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Biomedical subjects

Anjan Chatterjee

Publications and source records attributed to Anjan Chatterjee.

At least 19 recordsLinked to original sources
PubMed2006

Biochemical and pathological characterization of frontotemporal dementia due to a Leu266Val mutation in microtubule-associated protein tau in an African American individual.

Frontotemporal dementia (FTD) is a clinically heterogeneous disorder characterized by alterations in language and/or behavior, often in association with Parkinsonism or motor neuron disease. A familial form of FTD is associated with mutations in the microtubule-associated protein tau (MAPT) gene. We report here on the clinical, neuroimaging, cerebral spinal fluid biomarker, genetic, biochemical and postmortem neuropathological analyses of a case of familial FTD with a Leu266Val MAPT mutation which results in a very early age of onset and a rapid course of disease. This is also the first reported case of any MAPT mutation in an individual of African American ethnicity.

Adult↗
PubMed2006

Working memory for conjunctions relies on the medial temporal lobe.

A prominent theory of hippocampal function proposes that the hippocampus is importantly involved in relating or binding together separate pieces of information to form an episodic representation. This hypothesis has only been applied to studies of long-term memory because the paradigmatic view of the hippocampus is that it is not critical for short-term forms of memory. However, relational processing is important in many working memory tasks, especially tasks using visual stimuli. Here, we test the hypothesis that the medial temporal lobes are important for relational memory even over short delays. The task required patients with medial temporal lobe amnesia and controls to remember three objects, locations, or object-location conjunctions over 1 or 8 s delays. The results show that working memory for objects and locations was at normal levels, but that memory for conjunctions was severely impaired at 8 s delays. Additional analyses suggest that the hippocampus per se is critical for accurate conjunction working memory. We propose that the hippocampus is critically involved in memory for conjunctions at both short and long delays.

Aged↗
PubMed2006

A placebo-controlled trial of constraint-induced movement therapy for upper extremity after stroke.

BACKGROUND AND PURPOSE: Constraint-Induced Movement therapy (CI therapy) is a neurorehabilitation technique developed to improve use of the more affected upper extremity after stroke. A number of studies have reported positive effects for this intervention, but an experiment with a credible placebo control group has not yet been published. METHODS: We conducted a placebo-controlled trial of CI therapy in patients with mild to moderate chronic (mean=4.5 years after stroke) motor deficit after stroke. The CI therapy group received intensive training (shaping) of the more affected upper extremity for 6 hours per day on 10 consecutive weekdays, restraint of the less affected extremity for a target of 90% of waking hours during the 2-week treatment period, and application of a number of other techniques designed to produce transfer to the life situation. The placebo group received a program of physical fitness, cognitive, and relaxation exercises for the same length of time and with the same amount of therapist interaction as the experimental group. RESULTS: After CI therapy, patients showed large (Wolf Motor Function Test) to very large improvements in the functional use of their more affected arm in their daily lives (Motor Activity Log; P<0.0001). The changes persisted over the 2 years tested. Placebo subjects showed no significant changes. CONCLUSIONS: The results support the efficacy of CI therapy for rehabilitating upper extremity motor function in patients with chronic stroke.

Adult↗
PubMed2006

Frontotemporal dementia: clinicopathological correlations.

OBJECTIVE: Frontotemporal lobar degeneration (FTLD) is characterized by impairments in social, behavioral, and/or language function, but postmortem studies indicate that multiple neuropathological entities lead to FTLD. This study assessed whether specific clinical features predict the underlying pathology. METHODS: A clinicopathological correlation was performed on 90 consecutive patients with a pathological diagnosis of frontotemporal dementia and was compared with an additional 24 cases accrued during the same time period with a clinical diagnosis of FTLD, but with pathology not typically associated with frontotemporal dementia. RESULTS: Postmortem examination showed multiple pathologies including tauopathies (46%), FTLD with ubiquitin-positive inclusions (29%), and Alzheimer's disease (17%). The pathological groups manifested some distinct demographic, clinical, and neuropsychological features, although these attributes showed only a statistical association with the underlying pathology. FTLD with ubiquitin-positive inclusions was more likely to present with both social and language dysfunction, and motor neuron disease was more likely to emerge in these patients. Tauopathies were more commonly associated with an extrapyramidal disorder. Alzheimer's disease was associated with relatively greater deficits in memory and executive function. INTERPRETATION: Clinical and neuropsychological features contribute to delineating the spectrum of pathology underlying a patient diagnosed with FTLD, but biomarkers are needed that, together with the clinical phenotype, can predict the underlying neuropathology.

