Tomographic mapping of human cerebral metabolism: subcortical responses to auditory and visual stimulation

We measured cerebral glucose metabolism with positron computed tomography during audio-visual stimulation in 42 studies of 21 subjects. Metabolic activations and stimulus-induced asymmetries were examined in subcortical structures (thalamus, caudate, lenticular nuclei). Bilateral activations of the thalamus occurred with verbal stimuli. The head of the left caudate was activated when subjects used visual imagery as a strategy to identify sequences of tones. These two types of stimuli produced dominant (left) hemisphere cortical activations in this same group of subjects. Clinical evidence has implicated the participation of subcortical (thalamus and basal ganglia) structures in the processing of language and auditory information. The present results demonstrate this functional role directly in normal subjects.     

Cerebellar Asymmetry and Cortical Connectivity in Monozygotic Twins with Discordant Handedness

Handedness differentiates patterns of neural asymmetry and interhemispheric connectivity in cortical systems that underpin manual and language functions. Contemporary models of cerebellar function incorporate complex motor behaviour and higher-order cognition, expanding upon earlier, traditional associations between the cerebellum and motor control. Structural MRI defined cerebellar volume asymmetries and correlations with corpus callosum (CC) size were compared in 19 pairs of adult female monozygotic twins strongly discordant for handedness (MZHd). Volume and asymmetry of cerebellar lobules were obtained using automated parcellation.CC area and regional widths were obtained from midsagittal planimetric measurements. Within the cerebellum and CC, neurofunctional distinctions were drawn between motor and higher-order cognitive systems. Relationships amongst regional cerebellar asymmetry and cortical connectivity (as indicated by CC widths) were investigated. Interactions between hemisphere and handedness in the anterior cerebellum were due to a larger right-greater-than-left hemispheric asymmetry in right-handed (RH) compared to left-handed (LH) twins. In LH twins only, anterior cerebellar lobule volumes (IV, V) for motor control were associated with CC size, particularly in callosal regions associated with motor cortex connectivity. Superior posterior cerebellar lobule volumes (VI, Crus I, Crus II, VIIb) showed no correlation with CC size in either handedness group. These novel results reflected distinct patterns of cerebellar-cortical relationships delineated by specific CC regions and an anterior-posterior cerebellar topographical mapping. Hence, anterior cerebellar asymmetry may contribute to the greater degree of bilateral cortical organisation of frontal motor function in LH individuals.     

A tale of two recognition systems: implications of the fusiform face area and the visual word form area for lateralized object recognition models

Two areas of current intense interest in the neuroimaging literature are that of the visual word form area (VWFA) and of the fusiform face area (FFA) and their roles in word and face perception, respectively. These two areas are of particular relevance to laterality research because visual word identification and face identification have long been shown to be especially lateralized to the left hemisphere and the right hemisphere, respectively. This review therefore seeks to evaluate their significance for the broader understanding of lateralization of object recognition. A multi-level model of lateralized object recognition is proposed based on a combination of behavioral and neuroimaging findings. Rather than seek to characterize hemispheric asymmetries according to a single principle (e.g., serial-parallel), it is suggested that current observations can be understood in terms of three asymmetric levels of processing, using the framework of the Janus model of hemispheric function. It is suggested that the left hemisphere represents features using an abstract-category code whereas the RH utilizes a specific-exemplar code. The relationships between these features are also coded asymmetrically, with the LH relying on associative co-occurrence values and the RH relying on spatial metrics. Finally, the LH controlled selection system focuses on isolating features and the RH focuses on conjoining features. It is suggested that each hemisphere utilizes efficient (apparently parallel) processing when stimuli are congruent with its preferred processing style and inefficient (apparently serial) processing when they are not, resulting in the typical left-lateralization for orthographic analysis and right-lateralization for face analysis.     

