From Phineas Gage and Monsieur Leborgne to H.M.: Revisiting Disconnection Syndromes.

On the 50th anniversary of Norman Geschwind's seminal paper entitled 'Disconnexion syndrome in animal and man', we pay tribute to his ideas by applying contemporary tractography methods to understand white matter disconnection in 3 classic cases that made history in behavioral neurology. We first documented the locus and extent of the brain lesion from the computerized tomography of Phineas Gage's skull and the magnetic resonance images of Louis Victor Leborgne's brain, Broca's first patient, and Henry Gustave Molaison. We then applied the reconstructed lesions to an atlas of white matter connections obtained from diffusion tractography of 129 healthy adults.

H.M. never again! An analysis of H.M.'s epilepsy and treatment.

On August 25, 1953, the patient H.M., aged 27, underwent a bilateral surgical destruction of the inner aspect of his temporal lobes performed by William Beecher Scoville with the aim to control H.

H.M.'s contributions to neuroscience: a review and autopsy studies.

H.M., Henry Molaison, was one of the world's most famous amnesic patients.

Motor impulsivity in Parkinson disease: associations with COMT and DRD2 polymorphisms.

Parkinson disease (PD) is an age-related degenerative disease of the brain, characterized by motor, cognitive, and psychiatric symptoms. Neurologists and neuroscientists now understand that several symptoms of the disease, including hallucinations and impulse control behaviors, stem from the dopaminergic medications used to control the motor aspects of PD. Converging evidence from animals and humans suggests that individual differences in the genes that affect the dopamine system influence the response of PD patients to dopaminergic medication.

Postmortem examination of patient H.M.'s brain based on histological sectioning and digital 3D reconstruction.

Modern scientific knowledge of how memory functions are organized in the human brain originated from the case of Henry G. Molaison (H.M.

New MRI Biomarkers Advance the Characterization of Parkinson Disease.

The pathophysiology of idiopathic Parkinson disease (PD) is traditionally characterized as substantia nigra degeneration, but careful examination of the widespread neuropathological changes suggests individual differences in neuronal vulnerability. A major limitation to studies of disease progression in PD has been that conventional MRI techniques provide relatively poor contrast for the structures that are affected by the disease, and thus are not typically used in experimental or clinical studies. Here, we review the current state of structural MRI as applied to the analysis of the PD brain.

Substantia nigra volume loss before basal forebrain degeneration in early Parkinson disease.

Objective: To test the hypothesis that degeneration of the substantia nigra pars compacta (SNc) precedes that of the cholinergic basal forebrain (BF) in Parkinson disease (PD) using new multispectral structural magnetic resonance (MR) imaging tools to measure the volumes of the SNc and BF.

Design: Matched case-control study.

Setting: The Athinoula A.

Sex and the city in decline: Midnight Cowboy (1969) and Klute (1971).

This essay looks at two popular and influential films of the late 1960s and early 1970s, which were both shot in New York City: Midnight Cowboy (1969) and Klute (1971). It places them in film history, New York City history, and U.S.

Transformations in oscillatory activity and evoked responses in primary somatosensory cortex in middle age: a combined computational neural modeling and MEG study.

Oscillatory brain rhythms and evoked responses are widely believed to impact cognition, but relatively little is known about how these measures are affected by healthy aging. The present study used MEG to examine age-related changes in spontaneous oscillations and tactile evoked responses in primary somatosensory cortex (SI) in healthy young (YA) and middle-aged (MA) adults. To make specific predictions about neurophysiological changes that mediate age-related MEG changes, we applied a biophysically realistic model of SI that accurately reproduces SI MEG mu rhythms, containing alpha (7-14 Hz) and beta (15-30 Hz) components, and evoked responses.

Cognition in healthy aging is related to regional white matter integrity, but not cortical thickness.

It is well established that healthy aging is accompanied by structural changes in many brain regions and functional decline in a number of cognitive domains. The goal of this study was to determine (1) whether the regional distribution of age-related brain changes is similar in gray matter (GM) and white matter (WM) regions, or whether these two tissue types are affected differently by aging, and (2) whether measures of cognitive performance are more closely linked to alterations in the cerebral cortex or in the underlying WM in older adults (OA). To address these questions, we collected high-resolution magnetic resonance imaging (MRI) data from a large sample of healthy young adults (YA; aged 18-28) and OA (aged 61-86 years).

Reliability of MRI-derived cortical and subcortical morphometric measures: effects of pulse sequence, voxel geometry, and parallel imaging.

Advances in magnetic resonance imaging (MRI) have contributed greatly to the study of neurodegenerative processes, psychiatric disorders, and normal human development, but the effect of such improvements on the reliability of downstream morphometric measures has not been extensively studied. We examined how MRI-derived neurostructural measures are affected by three technological advancements: parallel acceleration, increased spatial resolution, and the use of a high bandwidth multiecho sequence. Test-retest data were collected from 11 healthy participants during 2 imaging sessions occurring approximately 2 weeks apart.

False memory in aging: effects of emotional valence on word recognition accuracy.

Memory is susceptible to distortions. Valence and increasing age are variables known to affect memory accuracy and may increase false alarm production. Interaction between these variables and their impact on false memory was investigated in 36 young (18-28 years) and 36 older (61-83 years) healthy adults.