Adult↗
PubMed2006

Letter selection and letter assembly in acquired dysgraphia.

OBJECTIVE: We explored the constituents of the graphemic buffer in a patient with acquired dysgraphia and tested the hypothesis that the graphemic buffer is composed of 2 dissociable components: letter selection and letter assembly. BACKGROUND: Research on dysgraphia has established the graphemic buffer as a component of the spelling mechanism, and the buffer is considered a short-term memory store that is critical for letter production. However, little is known about the components within the buffer. METHOD: We devised 2 spelling tasks that rely differentially on letter selection and letter assembly. In the selection task, our patient produced the letters that composed a target word, but she did not have to provide serial position information. In the assembly task, B.H. was given all the letters of a target word and was asked to spell the word by arranging the letters in the proper serial order. RESULTS: Compared to spelling to dictation, our patient did not benefit from being given letter identity information (ie, assembly task), but her performance improved significantly when position information was available (ie, selection task). CONCLUSIONS: Based on these data, and the comparison of her performance with another dysgraphic patient, we propose that the graphemic buffer engages in both letter selection and letter assembly.

Aged↗
PubMed2006

Art produced by a patient with Parkinson's disease.

Artists with neurological diseases sometimes produce remarkably appealing art. Here we present the art of a patient with Parkinson's disease, who demonstrated remarkable creativity and productivity well into the course of his disease. Despite his manifest motor impairments, he produced paintings and drawings with fluid sinuous movements. He also became preoccupied with his art in an unprecedented way, raising the possibility that his disease and medications were contributing to his creative drive.

Aged↗
PubMed2006

Fractionating the left frontal response to tools: dissociable effects of motor experience and lexical competition.

A number of theories about the evolution of language posit a close (and perhaps causal) relationship between tool use and speech. Consistent with this idea, neuroimaging studies have found that tool knowledge retrieval activates not only a region of the left premotor cortex involved in hand action, but also an adjacent region that is typically described as a language center. We examined whether this pattern of activation is best described as the result of a single process, related to both action and language, or the result of two independent processes. We identified two distinct neural components that jointly contribute to this response: a posterior region centered in the premotor cortex, which responds to motor knowledge retrieval, and an anterior region centered in the left frontal operculum, which responds to lexical competition. Crucial to the interpretation of the premotor response, individual variation in motor experience was highly correlated with the magnitude of the response in the premotor cortex, but not in the prefrontal cortex.

Adolescent↗
PubMed2006

The frontal cortex and exogenous attentional orienting.

Normal functioning of the attentional orienting system is critical for effective behavior and is predicated on a balanced interaction between goal-directed (endogenous) processes and stimulus-driven (exogenous) processes. Although both systems have been subject to much investigation, little is known about the neural underpinnings of exogenous orienting. In the present study, we examined the early facilitatory effects and later inhibition of return effects of exogenous cues in patients with frontal and parietal lesions. Three novel findings emerged from this study. First, unilateral frontoparietal damage appears not to affect the early facilitation effects of exogenous cues. Second, dorsolateral prefrontal damage, especially lesions involving the inferior frontal gyrus, produces an exogenous disengage deficit (i.e., the sluggish withdrawal of attention from the ipsilesional to the contralesional field). Third, a subset of patients with dorsolateral prefrontal damage, with lesions involving the middle frontal gyrus, have a reorienting deficit that extends in duration well beyond established boundaries of the normal reflexive orienting system. These results suggest that the dorsolateral prefrontal cortex plays an important role in exogenous orienting and that component processes of this system may be differentially impaired by damage to different parts of the dorsolateral prefrontal cortex.

Aged↗
PubMed2006

Visual working memory is impaired when the medial temporal lobe is damaged.

The canonical description of the role of the medial temporal lobes (MTLs) in memory is that short-term forms of memory (e.g., working memory [WM]) are spared when the MTL is damaged, but longer term forms of memory are impaired. Tests used to assess this have typically had a heavy verbal component, potentially allowing explicit rehearsal strategies to maintain the WM trace over the memory delay period. Here we test the hypothesis that the MTL is necessary for visual WM when verbal rehearsal strategies are difficult to implement. In three patients with MTL damage we found impairments in spatial, face, and color WM, at delays as short as 4 sec. Impaired memory could not be attributed to memory load or perceptual problems. These findings suggest that the MTLs are critical for accurate visual WM.

