysis revealed atrophy in the left lateral orbitofrontal cortex in the h-COV group compared to HCs. A significant low positive correlation of varying degrees was detected between discrimination and identification scores and both OB and left orbital sulci. CONCLUSION: Temporary or permanent hyposmia after COVID-19 infection leads to atrophy in the OB and olfactory-related cortical structures and subtle cognitive problems in the long term.

Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study.

INTRODUCTION: Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype. METHODS: Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments. RESULTS: Common symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations. DISCUSSION: This study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients. HIGHLIGHTS: This project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.

Quantitative Gait and Balance Outcomes for Ataxia Trials: Consensus Recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers.

With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait and balance disturbances most often present as the first signs of degenerative cerebellar ataxia and are the most reported disabling features in disease progression. Thus, digital gait and balance measures constitute promising and relevant performance outcomes for clinical trials.This narrative review with embedded consensus will describe evidence for the sensitivity of digital gait and balance measures for evaluating ataxia severity and progression, propose a consensus protocol for establishing gait and balance metrics in natural history studies and clinical trials, and discuss relevant issues for their use as performance outcomes.

A comprehensive analysis of copy number variation in a Turkish dementia cohort.

BACKGROUND: Copy number variants (CNVs) include deletions or multiplications spanning genomic regions. These regions vary in size and may span genes known to play a role in human diseases. As examples, duplications and triplications of SNCA have been shown to cause forms of Parkinson's disease, while duplications of APP cause early onset Alzheimer's disease (AD). RESULTS: Here, we performed a systematic analysis of CNVs in a Turkish dementia cohort in order to further characterize the genetic causes of dementia in this population. One hundred twenty-four Turkish individuals, either at risk of dementia due to family history, diagnosed with mild cognitive impairment, AD, or frontotemporal dementia, were whole-genome genotyped and CNVs were detected. We integrated family analysis with a comprehensive assessment of potentially disease-associated CNVs in this Turkish dementia cohort. We also utilized both dementia and non-dementia individuals from the UK Biobank in order to further elucidate the potential role of the identified CNVs in neurodegenerative diseases. We report CNVs overlapping the previously implicated genes ZNF804A, SNORA70B, USP34, XPO1, and a locus on chromosome 9 which includes a cluster of olfactory receptors and ABCA1. Additionally, we also describe novel CNVs potentially associated with dementia, overlapping the genes AFG1L, SNX3, VWDE, and BC039545. CONCLUSIONS: Genotyping data from understudied populations can be utilized to identify copy number variation which may contribute to dementia.

TREM2 variants as a possible cause of frontotemporal dementia with distinct neuroimaging features.

BACKGROUND AND PURPOSE: Nasu-Hakola disease (NHD) is a rare, autosomal recessive disorder characterized by skeletal and neurological symptoms. Behavioral symptoms with cognitive impairment may mimic the behavioral variant of frontotemporal dementia (bvFTD) and other early-onset dementias. Our patients were analyzed and the literature was reviewed to delineate neurological and neuroimaging findings suggestive of NHD. METHOD: Fourteen patients carrying a pathogenic mutation in the TREM2 gene were found in our database. Demographic, clinical, laboratory and radiological data were retrieved and analyzed. RESULTS: The presenting clinical picture was behavioral changes with cognitive decline resembling bvFTD in all patients. The mean age was 37.1 ± 4.97 years and the mean duration of the disease was 8.9 ± 3.51 years. Only two patients had typical bone cysts. Seven patients had bilateral calcification of the basal ganglia in computed tomography of the brain. Magnetic resonance imaging of the brain revealed severe atrophy of the corpus callosum, enlargement of the ventricles, atrophy of the caudate nuclei and periventricular white matter changes in all patients. Symmetrical global atrophy of the brain mainly affecting frontoparietal and lateral temporal regions were observed in all cases, and 13 patients had atrophy of the hippocampus. Cerebrospinal fluid examination of 10 patients showed elevated protein levels in six and the presence of oligoclonal bands in four patients. CONCLUSION: A combination of white matter changes, enlarged ventricles, atrophy of the caudate nuclei and thinning of the corpus callosum in magnetic resonance imaging strongly suggests NHD in patients with FTD syndrome. Molecular genetic analysis should be performed in suspected cases, and families should receive genetic counseling.

