Working Memory Deficits After Lesions Involving the Supplementary Motor Area.
ABSTRACT: The Supplementary Motor Area (SMA)-located in the superior and medial aspects of the superior frontal gyrus-is a preferential site of certain brain tumors and arteriovenous malformations, which often provoke the so-called SMA syndrome. The bulk of the literature studying this syndrome has focused on two of its most apparent symptoms: contralateral motor and speech deficits. Surprisingly, little attention has been given to working memory (WM) even though neuroimaging studies have implicated the SMA in this cognitive process. Given its relevance for higher-order functions, our main goal was to examine whether WM is compromised in SMA lesions. We also asked whether WM deficits might be reducible to processing speed (PS) difficulties. Given the connectivity of the SMA with prefrontal regions related to executive control (EC), as a secondary goal we examined whether SMA lesions also hampered EC. To this end, we tested 12 patients with lesions involving the left (i.e., the dominant) SMA. We also tested 12 healthy controls matched with patients for socio-demographic variables. To ensure that the results of this study can be easily transferred and implemented in clinical practice, we used widely-known clinical neuropsychological tests: WM and PS were measured with their respective Wechsler Adult Intelligence Scale indexes, and EC was tested with phonemic and semantic verbal fluency tasks. Non-parametric statistical methods revealed that patients showed deficits in the executive component of WM: they were able to sustain information temporarily but not to mentally manipulate this information. Such WM deficits were not subject to patients' marginal PS impairment. Patients also showed reduced phonemic fluency, which disappeared after controlling for the influence of WM. This observation suggests that SMA damage does not seem to affect cognitive processes engaged by verbal fluency other than WM. In conclusion, WM impairment needs to be considered as part of the SMA syndrome. These findings represent the first evidence about the cognitive consequences (other than language) of damage to the SMA. Further research is needed to establish a more specific profile of WM impairment in SMA patients and determine the consequences of SMA damage for other cognitive functions.
Project description:Fluency tasks have been widely used to tap the voluntary generation of responses. The anatomical correlates of fluency tasks and their sensitivity and specificity have been hotly debated. However, investigation of the cognitive processes involved in voluntary generation of responses and whether generation is supported by a common, general process (e.g. fluid intelligence) or specific cognitive processes underpinned by particular frontal regions has rarely been addressed. This study investigates a range of verbal and non-verbal fluency tasks in patients with unselected focal frontal (n=47) and posterior (n=20) lesions. Patients and controls (n=35) matched for education, age and sex were administered fluency tasks including word (phonemic/semantic), design, gesture and ideational fluency as well as background cognitive tests. Lesions were analysed by standard anterior/posterior and left/right frontal subdivisions as well as a finer-grained frontal localization method. Thus, patients with right and left lateral lesions were compared to patients with superior medial lesions. The results show that all eight fluency tasks are sensitive to frontal lobe damage although only the phonemic word and design fluency tasks were specific to the frontal region. Superior medial patients were the only group to be impaired on all eight fluency tasks, relative to controls, consistent with an energization deficit. The most marked fluency deficits for lateral patients were along material specific lines (i.e. left-phonemic and right-design). Phonemic word fluency that requires greater selection was most severely impaired following left inferior frontal damage. Overall, our results support the notion that frontal functions comprise a set of specialized cognitive processes, supported by distinct frontal regions.
Project description:<b>Background:</b> Verbal fluency (VF) has been associated with several cognitive functions, but the cognitive processes underlying verbal fluency deficits in Multiple Sclerosis (MS) are controversial. Further knowledge about VF could be useful in clinical practice, because these tasks are brief, applicable, and reliable in MS patients. In this study, we aimed to evaluate the cognitive processes related to VF and to develop machine-learning algorithms to predict those patients with cognitive deficits using only VF-derived scores. <b>Methods:</b> Two hundred participants with MS were enrolled and examined using a comprehensive neuropsychological battery, including semantic and phonemic fluencies. Automatic linear modeling was used to identify the neuropsychological test predictors of VF scores. Furthermore, machine-learning algorithms (support vector machines, random forest) were developed to predict those patients with cognitive deficits using only VF-derived scores. <b>Results:</b> Neuropsychological tests associated with attention-executive functioning, memory, and language were the main predictors of the different fluency scores. However, the importance of memory was greater in semantic fluency and clustering scores, and executive functioning in phonemic fluency and switching. Machine learning algorithms predicted general cognitive impairment and executive dysfunction, with F1-scores over 67-71%. <b>Conclusions:</b> VF was influenced by many other cognitive processes, mainly including attention-executive functioning, episodic memory, and language. Semantic fluency and clustering were more explained by memory function, while phonemic fluency and switching were more related to executive functioning. Our study supports that the multiple cognitive components underlying VF tasks in MS could serve for screening purposes and the detection of executive dysfunction.
