Frontal Cognitive Dysfunction Research Articles

Predicting Disability in Progressive Supranuclear Palsy Using Bedside Frontal-Lobe Signs.

Frontal lobe signs in progressive supranuclear palsy (PSP) are prevalent and occur early in the disease. Although they are recognized in clinical practice, studies are needed to systematically investigate them for an in-depth understanding of the neurological substrate and their potential prognostic implications in the disease. To study the predictive role of frontal lobe signs in PSP, as well as to describe their neuropsychological and anatomical correlations. Nine recognized signs of frontal lobe dysfunction were assessed in 61 patients with PSP. Those signs able to predict PSP Rating Scale (PSPRS) score at baseline were selected, a survival analysis was performed and associations with neuropsychological tests and cortical thickness parameters in brain MRI were studied. Grasping, anosognosia and orobuccal apraxia predicted the PSPRS score independently of age, gender, clinical subtype and disease duration. The occurrence of groping in the first 4 years could be a predictor of survival. Grasping and anosognosia were associated with frontal cognitive dysfunction, whereas orobuccal apraxia and groping were related to a more widespread cognitive impairment, involving temporal-parietal areas. Presence of groping showed an extensive cortical atrophy, with predominant prefrontal, temporal and superior parietal cortical thinning. Grasping, groping, anosognosia and orobuccal apraxia are easily evaluable bedside clinical signs that reflect distinct stages of disease progression. Grasping, anosognosia and orobuccal apraxia predict disease disability in patients with PSP, and early onset groping could be a survival predictor.

Best Practices in the Clinical Management of Progressive Supranuclear Palsy and Corticobasal Syndrome: A Consensus Statement of the CurePSP Centers of Care.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS; the most common phenotype of corticobasal degeneration) are tauopathies with a relentless course, usually starting in the mid-60s and leading to death after an average of 7 years. There is as yet no specific or disease-modifying treatment. Clinical deficits in PSP are numerous, involve the entire neuraxis, and present as several discrete phenotypes. They center on rigidity, bradykinesia, postural instability, gait freezing, supranuclear ocular motor impairment, dysarthria, dysphagia, incontinence, sleep disorders, frontal cognitive dysfunction, and a variety of behavioral changes. CBS presents with prominent and usually asymmetric dystonia, apraxia, myoclonus, pyramidal signs, and cortical sensory loss. The symptoms and deficits of PSP and CBS are amenable to a variety of treatment strategies but most physicians, including many neurologists, are reluctant to care for patients with these conditions because of unfamiliarity with their multiplicity of interacting symptoms and deficits. CurePSP, the organization devoted to support, research, and education for PSP and CBS, created its CurePSP Centers of Care network in North America in 2017 to improve patient access to clinical expertise and develop collaborations. The directors of the 25 centers have created this consensus document outlining best practices in the management of PSP and CBS. They formed a writing committee for each of 12 sub-topics. A 4-member Steering Committee collated and edited the contributions. The result was returned to the entire cohort of authors for further comments, which were considered for incorporation by the Steering Committee. The authors hope that this publication will serve as a convenient guide for all clinicians caring for patients with PSP and CBS and that it will improve care for patients with these devastating but manageable disorders.

Progression of brain functional connectivity and frontal cognitive dysfunction in ALS

ObjectiveTo investigate the progression of resting-state functional connectivity (rs-FC) changes in patients with amyotrophic lateral sclerosis (ALS) and their relationship with frontal cognitive alterations. MethodsThis is a multicentre, observational and longitudinal study. At baseline and after six months, 25 ALS patients underwent 3D T1-weighted MRI, resting-state functional MRI (rs-fMRI), and the computerized Test of Attentional Performance (TAP). Using independent component analysis, rs-FC changes of brain networks involving connections to frontal lobes and their relationship with baseline cognitive scores and cognitive changes over time were assessed. With a seed-based approach, rs-FC longitudinal changes of the middle frontal gyrus (MFG) were also explored. ResultsAfter six months, ALS patients showed an increased rs-FC of the left anterior cingulate, left middle frontal gyrus (MFG) and left superior frontal gyrus within the frontostriatal network, and of the left MFG, left supramarginal gyrus and right angular gyrus within the left frontoparietal network. Within the frontostriatal network, a worse baseline performance at TAP divided attention task was associated with an increased rs-FC over time in the left MFG and a worse baseline performance at the category fluency index was related with increased rs-FC over time in the left frontal superior gyrus. After six months, the seed-based rs-FC analysis of the MFG with the whole brain showed decreased rs-FC of the right MFG with frontoparietal regions in patients compared to controls. ConclusionsRs-FC changes in ALS patients progressed over time within the frontostriatal and the frontoparietal networks and are related to frontal-executive dysfunction. The MFG seems a potential core region in the framework of a frontoparietal functional breakdown, which is typical of frontotemporal lobar degeneration. These findings offer new potential markers for monitoring extra-motor progression in ALS.