A novel SACS p.Pro4154GlnfsTer20 mutation in a family with autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Loss-of-function mutations in the sacsin (SACS) gene lead to autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), impairing the function of sacsin. Genotype-phenotype correlations are still unclear for the different mutations reported in ARSACS. Here, we present a Turkish ARSACS family in whom the novel homozygous frameshift mutation in SACS c.12461delC (p.Pro4154GlnfsTer20) was detected by next-generation sequencing (NGS). The index patient was admitted with progressive spastic ataxia and dysarthria. Since no common mutation in autosomal recessive (AR) cerebellar ataxias, whole gene sequencing provide an advantage to detect novel mutations and may be more effective for clinical diagnosis.

Neurological features and outcomes of Wilson's disease: a single-center experience.

Wilson's disease (WD) is an autosomal recessive genetic disorder of copper metabolism, and WD patients can present with neurologic symptoms. We aimed to report the general characteristics and prognosis of a Turkish series of WD patients with neurological manifestations. A total of 12,352 patients were screened from the patient database, and 53 WD patients were included. Patients were classified based on the predominant neurological syndrome type including tremor, dystonia, parkinsonism, or discrete neurological signs and were classified as having "good outcome," "stable," and "poor outcome" according to their treatment response. There were 32 male and 21 female patients, aged 20-66 years. The mean follow-up was 11.3 ± 4.56 years. Sixty-two percent of patients presented predominantly with neurological symptoms. Neurological WD diagnosis was established after a mean time delay of 2.3 years from the WD diagnosis. The most common neurological manifestation was dystonia, followed by tremor and parkinsonism. Fifteen patients had a family history of WD. Consanguinity was present in 20 patients. Patients were treated with D-penicillamine, trientine, zinc salts, or their combinations. Besides the main treatments, 41 patients were on symptomatic treatment for neurologic symptoms. Thirty-six patients had a "good outcome," five patients were stable, and six patients had "poor outcome." Post-chelation neurological worsening was observed in 11 patients. WD should be considered in differential diagnosis in any patient with unexplained neurologic symptoms. Early diagnosis is important, and appropriate treatment should be promptly initiated to prevent progressive and irreversible damage, with good prognosis and stable disease in the majority of the patients with treatment compliance.

A novel PSEN2 p.Ser175Phe variant in a family with Alzheimer's disease.

Alzheimer's disease (AD) can be either sporadic or familial, and familial forms of AD accounts for only 5% of the cases. So far, autosomal dominantly inherited mutations in "Presenilin 1" (PSEN1), "Presenilin 2" (PSEN2), and "Amyloid precursor protein" (APP) genes were associated with familial AD. Amid the others, pathogenic mutations in the PSEN2 gene are less common. In this study, we describe a novel heterozygous PSEN2 (c.524C>T, p.Ser175Phe) alteration identified in a 58-year-old Turkish patient from a family with multiple dementia cases. This variant was further present in the patient's clinically affected maternal cousin as well as in the asymptomatic mother and two maternal aunts who were carriers of the APOE ε2/ε3 genotype. The variant is located in the conserved residue of transmembrane domain III encoded by exon 6 of the major transcript. In silico protein structure analyses predicted that this variant might change the architecture of interaction between the two alpha helixes of PSEN2. We propose that p.Ser175Phe may have a pathogenic effect on protein function and may play a significant role in the molecular pathways leading to Alzheimer's disease in this family.

A novel PNPLA6 mutation in a Turkish family with intractable Holmes tremor and spastic ataxia.

