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BackgroundTreatment options for chronic osmotic demyelination syndrome are limited to case reports and only a very few show complete recovery. We report a case of complete recovery of chronic osmotic demyelination syndrome with plasmapheresis.Case presentationA 43-year-old Sri Lankan man presented with fever, repeated vomiting, unsteady gait, increased tonicity of his right upper limb and paucity of speech for three days. He was treated in the local hospital with antibiotics and antivirals as per central nervous system infection. He had hyponatraemia, which was rapidly corrected with hypertonic saline from 97 to 119 mmol/L. He was transferred to our hospital because of progressive reduction of consciousness, rapidly worsening rigidity and bradykinesia of all four limbs and worsening dysarthria and bradyphrenia. Magnetic resonance imaging of the brain was compatible with osmotic demyelination syndrome. He was commenced on plasmapheresis twenty-two days after rapid correction of sodium. He regained independent mobility with complete resolution of rigidity, bradykinesia and speech dysfunction after five cycles of alternate day plasmapheresis.ConclusionPlasmapheresis can be considered as an effective treatment modality in chronic osmotic demyelination syndrome.

Familial Alzheimer’s disease (AD) accounts for less than 1% of the total cases of AD and is characterized by a cognitive decline typically initiated before the age of 65 with a positive familial history, usually with a dominant inherence pattern. A 35-year-old man, whose mother died at the age of 36 with an undetermined rapidly progressive dementia, developed memory impairment and depression at the age of 33 followed by spatial disorientation, behavioral changes, and hallucinations at the age of 35. His neurological examination revealed bradyphrenia with a poor perseverative speech, executive dysfunction, dyscalculia, and bilateral frontal release signs. Blood analysis and brain MRI were normal; however, cerebrospinal fluid showed an elevated phosphorylated tau/beta-amyloid ratio, and SPECT revealed a global hypoperfusion. Therefore, a genetic testing for autosomal dominant variants of AD was performed, disclosing a presenilin 1 (PSEN1) mutation, Pro117Leu, which confirms the diagnosis of familial Alzheimer’s disease. One year later, he had developed severe cognitive impairment with pyramidal and extrapyramidal signs, regardless of donepezil therapeutic regimen. PSEN1 mutation is the most common cause of familial AD and, compared to the other mutations, is associated with the youngest age of onset and with the presence of atypical neurological signs. To our knowledge, this is one of the cases with younger age of onset described in the literature.

5560 patients with the diagnosis “Other cerebral vascular diseases” per 100 000 of elderly population were registered in RF in 2017. Usually this is a code for chronic brain ischemia (CBI) – the most popular diagnosis in Russian neurological practice. However, diagnostic criteria of CBI are not well defined and need to be ascertained. Recent studies show that the most reliable clinical feature of CBI could be cognitive impairment. It is developed before other clinical signs and correlate with severity of vascular brain lesions. Typically, cognitive impairment is subcortical with prominent bradyphrenia, attentional, dysexecutive and visuospatial deficit and relative sparing of memory. However clinical diagnosis of CBI could be only hypothetical. Diagnosis should be verified by MRI or other visualization technic. Diagnosis is verified if neuroimaging revealed silent strokes, microbleeds and vascular leukoencephalopathy. The most important objective of chronic brain ischemia management is the control of basic vascular disease. Besides this, pathogenetic therapy should be performed to improve cerebral microcirculation, neuronal metabolism and to provide neuroprotection. There is positive data on dipyridamole usage in chronic brain ischemia. It has desagregative, vasotropic, antioxidative and antiinflammation properties. Dypiridamole treatment in CBI patients lead to decrease of neuropsychiatric symptoms and improvement of well-being.

A 60-year old previously healthy left-handed man presented to clinic with 6 months of progressive slowness and stiffness on the left side. He described loss of dexterity in the left hand and feeling of “heaviness” in the left leg. On exam, he exhibited mild bradyphrenia and hypophonia, moderate left arm and leg bradykinesia and rigidity, and left leg hesitations and reduced left arm-swing upon walking (video 1). A month prior, he had undergone MRIs of the brain and cervical spine with and without gadolinium that were unremarkable. Initial serum testing including complete blood count, comprehensive metabolic panel, thyroid stimulating hormone, ceruloplasmin, and vitamin B12 levels were all unremarkable. The differential diagnosis at presentation included the spectrum of parkinsonian disorders with Parkinson's Disease being the most likely given his age group and the asymmetric parkinsonism. He was diagnosed with suspected Parkinson's Disease and levodopa therapy was initiated as the he felt his symptoms were functionally-limiting.

Digital health technologies (DHTs) enable remote and therefore frequent measurement of motor signs, potentially providing reliable and valid estimates of motor sign severity and progression in Parkinson’s disease (PD). The Roche PD Mobile Application v1 was revised to v2 to include more measures of bradykinesia, and bradyphrenia and speech tests, to optimize suitability for early-stage PD. It was studied in 316 early-stage PD participants who performed daily active tests at home then carried a smartphone and wore a smartwatch throughout the day for passive monitoring (study NCT03100149). Adherence was excellent (96.29%). All pre-specified sensor features exhibited good-to-excellent test-retest reliability (median intraclass correlation coefficient = 0.9), and correlated with corresponding Movement Disorder Society - Unified Parkinson’s Disease Rating Scale items (rho: 0.12–0.71). These findings demonstrate the preliminary reliability and validity of remote at-home quantification of motor sign severity with the Roche PD Mobile Application v2 in individuals with early PD.

Novel coronavirus disease (COVID‐19) first described in Wuhan, China in December 2019, has rapidly spread across the world and become a global public health emergency. Literature on the neurological manifestations of COVID‐19 is limited. We report a 24‐year‐old male, who presented with vertigo, dysarthria, and bradyphrenia 3 weeks after being diagnosed with COVID‐19 on nasopharyngeal reverse transcription polymerase chain reaction. The patient was diagnosed with acute cerebellitis based on magnetic resonance imaging features and showed improvement posttreatment with intravenous methylprednisone for 5 days. The scope of this article is to highlight the importance of early identification of neurological symptoms and timely management as the outcomes may be catastrophic.