Frontal defect contribution to decreasing of body mass index in Parkinson's disease patients

ObjectiveWeight loss is common in patients with Parkinson’s disease (PD). It has been reported that low Body Mass Index (BMI) is associated with disease progression in these patients, but only a few data are available on the relationship between BMI and cognitive dysfunctions in PD patients. In the present study we systematically assessed the possible relationship between BMI index and specific cognitive defects. MethodWe enrolled a prospective sample of 37 PD individuals and 30 healthy controls (HC) of similar age, sex, and education. The BMI was calculated in each participant, who underwent a neuropsychological assessment exploring the general cognitive skills, frontal/executive, visuo-spatial, visuo-constructional and memory abilities. ResultsWe showed that PD group had significant lower BMI value compared to HC group. In PD patients, the BMI was negatively correlated to disease duration and number of errors at the Stroop-Color Word Test, and positively to score on Frontal Assessment Battery (FAB). Moreover, a regression analysis revealed that, the BMI in PD patients was associated with disease duration and score on FAB. ConclusionsOur findings contribute to reveal that the relationship between height and weight is strongly related to frontal cognitive dysfunctions in PD patients.

Frontal vs. Posterior cognitive dysfunction: Does greater risk of dementia lead to a differential gait in Parkinson’s disease?

Background: Gait impairment is suggested to predict the onset of dementia in Parkinson’s disease (PD). Interestingly, studies have shown that PD patients with cognitive deficits mediated by posterior brain areas are at greater risk of developing dementia than those with frontal deficits. Yet, it remains unknown whether PD patients with posterior cognitive deficits show differences in gait when compared to those with frontal deficits. Aim: This study aimed to compare gait of individuals with PD showing “posterior”, “frontal”, or no cognitive impairment (NCI). Methods: Based on a sample of 64 individuals with PD, median scores were calculated for three neuropsychological tests relying on “frontal” and three relying on “posterior” brain areas. Individuals assigned into the Frontal or Posterior groups showed at least 2 out of 3 scores lower than the median in frontal or posterior tests, respectively. Those with 0 or 1 score lower than the median were classified as NCI. Participants walked under single and dual task conditions. Results: All groups walked slower, with greater variability, wider base of support, and longer double support in the dual task condition. Interpretation: PD patients with posterior cognitive deficits walk similarly to those with frontal deficits and those with normal cognition.

Finger tapping and verbal fluency post-tap test improvement in INPH: its value in differential diagnosis and shunt-treatment outcomes prognosis.

Idiopathic normal pressure hydrocephalus (INPH) diagnosis is challenging as it can be mimicked by other neurological conditions, such as neurodegenerative dementia and motor syndromes. Additionally, outcomes after lumbar puncture (LP) tap test and shunt treatment may vary due to the lack of a common protocol in INPH assessment. The present study aimed to assess whether a post-LP test amelioration of frontal cognitive dysfunctions, characterizing this syndrome, can differentiate INPH from similar neurological conditions and whether this improvement can predict INPH post-shunt outcomes. Seventy-one consecutive patients referred for INPH suspicion and LP testing, were enrolled. According to the consensus guidelines criteria, 29 patients were diagnosed as INPH and 42 were assigned an alternative diagnosis (INPH-like group) after reviewing clinical, neuropsychological and imaging data, and before LP results. A comprehensive neuropsychological assessment for frontal executive, upper extremity fine motor functions, aphasias, apraxias, agnosias and gait evaluation were administered at baseline. Executive, fine motor functions and gait were re-examined post-LP test in all patients and post-shunt placement in INPH patients. Of the INPH patients, 86.2% showed cognitive amelioration in the post-LP test; in addition, all but one (97%) presented with neurocognitive and gait improvement post-shunt. Verbal phonological fluency and finger tapping task post-LP improvement predicted positive clinical outcome post-shunt. None of the INPH-like group presented with neurocognitive improvement post-LP. Post-LP amelioration of verbal fluency and finger tapping deficits can differentiate INPH from similar disorders and predict positive post-shunt clinical outcome in INPH. This becomes of great importance when gait assessment is difficult to perform in clinical practice.