Autosomal recessive cerebellar ataxias are a group of rare neurological diseases with a genetic origin. Recently, the mutations in the PNPLA6 gene were suggested to lead to ataxia and also to other specific syndromes such as Boucher-Neuhauser (ataxia, hypogonadism, and chorioretinal dystrophy) or Gordon-Holmes Syndromes (ataxia, hypogonadism, and brisk reflexes) within a broad spectrum of neurodegenerative diseases. Here we report three patients from a single-family with a novel pathogenic mutation in the PNPLA6 gene which led to predominantly spastic-ataxia, and intractable Holmes tremor. The PNPLA6-related disease should be considered in the differential diagnosis of spastic-ataxias even in the absence of chorioretinal dystrophy, and hypogonadotropic hypogonadism. Further studies should unravel the factors which account for the phenotypic variability present in patients with PNPLA6 gene mutations.

Olfactory dysfunction in patients with cluster headache.

OBJECTIVE: Cluster headache (CH) is a primary headache characterized by strictly unilateral, short-lasting severe headache attacks accompanied by at least one ipsilateral autonomic symptom. Our study aimed to determine whether CH patients had olfactory dysfunction and to correlate it with clinical characteristics. MATERIALS AND METHODS: Twenty patients and 57 healthy volunteers were included in the study. All participants were examined in the otorhinolaryngology outpatient clinics to exclude other clinical problems causing olfactory dysfunction. The Sniffin' Sticks test was performed, and threshold (T), discrimination (D), identification (I) scores, and TDI global olfactory score were evaluated. RESULTS: The CH patients had significantly lower threshold scores than healthy controls (6.9 ± 1.70 vs. 7.8 ± 1.08, p = 0.007). The mean threshold scores of CH patients during in-bout (n = 9) were significantly lower than CH patients during out-of-bout (n = 11) in subgroup analysis (5.9 ± 1.16 vs. 7.6 ± 1.76, p = 0.038). CH patients with left-sided headache had significantly lower discrimination scores compared to CH patients with right-sided headache (12.8 ± 1.24 vs. 14.4 ± 1.51, p = 0.03). CONCLUSION: There is marked impairment in olfactory function in CH patients compared to healthy controls.

Peripheral TREM2 mRNA levels in early and late-onset Alzheimer disease's patients.

'Triggering receptor expressed on myeloid cells 2' (TREM2) gene is involved in Alzheimer's disease (AD) and TREM2 mRNA expression is known to be increased in the peripheral blood cells of AD patients. In this study, we examined the expression levels of TREM2 mRNA in peripheral leukocytes of early and late-onset AD patients. We have also investigated the effect of the presence of APOE ε4 allele on TREM2 expression. TREM2 mRNA expression was analyzed in 30 early-onset AD (EOAD) patients, 38 late-onset AD (LOAD) patients, and in their age-matched controls by using quantitative real-time polymerase chain reaction. TREM2 levels in LOAD patients were higher than EOAD. Also, in elderly controls significantly higher TREM2 levels were found compared with young controls. Moreover, APOE ε4 carriers in LOAD patients exhibited significantly higher TREM2 expression levels than APOE ε4 non-carriers and elderly controls. Also, correlation analysis showed that TREM2 mRNA expression was increased by age. The differential expression of TREM2 mRNA levels between EOAD and LOAD patients might be independent of the AD disease status and results from an age-related increase in TREM2 expression. In LOAD patients, increased age and the presence of APOE ε4 allele further increase TREM2 expression. Taken together, we can suggest that age is a factor that increases TREM2 expression, and TREM2 and APOE ε4 may interact together in the pathogenesis of LOAD.

Functional neural substrates of football fanaticism: Different pattern of brain responses and connectivity in fanatics.