We report the case of a 67-year-old male who presented with a six-week history of progressive unsteadiness, cognitive impairment and weight loss, in the context of a recent bereavement. Magnetic resonance imaging (MRI) performed several weeks earlier excluded acute stroke. Examination revealed gross bilateral ataxia, bradyphrenia and physical manifestations of depression. Collateral history suggested rapidly progressing symptoms over three months. Repeat MRI head showed features suggestive of Creutzfeldt-Jakob disease (CJD) including T2 hyperintensities in the basal ganglia. Cerebrospinal fluid (CSF) samples were positive for 14-3-3 protein, S100b and real-time quaking-induced conversion (RT-QuIC) proteins confirming the diagnosis of sporadic CJD (sCJD).

The article describes epilepsy as a chronic disease of the central nervous system with a wide range of neuropsychiatric disorders, which include cognitive, affective and behavioral disorders. It is important to detect the presence of comorbid conditions in patients with epilepsy as early as possible to ensure early identification, diagnosis and proper monitoring of such co-morbidities. The most frequent manifestations of cognitive dysfunction in epilepsy include depression, impaired memory, attention, and bradyphrenia in the attack-free interval. Various factors play an important role in the pathogenesis of these disorders: organic brain damage, neuronal dysfunction, interictal epileptic activity, repeated seizures, and intake of certain anti-epileptic drugs. Various anti-epileptic drugs are considered from the point of view of influencing the cognitive functions, affective sphere and behavior of patients. Valproic acid preparations, which generally have a good cognitive profile, are presented in detail. A special attention is paid to Convulex, which has multi-dose presentations to provide further advantages in terms of dose flexibility.

Introduction Bradyphrenia is a key cognitive feature in Parkinson's disease (PD). There is no consensus on whether information processing speed is impaired or not beyond motor performance. Objective This study aims to explore which perceptual, motor, or cognitive components of information processing are involved in the slowdown affecting cognitive performance. Methods The study included 48 patients with PD (age: 63, 3 ± 8, 18; HY I‐III; UPDRS 15,46 ± 7,76) and 53 healthy controls (age: 60,09 ± 12,83). Five reaction time (RT) tasks were administered to all participants. The average RT in each of the tasks and the percentage of correct answers were measured. Patients with PD were in "ON state" at the time of the evaluation. Perceptual, motor, and cognitive components were isolated by means of a series of ANCOVAs. Results As expected, the motor component was slowed down in patients with PD. Moreover, while patients with PD showed slower RT than controls in all tasks, differences between groups did not exponentially increase with the increasing task complexity. ANCOVA analyses also revealed that the perceptual and sustained alert component resulted to be slowed down, with no differences being found in any of the remaining isolated cognitive components (i.e., response strategy‐inhibition, decisional, visual search, or interference control). Conclusions The results revealed that slowness of information processing in PD was mainly associated with an impaired processing speed of the motor and perceptual‐alertness components analyzed. The results may help designing new neurorehabilitation strategies, focusing on the improvement of perceptual and alertness mechanisms., The level of cognitive deceleration in PD is determined by a deterioration focused on perceptual and motor components and independently of the task complexity. Alterations in the brain networks involved in alertness to react to stimuli could justify the slowness of information processing in Parkinson´s disease

Cognitive inflexibility is a well-documented, yet non-specific corollary of many neurological diseases. Computational modeling of covert cognitive processes supporting cognitive flexibility may provide progress toward nosologically specific aspects of cognitive inflexibility. We review computational models of the Wisconsin Card Sorting Test (WCST), which represents a gold standard for the clinical assessment of cognitive flexibility. A parallel reinforcement-learning (RL) model provides the best conceptualization of individual trial-by-trial WCST responses among all models considered. Clinical applications of the parallel RL model suggest that patients with Parkinson’s disease (PD) and patients with amyotrophic lateral sclerosis (ALS) share a non-specific covert cognitive symptom: bradyphrenia. Impaired stimulus-response learning appears to occur specifically in patients with PD, whereas haphazard responding seems to occur specifically in patients with ALS. Computational modeling hence possesses the potential to reveal nosologically specific profiles of covert cognitive symptoms, which remain undetectable by traditionally applied behavioral methods. The present review exemplifies how computational neuropsychology may advance the assessment of cognitive flexibility. We discuss implications for neuropsychological assessment and directions for future research.

Executive dysfunction is a well-documented, yet nonspecific corollary of various neurological diseases and psychiatric disorders. Here, we applied computational modeling of latent cognition for executive control in amyotrophic lateral sclerosis (ALS) patients. We utilized a parallel reinforcement learning model of trial-by-trial Wisconsin Card Sorting Test (WCST) behavior. Eighteen ALS patients and 21 matched healthy control participants were assessed on a computerized variant of the WCST (cWCST). ALS patients showed latent cognitive symptoms, which can be characterized as bradyphrenia and haphazard responding. A comparison with results from a recent computational Parkinson&rsquo, s disease (PD) study (Steinke et al., 2020, J Clin Med) suggests that bradyphrenia represents a disease-nonspecific latent cognitive symptom of ALS and PD patients alike. Haphazard responding seems to be a disease-specific latent cognitive symptom of ALS, whereas impaired stimulus-response learning seems to be a disease-specific latent cognitive symptom of PD. These data were obtained from the careful modeling of trial-by-trial behavior on the cWCST, and they suggest that computational cognitive neuropsychology provides nosologically specific indicators of latent facets of executive dysfunction in ALS (and PD) patients, which remain undiscoverable for traditional behavioral cognitive neuropsychology. We discuss implications for neuropsychological assessment, and we discuss opportunities for confirmatory computational brain imaging studies.

