Search

Upon his death in 1955, Albert Einstein’s brain was removed, fixed and photographed from multiple angles. It was then sectioned into 240 blocks, and histological slides were prepared. At the time, a roadmap was drawn that illustrates the location within the brain of each block and its associated slides. Here we describe the external gross neuroanatomy of Einstein’s entire cerebral cortex from 14 recently discovered photographs, most of which were taken from unconventional angles. Two of the photographs reveal sulcal patterns of the medial surfaces of the hemispheres, and another shows the neuroanatomy of the right (exposed) insula. Most of Einstein’s sulci are identified, and sulcal patterns in various parts of the brain are compared with those of 85 human brains that have been described in the literature. To the extent currently possible, unusual features of Einstein’s brain are tentatively interpreted in light of what is known about the evolution of higher cognitive processes in humans. As an aid to future investigators, these (and other) features are correlated with blocks on the roadmap (and therefore histological slides). Einstein’s brain has an extraordinary prefrontal cortex, which may have contributed to the neurological substrates for some of his remarkable cognitive abilities. The primary somatosensory and motor cortices near the regions that typically represent face and tongue are greatly expanded in the left hemisphere. Einstein’s parietal lobes are also unusual and may have provided some of the neurological underpinnings for his visuospatial and mathematical skills, as others have hypothesized. Einstein’s brain has typical frontal and occipital shape asymmetries (petalias) and grossly asymmetrical inferior and superior parietal lobules. Contrary to the literature, Einstein’s brain is not spherical, does not lack parietal opercula and has non-confluent Sylvian and inferior postcentral sulci. * Abbreviation : BA : Brodmann area

The extent to which the human brain shows evidence of functional plasticity across the lifespan has been addressed in the context of pathological brain changes and, more recently, of the changes that take place during healthy ageing. Here we examine the potential for plasticity by asking whether a strongly left-lateralized system can successfully reorganize to the right-hemisphere following left-hemisphere brain damage. To do this, we focus on syntax, a key linguistic function considered to be strongly left-lateralized, combining measures of tissue integrity, neural activation and behavioural performance. In a functional neuroimaging study participants heard spoken sentences that differentially loaded on syntactic and semantic information. While healthy controls activated a left-hemisphere network of correlated activity including Brodmann areas 45/47 and posterior middle temporal gyrus during syntactic processing, patients activated Brodmann areas 45/47 bilaterally and right middle temporal gyrus. However, voxel-based morphometry analyses showed that only tissue integrity in left Brodmann areas 45/47 was correlated with activity and performance; poor tissue integrity in left Brodmann area 45 was associated with reduced functional activity and increased syntactic deficits. Activity in the right-hemisphere was not correlated with damage in the left-hemisphere or with performance. Reduced neural integrity in the left-hemisphere through brain damage or healthy ageing results in increased right-hemisphere activation in homologous regions to those left-hemisphere regions typically involved in the young. However, these regions do not support the same linguistic functions as those in the left-hemisphere and only indirectly contribute to preserved syntactic capacity. This establishes the unique role of the left hemisphere in syntax, a core component in human language.

Patients with clinically isolated syndromes suggestive of multiple sclerosis have evidence for abnormality in normal appearing grey matter detected using the magnetization transfer ratio (MTR), a quantitative MRI measure. One potential mechanism for the decreased grey matter MTR (GM MTR) observed is trans-synaptic morphological abnormality secondary to demyelinating lesions that are in an anatomically linked pathway but remote location. We investigated this potential association by studying the location of abnormalities using voxel-based analysis of GM MTR maps in a group of 80 patients studied within 6 months of presenting with isolated optic neuritis and compared the findings with those seen in 50 age- and sex-matched healthy controls. Occipital cortex and whole brain analysis comparing all optic neuritis patients and controls revealed a selective decrease of MTR bilaterally in the visual cortex in patients [Brodmann area (BA) 17]. Whole brain analysis of patients fulfilling the McDonald criteria for multiple sclerosis (n = 20) showed a lower MTR compared to controls bilaterally in the visual cortex (BA 17/18), left hippocampus, bilateral superior temporal gyrus, bilateral lenticular nuclei and the right cerebellum. There was no significant difference in the percentage of grey matter between patients and controls in the regions of abnormal MTR detected in the visual cortex. The intrinsic MTR decrease seen in patients suggests that there are structural changes in the visual cortex following an attack of optic neuritis. Potential mechanisms for this include trans-synaptic neuronal degeneration and cortical synaptic morphological changes; such abnormalities may also contribute to MTR abnormalities observed in the normal appearing grey matter in multiple sclerosis.