Project description:Disproportionately greater deficits in semantic relative to phonemic verbal fluency are seen in Alzheimer's disease (AD) and have been attributed to neurodegenerative changes in the temporal lobe. Amnestic (AMN) mild cognitive impairment (MCI), which often represents incipient AD, is also characterized by early temporal lobe neuropathology, but previous comparisons of verbal fluency between AD and AMN MCI have yielded mixed results. We examined semantic and phonemic verbal fluency performance in 399 individuals (78 AD, 138 AMN MCI, 72 non-amnestic MCI, and 111 cognitively normal controls). Similar verbal fluency patterns were seen in AMN MCI and AD; both groups exhibited disproportionately poorer performance on semantic verbal fluency relative to normal controls. However, relative verbal fluency indices performed more poorly than individual semantic or phonemic verbal fluency indices for discriminating AMN MCI or AD participants from normal controls, suggesting that they are unlikely to provide additional utility for predicting progression from MCI to AD.
Project description:The decrease in verbal fluency in patients with Parkinson's disease (PD) undergoing subthalamic nucleus deep brain stimulation (STN-DBS) is usually assumed to reflect a frontal lobe-related cognitive dysfunction, although evidence for this is lacking.To explore its underlying mechanisms, we combined neuropsychological, psychiatric and motor assessments with an examination of brain metabolism using F-18 fluorodeoxyglucose positron emission tomography, in 26 patients with PD, 3 months before and after surgery. We divided these patients into two groups, depending on whether or not they exhibited a postoperative deterioration in either phonemic (10 patients) or semantic (8 patients) fluency. We then compared the STN-DBS groups with and without verbal deterioration on changes in clinical measures and brain metabolism.We did not find any neuropsychological change supporting the presence of an executive dysfunction in patients with a deficit in either phonemic or semantic fluency. Similarly, a comparison of patients with or without impaired fluency on brain metabolism failed to highlight any frontal areas involved in cognitive functions. However, greater changes in cognitive slowdown and apathy were observed in patients with a postoperative decrease in verbal fluency.These results suggest that frontal lobe-related cognitive dysfunction could play only a minor role in the postoperative impairment of phonemic or semantic fluency, and that cognitive slowdown and apathy could have a more decisive influence. Furthermore, the phonemic and semantic impairments appeared to result from the disturbance of distinct mechanisms.
Project description:BACKGROUND:Verbal fluency deficits are common in patients with Parkinson's disease. The association of these impairments with regional neuropathological changes is unexplored. OBJECTIVES:Determine if patients with verbal fluency impairments have greater neuropathological burden in frontal, temporal, and limbic regions and if Lewy bodies or neurofibrillary tangles were associated with verbal fluency impairments. METHODS:Data was derived from the Arizona Study of Aging and Neurodegenerative Disorders. 47 individuals who completed phonemic and semantic verbal fluency tasks and met clinicopathological criteria for Parkinson's disease (with and without comorbid Alzheimer's disease) were included. Impairment on fluency tasks was defined by normative data, and the density of neuropathology in temporal, limbic, and frontal regions was compared between groups. RESULTS:Individuals with semantic fluency impairments had greater total pathology (Lewy bodies + neurofibrillary tangles) in limbic structures (W = 320.0, p?=?.033, rpb?=?.33), while those who had phonemic fluency impairments had increased total neuropathology in frontal (W?=?364.5, p?=?.011, rpb?=?.37), temporal (W?=?356.5, p?=?.022, rpb?=?.34), and limbic regions (W?=?357.0, p?=?.024, rpb?=?.34). Greater Lewy body density was found in those with verbal fluency impairments, though trends for greater neurofibrillary tangle density were noted as well. CONCLUSIONS:Impaired phonemic fluency was associated with higher Lewy body and tangle burden in frontal, temporal, and limbic regions, while impaired semantic fluency was associated with greater limbic pathology. Though neurofibrillary tangles trended higher in several regions in those with impaired verbal fluency, higher Lewy body density in general was associated with verbal fluency deficits. Implications for research and clinical practice are discussed.