Aged↗
PubMed2006

Specificity of action representations in the lateral occipitotemporal cortex.

The ability to recognize actions is important for cognitive development and social cognition. Areas in the lateral occipitotemporal cortex show increased activity when subjects view action sequences; however, whether this activity distinguishes between specific actions as necessary for action recognition is unclear. We used a functional magnetic resonance imaging adaptation paradigm to test for brain regions that exhibit action-specific activity. Subjects watched a series of action sequences in which the action performed or the person performing the action could be repeated from a previous scan. Three regions-the superior temporal sulcus (pSTS), human motion-sensitive cortex (MT/MST), and extrastriate body area (EBA)-showed decreased activity for previously seen actions, even when the actions were novel exemplars because the persons involved had not been seen previously. These action-specific adaptation effects provide compelling evidence that representations in the pSTS, MT/MST, and EBA abstract actions from the agents involved and distinguish between different particular actions.

Adaptation, Physiological↗
PubMed2005

Visuomotor links in awareness: evidence from extinction.

In patients with extinction, ipsilesional stimuli may abolish awareness of contralesional stimuli. Explanations of extinction often assume a serial model of processing in which sensory competition and identification precedes the selection of responses. We tested the adequacy of this assumption by examining the effects of response variables on visual awareness in six patients using signal detection analysis. Ipsilesional stimuli modulated patients' response criteria in deciding whether a contralesional stimulus was a target, and response modality (verbal or motor) modulated patients' abilities to discriminate between contralesional targets and distractors. This pattern of input variables modulating response criteria and output variables modulating discriminability indicates the extent to which attentional and intentional systems are tightly intertwined, with bi-directional effects in producing visual awareness.

Aged↗
PubMed2005

Cerebrospinal fluid profile in frontotemporal dementia and Alzheimer's disease.

We assessed cerebrospinal fluid (CSF) levels of tau and other biomarkers of neurodegenerative disease. CSF tau levels vary widely in reports of frontotemporal dementia (FTD). CSF samples were assayed for tau, amyloid beta1-42 (A1-42), and the isoprostane 8,12-iso-iPF2a-VI (iP) prospectively in 64 patients with FTD, retrospectively in 26 autopsied cases with FTD or Alzheimer's disease (AD), and in 13 healthy seniors. To validate our observations in vivo, we correlated CSF tau levels with cortical atrophy in 17 FTD patients using voxel-based morphometry analyses of high-resolution magnetic resonance imaging. CSF levels of tau, Abeta1-42, and iP differed significantly in FTD compared with AD. Individual patient analyses showed that 34% of FD patients had significantly low levels of CSF tau, although this was never seen in AD. A discriminant analysis based on CSF levels of tau, Abeta1-42, and iP was able to classify 88.5% of these patients in a manner that corresponds to their clinical or autopsy diagnosis. Magnetic resonance imaging studies showed that CSF tau levels correlate significantly with right frontal and left temporal cortical atrophy, brain regions known to be atrophic in patients with autopsy-proved FTD. We conclude that CSF tau levels are significantly reduced in many patients with FTD.

Age of Onset↗
PubMed2005

Reduced endogenous control in alien hand syndrome: evidence from naturalistic action.

Patients with alien hand (AH) syndrome from medial frontal lesions exhibit involuntary but seemingly purposeful contralesional upper limb movements. Two observations about AH patients have received little, if any, experimental confirmation. The first is that AH is triggered opportunistically by nearby objects. The second is that AH behaviors are increased in conditions of fatigue or anxiety, i.e. under reduced attentional control. A prominent account explains AH as reduced intention-driven (endogenous) executive control. This account predicts that erroneous AH behaviors should be driven by environmental (i.e. exogenous) factors, such as distractor proximity to the hand. AH errors should be less influenced by the intention or action plan (i.e. endogenous factors), such as the semantic relatedness of distractors to targets. Moreover, due to capacity limitations of the endogenous controller, AH behaviors should increase under conditions of secondary task load. We tested these predictions with an AH patient in two experiments using a naturalistic coffee-making task. Experiment 1 demonstrated that the affected hand was highly perseverative and strongly influenced by exogenous but not endogenous factors. The non-alien hand made fewer errors. Experiment 2 showed that there was a disproportionate increase in perseverations and exogenous errors of the affected hand under secondary task load. The non-alien hand was significantly less disrupted by dual task conditions. These data provide experimental support for previous anecdotal observations about AH behavior in naturalistic settings, and are consistent with a unilateral defect in endogenous control.