FRONTAL COGNITIVE DYSFUNCTION WITH APRAXIA OF EYELID OPENING AFTER TRAUMATIC BRAIN INJURY: A SLOWLY PROGRESSIVE DELAYED COMPLICATION

Apraxia of eyelid opening (AEO) has been suggested to be a dysfunction of the supranuclear control of the levator palpebrae superioris caused mainly by basal ganglial lesion. The hypometabolism of the medial frontal lobe may be a pathophysiologic mechanism in frontal lobe dysfunction and AEO. We report two patients who developed frontal cognitive dysfunction with AEO, as a delayed complication, 4–6 years after traumatic brain injury (TBI) progressively. Their MRI showed encephalomalacia with low signal intensity in medial frontal cortex which suggests loss of cortico-spinal tract fibers in the medial frontal cortex, which was not shown in initial brain CT scans. Delayed pathologic changes after TBI may contribute to the development of frontal cognitive dysfunction and AEO in these cases. Therefore we need to make close observation if the patients have TBI, especially severe enough to loss of consciousness even their brain imaging scans do not show abnormal finding initially.

Microstructural alterations of white matter in juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is a common type of idiopathic generalized epilepsy that is characterized by myoclonic jerks of the upper limbs and generalized tonic-clonic seizures. Frontal cognitive dysfunctions and abnormal coupling of the thalamocortical system have been found in neuropsychological and neuroimaging studies. This study intended to explore white matter (WM) measurement changes in JME using MRI. Twenty-six patients with JME and 25 healthy controls (HC) were recruited for the acquisition of diffusion MRI and structural MRI data. Then, a tract-based spatial statistics approach was used to investigate the disease effects on WM microstructural diffusion characteristics. Subsequently, the associations between clinical features and characteristics of the tracts that connect the impacted regions were also evaluated. Compared with HC, JME showed an increased mean diffusivity in the anterior corpus callosum connected to the bilateral frontal lobe. Decreased axial diffusivity was observed in the body of the corpus callosum connected to the bilateral supplementary motor area as well as, in the region connecting the left thalamic radiation, the superior longitudinal fasciculus and corticospinal tract. Furthermore, the microstructural metrics of the tracts connecting these regions, especially the projection fibres that connect the cerebral cortex, subcortical regions and cerebellum, were correlated with disease duration. These findings likely reflect the alterations in WM microstructural connectivity, which may be associated with frontal cognitive and motor dysfunction in JME. In addition, the projection fibres connecting these impacted regions are progressively affected by the disease duration. Based on our findings, we propose that the cerebellum may play a potential role in the pathomechanism of JME.

Interictal epileptic discharge correlates with global and frontal cognitive dysfunction in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) with hippocampal sclerosis has widespread effects on structural and functional connectivity and often entails cognitive dysfunction. EEG is mandatory to disentangle interactions in epileptic and physiological networks which underlie these cognitive comorbidities. Here, we examined how interictal epileptic discharges (IEDs) affect cognitive performance. Thirty-four patients (right TLE=17, left TLE=17) were examined with 24-hour video-EEG and a battery of neuropsychological tests to measure intelligence quotient and separate frontal and temporal lobe functions. Hippocampal segmentation of high-resolution T1-weighted imaging was performed with FreeSurfer. Partial correlations were used to compare the number and distribution of clinical interictal spikes and sharp waves with data from imagery and psychological tests. The number of IEDs was negatively correlated with executive functions, including verbal fluency and intelligence quotient (IQ). Interictal epileptic discharge affected cognitive function in patients with left and right TLE differentially, with verbal fluency strongly related to temporofrontal spiking. In contrast, IEDs had no clear effects on memory functions after corrections with partial correlations for age, age at disease onset, disease duration, and hippocampal volume. In patients with TLE of long duration, IED occurrence was strongly related to cognitive deficits, most pronounced for frontal lobe function. These data suggest that IEDs reflect dysfunctional brain circuitry and may serve as an independent biomarker for cognitive comorbidity.