Depression is associated with constipation within and outside Parkinson&rsquo, s disease (PD). Since inefficient cognitive-processing (bradyphrenia) features in PD and an enterokinetic agent improved cognitive performance in healthy individuals, bradyphrenia may be associated with constipation. We aim to define the archetypical bowel function of PD, and its association with cognition, mood, and motor features within and outside PD. We assessed colonic transit time (oral radio-opaque markers over 6 days), bowel function and psychometric questionnaires and measures of PD facets, including bradyphrenia, in 58 participants with diagnosed PD, and 71 without (controls). The best abdominal X-ray (day 7) predictors of PD status were total retained marker count and transverse colon segmental delay. However, Rome functional constipation status complemented segmental delay better, giving good specificity (85%) but low sensitivity (56%). Transverse colon marker count appeared to be age-associated only in PD. In PD, those correctly classified by bowel dysfunction had higher depression scores (p = 0.02) and longer cognitive-processing times than the misclassified (p = 0.05). Controls misclassified as PD by bowel dysfunction had higher depression and anxiety scores than the correctly classified (p = 0.002 and 0.003, respectively), but not slower cognitive processing. Measures of motor features were independent of sub-classification by bowel function in PD and in controls. In conclusion, constipation in PD has distinct localized pathophysiology, and is associated with bradyphrenia.

Author(s): Piot, Ines; Schweyer, Kerstin; Respondek, Gesine; Stamelou, Maria; DescribePSP study group; ProPSP study group; MDS-endorsed PSP study group; Sckopke, Philipp; Schenk, Thomas; Goetz, Christopher G; Stebbins, Glenn T; Hoglinger, Gunter U | Abstract: BackgroundThere is currently no undisputed, validated, clinically meaningful measure for deficits in the broad spectrum of PSP phenotypes.ObjectiveTo develop a scale to monitor clinical deficits in patients with PSP across its broad phenotypes.MethodsThe Progressive Supranuclear Palsy Clinical Deficits Scale was conceptualized to cover seven clinical domains (Akinesia-rigidity, Bradyphrenia, Communication, Dysphagia, Eye movements, Finger dexterity, and Gait a balance), each scored from 0 to 3 (no, mild, moderate, or severe deficits). User guidelines were developed to standardize its application. Progressive Supranuclear Palsy Clinical Deficits Scale scores were collected in patients fulfilling the MDS-PSP diagnostic criteria in two independent, multicenter, observational studies, both cross-sectionally (exploratory DescribePSP cohort; confirmatory ProPSP cohort) and longitudinally (12-months' follow-up, both cohorts).ResultsCognitive pretesting demonstrated easy scale utility. In total, 164 patients were scored (70.4 ± 7.6 years; 62% males, 35% variant phenotypes). Mean Progressive Supranuclear Palsy Clinical Deficits Scale completion time was 4 minutes. The Progressive Supranuclear Palsy Clinical Deficits Scale total score correlated with existing scales (e.g., Progressive Supranuclear Palsy Rating Scale: R = 0.88; P l 0.001). Individual Progressive Supranuclear Palsy Clinical Deficits Scale items correlated well with similar constructs in existing scales. Internal consistency (Cronbach's alpha: 0.75), inter-rater reliability (0.96), and test-retest stability (0.99) were acceptable. The PSP-CDS showed significant 12-month change (baseline, 8.6 ± 3.6; follow-up: 10.8 ± 3.6; annualized difference: 3.4 ± 3.4; n = 49; P l 0.0001). Sample sizes required per arm for a two-arm, 1-year follow-up therapeutic trial to detect 50% change in Progressive Supranuclear Palsy Clinical Deficits Scale progression was estimated to be 65 (two-sided, two-sample t test).ConclusionThe Progressive Supranuclear Palsy Clinical Deficits Scale is a rapidly completed, clinimetrically sound scale for clinical care and research involving PSP. © 2020 International Parkinson and Movement Disorder Society.

Axial signs and cognitive disorders are the major source of disability in progressive supranuclear palsy (PSP). Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN), a structure involved in locomotion and posture control, has showed to improve freezing and falls in patients with Parkinson’s disease (PD).1 In this pilot trial, we investigated the effectiveness and safety of unilateral PPN DBS on gait and balance in patients with Richardson’s syndrome (RS) phenotype of PSP. Between April 2006 and December 2010, eight patients with RS-PSP were enrolled at the Movement Disorders Center of the Toronto Western Hospital. The study was approved by the University Health Network, and the Toronto Rehab Research Ethics Boards. All patients gave their written consent to the study. Both the surgical procedure and the PPN DBS programming were similar to those already used in patients with PD.2 Patients were assessed at baseline, and at 6 and 12 months after surgery, when they were randomly assigned to be evaluated both in the OFF and in the ON stimulation condition, after being 1 week in each stimulation condition. Patients and raters were blinded to the stimulation conditions. All assessments were videotaped, and adverse events were recorded. Main outcome was the difference between the ON and OFF stimulation conditions at 6 and 12-month follow-up in gait, postural stability and fall subitems of the PSP Rating Scale (PSPRS). Secondary outcomes were differences in the total scores of the motor Unified Parkinson Disease Rating Scale (UPDRS) and PSPRS; the PSP Staging System (PSPSS) score; rigidity, bradykinesia, arising from a chair and posture UPDRS items; history, mental, bulbar examination, supranuclear ocular motor examination, limb examination and gait/midline examination subscores of the PSPRS; withdrawal, sleep difficulty, disorientation, bradyphrenia and emotional incontinence items of the PSPRS. …

Introduction Among transmissible spongiform encephalopathies, Creuzfeldt-Jakob disease is considered a rare neurodegenerative disorder. The clinical features include rapid progressive dementia and myoclonic jerks, which progresses to death. Case description We report a case of a 65-year-old man, with progressive gait instability and impaired cognition with normal brain MRI. After 1 week, his symptoms became worse, EEG showed periodic sharp wave complexes, suggestive of Creuzfeldt-Jakob disease, and CSF was normal. One week later, he developed bradyphrenia and myoclonic fits. Brain MRI showed hyper-intensities mainly in the right frontal and occipital cortical gyri and caudate areas. After a few days, the patient developed akinetic mutism intractable fits, was admitted to the ICU, and was deceased after a few days. Discussion and evaluation Based on the 2010 CDC Criteria, our case was diagnosed as probable sporadic Creutzfeldt-Jakob disease (sCJD). The main findings were rapidly progressive dementia, ataxia, akinetic mutism, and myoclonus. EEG and MRI findings support the diagnosis. Conclusions Our case showed clinical, electrophysiological, and radiological features typical of probable sCJD—a rare, incurable, and fatal disease.