AIM: Sports activities provide social interaction for humans. Commitment to a given team is a salient feature of being a sports fan and becomes a prominent part of self-identification for fanatics. Emotion, subjective hedonic experience, and non-romantic love are related to fan behaviors. Few studies have evaluated the neural basis of sports fanaticism. METHODS: Thirty men, including 16 football fanatics and 14 non-fanatics, with a mean age of 27.4 ± 6.4 years (range, 20-48 years) were enrolled. Subjects underwent functional MRI while watching a set of goals scored by favorite, rival, and neutral teams. RESULTS: The analysis of variance in a general linear model revealed a significant Group × Condition interaction effect in the bilateral dorsal anterior cingulate cortex (dACC) that was more prominent in the left hemisphere. In the post-hoc comparisons, fanatics showed increased activation in bilateral dACC, supplementary motor area, superior frontal cortex, right dorsolateral prefrontal cortex, and right insula for Favorite > Neutral contrast and an increased activation in bilateral dACC and supplementary motor area for Rival > Neutral contrast. Seed-based connectivity analyses using the areas with significant activation differences revealed increased connectivity between dACC and several regions, including the left posterior lateral temporal area, insula, bilateral medial temporal area, and medial superior frontal area as well as the basal ganglia in fanatics compared to non-fanatics. CONCLUSION: Our results suggest that football fanatics exhibit a different brain activation and connectivity pattern from non-fanatics, both under favorable and unfavorable conditions. This brain activity and connectivity pattern under emotionally laden conditions may represent higher responses to rewards, higher emotional valence attribution, and stronger motivational state of football fanatics, which might underlie their unusual behavioral responses.

Assessment of the Olfactory Function in Patients With Idiopathic Intracranial Hypertension Using the Sniffin' Sticks Test: A Case-Control Study.

OBJECTIVE: Despite the lack of recognition in clinical practice, there is increasing evidence that patients with idiopathic intracranial hypertension may suffer from hyposmia. The current case-control study aims to evaluate olfactory dysfunction in a large series of patients with idiopathic intracranial hypertension. METHODS: All subjects, 44 idiopathic intracranial hypertension patients and 57 healthy controls, underwent olfactory function assessment using standardized "Sniffin' Sticks" test at a tertiary referral center of a university hospital. Threshold, discrimination, identification, and total threshold-discrimination-identification scores have been determined and analyzed statistically. RESULTS: Idiopathic intracranial hypertension patients had significantly lower threshold (6.5 [3.69] vs 8 [1.88], P < .001, 95% CI [-2.250, -0.750]) and threshold-discrimination-identification scores (29.75 [5.56] vs 32.5 [5.25], P = .003, 95% CI [-4.250, -0.750]). Twenty-five patients (57%) were diagnosed with hyposmia. Test scores of patients with active idiopathic intracranial hypertension (n = 18) were not statistically different from patients with inactive disease (n = 26), except for discrimination score (14 [2.50] vs 11 [2.25], P = .005, 95% CI [-3.000, -1.000]). Although idiopathic intracranial hypertension patients with a cerebrospinal fluid opening pressure of ≥330 mmH2 O had lower test scores, the difference was significant only for total threshold-discrimination-identification scores (28.5 [5.50] vs 30.5 [4.38], P = .044, 95% CI [0.750, 5.500]). Multiple regression analysis revealed that test scores were related to disease activity, cerebrospinal fluid opening pressure, papilledema, headache, and medication. CONCLUSION: Our clinical study revealed significant olfactory dysfunction in patients with idiopathic intracranial hypertension compared with healthy controls. Future research should employ larger samples to search for usability of olfactory testing in clinical management of patients with idiopathic intracranial hypertension.

Bibliometric analysis of the top-cited articles on idiopathic intracranial hypertension.