Cortical reorganization has been demonstrated in the motor network that mediates performance of a motor task in patients with multiple sclerosis. How this network responds to motor training is not known. This study examined functional MRI (fMRI) activation patterns associated with performance of a motor task, consisting of repetition of directionally specific voluntary thumb movements, before and after motor training in a group of multiple sclerosis patients with mild motor impairment of the right upper extremity. Patients and healthy subjects were scanned in one session before, during and after a 30 min training period. fMRI data obtained during rest, thumb flexion (trained movement) and thumb extension (untrained movement) were analysed using random effects analysis (SPM99). Motor kinematics of training motions and EMG from the resting hand were monitored with an accelerometer and surface EMG electrodes. Kinematics of thumb movements before, during and after training were comparable in the absence of mirror EMG activity in the resting hand. Before training, thumb movements elicited more prominent activation of the contralateral dorsal premotor cortex [PMd, Brodmann area (BA) 6] in multiple sclerosis patients than in controls. After training, unlike the control group, multiple sclerosis patients did not exhibit task-specific reductions in activation in the contralateral primary somatosensory (S1), motor (M1) and adjacent parietal association (BA 40) cortices. These results indicate that patients engage the contralateral PMd more than controls in order to perform directionally specific movements before training. The absence of training-dependent reductions in activation in S1, M1 and BA 40 is consistent with a decreased capacity to optimize recruitment of the motor network with practice.

Summary To analyse the functions of different parts of the prefrontal cortex in emotion, patients with different prefrontal surgical excisions were compared on four measures of emotion: voice and face emotional expression identification, social behaviour, and the subjective experience of emotion. Some patients with bilateral lesions of the orbitofrontal cortex (OFC) had deficits in voice and face expression identification, and the group had impairments in social behaviour and significant changes in their subjective emotional state. Some patients with unilateral damage restricted to the OFC also had deficits in voice expression identification, and the group did not have significant changes in social behaviour or in their subjective emotional state. Patients with unilateral lesions of the antero-ventral part of the anterior cingulate cortex (ACC) and/or medial Brodmann area (BA) 9 were, in some cases, impaired on voice and face expression identification, had some change in social behaviour, and had significant changes in their subjective emotional state. Patients with unilateral lesions of the OFC and of the ACC and/or medial BA 9 were, in some cases, impaired on voice and face expression identification, had some changes in social behaviour, and had significant changes in their subjective emotional state. Patients with dorsolateral prefrontal cortex lesions or with medial lesions outside ACC and medial BA 9 areas (dorsolateral/other medial group) were unimpaired on any of these measures of emotion. In all cases in which voice expression identification was impaired, there were no deficits in control tests of the discrimination of unfamiliar voices and the recognition of environmental sounds. Thus bilateral or unilateral lesions circumscribed surgically within the OFC can impair emotional voice and/or face expression identification, but significant changes in social behaviour and in subjective emotional state are related to bilateral lesions. Importantly, unilateral lesions of the ACC (including some of medial BA 9) can produce voice and/or face expression identification deficits, and marked changes in subjective emotional state. These findings with surgically circumscribed lesions show that within the prefrontal cortex, both the OFC and the ACC/medial BA 9 region are involved in a number of aspects of emotion in humans including emotion identification, social behaviour and subjective emotional state, and that the dorsolateral prefrontal areas are not involved in emotion in these ways.

Age-related neurodegenerative and neurochemical changes are thought to underlie decline in motor and cognitive functions, but compensatory processes in cortical and subcortical function may allow maintenance of performance level in some people. Our objective was to investigate age-related changes in the motor system of the human brain using functional MRI. Twenty six right handed volunteers were scanned whilst performing an isometric, dynamic, visually paced hand grip task, using dominant (right) and non-dominant (left) hands in separate sessions. Hand grip with visual feedback activated a network of cortical and subcortical regions known to be involved in the generation of simple motor acts. In addition, activation was seen in a putative human 'grasping circuit', involving rostral ventral premotor cortex (Brodmann area 44) and intraparietal sulcus. Within this network, a number of regions were more likely to be activated the older the subject. In particular, age-related changes in task- specific activations were demonstrated in left deep anterior central sulcus when using the dominant or non-dominant hand. Additional age-related increases were seen in caudal dorsal premotor cortex, caudal cingulate sulcus, intraparietal sulcus, insula, frontal operculum and cerebellar vermis. We have demonstrated a clear age-related effect in the neural correlates of motor performance, and furthermore suggest that these changes are non-linear. These results support the notion that an adaptable and plastic motor network is able to respond to age-related degenerative changes in order to maintain performance levels.

