Frequency of Impulsive-Compulsive Behavior and Associated Psychological Factors in Parkinson's Disease: Lack of Control or Too Much of It?

Background and Objectives: Impulse Control Disorders (ICDs) including pathological gambling, hypersexuality, compulsive eating, compulsive buying, and other related behaviors are well-known distinct non-motor symptoms in Parkinson's Disease (PD). Some large-scale studies present a prevalence of at least 10%, however, there are other reports providing much higher rates. The majority of the conducted studies investigating ICDs focus mainly on pharmacological factors, however, from a psychological perspective, there is yet enough room for investigation. In order to address the above issues, we designed a two-part study. Materials and Methods: First, we aimed to identify the incidence of ICD and related behaviors in a cohort of 892 Greek PD patients. Second, we administered a comprehensive battery of psychometric tools to assess psychological factors such as personality dimensions, quality of life, defenses, coherence, and resilience as well as to screen general cognitive capacity in PD patients with ICD manifestations. Results: With regard to the first part, we identified ICD manifestations in 12.4% of the patients. Preliminary findings from the second part indicate elevated activity, rather than impulsivity, as well as interrelations between several variables, including measures of activity, coping mechanisms, and quality of life. Conclusions: We present a working hypothesis for the contribution of high activity channeled to specific behavioral patterns through specific coping mechanisms, concerning the emergence of ICDs and related behaviors in PD, and further stress the importance of compulsivity rather than impulsivity in this process.

Structural and functional brain changes in X-linked Charcot-Marie-Tooth disease: insights from a multimodal neuroimaging study.

PURPOSE: Brain involvement in X-linked Charcot-Marie-Tooth disease (CMTX) has been previously reported. We studied the brain structural and functional integrity using a multimodal neuroimaging approach in patients with no current central nervous system (CNS) symptoms, in order to further delineate the disease's phenotype. METHODS: Seventeen CMTX patients with no current CNS symptoms and 24 matched healthy controls underwent brain magnetic resonance imaging (MRI). Structural integrity was evaluated performing Gray matter analysis with voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI). Functional integrity was evaluated with resting-state functional MRI (rs-fMRI). RESULTS: Decreased gray matter density was detected in CMTX patients compared to healthy controls in bilateral hippocampus, left thalamus, left postcentral gyrus, left superior parietal lobule, left cerebellum crus I and II, and vermis VI. DTI analysis showed increased fractional anisotropy and radial diffusivity in the right anterior insula and increased axial diffusivity in right cerebellum crus I in CMTX patients. rs-fMRI revealed decreased spontaneous neural activity on left precentral gyrus in patients compared to healthy controls. CONCLUSION: Advanced magnetic resonance (MR) neuroimaging techniques in CMTX patients revealed structural and functional involvement of multiple motor and extra-motor brain areas. MR neuroimaging techniques have the potential to delineate the CNS phenotype of a peripheral neuropathy like CMTX.

Silent Pauses and Speech Indices as Biomarkers for Primary Progressive Aphasia.

Background and Objectives: Recent studies highlight the importance of investigating biomarkers for diagnosing and classifying patients with primary progressive aphasia (PPA). Even though there is ongoing research on pathophysiological indices in this field, the use of behavioral variables, and especially speech-derived factors, has drawn little attention in the relevant literature. The present study aims to investigate the possible utility of speech-derived indices, particularly silent pauses, as biomarkers for primary progressive aphasia (PPA). Materials and Methods: We recruited 22 PPA patients and 17 healthy controls, from whom we obtained speech samples based on two elicitation tasks, i.e., cookie theft picture description (CTP) and the patients' personal narration of the disease onset and course. Results: Four main indices were derived from these speech samples: speech rate, articulation rate, pause frequency, and pause duration. In order to investigate whether these indices could be used to discriminate between the four groups of participants (healthy individuals and the three patient subgroups corresponding to the three variants of PPA), we conducted three sets of analyses: a series of ANOVAs, two principal component analyses (PCAs), and two hierarchical cluster analyses (HCAs). The ANOVAs revealed significant differences between the four subgroups for all four variables, with the CTP results being more robust. The subsequent PCAs and HCAs were in accordance with the initial statistical comparisons, revealing that the speech-derived indices for CTP provided a clearer classification and were especially useful for distinguishing the non-fluent variant from healthy participants as well as from the two other PPA taxonomic categories. Conclusions: In sum, we argue that speech-derived indices, and especially silent pauses, could be used as complementary biomarkers to efficiently discriminate between PPA and healthy speakers, as well as between the three variants of the disease.