OBJECTIVE: To identify and characterize the top-cited articles on idiopathic intracranial hypertension. METHODS: We used "Web of Science database" to identify the top-cited articles published between the years of 1975-2017. The articles were evaluated using citation count and other factors that have an effect on the citation count. RESULTS: The search yielded a total of 2,141 articles and the most frequently cited articles received between 58-476 citations. Most articles were published between the years 1990-1999. The most popular study design involved natural history studies. USA ranked first in productivity with 72 articles and the leading institution was University of Iowa. The journal "Neurology" published the greatest number of articles. In assessing the specialties, neurology contributed to 32% of top 100 articles. There was no correlation between the citation count and number of references, years since publication, number of authors, authors' H-index, and number of institutions that had collaborated. There were positive correlations between the citation count and journal impact factor, Scimago journal rank and journal source-normalized impact per paper values. While descriptive keywords were more frequent between 1980s and 1990s, keywords describing surgical management options such as "nerve sheath decompression" and "cerebrospinal-fluid diversion" were top-listed keywords after the year 2000. CONCLUSIONS: Our study can help researchers identify the most significant and impactful articles on idiopathic intracranial hypertension, as well as to provide insight into the most noteworthy scientific trends and to visualize future research needs of the topic.

Evidence for potential involvement of pro-inflammatory adipokines in the pathogenesis of idiopathic intracranial hypertension.

Background Although specific role players are currently unknown, contribution of inflammatory mediators has been suggested in the pathophysiology of idiopathic intracranial hypertension (IIH), which is a disease more prevalent in obese female individuals of childbearing age. We aimed to investigate the levels of adipokines and cytokines to demonstrate possible markers for inflammation that participate in IIH pathophysiology and their association with clinical features of IIH. Methods IIH patients, diagnosed according to the revised criteria, and age-, gender- and body mass index (BMI)-matched healthy controls were enrolled in this study. Serum samples were evaluated for insulin-like growth factor 1, insulin, nesfatin, adiponectin, interleukin (IL)-1ß, IL-6, IL-8, leptin, plasminogen activator inhibitor type-1, resistin, tumour necrosis factor-alpha (TNF-α) and monocyte chemotactic protein 1 via enzyme-linked immunosorbent assay or multiplex immunoassays. Results IL-1ß level was significantly higher ( p = 0.012), and IL-8 and TNF-α levels were significantly lower in the IIH group ( p < 0.001 and p = 0.008, respectively) compared to the control group. There were no correlations between the cytokine/adipokine levels and age, BMI, disease duration, and cerebrospinal fluid oligoclonal bands. There were also no significant differences in cytokine and adipokine levels between IIH patients regarding visual impairment. However, statistically significant differences were found between IIH patients with relapse versus healthy controls regarding IL-1ß ( p = 0.007), IL-8 ( p = 0.001) and TNF-α ( p = 0.017) levels. Other investigated cytokines and adipokines showed no significant alterations in IIH patients investigated in the remission period. Conclusion Altered serum levels of IL-1ß, IL-8 and TNF-α seem to be associated with IIH pathogenesis, and these cytokines may be used as prognostic markers in IIH to predict relapse.

Glial and neuronal antibodies in patients with idiopathic intracranial hypertension.

Headache and visual disturbances are the main presenting symptoms of idiopathic intracranial hypertension (IIH) characterized by increased intracranial pressure (ICP) with an unknown cause. We aimed to investigate the antibodies against optic neuritis-associated glial antigens, aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) and uncharacterized neuronal membrane antigens in IIH patients. Consecutive patients diagnosed according to Friedman revised diagnostic criteria and control subjects were included after their consent. All serum samples were analyzed for antibodies against AQP4 and MOG using cell-based immunofluorescent assays and for uncharacterized neuronal membrane antigens by indirect immunocytochemistry utilizing live neurons. Sera of 34 patients with IIH and 40 control subjects were investigated but none of the patients showed AQP4 and MOG antibodies. However, serum IgG of five IIH patients showed reactivity against membrane antigens of rat hippocampal and cortical neurons. Interestingly, three out of these five patients had nonspecific white matter lesions on MRI, whereas only four of all other patients had these lesions (p = 0.048). AQP4 and MOG antibodies do not seem to have a role in the pathophysiology of IIH. However, association of immunocytochemistry findings with the presence of white matter lesions may suggest that immunological factors contribute to the pathogenesis of IIH in at least some of the patients.