The morphology of the region of the primary motor cortex in the human brain is variable, and putative asymmetries between the hemispheres have been noted since the beginning of last century. Such variability may confound the results of clinical lesion or functional activation studies. We measured Brodmann area (BA) 4 and the identifiable precentral component of the pyramidal tract (PRPT) in 11 human post-mortem brains using techniques of quantitative cytoarchitectonic and myeloarchitectonic image analysis. Topography and variability in the localization of architectonic borders were analysed and mapped to a computerized spatial reference system, which consists of an individual in vivo MRI brain. All maps were superimposed to produce probabilistic maps of BA 4 and PRPT which can be co-registered with any image of brain structure or function that has also been transformed to Talairach coordinates. These maps can be readily applied to future brain mapping studies. We observed a considerable degree of variability between hemispheres (intra-individual) and between brains (inter-individual). The variation zones of BA 4 and PRPT differ from the templates of the Talairach atlas. Voxel-based morphometry shows significant side differences with larger volumes of PRPT in the left hemisphere than in the right hemisphere. This larger volume of the descending cortical motor fibres may be related to the known left-hemisphere dominance for handedness in >90% of the population. In contrast, BA 4 was symmetrically organized. The lack of a significant correlation between the size of BA 4 and the size of PRPT may relate to the fact that additional non-primary motor and sensory cortices contribute to the origins and size of the pyramidal tract proper.

Regional cerebral blood flow (rCBF) was measured with PET in seven healthy subjects while they carried out a mental rotation task in which they decided whether alphanumeric characters presented in different orientations were in their canonical form or mirror-reversed. Consistent with previous findings, subjects took proportionally longer to respond as characters were rotated further from the upright, indicating that they were mentally rotating the characters to the upright position before making a decision. We used a parametric design in which we varied the mental rotation demands in an incremental fashion while keeping all other aspects of the task constant. In four different scanning conditions, 10, 40, 70 or 100% of the stimuli presented during the scan required mental rotation while the rest were upright. The statistical parametric mapping technique was used to identify areas where changes in rCBF were correlated with the rotational demands of the task. Significant activation was found in only one area located in the right posterior parietal lobe, centred on the intraparietal sulcus (Brodmann area 7). The experimental literature on monkeys and humans suggests that this area is involved in a variety of spatial transformations. Our results contribute evidence that such transformations are recruited during mental rotation and add to a body of evidence which suggests that the right posterior parietal lobe is important for carrying out visuospatial transformations.

Professor Weiskrantz, from the University of Oxford, and his colleagues at Queen Square set the scene for their case report in detail of what—drawing on the linguistically economical 19th century terminologies of ‘word-blindness’ and ‘word-deafness’—they call ‘blind-sight’ by reference to the magisterial descriptions of visual field loss based on the analysis of penetrating injuries of the head by Gordon Holmes (1918) and George Riddoch (1917) after the Great War, and by Edward Tauber, William Battersby and Morris Bender (1960) following the Second World War. But these giants of descriptive neurology, restricted to knowledge gained from human, not monkey, neuroscience and limiting their gaze to the gross deficits that follow extensive occipital lesions, may have missed some subtleties of the visual experience that result from damage to the striate cortex. Proceeding with commendable caution, the authors prepare readers for the revelation that the cortex, with lesions restricted to Brodmann area 17, can still see: ‘… voluntary ocular fixation responses can be controlled (albeit rather weakly) by visual stimuli placed in regions of blindness … even though the patients deny seeing the stimuli … such an ability (if confirmed) [might] depend on the direct input to the mid-brain from the retina [and] it would be important to examine this … in patients with striate cortex damage but with only minimal damage to the posterior association cortex, as the latter receives a projection … from the superior colliculus’. A birth notice of this case had already been posted in the Lancet in an account led by Michael Sanders, clinical neuro-ophthalmologist to the team, who first noticed the unusual visual experiences of D.B. Michael Sanders recalls now that his interest and skills in cortical visual neurology had been honed whilst working with Bill Hoyt at Johns Hopkins Hospital, so he was alert to the …