The effect of cognitive load on hemispheric asymmetries in true and false memory

Studies examining hemispheric asymmetries in false memory have shown that the right hemisphere (RH) is more susceptible to false memories compared to the left hemisphere (LH). Theories suggest that hemispheric asymmetries in true and false memory may be due to differences in representational coding and the use of top-down mechanisms in each hemisphere. In the current study, the Deese–Roediger–McDermott false memory paradigmwas used in conjunction with divided visual field presentation to examine the role of top-down mechanisms in hemispheric asymmetries of true and false memory. In Experiment 1, participants studied lists of related words while completing secondary cognitive load tasks. In Experiment 2, the secondary tasks were administered during memory retrieval instead of memory encoding. Results revealed that cognitive loads imposed during the study phase influenced veridical memory in the LH more than the RH, but cognitive loads imposed during retrieval did not influence veridical memory in either hemisphere. Surprisingly, false memory rates were not influenced by cognitive loads and were higher in the LH. These data provide evidence that, at least for veridical memory, top-down control mechanisms are used more readily for the encoding of information into memory in the LH compared to the RH.     

Predicting auditory feedback control of speech production from subregional shape of subcortical structures

Although a growing body of research has focused on the cortical sensorimotor mechanisms that support auditory feedback control of speech production, much less is known about the subcortical contributions to this control process. This study examined whether subregional anatomy of subcortical structures assessed by statistical shape analysis is associated with vocal compensations and cortical event‐related potentials in response to pitch feedback errors. The results revealed significant negative correlations between the magnitudes of vocal compensations and subregional shape of the right thalamus, between the latencies of vocal compensations and subregional shape of the left caudate and pallidum, and between the latencies of cortical N1 responses and subregional shape of the left putamen. These associations indicate that smaller local volumes of the basal ganglia and thalamus are predictive of slower and larger neurobehavioral responses to vocal pitch errors. Furthermore, increased local volumes of the left hippocampus and right amygdala were predictive of larger vocal compensations, suggesting that there is an interplay between the memory‐related subcortical structures and auditory‐vocal integration. These results, for the first time, provide evidence for differential associations of subregional morphology of the basal ganglia, thalamus, hippocampus, and amygdala with neurobehavioral processing of vocal pitch errors, suggesting that subregional shape measures of subcortical structures can predict behavioral outcome of auditory‐vocal integration and associated neural features. Hum Brain Mapp 39:459–471, 2018. © 2017 Wiley Periodicals, Inc.     

FMRI correlates of execution and observation of foot movements in left-handers

While several studies have assessed the brain patterns of cortical activations following executed and observed movements of the dominant and non-dominant lower limbs in right-handed (RH) subjects, the functional correlates of foot movement in left-handed (LH) subjects have not been investigated, yet. We investigated brain function lateralization during action execution and observation with the dominant and non-dominant feet in 8 left-handers (LH). Thirteen right-handers (RH) were also studied while performing the same tasks with their right-foot.Compared to left-foot movement, during right-foot movement, LH had greater activations of the left primary sensorimotor cortex (SMC) and the right cerebellum. Compared to right-foot movement, during left-foot movement, LH subjects activated areas of the sensorimotor network, the mirror-neurons system (MNS) and the visual network lateralized to the contralateral hemisphere. During right-foot movement no between-group difference was found.LH had a pattern of activations lateralized to the right hemisphere during right-foot observation and to the left hemisphere during left-foot observation. Compared to left-foot observation, during right-foot observation, LH had greater activations of frontal and parietal regions and visual areas. The opposite contrast showed higher activation of the right lateral occipito-temporal cortex in LH during left-foot observation. During right-foot observation, compared to RH, LH had greater activations of the bilateral primary SMC and of MNS and visual system regions.In LH, the performance of simple motor acts with the dominant lower limb might be achieved through a complex adaptation and interaction between different neuronal pathways and the daily-life environment.     