Cognitive dysfunction associated with falls in progressive supranuclear palsy

BackgroundAttentional and executive dysfunctions are associated with falls in community-dwelling elderly individuals and patients with PD. Frontal cognitive dysfunction and falls are frequent symptoms of PSP. We studied to identify the cognitive domains associated with recurrent falls in patients with PSP. MethodsWe performed a battery of neuropsychological tests in 59 individuals with probable PSP. We categorized patients into infrequent fall (≤one fall during the last 12 months, n=29) or recurrent fall (≥two falls during the last 12 months, n=30) groups. ResultsUPDRS subscores for axial deficits were significantly higher in the recurrent fall group than the infrequent fall group, but there were no significant differences in UPDRS total motor scores or subscores for bradykinesia, rigidity, and tremor. There was no difference between groups in MMSE scores. ANCOVA with adjustment for confounding factors showed that, recurrent falls were associated with abnormalities in alternating hand movement, alternating square and triangle, RCFT copying task, and ideomotor apraxia. Group difference of abnormalities in Stroop test was marginal (p=0.054). However, there were no group differences in the frequency of abnormalities in forward or backward digit span, motor impersistence, fist-edge-palm, contrast programming, go-no-go, Luria loop drawing, or Controlled Oral Word Association Tests. Recurrent falls were not associated with memory or language dysfunction. ConclusionsRecurrent falls in patients with PSP were associated mainly with executive and visuospatial dysfunctions, including (1) impaired coordinated alternating uni- and bimanual motor programming and execution, (2) deficit of attention and decision making in the presence of interference, (3) visuospatial misperception and (4) ideomotor apraxia.

Volumetric and shape analysis of thalamus in idiopathic generalized epilepsy

Previous studies using voxel-based morphometry (VBM) provided emerging evidence of structural changes of the thalamus in idiopathic generalized epilepsy (IGE). However, the location of atrophy within the thalamus in IGE has been somewhat inconsistent across the studies. We, therefore, examined the location of thalamic atrophy and its relationship with clinical factors in IGE, using multiple analytic methods. Fifty IGE patients and 50 controls were scanned on a 3T MRI. Structural evaluation consisted of automated thalamic volumetry, VBM, and thalamic shape analysis. Group comparison between patients and controls was made to assess thalamic atrophy. Within-group correlations between thalamic atrophy and clinical variables were further performed in patients. Both thalamic volumes were reduced in IGE patients, and were negatively correlated with disease duration. The VBM showed a significant regional grey matter volume reduction in bilateral anterior-medial thalami in patients compared to controls. Voxel values extracted from the anterior-medial thalamic cluster were negatively correlated with disease duration. Vertex-based shape analysis revealed regional atrophy on the anterior-medial and posterior-dorsal aspects of thalamus bilaterally in patients compared to controls. Correlation analysis showed that anterior-medial and posterior-dorsal aspects of bilateral thalami were negatively correlated with disease duration. Combining multiple analyses, we demonstrated regional atrophy of anterior-medial and posterior-dorsal thalamus in patients with IGE. Given the anatomical connection of these thalamic regions with the frontal lobe, our finding of greater thalamic atrophy in relation to increasing disease duration further supports the pathophysiological concept of thalamo-frontal network abnormality underlying IGE, and may implicate frontal cognitive dysfunctions and disease progression.

Microstructural white matter abnormality and frontal cognitive dysfunctions in juvenile myoclonic epilepsy