This work explores the cerebral structures involved in the appreciation of music. We studied six young healthy subjects (right handed, French, without musical talent), using a high resolution PET device (CTI 953B) and 15O-labelled water. In three tasks, we studied the effects of selective attention to pitch, timbre and rhythm; a final task studied semantic familiarity with tunes (considered as divided attention for pitch and rhythm). These four tasks were performed on the same material (a tape consisting of 30 randomly arranged sequences of notes). We selected a paradigm, without a reference task, to compare the activations produced by attention to different parameters of the same stimulus. We expected that the activations recorded during each task would differ according to the differences in cognitive operations. We found activations preferentially in the left hemisphere for familiarity, pitch tasks and rhythm, and in the right hemisphere for the timbre task. The familiarity task activated the left inferior frontal gyrus, Brodmann area (BA) 47, and superior temporal gyrus (in its anterior part, BA 22). These activations presumably represent lexico-semantic access to melodic representations. In the pitch task, activations were observed in the left cuneus/precuneus (BA 18/19). These results were unexpected and we interpret them as reflecting a visual mental imagery strategy employed to carry out this task. The rhythm task activated left inferior Broca's area (BA 44/6), with extention into the neighbouring insula, suggesting a role for this cerebral region in the processing of sequential sounds.

Prompted by the observation of decreased glucose metabolism in the striate and extrastriate visual cortex in a patient with opsoclonus, we studied the influence of involuntary eye movements on visual cortex activity. Repeated measurements of cerebral blood flow (CBF) by PET were performed in 12 healthy volunteers using H2(15)O-bolus technique after ear canal irrigation with ice cold or warm (44 degrees C) water with the subjects eyes closed. In addition to blood flow increases in areas involved in central vestibular processing, statistical subtraction analysis revealed a nearly symmetrical, bilateral, highly significant decrease in the occipital cortex covering Brodmann areas 17, 18, and 19 after ice water stimulation of either ears. Region of interest analysis revealed in all subjects a mean decrease in regional CBF (rCBF) of 12.8% (range 4.6-21.0%) in these areas. A similar but less pronounced effect (mean rCBF decrease in visual cortex 4.8%, range 1.1-11.5%) was observed after warm water irrigation. The observations suggest that deactivation of the visual cortex is induced by involuntary ocular oscillations. This deactivation is not dependent on changes of the retinal input (eyes closed). The physiological significance of this hitherto unknown phenomenon may be the protection from inadequate visual input (oscillopsia) during involuntary ocular oscillations.

A patient with a rapidly developing fluent progressive aphasia was tested prospectively up to the time of death and examined neuropathologically. Severe impairment in accessing semantic skills with substantially intact phonological, syntactic and discourse skills was found. Some social behavioural difficulties were also noted. This case presented a unique opportunity to relate this significant language impairment to the pattern of neurodegeneration, a difficult task in most neuropathological studies of severe end-stage dementia. A detailed neuropathological examination revealed focal atrophy with neuronal loss without neuronal inclusions (Pick bodies, Lewy bodies, neurofibrillary tangles or senile plaques) or neuronal changes (shrinkage or swelling). In addition, spongiform degeneration (confined to layer two of the cortex) and gliosis were detected at atrophic sites. To establish the amount of tissue loss and pathology associated with the focal language deficit, volume analyses were performed and compared with two age- and sex-matched, neurologically normal controls. Both the left and right angular gyri and Brodmann's area 37 showed marked volume reduction compared with controls. The predominant language impairment seen in this case is likely to reflect these marked changes in the posterior parieto-temporal areas. The milder unilateral atrophy was concentrated in the right temporal lobe as well as the right hemisphere homologue of Broca's area. Recent work suggests a relationship between such unilateral changes and the social behavioural difficulties which were noted in this case. The hippocampus and other gyri such as the supramarginal gyrus showed no volume loss compared with controls correlating with the relative preservation of other language skills.