Idiopathic normal pressure hydrocephalus (INPH) is a syndrome characterized by the classic triad of gait disturbance, potentially reversible dementia (progressive mental deterioration) and urinary incontinence. The dementia can involve executive dysfunction, memory failures and bradyphrenia. The criteria for referral for ventriculoperitoneal shunting are still controversial but include the results of a spinal tap, which is performed to simulate the effect of shunting and to analyze the impact of cerebrospinal fluid (CSF) drainage on the patient's gait. Objective: To evaluate the immediate effect of a spinal tap on the executive functions of patients with a diagnosis of probable INPH. Methods: Seventeen participants (seven men and ten women) aged 76.41+6.24 years (mean+SD) with 9.01+4.40 years (mean+SD) of schooling were selected from a group of 130 individuals tested. The neuropsychological tests of executive functions used were the Stroop test, digit span task, verbal fluency (animals and letters) (FAR) and MMSE. Patients were evaluated in three stages: before the first CSF drainage and after the first and second CSF drainages. Results: Statistical analysis showed significant differences between the pre-spinal tap and post-spinal tap results in the forward (p

Introduction: Motor slowness (bradykinesia) is a core feature of Parkinson's disease (PD). It is often assumed that patients show mental slowness (bradyphrenia) as well; however, evidence for this is debated. The aims of this study were to determine whether PD patients show mental slowness apart from motor slowness and, if this is the case, to what extent this affects their performance on neuropsychological tests of attention, memory, and executive functions (EF). Method: Fifty-five nondemented PD patients and 65 healthy controls were assessed with a simple information-processing task in which reaction and motor times could be separated. In addition, all patients and a second control group (N = 138) were assessed with neuropsychological tests of attention, memory, and EF. Results: While PD patients showed significantly longer reaction times than healthy controls, their motor times were not significantly longer. Reaction and motor times were only moderately correlated and were not related to clinical measures of disease severity. PD patients performed significantly worse on tests of attention and EF, and for the majority of neuropsychological tests 11-51% of the patients showed a clinically impaired performance. Reaction times did not, however, predict patients' test performance, while motor times were found to have a significant negative influence on tests of attention. Conclusions: PD patients show mental slowness, which can be separated from motor slowness. Neuropsychological test performance is not influenced by mental slowness; however, motor slowness can have a negative impact. When interpreting neuropsychological test performance of PD patients in clinical practice, motor slowness needs to be taken into account.

The neural mechanisms of cognitive dysfunctions in neurological diseases remain poorly understood. Here, we conjecture that this unsatisfying state-of-the-art is in part due to the non-specificity of the typical behavioral indicators for cognitive dysfunctions. Our study addresses the topic by advancing the assessment of cognitive dysfunctions through computational modeling. We investigate bradyphrenia in Parkinson&rsquo, s disease (PD) as an exemplary case of cognitive dysfunctions in neurological diseases. Our computational model conceptualizes trial-by-trial behavioral data as resulting from parallel cognitive and sensorimotor reinforcement learning. We assessed PD patients &lsquo, on&rsquo, and &lsquo, off&rsquo, their dopaminergic medication and matched healthy control (HC) participants on a computerized version of the Wisconsin Card Sorting Test. PD patients showed increased retention of learned cognitive information and decreased retention of learned sensorimotor information from previous trials in comparison to HC participants. Systemic dopamine replacement therapy did not remedy these cognitive dysfunctions in PD patients but incurred non-desirable side effects such as decreasing cognitive learning from positive feedback. Our results reveal novel insights into facets of bradyphrenia that are indiscernible by observable behavioral indicators of cognitive dysfunctions. We discuss how computational modeling may contribute to the advancement of future research on brain&ndash, behavior relationships and neuropsychological assessment.

Background Catatonia is frequently associated with mood and psychotic disorders as well as with general medical conditions, especially with seizures. In the case of the latter, catatonia mostly resolves when the seizures respond to the anticonvulsive treatment. We report, to our knowledge, the first case of a patient without affective or psychotic disorder, who developed catatonia in the postictum and whose catatonia did not resolve with anticonvulsive treatment, but did so with lorazepam. Case presentation We describe a 36-year-old man, with no psychiatric history, except for a possible disorder in the use of cannabis, who developed catatonia after epileptic seizures. The catatonia did not respond to the anticonvulsant therapy, but did so to lorazepam 17 mg/d. Lorazepam could be tapered slowly and stopped without reemergence of catatonic signs. Conclusion Catatonia should be part of the differential diagnosis in patients with bradyphrenia and/or remarkable postictal behavior. This report shows that lorazepam should be taken into consideration (before moving to ECT), in cases of unresolved catatonia, even if the seizures are reduced with anticonvulsants.