Previous neuroimaging studies provide growing evidence that patients with juvenile myoclonic epilepsy (JME) have both structural and functional abnormalities of the thalamus and frontal lobe gray matter. However, limited data are available regarding the issue of white matter (WM) involvement, making the microstructural WM changes in JME largely unknown. In the present study we investigated changes of WM integrity in patients with JME, and their relationships with cognitive functions and epilepsy-specific clinical factors. We performed diffusion tensor imaging (DTI) and neuropsychological assessment in 25 patients with JME and 30 control subjects matched for age, gender, and education level. Between-group comparisons of fractional anisotropy (FA) and mean diffusivity (MD) were carried out in a whole-brain voxel-wise manner by using tract-based spatial statistics (TBSS). In addition, both FA and MD were correlated with cognitive performance and epilepsy-specific clinical variables to investigate the influence of these clinical and cognitive factors on WM integrity changes. Neuropsychological evaluation revealed that patients with JME had poorer performance than control subjects on most of the frontal function tests. TBSS demonstrated that, compared to controls, patients with JME had significantly reduced FA and increased MD in bilateral anterior and superior corona radiata, genu and body of corpus callosum, and multiple frontal WM tracts. Disease severity, as assessed by the number of generalized tonic-clonic seizures in given years, was negatively correlated with FA and positively correlated with MD extracted from regions of significant differences between patients and controls in TBSS. Our findings of widespread disturbance of microstructural WM integrity in the frontal lobe and corpus callosum that interconnects frontal cortices could further support the pathophysiologic hypothesis of thalamofrontal network abnormality in JME. These WM abnormalities may implicate frontal cognitive dysfunctions and disease progression in JME.

Severe Anxiety and Frontal Cognitive Dysfunction Heralding a Progressive Supranuclear Palsy-Corticobasal Overlap Syndrome (P07.190)

Objective: To describe the evolution of behavioral, cognitive, and motor symptoms and ancillary testing in a case of progressive supranuclear palsy-corticobasal overlap syndrome. Background Progressive supranuclear palsy (PSP) and corticobasal degeneration have genetic and pathologic similarities, but different phenotypes. Occasionally, the clinical diagnosis between PSP and corticobasal syndrome (CBS) is blurred, and patients are felt to have an overlap syndrome. In such cases, less is known about the spectrum of behavioral and cognitive features that can be seen, especially those preceeding the movement symptoms. Design/Methods: We review the clinical evolution, brain MRI and brain PET scans and videotaped examination findings in this case. Results: This patient is a 76-year-old woman who developed severe and constant anxiety and obsessive-compulsive features including strict rule-bound activities for herself and family, self-harm threats if separated from her spouse, mental rigidity, and bizarre and time-consuming rituals. This was followed by impaired problem solving and perspective-taking, childlike behavior, and pathological laughing and crying. One and a half years later, she developed repeated falls, slow and soft speech, largely symmetric bradykinesia, and axial symptoms of neck rigidity and worsened postural instability, but only slightly slowed downward saccades. Subsequently, right-sided predominant rigidity, myoclonus, and mild apraxia developed. Brain MRI at 3 months and brain PET at 1 year after motor onset, revealed left-sided predominant parietal, medial prefrontal, and anterior temporal mild atrophy and hypometabolism, respectively. Anxiety and obsessive-compulsive features were somewhat responsive to sertraline and behavioral strategies were also employed. Conclusions: Severe anxiety with frontal cognitive symptoms may preceed a PSP-CBS overlap disorder but often go unrecognized, yet may respond to pharmacotherapy and family education. This symptom cluster requires additional study to determine its abillty early on to predict PSP-CBS syndromes. Disclosure: Dr. Smyth has nothing to disclose. Dr. Riley has received personal compensation for activities with Allergan, Ipsen, Lundbeck, Merz and Teva as a consultant.Dr. Riley has received research support from Cleveland Medical Devices. Dr. Lerner has nothing to disclose.

Fahr and #8217;s disease and frontal lobe-like cognitive dysfunction

Giris: Idiyopatik, bilateral ve simetrik striatopallidodentate kalsinozis (veya Fahr hastaligi) genellikle anormal hareketler, parkinsonizm, nobetler ve bilissel islev bozuklugun gibi belirtilerin degisken birliktelikleri ile yasamin dorduncu, altinci ve onuncu yillari arasinda nadir gorulen bir hastaliktir. Beyin BT goruntulemesinin yaygin kullanimi sebebi ile belirtisiz olgularin teshisi giderek artmaktadir. Olgu sunumu: Biz yaygin beyin ici kalsifikasyon ve normal kalsiyum metabolizmasina sahip; bellek bozuklugu, zihinsel yavaslik, irritabilite, apati, kotu gece uykusu ve sosyal izolasyon gibi belirtilerin eslik ettigi 6 yil icinde giderek artan frontal-lob benzeri bilissel yikimla seyreden 25 yasinda bir kadin hastayi sunuyoruz. Hastanin genel bir rijiditesi vardi fakat titremesi yoktu. Bir bucuk yildan fazla bir suredir devam eden takipleri sirasinda hastada nobet gelismedi. Sonuc: Fahr hastaligi karsimiza sadece frontal lob benzeri bilissel islev bozuklugu olarak ve beynin radyolojik bulgularinin klinik belirtileri ve hastaligin gidisatini ongoremedigi bir klinik tablo ile ortaya cikabilir.