Summary Mental imagery is an important cognitive method for problem solving, and the mental rotation of complex objects, as originally described by Shepard and Metzler (1971), is among the best studied of mental imagery tasks. Functional MRI was used to observe focal changes in blood flow in the brains of 10 healthy volunteers performing a mental rotation task. On each trial, subjects viewed a pair of perspective drawings of three-dimensional shapes, mentally rotated one into congruence with the other, and then determined whether the two forms were identical or mirror-images. The control task, which we have called the ‘comparison’ condition, was identical except that both members of each pair appeared at the same orientation, and hence the same encoding, comparison and decision processes were used but mental rotation was not required. These tasks were interleaved with a baseline ‘fixation’ condition, in which the subjects viewed a crosshair. Technically adequate studies were obtained in eight of the 10 subjects. Areas of increased signal were identified according to sulcal landmarks and are described in terms of the Brodmann's area (BA) definitions that correspond according to the atlas of Talaraich and Tournoux. When the rotation task was contrasted with the comparison condition, all subjects showed consistent foci of activation in BAs 7a and 7b (sometimes spreading to BA 40); 88% had increased signal in middle frontal gyrus (BA 8) and 75% showed extrastriate activation, including particularly BAs 39 and 19, in a position consistent with area V5/human MT as localized by functional and histological assays. In more than half of the subjects, hand somatosensory cortex (3-1-2) was engaged, and in 50% of subjects there was elevated signal in BA 18. In frontal cortex, activation was above threshold in half the subjects in BAs 9 and/or 46 (dorsolateral prefrontal cortex). Some (four out of eight) subjects also showed signal increases in BAs 44 and/or 46. Premotor cortex (BA 6) was active in half of the subjects during the rotation task. There was little evidence for lateralization of the cortical activity or of engagement of motor cortex. These data are consistent with the hypothesis that mental rotation engages cortical areas involved in tracking moving objects and encoding spatial relations, as well as the more general understanding that mental imagery engages the same, or similar, neural imagery as direct perception.

We tested motion perception and smooth pursuit in 26 patients with unilateral cerebral hemispheric lesions. We used random dot cinematograms to test motion direction discrimination. We measured pursuit gain as they followed a predictable sinusoidal target moving horizontally at three different frequencies, and an unpredictable horizontal step-ramp target in the ipsilateral hemi-field. Six patients had defects in motion perception when the targets were moving towards the side of the lesions ('ipsi-directional' defects) and two had bi-directional defects. Motion perception defects occurred with lesions of the junction of Brodmann areas 19 and 37, a putative human homologue of the monkey V5 complex. Seven patients had ipsi-directional pursuit defects, five of whom had damage to the posterior limb of the internal capsule. Only two patients had ipsi-directional defects of both motion perception and sinusoidal smooth pursuit. Four patients had ipsi-directional defects of motion perception alone, and five patients had ipsi-directional pursuit defects alone. The two patients with bi-directional defects in motion perception had normal sinusoidal smooth pursuit. Patients with lesions at the 19/37 junction and defects of motion perception alone had normal pursuit of unpredictable step-ramp targets in the ipsilateral hemi-field. In contrast, patients with ipsi-directional sinusoidal pursuit defects had decreased ipsi-directional and increased contra-directional velocities with step-ramp targets. No patient group had a motion-specific directional defect in saccadic accuracy. We conclude that neither predictable nor unpredictable pursuit is necessarily impaired by lesions of the 19/37 junction that cause ipsi-directional defects of motion perception. These dissociations between smooth pursuit and motion perception provide evidence that the pursuit system operates as an interconnected network with parallel pathways, rather than as a simple sequential hierarchy of cortical areas.

Poor decision-making is often observed clinically in the manic syndrome. In normal volunteers, decision-making has been associated with activation in the ventral prefrontal cortex and the anterior cingulate gyrus. The aim of this study was to evaluate task-related activation in bipolar manic patients in these regions of the prefrontal cortex using PET. Six subjects with mania, 10 controls and six subjects with unipolar depression (an affective patient control group) were scanned using the bolus H(2)(15)O method while they were performing a decision-making task. Activations associated with the decision-making task were observed at two levels of difficulty. Task-related activation was increased in the manic patients compared with the control patients in the left dorsal anterior cingulate [Brodmann area (BA) 32] but decreased in the right frontal polar region (BA 10). In addition, controls showed greater task-related activation in the inferior frontal gyrus (BA 47) than manic patients. A positive correlation (r(s) = 0.88) between task-related activation in the anterior cingulate and increasing severity of manic symptoms was found. Depressed patients did not show significant task-related differences in activation compared with control subjects in the regions of interest. In conclusion, these patterns of activation point to abnormal task-related responses in specific frontal regions in manic patients. Moreover, they are consistent with neuropsychological observations in patients with lesions in the ventromedial prefrontal cortex, who show similar difficulties with decision-making and provide early evidence for context-specific neural correlates of mania.