Parkinson’s disease (PD) is primarily associated with the degeneration of midbrain dopamine neurons, but it is now appreciated that pathological processes like Lewy-body inclusions and cell loss affect several other brain regions, including the central lateral (CL) and centromedian/parafascicular (CM/PF) thalamic regions. These thalamic glutamatergic neurons provide a non-cortical excitatory input to the dorsal striatum, a major projection field of dopamine neurons. To determine how thalamostriatal signaling may contribute to cognitive and motor abnormalities found in PD, we used a viral vector approach to generate mice with loss of thalamostriatal glutamate signaling specifically restricted to the dorsal striatum (CAV2Cre-Slc17a6lox/lox mice). We measured motor function and behaviors corresponding to cognitive domains (visuospatial function, attention, executive function, and working memory) affected in PD. CAV2Cre-Slc17a6lox/lox mice were impaired in motor coordination tasks such as the rotarod and beam-walk tests compared with controls (CAV2Cre-Slc17a6+/+ mice). They did not demonstrate much cognitive impairment in the Morris water maze or a water U-maze, but had slower processing reaction times in those tests and in a two-way active avoidance task. These mice could model an aspect of bradyphrenia, the slowness of thought that is often seen in patients with PD and other neurological disorders., Brain connectivity: Interrupting cognitive processing speed Mice in which glutamate signaling from the thalamus to dorsal striatum has been genetically inactivated mimic the slowness of thought that is often observed in patients with Parkinson’s disease (PD). The midbrain and striatum are the brain regions that are most affected in PD, however, it is increasingly recognized that cell loss in other areas of the brain also contribute to disease symptoms. Martin Darvas at the University of Washington, Seattle, USA, and colleagues found that disrupting the excitatory input from thalamic projection neurons into the dorsal striatum affected motor coordination and balance in mice. Although these mice did not have significant impairments in spatial learning and memory, they were slower at reacting to cues and executing learned behaviors suggesting that they could be used to test new approaches for treating this specific cognitive symptom of PD.

A significant symptom of Lewy body dementia (LBD) is slow cognitive processing or bradyphrenia. In a previous fMRI task-based study, we found slower responses in LBD, accompanied by greater deactivation in the default mode network. In this study, we investigated the timing and magnitude of the activations and deactivations with respect to reaction time to determine whether the slower responses in LBD were associated with delayed neuronal activity. Using fMRI, we examined the magnitude and latency of activations and deactivations during an event-related attention task in 32 patients with LBD and 23 healthy controls using predefined regions of interest. Default mode network deactivations did not significantly differ in their timing between groups or task conditions, while the task-related activations in the parietal, occipital, frontal, and motor cortex were all significantly later in the LBD group. Repeating the analysis with reaction time as a parametric modulator of activation magnitude produced similar findings, with the reaction time modulator being significant in a number of regions including the default mode network, suggesting that the increased deactivation in LBD is partly explained by slower task completion. Our data suggest that the default mode network deactivation is initiated at the start of the task, and remains deactivated until its end, with the increased magnitude of deactivation in LBD reflecting the more prolonged cognitive processing in these patients. These data add substantially to our understanding of the neural origins of bradyphrenia, which will be essential for determining optimum therapeutic strategies for cognitive impairment in LBD.

A significant symptom of Lewy body dementia (LBD) is slow cognitive processing or bradyphrenia. In a previous fMRI task‐based study, we found slower responses in LBD, accompanied by greater deactivation in the default mode network. In this study, we investigated the timing and magnitude of the activations and deactivations with respect to reaction time to determine whether the slower responses in LBD were associated with delayed neuronal activity. Using fMRI, we examined the magnitude and latency of activations and deactivations during an event‐related attention task in 32 patients with LBD and 23 healthy controls using predefined regions of interest. Default mode network deactivations did not significantly differ in their timing between groups or task conditions, while the task‐related activations in the parietal, occipital, frontal, and motor cortex were all significantly later in the LBD group. Repeating the analysis with reaction time as a parametric modulator of activation magnitude produced similar findings, with the reaction time modulator being significant in a number of regions including the default mode network, suggesting that the increased deactivation in LBD is partly explained by slower task completion. Our data suggest that the default mode network deactivation is initiated at the start of the task, and remains deactivated until its end, with the increased magnitude of deactivation in LBD reflecting the more prolonged cognitive processing in these patients. These data add substantially to our understanding of the neural origins of bradyphrenia, which will be essential for determining optimum therapeutic strategies for cognitive impairment in LBD. Hum Brain Mapp 39:633–643, 2018. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Objective: While cognitive deficits are well documented in Parkinson disease (PD), identifying a theoretical framework in which to interpret these findings has been less studied. Theories of cognitive aging suggest that processing speed is likely a critical factor in normal cognitive function that explains a large portion of the interindividual variance associated with age-related cognitive decline. We tested the hypotheses that measures of processing speed underlie deficits in working memory and inhibition in PD as well. Methods: We measured cognitive function in a group of 77 medicated individuals with PD without dementia and 54 controls. Participants completed a battery of behavioral tests, including measures of processing speed (SDMT), working memory (Digit Span Backward), inhibition (DKEFS Color Word Interference), attention (Digit Span Forward) and depression (GDS). We compared performance across groups using analysis of variance. In addition, we used mediation analysis to examine the effect of processing speed on the relationship between age and both working memory and inhibition. Results: Groups were similar for age, years of education, MMSE score and premorbid IQ. Performance on measures of processing speed and inhibition were significantly worse in the PD than control group. Furthermore, we found that processing speed mediated the relationship between age and inhibition in the PD and control groups. However, the decrease in working memory performance in the PD group was a statistical trend and the relationship between working memory and age was not mediated by processing speed in either group. Conclusion: The pattern of cognitive aging consistent with the processing speed theory may be exacerbated in PD. However, while the working memory measure was correlated with processing speed, it was not correlated with age. The processing speed theory of cognitive decline provides a framework for hypothesis testing about the complex concept of bradyphrenia.

This paper presented original study results concerning the prevalence and clinical characteristics of cognitive impairment associated with brain concussion. The cognitive functions of 80 consecutive patients (mean age = 37.40±11.74 years; 50 men and 30 women) admitted to the hospital with brain concussions were evaluated. Their cognitive scores were compared with 40 age- and education-matched healthy volunteers without history of cranial trauma. Cognitive impairment without dementia was found in 93% of the patients. Cognitive impairment in brain concussion was also characterized by prominent cognitive slowness (bradyphrenia), concentration decrease, free recall insufficiency, and visual-spatial dysfunction. Age and severity of anxiety significantly influence the cognitive performance of patients.