Trazodone: properties and utility in multiple disorders

Trazodone is an established antidepressant that is prescribed frequently as an off-label hypnotic with wide acceptance among psychiatrists. Owing to its atypical mixed serotonergic and adrenolytic pharmacology, trazodone has been investigated in a number of disorders besides depression and insomnia, including anxiety disorders, chronic pain, frontal cognitive dysfunctions, erectile dysfunction and others. Clinical studies using subjective and objective measures generally tend to support its efficacy as a hypnotic in depressed subjects. Various other attributes of trazodone, including interaction with adrenergic receptors, formation of an active metabolite with potent serotonergic activity, low abuse potential and putative utility in various disorders, warrant further exploration. The adverse effects of trazodone generally mirror its serotonergic activity and include sedation, headache, sweating, weight changes and gastrointestinal effects such as nausea and vomiting. Clinicians and patients should be cognizant of the risk for potential, but rare, cardiovascular adverse effects of trazodone. The safety and toxicology of trazodone should be examined under current standards of drug development before exposure to new patient populations. This article provides an overview of trazodone with a focus on its clinical pharmacology and opportunities, gaps and scientific strategies in developing it for new indications such as insomnia, anxiety disorders, chronic pain and frontal cognitive dysfunction. Modified release formulations, alternate forms of drug delivery and combination products are discussed as strategies to optimize the efficacy of trazodone and improve its safety profile.

Piribedil: Antiparkinsonian Properties and Potential Clinical Utility in Dopaminergic Disorders

Piribedil is a relatively unknown non-ergot dopamine agonist that has been in clinical use for over 3 decades for the symptomatic management of Parkinsons disease (PD). Piribedil is currently not approved for therapeutic use in the United States. It has unique pharmacological and pharmacokinetic attributes with a profile that is unlike many direct dopamine agonists. In addition to proven motor effects in PD, nonclinical and clinical evidence over the last few years indicate that piribedil may also exert beneficial non-motor effects such as in mild cognitive impairment and frontal cognitive dysfunctions prevalent in PD patients. This review presents the pharmaceutics, pharmacological pleiotropy, and clinical properties of piribedil with a focus on its utility in the therapy of motor and non-motor symptoms in PD and related dopaminergic disorders. The varied pharmacological, behavioral, and clinical properties of piribedil are related to current knowledge on its multifunctional pharmacology. Properties of piribedil that may differentiate it from other dopamine direct agonists are noted. As a partial agonist of dopamine D2 and D3 receptors with functional α2 adrenolytic activity, piribedil may be an alternative to the inherent anti-akinetic (beneficial) and dyskinetic (unwanted) effects of some dopamine replacement therapies. The activation of limbic dopamine receptors by piribedil and stimulation of acetylcholine release in the frontal cortex provide a basis for improving mood and cognitive disturbances. Additionally, α2 antagonism and weak 5-HT1A agonism may provide beneficial effects on dyskinesias, neuropsychiatric symptoms in PD, neurotrophic effects, and reduced sedation. The adverse effects of piribedil generally mirror its monoaminergic activity and include nausea, vomiting, abnormal sleep events, and psychiatric effects such as psychosis and compulsive disorders. While the therapeutic potential of piribedil may yet to be fully realized, investigations of its safety and toxicology under current standards of drug development are warranted before exposure to new patient populations.

