Anjan Chatterjee

Frontotemporal dementia: clinicopathological correlations.

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.

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. Conclusion— The results support the efficacy of CI therapy for rehabilitating upper extremity motor function in patients with chronic stroke.

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.

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 β1‐42 (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 Alzheimers 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, Aβ1‐42, 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, Aβ1‐42, 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. Ann Neurol 2005;57:721–729

Neural Substrates of Action Event Knowledge

Human concepts can be roughly divided into entities (prototypically referred to in language by nouns) and events (prototypically referred to in language by verbs). While much work in cognitive neuroscience has investigated how the brain represents different categories of entities, less attention has been given to the more basic distinction between entities and events. We used functional magnetic resonance imaging to examine brain activity while subjects performed a conceptual matching task that required them to access knowledge of objects and actions, using either pictures or words. Since action events involve movement through space, we hypothesized that accessing knowledge of actions would cause greater activation in brain regions involved in motion or spatial processing. In comparison to objects, accessing knowledge of actions through pictures was accompanied by increased activity bilaterally in the human MT/MST and nearby regions of the lateral temporal cortex. Accessing knowledge of actions through words activated areas just anterior and dorsal to area MT/MST on the left, within the posterior aspect of the middle and superior temporal gyri. We propose that the lateral occipital temporal cortex contains a mosaic of neural regions that processes different kinds of motion, ranging from the perception of objects moving in the world to the conception of movement implied in action verbs. The lateral occipital temporal cortex mediates the perceptual and conceptual features of action events, similar to the way that the ventral occipital temporal cortex processes the perceptual and conceptual features of entities.

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.

Cosmetic neurology: The controversy over enhancing movement, mentation, and mood

Advances in cognitive neuroscience and neuropharmacology are yielding exciting treatments for neurologic diseases. Many of these treatments are also likely to have uses for people without disease. Here, I review the ways in which medicine might make bodies and brains function better by modulating motor, cognitive, and affective systems. These potential “quality of life” interventions raise ethical concerns, some related to the individual and others related to society. Despite these concerns, I argue that major restraints on the development of cosmetic neurology are not likely. Neurologists and other clinicians are likely to encounter patient-consumers who view physicians as gatekeepers in their own pursuit of happiness.

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.

Neuroaesthetics: A coming of age story

Neuroaesthetics is gaining momentum. At this early juncture, it is worth taking stock of where the field is and what lies ahead. Here, I review writings that fall under the rubric of neuroaesthetics. These writings include discussions of the parallel organizational principles of the brain and the intent and practices of artists, the description of informative anecdotes, and the emergence of experimental neuroaesthetics. I then suggest a few areas within neuroaesthetics that might be pursued profitably. Finally, I raise some challenges for the field. These challenges are not unique to neuroaesthetics. As neuroaesthetics comes of age, it might take advantage of the lessons learned from more mature domains of inquiry within cognitive neuroscience.

Language and space: some interactions

Is language linked to mental representations of space? There are several reasons to think that language and space might be separated in our cognitive systems, but they nevertheless interact in important ways. These interactions are evident in language viewed as a means of communication and in language considered a form of representation. In communication, spatial factors may be explicit in language itself, such as the spatial-gestural system of American Sign Language. Even the act of conversing with others is a spatial behavior because we orient to the locations of other participants. Language and spatial representations probably converge at an abstract level of concepts and simple spatial schemas.