Background Mental rotation performance may be used as an index of mental slowing or bradyphrenia, and may reflect, in particular, speed of motor preparation. Previous studies suggest depressive patients present the correlates of impaired behavioural performance for mental rotation and psychomotor disturbance. The aim of this study is to compare the mental rotation abilities of patients with a first episode of depression, recurrent depression and healthy control subjects with regard to hand tasks. Methods We tested 32 first episode of depression, 38 recurrent depression and 36 healthy control subjects by evaluating the performance of depressed patients with regard to the hand mental rotation tasks. Results First, the first episode and recurrent depression subjects were significantly slower and made more errors than controls in mentally rotating hands. Second, the first depressive episode but not the recurrent depression displayed the same pattern of response times to stimuli at various orientations relative to control subjects in the hand task. Third, in particular, recurrent depression subjects were significantly slower and made more errors during the mental transformation of hands than first depressive episode relative to control subjects and the differences were significantly larger in female than male subjects in the mental rotation hand task. Limitations Patients were on antidepressant medication. Conclusions These results suggest that the impaired behavioural performance for mental representation processing are related to the number of previous episodes. Moreover, the recurrent major depressive episodes may contribute to the reinforcement of cognitive impairments and further the development or maintenance of mental representation dysfunctions, especially in female patients. A deficit on mental rotation in the depressive patients may be potential biomarkers for recurrence chronically.

Objective: Characterize the onset and timing of cognitive decline in Parkinson disease (PD) from the first recognizable stage of cognitively symptomatic PD-mild cognitive impairment (PD-MCI) to PD dementia (PDD). Thirty-nine participants progressed from PD to PDD and 25 remained cognitively normal. Methods: Bayesian-estimated disease-state models described the onset of an individual’s cognitive decline across 12 subtests with a change point. Results: Subtests measuring working memory, visuospatial processing ability, and crystalized memory changed significantly 3 to 5 years before their first nonzero Clinical Dementia Rating and progressively worsened from PD to PD-MCI to PDD. Crystalized memory deficits were the hallmark feature of imminent conversion of cognitive status. Episodic memory tasks were not sensitive to onset of PD-MCI. For cognitively intact PD, all 12 subtests showed modest linear decline without evidence of a change point. Conclusions: Longitudinal disease-state models support a prodromal dementia stage (PD-MCI) marked by early declines in working memory and visuospatial processing beginning 5 years before clinical diagnosis of PDD. Cognitive declines in PD affect motor ability (bradykinesia), working memory, and processing speed (bradyphrenia) resulting in PD-MCI where visuospatial imagery and memory retrieval deficits manifest before eventual development of overt dementia. Tests of episodic memory may not be sufficient to detect and quantify cognitive decline in PD.

Parkinson’s disease (PD) is a predominant movement disorder, but profound cognitive deficits (e.g. bradyphrenia, memory, and set shifting) also occur. To model the deficits in set shifting using internal and external cues in rats we developed a continuous reversal task in which the active lever, left or right lever, alternated after a variable number of lever presses. In one task the active lever was signaled by a light (external cue condition, EC) whereas in the other task the active lever was not signaled (internal cue condition, IC). In this study we evaluated the effects of a partial bilateral striatal 6-OHDA lesion as model for PD on the performance in both tasks. Following behavioral testing the lesions were verified using tyrosine hydroxylase (TH) immunohistochemistry. The 6-OHDA lesioned animals were specifically impaired in the IC condition and not in the EC task. In other words, the lesioned animals kept pressing a lever longer although it was not longer active. The present response switching task is sensitive to 6-OHDA lesions and may mimic set-shifting deficits in PD. J. Exp. Clin. Med., 2012; 29:183-186

BACKGROUND: Early cognitive dysfunction in Huntington's Disease (HD) is typically of a subcortical frontal executive type, with bradyphrenia, poor spatial and working memory, poor planning and organization, a lack of judgment, and poor mental flexibility. Although there is literature suggesting a correlation between deficits in speed of processing, working memory and executive function on driving competency, there is little direct evidence comparing these declines on tests to actual driving skills. OBJECTIVE: The current study examines the utility of specific neuropsychological measures in predicting actual driving competency in patients with HD. METHODS: Fifty-two patients at the UConn Health HD Program underwent yearly neuropsychological evaluations and were included in this study. Four scales were chosen a priori to predict driving impairment because of their reported relationship to driving ability. Within each test category, subjects who scored below the threshold suggestive of neurological impairment were found to have results within the impaired range (1.5 standard deviations below corrective normative data). A referral to the Connecticut Department of Motor Vehicles (DMV) for a driving evaluation was subsequently made on patients who were found impaired on any two of these tests. RESULTS: The authors found a strong relationship between scores on a simple battery of four neuropsychological tests and driving competency. CONCLUSIONS: This short battery may prove of pragmatic value for clinicians working with people with HD and their families. Language: en

Paradichlorobenzene (PDB) is a common household deodorant and pesticide found in room deodorizers, toilet bowl fresheners, and some mothballs. Although human exposure to the compound is generally limited and harmless, PDB in larger doses can produce neurotoxic effects, including a chemical "high" similar to that seen with inhalants such as toluene. Although rare, frank addiction to PDB has been reported, and, in such cases, has been associated with gait ataxia, tremor, dysarthria, limb weakness, and bradyphrenia, in various combinations. In such cases, the adverse neurologic consequences have been presumed to result from a direct toxic effect of this small, organic molecule. We report a case of chronic mothball ingestion where profound encephalopathy with cognitive, pyramidal, extrapyramidal, and cerebellar features appears to have been largely the result of PDB withdrawal, rather than direct toxicity. This case raises important questions about the mechanism of PDB neurotoxicity and possible treatment options for PDB-addicted patients. We propose that in cases with clear clinical deterioration after abstinence, readministration and gradual taper of PDB might be considered a therapeutic option.