Interaction between aging and neurodegeneration in amyotrophic lateral sclerosis

We assessed the spontaneous blood-oxygen-level-dependent signal fluctuations in the resting-state brain networks of amyotrophic lateral sclerosis patients and their relation to physiologically sensitive and disease modified functional magnetic resonance imaging parameters.Resting-state functional magnetic resonance imaging was performed at 3 Tesla on 20 amyotrophic lateral sclerosis patients with minimal frontal cognitive dysfunction and 20 age- and sex-matched healthy volunteers. Resting-state network maps were extracted with independent component analysis and group-level statistical analyses were performed to detect disease and disease-by-age interaction effects. Whole-brain global and regional atrophy measures were obtained from same-session structural scans.The sensori-motor network showed significant disease effects, with signals suppressed in patients bilaterally in the primary motor cortex. The default-mode network showed a significant disease-by-age interaction in the posterior cingulate cortex, where signals correlated with age positively in patients and negatively in controls. Both disease and disease-by-age interaction effects were detected in the right fronto-parietal network. Although global atrophy did not show significant differences, regions of reduced gray matter volume were detected in patients compared with controls adjacent to regions of reduced functional connectivity.Our results confirm that resting-state functional magnetic resonance imaging signals in the sensori-motor network are suppressed in amyotrophic lateral sclerosis. A similar suppression is evident in the right fronto-parietal network, possibly reflecting the patients' frontal dysfunction and right-lateralized patterns of regional atrophy. The interaction between disease and aging in the default-mode network unravels a possible mechanism of compensation between motor and extramotor systems emerging as a supplementary functional push to help motor disturbances.

A Frontal Assault on the Generalized Nature of Juvenile Myoclonic Epilepsy

Frontal Cognitive Dysfunction in Juvenile Myoclonic Epilepsy. Piazzini A, Turner K, Vignoli A, Canger R, Canevini M P. Epilepsia 2008;49(4):657–662. PURPOSE: The aim of the present study was to investigate the possible frontal cognitive dysfunction in patients with juvenile myoclonic epilepsy (JME) and to compare the results with those of patients with frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE), as well as with controls. METHODS: A total of 50 patients with JME, 40 patients with FLE, 40 patients with TLE, and 40 normal controls, all matched for age, education, and IQ, were administered tests to assess frontal functions (the Word Fluency Test and the Wisconsin Card Sorting Test [WCST]). All participants had a normal intelligence level based on the Wechsler Adult Intelligence Scale, and did not take medications other than antiepileptics (AEDs) or have a psychiatric history. RESULTS: Patients with JME had severe impairment in all administered tasks, similar to that of patients with FLE; TLE patients and controls followed in order. Multiple regression analysis did not disclose any significant effect of clinical variables on the cognitive deficits. DISCUSSION: These results clearly suggest that JME patients can show some frontal dysfunction, which may affect both epileptogenic features and cognitive processes. Further studies are needed to confirm these findings.

Frontal cognitive dysfunction in juvenile myoclonic epilepsy

The aim of the present study was to investigate the possible frontal cognitive dysfunction in patients with juvenile myoclonic epilepsy (JME) and to compare the results with those of patients with frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE), as well as with controls. A total of 50 patients with JME, 40 patients with FLE, 40 patients with TLE, and 40 normal controls, all matched for age, education, and IQ, were administered tests to assess frontal functions (the Word Fluency Test and the Wisconsin Card Sorting Test [WCST]). All participants had a normal intelligence level based on the Wechsler Adult Intelligence Scale, and did not take medications other than antiepileptics (AEDs) or have a psychiatric history. Patients with JME had severe impairment in all administered tasks, similar to that of patients with FLE; TLE patients and controls followed in order. Multiple regression analysis did not disclose any significant effect of clinical variables on the cognitive deficits. These results clearly suggest that JME patients can show some frontal dysfunction, which may affect both epileptogenic features and cognitive processes. Further studies are needed to confirm these findings.

Frontal lobe dysfunctions in borderline personality disorder? Neuropsychological findings.

This study aims to determine whether specific neuropsychological performance impairments in borderline patients can be objectified and whether these findings indicate frontal dysfunctions. Twenty-three patients with borderline personality disorder and 23 normal controls were examined using a neuropsychological test battery to assess intelligence, attentiveness, proneness to interference, learning and memory, as well as planning and problem solving. All subjects filled out standardized questionnaires to assess aggressiveness and impulsiveness in the context of these cognitive performance areas. The neuropsychological test results of the borderline patients were comparable to those of the controls. Although there were no indications of frontal dysfunction of cognitive information processing, inverse correlations were found between the severity of borderline-related personality traits regarding impulsiveness and various areas of cognitive performance. Borderline personality patients show no indications of frontal cognitive dysfunction. Further research is needed to clarify the relationship between impulsiveness and cognitive information processing in borderline personality disorder, including a dimensional approach to personality and personality disorder.