Activities of Daily Living↗
PubMed2005

Biases in attentional orientation and magnitude estimation explain crossover: neglect is a disorder of both.

Crossover refers to a pattern of performance on the line bisection test in which short lines are bisected on the side opposite the true center of long lines. Although most patients with spatial neglect demonstrate crossover, contemporary theories of neglect cannot explain it. In contrast, we show that blending the psychophysical construct of magnitude estimation with neglect theory not only explains crossover, but also addresses a quantitative feature of neglect that is independent of spatial deficits. We report a prospective validation study of the orientation/estimation hypothesis of crossover. Forty subjects (17 patients with and without neglect following unilateral brain injury and 23 normal controls) completed four experiments that examined crossover using line bisection, line bisection with cueing, and reproducing line lengths from both memory and a standard. Replicating earlier findings, all except one subject group exhibited crossover on the standard line bisection test, all groups showed a spontaneous preference to orient attention to one end of the lines, and all groups overestimated the length of short lines and underestimated long lines. Biases in attentional orientation and magnitude estimation are exaggerated in patients with neglect. The truly novel finding of this study occurred when, after removing the line from the bisection task, the direction of crossover was completely reversed in all subject groups depending on where attention was oriented. These findings are consistent with our hypothesis of crossover: (1) crossover is a normal component of performance on line bisection; (2) crossover results from the interplay of biases in attentional orientation and magnitude estimation; and (3) attentional orientation predicts the direction of crossover, whereas a disorder of magnitude estimation, not previously emphasized in neglect, accounts for the quantitative changes in length estimation that make crossover more obvious in neglect subjects. Paradoxically, we observed that the traditional line bisection test is suboptimal for exploring crossover because lines elicit spontaneous orientation responses from subjects that confound experimental manipulations of attention. We conclude that attentional orientation and magnitude estimation are necessary and sufficient to explain crossover and that bias in magnitude estimation is a core component of neglect.

Adult↗
PubMed2005

Conceptual representations of action in the lateral temporal cortex.

Retrieval of conceptual information from action pictures causes greater activation than from object pictures bilaterally in human motion areas (MT/MST) and nearby temporal regions. By contrast, retrieval of conceptual information from action words causes greater activation in left middle and superior temporal gyri, anterior and dorsal to the MT/MST. We performed two fMRI experiments to replicate and extend these findings regarding action words. In the first experiment, subjects performed conceptual judgments of action and object words under conditions that stressed visual semantic information. Under these conditions, action words again activated posterior temporal regions close to, but not identical with, the MT/MST. In the second experiment, we included conceptual judgments of manipulable object words in addition to judgments of action and animal words. Both action and manipulable object judgments caused greater activity than animal judgments in the posterior middle temporal gyrus. Both of these experiments support the hypothesis that middle temporal gyrus activation is related to accessing conceptual information about motion attributes, rather than alternative accounts on the basis of lexical or grammatical factors. Furthermore, these experiments provide additional support for the notion of a concrete to abstract gradient of motion representations with the lateral occipito-temporal cortex, extending anterior and dorsal from the MT/MST towards the peri-sylvian cortex.

Adult↗
PubMed2005

A comparison of self-report and caregiver assessment of depression, apathy, and irritability in Huntington's disease.

The natural history of psychiatric syndromes associated with Huntington's disease (HD) remains unclear, and longitudinal studies of symptoms such as depression, apathy, and irritability are required to better understand the progression and role of these syndromes and their effect on disability. Self-administered scales such as the Beck Depression Inventory (BDI) may be useful to document changes in symptoms over time, but the validity of self-report may be questionable with the inevitable progression of cognitive deficits. An alternative to the patient's self-report would be assessments by the caregiver. The authors assessed interrater agreement between patient self-assessment and caregiver assessment of patients status for the presence of depressed mood using the BDI and apathy and irritability using an apathy and irritability scale. Agreement between these scales across strata of cognitive status was also examined. Interrater agreement varied from moderate to good for the BDI, depending on patient cognitive status. Agreement for the apathy scores was low for patients with poor cognition and fair in patients with better cognition. Irritability scale agreement was fair at best and was the worst in patients with the most intact cognition. Caregiver assessment of patients' moods and apathy may be an acceptable alternative to patient self-report as patients' cognitive status worsens.

Adult↗