During the 1980s, the Cognitive Neuropsychology Laboratory at Good Samaritan Hospital, Portland, Oregon, made important strides in the study of brain injury. Created and headed by Oscar Marin and the author, in affiliation with the University of Oregon, the lab brought together students, fellows, and visiting experts in neurology, psychology, psychiatry, neuropsychology, neurobiology, neurophysiology, and computation. Their patient-focused collaborations produced groundbreaking research in language and its disorders, bradyphrenia, neglect, cerebellar function and impairment, and the psychology of music. The lab hosted the meeting that they documented in the influential 1985 book Attention and Performance XI: Mechanisms of Attention. The lab's members have gone on to lead distinguished careers and continue making major contributions to cognitive neuroscience.

A 60-year-old woman presented with discomfort during respiration and anxiety. One month later, she developed dysarthria and unsteadiness of gait that gradually progressed over 3 months. She was referred to our affiliated hospital. A neurologist noted muscle rigidity, parkinsonian gait, and bradyphrenia, but her general cognitive function was preserved, with a Mini-Mental State Examination (MMSE) score of 29/30. At this time, diffusion-weighted imaging (DWI) demonstrated multifocal spotty hyperintense signals in the cerebral cortex (figure, A). Six months later, she became unable to stand or walk because of limb and truncal ataxia, and she was admitted to our hospital. On admission, she showed marked cognitive decline (MMSE score of 14/30) and apathy. Neurologic examination revealed cerebellar ataxia and parkinsonism such as rigidity and akinesia, but myoclonus was not present. Laboratory findings were all normal except for those of the serologic tests for syphilis (STS) and the Treponema pallidum latex agglutination (TPLA) test. Both the STS and the TPLA test showed positivity for syphilis with a low titer, whereas the TPLA test of CSF showed negative results, indicating self-limited syphilis. DWI findings were not significantly different from those 5 months ago (figure, B). EEG showed 5-Hz slow waves but not periodic sharp wave complexes. Two months after admission, she developed urinary tract infection and subsequently severe inspiratory stridor with a high-pitched sound. Laryngeal fiberscope showed that the bilateral vocal cords were fixed in the midline position. After tracheostomy, her stridor disappeared. However, her condition deteriorated rapidly. She became mute and subsequently developed myoclonus. At this time, CSF analysis revealed a total tau protein level of 246 pg/mL (cutoff for the diagnosis of sporadic Creutzfeldt-Jakob disease [CJD] >1,300). The 14-3-3 protein was not detected in the CSF. However, RT-QUIC (real-time quaking-induced conversion) assay, which has a sensitivity of 83.3% for CJD,1 showed positivity for CJD. EEG showed 1-Hz periodic sharp wave complexes. DWI revealed hyperintense signals slightly spread (figure, C) and extended throughout the cerebral cortex and basal ganglia 4 months later (figure, D). The diagnosis of sporadic CJD was made on the basis of progressive dementia and myoclonus, EEG findings, and hyperintense lesions detected by DWI. Analysis of the prion protein gene PRNP showed no mutations. The polymorphic codon 129 was homozygous for methionine and codon 219 was homozygous for glutamate. Acknowledgment: The authors thank Dr. Kitamoto for genotyping and Dr. Satoh for analyses of CSF biomarkers.

Objective: To evaluate the relative contributions of motor and cognitive symptoms on speech output in persons with schizophrenia (SZ). Background: Studies of speech production in SZ suggest that atypical prosody (eg, pause) is related to clinical symptoms manifest in flat affect and alogia. Others have suggested that a more general motor slowing, bradykinesia, leads to measurable speech changes. Method: Thirteen participants with SZ and age-matched control subjects were included for between-group and by-task comparisons. Two levels of task complexity were analyzed acoustically to determine distinct and overlapping features of speech pause. Results: For the free-speech task, group differences were found on measures of average pause duration, pause variability, percent pause, and cumulative pause time. Conversely, for the rote-speech task, group differences were found only on measures of average pause duration and pause variability. Conclusions: In persons with SZ, differences in the average and variability of pause duration may be reflected in speech motor slowing, whereas more global measures (eg, percentage pause) may better reflect a paucity of thought and idea generation related to the cognitive-linguistic aspects of free speech. These findings corroborate and extend the paucity of thought hypothesis in SZ to include an influence of motor slowing on speech production.

Dear Editor, Tremor is a common clinical feature in dystonia. It can be seen in both affected and unaffected body parts in patients with dystonia. Clinically, it may not be easily distinguishable from essential tremor, currently defined as a bilateral, largely symmetric postural or kinetic tremor involving the hands and forearms that is visible and persistent, with an associated or isolated head tremor in the absence of abnormal posturing [1]. Efforts to differentiate these types of tremor include using neurophysiological tests such as somatosensory temporal discrimination threshold (TDT) testing, electromyography, accelerometry and reciprocal inhibition [2,3]. In patients with dystonia, TDT values have been found to be prolonged, postulated to reflect abnormalities in the basal ganglia [2,4-6]. On the other hand, investigations on patients diagnosed with essential tremor have revealed TDT values to be normal in those with upper limb tremor [2,7]. To illustrate the use of TDT in tremor diagnosis, we report a case of tremor in a 48-year-old right-handed man. His symptoms began 12 years prior to consult, initially task-specific, beginning in the left hand while playing the bassoon. The tremor progressed to involve both hands, the head, voice and trunk, often simultaneously. Tremor and head pulling to the right would worsen with manual activities and emotional stress. He was seen by several neurologists and was given varying diagnoses of dystonia and essential tremor. Sodium oxybate dampened the tremor, but had to be discontinued due to side effects. Current medications included propranolol extended-release 60 mg daily, topiramate 100 mg twice daily, clonazepam 1 mg twice daily and escitalopram 20 mg daily. The patient’s past medical history was positive for depression, alcoholism (sober for the past eight years) and asthma. There was no family history of tremor, and both parents have a history of strokes. He is a smoker, works as a priest, is separated and lives alone. Exam revealed mildly depressed affect, bradyphrenia and intermittent word-finding difficulty. The Montreal Cognitive Assessment score was 23/30 with errors in the following domains; executive, attention, language, and delayed recall. A high-frequency, asymmetric postural and kinetic tremor was noted in both upper extremities and trunk, as well as a vocal tremor. Right head tilt was present, most prominent on playing the bassoon. There were no sensory tricks. Bilateral arm posturing was noted with walking, greater on the right (Supplementary Video in the Online-only Data Supplement). Magnetic resonance imaging of the brain and a dopamine transporter single photon emission computed tomography scan were performed, which were both unremarkable. He did not undergo DYT gene testing. Somatosensory TDT testing was performed at our institution, with the patient appropriately focusing his attention on the task (reporting one stimulus vs. two). The mean and range (215.83 ± 14.29 ms) of the thresholds for bilateral upper extremities were markedly prolonged, compatible with the results seen in patients with dystonia (110 ± 31.3 ms) [2]. Our case illustrates a tremor in a 48-year-old man that was first noticed to occur in the left hand when playing the bassoon, eventually involving both hands, the head, voice and trunk. Differentiating tremor in dystonia from essential tremor based on clinical criteria alone can be difficult, as both types of tremor are often symmetric, postural and kinetic and the dystonia may not be obvious on initial examination. TDT testing may be a useful tool for this purpose, along with other neurophysiological testing methods [2]. Prolonged thresholds have been found in various dystonia phenotypes, including cervical dystonia, writer’s cramp, blepharospasm, musician’s dystonia and spasmodic dysphonia [2,4]. The dramatically prolonged TDT results, the cervical dystonia noted on examination and the history of nearly simultaneous onset of tremor in the neck and upper extremities suggest that this is likely tremor in dystonia. We are ascribing his cognitive problems to depression, but this aspect will require continued attention. Differentiating tremor in dystonia from essential tremor is important in considering treatment options and further testing, including genetic counseling. Thus, TDT may be another useful neurophysiological tool in making this distinction.