Evidence for Cognitive Deficits in X-Linked Charcot-Marie-Tooth Disease.

OBJECTIVE: X-linked Charcot-Marie-Tooth disease (CMTX) is an hereditary neuropathy caused by mutations in GJB1 coding for connexin-32, found in Schwann cells, but also expressed in oligodendrocytes. Reports have identified CNS involvement in CMTX, but no systematic study of cognitive function has been published. METHODS: We assessed 24 CMTX patients (13 males; 9GJB1 mutations) with a comprehensive neuropsychological battery, including tests of memory, language, and executive functions. RESULTS: No differences in cognitive performance were observed between males and females. A case-by-case investigation revealed selective deficits in individual patients. One subgroup (29%) demonstrated executive abnormalities; and a non-overlapping subgroup (29%), prominent reading (decoding) abnormalities. CONCLUSIONS: The present data provide evidence for cognitive deficits in CMTX. Emerging neuropsychological patterns are also discussed.

X linked Charcot-Marie-Tooth disease and multiple sclerosis: emerging evidence for an association.

OBJECTIVE: X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary neuropathy caused by mutations in GJB1 coding for connexin-32, a gap junction protein expressed in Schwann cells, but also found in oligodendrocytes. Four patients with CMTX developing central nervous system (CNS) demyelination compatible with multiple sclerosis (MS) have been individually published. We presently sought to systematically investigate the relationship between CMTX and MS. METHODS: Over 20 years, 70 consecutive patients (36 men) with GJB1 mutations were identified at our Neurogenetics Unit, Athens, Greece, and assessed for clinical features suggestive of MS. Additionally, 18 patients with CMTX without CNS symptoms and 18 matched controls underwent brain MRI to investigate incidental findings. Serum from patients with CMTX and MS was tested for CNS immunoreactivity. RESULTS: We identified three patients with CMTX who developed clinical features suggestive of inflammatory CNS demyelination fulfilling MS diagnostic criteria. The resulting 20-year MS incidence (4.3%) differed significantly from the highest background 20-year MS incidence ever reported from Greece (p=0.00039). The search for incidental brain MRI findings identified two CMTX cases (11%) with lesions suggestive of focal demyelination compared with 0 control. Moreover, 10 cases in the CMTX cohort had hyperintensity in the splenium of the corpus callosum compared with 0 control (p=0.0002). No specific CNS-reactive humoral factors were identified in patients with CMTX and MS. CONCLUSIONS: We have demonstrated a higher than expected frequency of MS in patients with CMTX and identified incidental focal demyelinating lesions on brain MRI in patients with CMTX without CNS symptoms. This provides circumstantial evidence for GJB1 mutations acting as a possible MS risk factor.

Verbal memory and sentence comprehension in aphasia: A case series.

This case series explores the relationship between verbal memory capacity and sentence comprehension in four patients with aphasia. Two sentence comprehension tasks showed that two patients, P1 and P2, had impaired syntactic comprehension, whereas P3 and P4's sentence comprehension was intact. The memory assessment tasks showed that P1 and P2 had severely impaired short-term memory, whereas P3 and P4 performed within the normal range in the short-term memory tasks. This finding suggests an association between short-term memory deficit and sentence comprehension difficulties. P1 and P3 exhibited impaired comparable working memory deficits, suggesting a dissociation between working memory and sentence comprehension.

Mixed language dominance: insights from a case of unexpected fluent aphasia with semantic jargon resulting from massive left perisylvian lesion.