Project description:Neural compensatory mechanisms associated with broad cognitive abilities have been studied. However, those associated with specific cognitive subdomains (e.g., verbal fluency) remain to be investigated in healthy aging. Here, we delineate: (a) neural substrates of verbal (phonemic) fluency, and (b) compensatory mechanisms mediating the association between these neural substrates and phonemic fluency. We analyzed resting-state functional magnetic resonance imaging from 133 right-handed, cognitively normal individuals who underwent the Controlled Oral Word Association Test (COWAT) to record their phonemic fluency. We evaluated functional connectivity in an established and extended language network comprising Wernicke, Broca, thalamic and anti-correlated modules. (a) We conducted voxel-wise multiple linear regression to identify the brain areas associated with phonemic fluency. (b) We used mediation effects of cognitive reserve, measured by the Wechsler Adult Intelligence Scale-Information subtest, upon the association between functional connectivity and phonemic fluency tested to investigate compensation. We found that: (a) Greater functional connectivity between the Wernicke module and brain areas within the anti-correlated module was associated with better performance in phonemic fluency, (b) Cognitive reserve was an unlikely mediator in younger adults. In contrast, cognitive reserve was a partial mediator of the association between functional connectivity and phonemic fluency in older adults, likely representing compensation to counter the effect of aging. We conclude that in healthy aging, higher performance in phonemic fluency at older ages could be attributed to greater functional connectivity partially facilitated by higher cognitive reserve, presumably reflecting compensatory mechanisms to minimize the effect of aging.
Project description:Although aging is associated with changes in brain structure and cognition it remains unclear which specific structural changes mediate individual cognitive changes. Several studies have reported that white matter (WM) integrity, as assessed by diffusion tensor imaging (DTI), mediates, in part, age-related differences in processing speed (PS). There is less evidence for WM integrity mediating age-related differences in higher order abilities (e.g., memory and executive functions). In 165 typically aging adults (age range 54-89) we show that WM integrity in select cerebral regions is associated with higher cognitive abilities and accounts variance not accounted for by PS or age. Specifically, voxel-wise analyses using tract-based spatial statistics (TBSS) revealed that WM integrity was associated with reasoning, cognitive flexibility and PS, but not memory or word fluency, after accounting for age and gender. While cerebral fractional anisotropy (FA) was only associated with PS; mean (MD), axial (AD) and radial (RD) diffusivity were associated with reasoning and flexibility. Reasoning was selectively associated with left prefrontal AD, while cognitive flexibility was associated with MD, AD and RD throughout the cerebrum. Average WM metrics within select WM regions of interest accounted for 18% and 29% of the variance in reasoning and flexibility, respectively, similar to the amount of variance accounted for by age. WM metrics mediated ~50% of the age-related variance in reasoning and flexibility and different proportions, 11% for reasoning and 44% for flexibility, of the variance accounted for by PS. In sum, (i) WM integrity is significantly, but variably, related to specific higher cognitive abilities and can account for a similar proportion of variance as age, and (ii) while FA is selectively associated with PS; while MD, AD and RD are associated with reasoning, flexibility and PS. This illustrates both the anatomical and cognitive selectivity of structure-cognition relationships in the aging brain.