Late onset aura may herald cerebral amyloid angiopathy: A case report.

BACKGROUND: Although migraine usually begins in the early decades of life, late onset of migraine with aura is occasionally observed and can occur without headache, causing confusion in the differential diagnosis. CASE REPORT: A 72-year-old man presented with recurrent episodes of visual aura lasting for 20 minutes. These episodes had started at 57 years of age and were only once accompanied by a severe headache. Magnetic resonance imaging revealed changes in the periventricular white matter, left occipital haemorrhage and subcortical haemosiderin deposits, compatible with cerebral amyloid angiopathy. Previous treatment with antiplatelet drugs was discontinued. His episodes of visual aura stopped on treatment with lamotrigine and add-on treatment with verapamil. CONCLUSION: In patients with a late onset of migraine aura, doctors must consider other under-recognized causes of transient neurological symptoms, such as cerebral amyloid angiopathy. Blood-sensitive magnetic resonance imaging sequences are the best tool for the early detection of an underlying pathology and therefore treatment with antiplatelet/anticoagulant drugs should be avoided as this may increase the risk of haemorrhage.

Habenula volume change in Parkinson's disease: A 7T MRI study.

OBJECTIVE: Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by motor and early non-motor symptoms. The habenula is implicated in the pathophysiology of depression. This study investigates habenular volume in PD patients without clinical depression to show the changes in PD unrelated to depression. METHODS: The study used high-resolution 7 Tesla MRI data from the TRACK-PD study involving 104 PD patients and 44 healthy controls (HCs). The habenula was manually segmented, and volumes were measured, considering demographic data and depression scores via the Beck Depression Inventory (BDI). RESULTS: No significant correlation was found between habenular volume and BDI scores in PD patients or HCs. However, the PD group exhibited a significantly larger mean and right habenular volume than HCs. Although PD patients showed higher BDI scores, indicating more subthreshold depression, these did not correlate with the habenular volume. CONCLUSION: The results suggest that while the habenula may be involved in the symptoms of PD, its role in depression within this cohort is unclear. The changes might be related to the role of the habenula in motor symptoms. This study provides a new perspective on the role of the habenula in PD, but future research could lead to a greater understanding of the neuroanatomical features of the habenula in PD.

The habenula in Parkinson's disease: Anatomy, function, and implications for mood disorders - A narrative review.

Parkinson's disease (PD), a widespread neurodegenerative disorder, often coexists with mood disorders. Degeneration of serotonergic neurons in brainstem raphe nuclei have been linked to depression and anxiety. Additionally, the locus coeruleus and its noradrenergic neurons are among the first areas to degenerate in PD and contribute to stress, emotional memory, motor, sensory, and autonomic symptoms. Another brain region of interest is habenula, which is especially related to anti-reward processing, and its function has recently been linked to PD and to mood-related symptoms. There are several neuroimaging studies that investigated role of the habenula in mood disorders. Differences in habenular size and hemispheric symmetry were found in healthy controls compared to individuals with mood disorders. The lateral habenula, as a link between the dopaminergic and serotonergic systems, is thought to contribute to depressive symptoms in PD. However, there is only one imaging study about role of habenula in mood disorders in PD, although the relationship between PD and mood disorders is known. There is little known about habenula pathology in PD but given these observations, the question arises whether habenular dysfunction could play a role in PD and the development of PD-related mood disorders. In this review, we evaluate neuroimaging techniques and studies that investigated the habenula in the context of PD and mood disorders. Future studies are important to understand habenula's role in PD patients with mood disorders. Thus, new potential diagnostic and treatment opportunities would be found for mood disorders in PD.