We report a right-handed patient with a massive lesion in left perisylvian language cortex, who unexpectedly presented with fluent aphasia with semantic jargon. Language deficits were assessed with a comprehensive battery of language tests. Comprehension, naming, reading, and writing were severely impaired, and verbal expression was moderately fluent with semantic jargon. Although the patient's lesion included brain areas typically essential for motor speech coordination, he was neither nonfluent nor apraxic. He exhibited strikingly unexpected aphasia with semantic jargon and prominent comprehension deficits, suggesting that this is a case of mixed dominance: the right hemisphere likely controls motor speech and basic syntactic skills, while the severely damaged left hemisphere controls semantic processing, predictably severely impaired.

A progressive breakdown of the body in space.

A 74 year-old woman (MD), free of previous neurological history, presented with difficulty in handling cutlery, clothes, writing with what was initially described as an atypical apraxia in acts related to space. Initial neurological evaluation revealed mixed, asymmetric pyramidal, and extrapyramidal semiology. Νeuropsychological testing revealed dressing and constructional deficits, ideomotor apraxia and signs of executive dysfunction in absence of memory, language, and visual perception pathology. The final diagnosis was that of a corticobasal degeneration, where the rare occurrence of a progressively emerging syndrome of self-management loss within peripersonal space is observed.

Anti-NMDA receptor encephalitis presenting as isolated aphasia in an adult.

Anti-NMDA receptor (NMDA-r) encephalitis is a relatively rare cause of autoimmune encephalitis with divergent clinical presentations. We report a case of an adult patient with anti-NMDA-r encephalitis presenting with isolated, abrupt-onset aphasia. Her condition remained unaltered over a period of 6 months. The patients' electroencephalogram findings were typical for NMDA-r encephalitis; however, her magnetic resonance imaging and cerebrospinal fluid analysis were normal. She responded well to immunotherapy, and aphasia eventually resolved. The natural course of the present case contradicts the rapidly progressive nature of typical NMDA-r encephalitis. Furthermore, it broadens the clinical spectrum of anti-NMDA-r encephalitis, to incorporate isolated, nonprogressive aphasia.

In Search of Executive Impairment in Pathological Gambling: A Neuropsychological Study on Non-treatment Seeking Gamblers.

Pathological gambling is characterized by a persisting maladaptive and recurrent behavior with severe social and psychological consequences. There is evidence of strong comorbidity with psychiatric manifestations as well as cognitive mainly involving executive functions. This study aimed to investigate impairment in executive functions and working memory, and personality traits in a sample of Greek gamblers. Twenty-four men involved in various gambling activities were recruited from ecological settings as probable pathological gamblers. They were assessed with a comprehensive neuropsychological battery involving several executive tasks, the Zuckerman-Kuhlman Personality Questionnaire, the Hospital Anxiety Depression Scale, and the Difficulties in Emotion Regulation Scale. An age- and education-level matched group of 21 men without history of habitual gambling served as controls. As a group, gamblers displayed significantly lower scores on indices of inhibition, decision making and self-reported emotional awareness, and scored higher on impulsivity/sensation seeking personality traits. Notably, gamblers scored similarly or significantly higher on measures of verbal and visuospatial working memory, cognitive flexibility, processing speed, verbal fluency, and sustained attention. Overall, we argue that gamblers do present with specific cognitive deficits, but there is no evidence for a generalized executive impairment, and further stress the importance of investigating cognitive, personality, and psychiatric aspects of gambling on the basis of an ecologically valid sampling.

Neuropsychological and psychiatric aspects of multiple sclerosis: preliminary investigation of discrete profiles across neurological subtypes.

Cognitive deficits affecting memory, attention, speed of information processing and executive functions are common in multiple sclerosis (MS). In this study we examine the possibility of discrete pattern of neuropsychological deficits of MS subtypes. 28 patients (13 RRMS, 6 CIS, and 9 SPMS) were assessed with a comprehensive neuropsycholgical battery. Results indicate that only the SPMS group demonstrates memory and executive impairment. This finding indicates possible differentiation of the three subtypes in terms of neuropsychological profiles. Psychiatric aspects of MS are also briefly discussed.

Frontotemporal Dysfunction in Amyotrophic Lateral Sclerosis: A Discriminant Function Analysis.