Project description:Rapid eye movement sleep behavior disorder (RBD) is associated with high likelihood of prodromal Parkinson's disease (PD) and is common in de novo PD. It is associated with greater cognitive impairment and brain atrophy. However, the relation between structural brain characteristics and cognition remains poorly understood. We aimed to investigate subcortical and cortical atrophy in de novo PD with probable RBD (PD-pRBD) and to relate it with cognitive impairment. We analyzed volumetry, cortical thickness, and cognitive measures from 79 PD-pRBD patients, 126 PD without probable RBD patients (PD-non pRBD), and 69 controls from the Parkinson's Progression Markers Initiative (PPMI). Regression models of cognition were tested using magnetic resonance imaging measures as predictors. We found lower left thalamus volume in PD-pRBD compared with PD-non pRBD. Compared with controls, PD-pRBD group showed atrophy in the bilateral putamen, left hippocampus, left amygdala, and thinning in the right superior temporal gyrus. Specific deep gray matter nuclei volumes were associated with impairment in global cognition, phonemic fluency, processing speed, and visuospatial function in PD-pRBD. In conclusion, cognitive impairment and gray matter atrophy are already present in de novo PD-pRBD. Thalamus, hippocampus, and putamen volumes were mainly associated with these cognitive deficits.
Project description:<h4>Background</h4>Psychosocial work characteristics may predict cognitive functioning after retirement. However, little research has explored specific cognitive domains associated with psychosocial work environments. Our study tested whether exposure to job demands, job control and their combination during working life predicted post-retirement performance on eight cognitive tests.<h4>Methods</h4>We used data from French GAZEL cohort members who had undergone post-retirement cognitive testing (n=2149). Psychosocial job characteristics were measured on average for 4 years before retirement using Karasek's Job Content Questionnaire (job demands, job control and demand-control combinations). We tested associations between these exposures and post-retirement performance on tests for executive function, visual-motor speed, psychomotor speed, verbal memory, and verbal fluency using ordinary least squares regression.<h4>Results</h4>Low job control during working life was negatively associated with executive function, psychomotor speed, phonemic fluency and semantic fluency after retirement (p's<0.05), even after adjustment for demographics, socioeconomic status, health and social behaviours and vascular risk factors. Both passive (low-demand, low-control) and high-strain (high-demand, low-control) jobs were associated with lower scores on phonemic and semantic fluency when compared to low-strain (low-demand, high-control) jobs.<h4>Conclusions</h4>Low job control, in combination with both high and low-job demands, is associated with post-retirement deficits in some, but not all, cognitive domains. In addition to work stress, associations between passive work and subsequent cognitive function may implicate lack of cognitive engagement at work as a risk factor for future cognitive difficulties.
Project description:Although the obesity paradox is an important modifiable factor in cardiovascular diseases, little research has been conducted to determine how it affects post-stroke cognitive function. We aimed to investigate the association between body mass index (BMI) and domain-specific cognitive outcomes, focusing on the subdivision of each frontal domain function in post-ischemic stroke survivors. A total of 335 ischemic stroke patients were included in the study after completion of the Korean-Mini Mental Status Examination (K-MMSE) and the vascular cognitive impairment harmonization standards neuropsychological protocol at 3 months after stroke. Frontal lobe functions were analyzed using semantic/phonemic fluency, processing speed, and mental set shifting. Our study participants were categorized into four groups according to BMI quartiles. The z-scores of K-MMSE at 3 months differed significantly between the groups after adjustment for initial stroke severity (p = 0.014). Global cognitive function in stroke survivors in the Q1 (the lowest quartile) BMI group was significantly lower than those in Q2 and Q4 (the highest quartile) BMI groups (K-MMSE z-scores, Q1: - 2.10 ± 3.40 vs. Q2: 0.71 ± 1.95 and Q4: - 1.21 ± 1.65). Controlled oral word association test findings indicated that phonemic and semantic word fluency was lower in Q4 BMI group participants than in Q2 BMI group participants (p = 0.016 and p = 0.023 respectively). BMI might differentially affect cognitive domains after ischemic stroke. Although being underweight may negatively affect global cognition post-stroke, obesity could induce frontal lobe dysfunctions, specifically phonemic and semantic word fluency.