White matter pathology isolates the hippocampal formation in Alzheimer's disease.

Prior work has demonstrated that the memory dysfunction of Alzheimer's disease (AD) is accompanied by marked cortical pathology in medial temporal lobe (MTL) gray matter. In contrast, changes in white matter (WM) of pathways associated with the MTL have rarely been studied. We used diffusion tensor imaging (DTI) to examine regional patterns of WM tissue changes in individuals with AD.

Posterior parahippocampal place learning in H.M.

In a previous experiment with patients who had undergone unilateral temporal thermocoagulation lesions to alleviate intractable epilepsy, we demonstrated that the right parahippocampal cortex was critical for the performance of a spatial memory task (Bohbot et al. (1998) Neuropsychologia 36:1217-1238). Based on this evidence, we predicted that H.

Neuroimaging H.M.: a 10-year follow-up examination.

In 1997, Corkin et al. described the anatomical boundaries of the amnesic patient H.M.

Age-related changes in prefrontal white matter measured by diffusion tensor imaging.

Age-related degeneration of brain white matter (WM) has received a great deal of attention, with recent studies demonstrating that such changes are correlated with cognitive decline and increased risk for the development of age-related neurodegenerative disease. Past studies have used magnetic resonance imaging (MRI) to measure the volume of normal and abnormal tissue signal as an index of tissue pathology. More recently, diffusion tensor MRI (DTI) has been employed to obtain regional measures of tissue microstructure, such as fractional anisotropy (FA), providing better spatial resolution and potentially more sensitive metrics of tissue damage than traditional volumetric measures.

Memories of an emotional and a nonemotional event: effects of aging and delay interval.

The present study compared the memory of young and older adults for details pertaining to two public events of close temporal proximity but varying emotional import-the Columbia shuttle explosion and the 2003 Super Bowl. Participants responded to surveys sent within 2 weeks of these events and then again 7 months later, providing information about event-related details (i.e.

Ecphory of autobiographical memories: an fMRI study of recent and remote memory retrieval.

Ecphory occurs when one recollects a past event cued by a trigger, such as a picture, odor, or name. It is a central component of autobiographical memory, which allows us to "travel mentally back in time" and re-experience specific events from our personal past. Using fMRI and focusing on the role of medial temporal lobe (MTL) structures, we investigated the brain bases of autobiographical memory and whether they change with the age of memories.

Memory for contextual details: effects of emotion and aging.

When individuals are confronted with a complex visual scene that includes some emotional element, memory for the emotional component often is enhanced, whereas memory for peripheral (nonemotional) details is reduced. The present study examined the effects of age and encoding instructions on this effect. With incidental encoding instructions, young and older adults showed this pattern of results, indicating that both groups focused attention on the emotional aspects of the scene.

Effects of verbal and nonverbal interference on spatial and object visual working memory.

We tested the hypothesis that a verbal coding mechanism is necessarily engaged by object, but not spatial, visual working memory tasks. We employed a dual-task procedure that paired n-back working memory tasks with domain-specific distractor trials inserted into each interstimulus interval of the n-back tasks. In two experiments, object n-back performance demonstrated greater sensitivity to verbal distraction, whereas spatial n-back performance demonstrated greater sensitivity to motion distraction.

Age-related alterations in white matter microstructure measured by diffusion tensor imaging.

Cerebral white matter (WM) undergoes various degenerative changes with normal aging, including decreases in myelin density and alterations in myelin structure. We acquired whole-head, high-resolution diffusion tensor images (DTI) in 38 participants across the adult age span. Maps of fractional anisotropy (FA), a measure of WM microstructure, were calculated for each participant to determine whether particular fiber systems of the brain are preferentially vulnerable to WM degeneration.

Medial temporal lobe structures are needed to re-experience remote autobiographical memories: evidence from H.M. and W.R.

The nature and extent of retrograde amnesia in patients with medial temporal lobe (MTL) lesions is currently under debate. While some investigators propose a temporally limited role for the MTL in episodic and semantic memory, others claim that MTL structures are needed for episodic memories of one's entire lifetime, and that only semantic memory becomes independent of the MTL. To address this issue, we tested two amnesic patients, H.

Puzzling thoughts for H. M.: can new semantic information be anchored to old semantic memories?

Researchers currently debate whether new semantic knowledge can be learned and retrieved despite extensive damage to medial temporal lobe (MTL) structures. The authors explored whether H. M.

The effects of emotional content and aging on false memories.

After studying a list of words related to a nonpresented lure word, people often falsely recall or recognize the nonpresented lure. Older adults are particularly susceptible to these forms of false memories. The age-related false memory enhancement likely occurs because older adults do not encode, or later retrieve, items in enough detail to allow them to discriminate between presented words and other associated but nonpresented items.

Evidence for semantic learning in profound amnesia: an investigation with patient H.M.

Until recently, it seemed unlikely that any semantic knowledge could be acquired following extensive bilateral damage to the medial temporal lobes (MTL). Although recent studies have demonstrated some semantic learning in amnesic patients, questions remain regarding the limits of this capacity and the extent to which it relies on those patients' residual MTL function. The present study examined whether detailed, semantic memory could be acquired by a patient with no functioning hippocampus.