BACKGROUND: There is growing evidence for extramotor dysfunction (EMd) in amyotrophic lateral sclerosis (ALS), with a reported prevalence of up to 52%. OBJECTIVE: In the present study, we explore the clinical utility of a brief neuropsychological battery for the investigation of cognitive, behavioral, and language deficits in patients with ALS. METHODS: Thirty-four consecutive ALS patients aged 44-89 years were tested with a brief neuropsychological battery, including executive, behavioral, and language measures. Patients were initially classified as EMd or non-EMd based on their scores on the frontal assessment battery (FAB). RESULTS: Between-group comparisons revealed significant differences in all measures (p < 0.01). Discriminant analysis resulted in a single canonical function, with all tests serving as significant predictors. This function agreed with the FAB in 13 of 17 patients screened as EMd and identified extramotor deficits in 2 additional patients. Overall sensitivity and specificity estimates against FAB were 88.2%. CONCLUSIONS: We stress the importance of discriminant function analysis in clinical neuropsychological assessment and argue that the proposed neuropsychological battery may be of clinical value, especially when the option of extensive and comprehensive neuropsychological testing is limited. The psychometric validity of an ALS-frontotemporal dementia diagnosis using neuropsychological tests is also discussed.

The dichotomous view on IFG lesion and non-fluent aphasia.

A lesion in inferior frontal gyrus (IFG) is traditionally considered to be crucial for the occurrence of non-fluent aphasia. However, recent studies question the axiomatic causality between a lesion in this area and the expected non-fluent aphasic syndrome. The aim of the present study is to investigate the relationship between IFG lesions and non-fluent aphasia. To address this question, we present radiological and neuropsychological data of 49 chronic aphasic patients. Lesions were identified based on CT and/or MRI scans. Aphasia was assessed using the Boston Diagnostic Aphasia Examination-short form. Analysis indicated a statistically significant association between IFG lesion and non-fluent aphasic disturbances. Nevertheless, a large proportion of our patients did not confirm the traditional prediction, namely that non-fluent patients' lesions would include the inferior frontal gyrus and the opposite would be true for fluent patients. Our results stress the importance of taking into account the size of particular estimates when conducting group analyses. We also argue in favor of examining individual data in clinical practice, and further suggest that the traditional lesion to syndrome correspondence seems to be oversimplified and should be thoroughly revisited.

Age-related decline in verbal learning is moderated by demographic factors, working memory capacity, and presence of amnestic mild cognitive impairment.

Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity.

A Methodological Approach to Quantifying Silent Pauses, Speech Rate, and Articulation Rate across Distinct Narrative Tasks: Introducing the Connected Speech Analysis Protocol (CSAP).

The examination of connected speech may serve as a valuable tool for exploring speech output in both healthy speakers and individuals with language disorders. Numerous studies incorporate various fluency and silence measures into their analyses to investigate speech output patterns in different populations, along with the underlying cognitive processes that occur while speaking. However, methodological inconsistencies across existing studies pose challenges in comparing their results. In the current study, we introduce CSAP (Connected Speech Analysis Protocol), which is a specific methodological approach to investigate fluency metrics, such as articulation rate and speech rate, as well as silence measures, including silent pauses' frequency and duration. We emphasize the importance of employing a comprehensive set of measures within a specific methodological framework to better understand speech output patterns. Additionally, we advocate for the use of distinct narrative tasks for a thorough investigation of speech output in different conditions. We provide an example of data on which we implement CSAP to showcase the proposed pipeline. In conclusion, CSAP offers a comprehensive framework for investigating speech output patterns, incorporating fluency metrics and silence measures in distinct narrative tasks, thus allowing a detailed quantification of connected speech in both healthy and clinical populations. We emphasize the significance of adopting a unified methodological approach in connected speech studies, enabling the integration of results for more robust and generalizable conclusions.

Reading fluency estimates of current intellectual function: demographic factors and effects of type of stimuli.