In healthy adults, deficits in identifying a second target following a previously attended target in Rapid Serial Visual Presentation (RSVP) occur between intertarget intervals of approximately 100-500 ms. This Attentional Blink (AB) is investigated in nondemented medicated Parkinson's patients using a modification of the standard paradigm that required the identification of two red letters embedded in a black letter distractor stream. Parkinson's patients and controls produced an equivalent AB, although with a different pattern of errors. Thus, the processing and clearance of information was largely preserved in nondemented Parkinson's patients, without evidence of bradyphrenia. However, perseveration of earlier RSVP items in short-term memory was thought to explain the different pattern of errors.

A 39-year-old old Jewish woman of Algerian origin developed a rapidly progressive neurocognitive disorder characterized by asymmetric rigidity, spasticity with bilateral Babinski's sign, bradykinesia, altered speech that progressed to mutism, and severe bradyphrenia. She partially responded to levodopa. The family history revealed 4 affected first-degree relatives (3 had already died). Genetic studies carried out in the proband and her living affected sister showed a P301S mutation in chromosome 17. © 2003 Movement Disorder Society

Mental rotation (MR) performance may be used as an index of mental slowing or bradyphrenia, and may reflect, in particular, speed of motor preparation. MR was employed with a sample of both melancholic (na 8) and non-melancholic (na 9) unipolar depressed patients and healthy controls (na 10) to determine if motor slowing associated with depression might be reflected in slowed motor preparation (as reflected in slope of the MR function) independent of actual motor slowing (overall response time). Both melancholic and non-melancholic patients showed a generalised slowing relative to controls, perhaps reflecting bradykinesia and akinesia. This effect was significantly greater in the melancholic group than in the non-melancholic group. Relative to both the controls and the non-melancholic groups, the melancholic patients showed a progressive slowing with increasing angle of orientation indicating a specific slowing of MR. This deficit suggests a role of slowed motor planning in the psychomotor retardation of patients with melancholic depression.

Mental rotation performance may be used as an index of mental slowing or bradyphrenia and may reflect speed of motor preparation. Previous studies suggest that major depressive disorder (MDD) presents correlates of impaired behavioral performance for mental rotation and psychomotor disturbance. Very little is known about the electrophysiological mechanism underlying this deficit. The present study was the first to investigate the event-related brain potential (ERP) correlates of mental rotation and their mental slowing or bradyphrenia in MDD. ERPs were recorded while we tested 25 MDD patients and 26 healthy controls by evaluating the performance of MDD patients on hand and letter rotation tasks at different orientations, and their 400-to-600-msec time window was measured and analyzed for latencies and peak amplitudes over the electrodes. First, individuals with MDD were slower and made more errors in mentally rotating hands and letters than healthy controls did, and individuals with MDD exhibited a greater difference in response times and errors than controls did between hands and letters. Second, the mean peak amplitude was significantly lower and the mean latency was significantly longer in the 400-to-600-msec time window at the parietal site in the hand tasks in MDD patients than in controls, but this was not seen in the letter task, with only lower mean peak amplitude. MDD patients present the absence of a typical mental rotation function for the amplitude of the rotation-related negativity in the hand and letter tasks. Third, the scalp activity maps in MDD patients exhibited the absence of activation in the left parietal site for the mental rotation of hands, as shown in healthy participants. In contrast, their brain activation for the letter task was similar to those of healthy participants. These data suggest that mental imagery of hands and letters relies on different cognitive and neural mechanisms and indicate that the left posterior parietal lobe is a necessary structure for mental transformations of human hands. Importantly, MDD deficits were more seriously present specific to the hands than the letters. Such impairment may also be an important and possibly defining marker of MDD in particular.

A 55-year-old woman was admitted with a 3 days history of increasing lethargy with bradyphrenia and apathy. She progressively developed severe somnolence with marked abulia, right hemiparesis, right hemianopsia, and pseudobulbar palsy. Brain magnetic resonance imaging showed the rare image of bilateral acute anterior choroidal artery infarction. Pseudobulbar mutism and in rare cases abulia have been described in acute anterior choroidal artery infarction contralateral to an older lesion in mirror position. Although neurologic deterioration is not infrequent in anterior choroidal artery territory infarcts, the absence of focal neurologic signs on admission is rare and did not raise suspicion of acute stroke.