The study explores the potential clinical value of reading fluency measures in complementing demographic variables as indices of current intellectual capacity. IQ estimates (based on the PPVT-R, WASI Vocabulary and Block Design subtests) were obtained from a representative, non-clinical sample of 386 Greek adults aged 48­87 years along with two measures of reading efficiency (one involving relatively high-frequency words­WRE­and the second comprised of phonotactically matched pseudowords­PsWRE). Both reading measures (number of items read correctly in 45 s) accounted for significant portions of variability in demographically adjusted verbal and performance IQ indices. Reading measures provided IQ estimates which were significantly closer to those predicted by demographic variables alone in up to 22% of individuals with fewer than 7 (across all ages) or 13 years of formal education (in the 70­87 year age range). PsWRE scores slightly outperformed WRE scores in predicting a person's estimated verbal or performance IQ. Results are discussed in the context of previous findings using reading accuracy measures for low-frequency words with exceptional spellings in less transparent orthographic systems such as English.

Unraveling the Thread of Aphasia Rehabilitation: A Translational Cognitive Perspective.

Translational neuroscience is a multidisciplinary field that aims to bridge the gap between basic science and clinical practice. Regarding aphasia rehabilitation, there are still several unresolved issues related to the neural mechanisms that optimize language treatment. Although there are studies providing indications toward a translational approach to the remediation of acquired language disorders, the incorporation of fundamental neuroplasticity principles into this field is still in progress. From that aspect, in this narrative review, we discuss some key neuroplasticity principles, which have been elucidated through animal studies and which could eventually be applied in the context of aphasia treatment. This translational approach could be further strengthened by the implementation of intervention strategies that incorporate the idea that language is supported by domain-general mechanisms, which highlights the impact of non-linguistic factors in post-stroke language recovery. Here, we highlight that translational research in aphasia has the potential to advance our knowledge of brain-language relationships. We further argue that advances in this field could lead to improvement in the remediation of acquired language disturbances by remodeling the rationale of aphasia-therapy approaches. Arguably, the complex anatomy and phenomenology of aphasia dictate the need for a multidisciplinary approach with one of its main pillars being translational research.

Exploring Pragmatic Deficits in Relation to Theory of Mind and Executive Functions: Evidence from Individuals with Right Hemisphere Stroke.

Research investigating pragmatic deficits in individuals with right hemisphere damage focuses on identifying the potential mechanisms responsible for the nature of these impairments. Nonetheless, the presumed shared cognitive mechanisms that could account for these deficits have not yet been established through data-based evidence from lesion studies. This study aimed to examine the co-occurrence of pragmatic language deficits, Theory of Mind impairments, and executive functions while also exploring their associations with brain lesion sites. Twenty-five patients suffering from unilateral right hemisphere stroke and thirty-seven healthy participants were recruited for this study. The two groups were tested in pragmatics, Theory of Mind, and executive function tasks. Structural imaging data were also obtained for the identification of the lesion sites. The findings of this study suggest a potential convergence among the three aforementioned cognitive mechanisms. Moreover, we postulate a hypothesis for a neural circuitry for communication impairments observed in individuals with right hemisphere damage.

Moyamoya Disease: Clinical and Radiological Characteristics in Adult Greek Patients.

BACKGROUND AND PURPOSE: The aim of our study is to present, for the first time, the clinical, radiological, and neurocognitive characteristics of Greek adult patients with Moyamoya disease (MMD). METHODS: We analyzed prospectively collected data of 12 patients referred to our department from 2004 to 2019. All patients underwent a thorough diagnostic work up, including extensive clinical, neuroradiological, and neurocognitive assessment. RESULTS: Our study population consisted of 7 females and the median age at the time of the diagnosis was 43.5 years. No patient had a positive family history of the disease and roughly 50% were hypertensives. Ten patients presented with transient or permanent cerebrovascular ischemia and two patients suffered from hemorrhagic complications. The median NIHSS was 7.5 (0-23) and clinical status remained stable during follow-up with conservative treatment in most of the patients. The majority (83.3%) had bilateral disease confirmed by DSA. All lesions exclusively affected the anterior circulation, with 50% of patients presenting with stenoocclusive changes. No aneurysm or AVM were revealed. The most common neurocognitive deficits were in the executive and language domains. CONCLUSIONS: Our MMD patients had a later onset of the disease and an absence of familial occurrence. The most common manifestation was ischemia, transient or permanent, and all lesions affected the anterior circulation, whereas no vascular malformations (AVM, aneurysms) were demonstrated in brain imaging. These findings in Greek patients imply a probable different, Mediterranean phenotype.