Effects of luminance and blur on hemispheric asymmetries in temporal integration

A task involving temporal integration of form was employed to examine the effects of input characteristics on hemispheric asymmetries. In Experiment 1, decreases in luminance produced greater improvement of right hemisphere (RH) performance. In Experiment 2, dioptric blur produced greater impairment of left hemisphere (LH) performance. The results suggest that spatial frequencies below nine cycles per degree are processed more efficiently in the RH. In Experiment 3, effects of input characteristics on hemispheric asymmetry were found to be dependent on the spatial frequencies required for processing by task demands, as mediated by interflash interval (IFI) duration. Increased blur produced greater impairment of LH performance at short IFI duration; at a longer IFI duration, however, increased blur produced equal impairment of RH and LH performance.     

Face processing, laterality and contrast sensitivity

Two separate reaction time studies concerning person recognition were conducted with ex-servicemen who incurred unilateral brain injury during the Second World War. The first experiment investigated the ability to construct a facial representation and involved deciding whether a stimulus represented a face or a "non-face" made by repositioning the facial features into an unnatural configuration. Men with posterior right hemisphere (RH) lesions performed this task more slowly than those with left hemisphere (LH) damage and control subjects; the latter two groups did not differ. The second experiment was designed to tap the most basic level of overt person recognition: awareness of familiarity. When faces were used as stimuli, the RH injured group again showed increased response latencies compared with the other two groups. The reverse pattern, slower reaction times for the men with LH lesions with no difference between RH injured and control subjects, emerged when written names were employed. Spatial contrast sensitivity functions were measured in both studies and although both LH and RH injured men showed impaired contrast sensitivity, no hemispheric difference was apparent. Instead, a double dissociation of impairments of contrast sensitivity and face processing was evident.     

Asymmetry in the cerebral hemispheres of the rat,mouse, rabbit,and cat: The right hemisphere is larger

The right and left cerebral hemispheres of the rat were compared by measuring wet brain weight, surface dimensions, cortical thickness, areas of the neocortex and hippocampus in coronal sections, and cross-sectional widths of various subcortical structures. The hemispheres of cats were compared by measuring dry brain weight and surface dimensions; the hemispheres of rabbits were compared by measuring surface dimensions; and the hemispheres of mice were compared by measuring wet brain weight. The right hemisphere of all four species is larger than the left hemisphere as measured by brain weight or surface dimensions. Detailed measurements of the rat brain revealed that although the neocortex of the right hemisphere is thicker than that of the left hemisphere, there were no significant left/right differences in cross-sectional area of the two hemispheres or of the two hippocampi. There were no reliable differences in the dimensions of the cerebellum, thalamus, hippocampus, or brain stem.     

What forgetting tells us about remembering: The influence of top–down control on hemispheric asymmetries in verbal memory

It has been suggested that left hemisphere (LH) advantages in verbal processing is due to superior top–down control of verbal information. It is not clear how top–down mechanisms affect the encoding and retrieval of verbal information from hemispheric memory and whether they only influence activation or also encompass the inhibition of verbal information. The directed forgetting method, in conjunction with divided visual field presentation, was used to examine the influence of top–down control mechanisms on hemispheric asymmetries in verbal memory. Participants were cued to remember or forget words. Cues were presented either simultaneously with targets or after a short delay. A recognition memory test using divided visual field presentation was then given. Response times (RTs) revealed effects of cue timing in the LH. With simultaneous cues, RTs were faster to “Remember” words compared to “Forget” words. With delayed cues, RTs for “Remember” and “Forget” words were equivalent. In the right hemisphere (RH), “Remember” words were consistently faster than “Forget” words, regardless of cue timing. These data provide evidence that top–down mechanisms influenced LH verbal memory retrieval more than RH verbal memory retrieval. Finally, there was little evidence to suggest the hemispheres differ in inhibitory processing.     

Abnormal hemodynamics in schizophrenia during an auditory oddball task.

BACKGROUND: Schizophrenia is a heterogeneous disorder characterized by diffuse brain abnormalities that affect many facets of cognitive function. One replicated finding in schizophrenia is abnormalities in the neural systems associated with processing salient stimuli in the context of oddball tasks. This deficit in the processing of salience stimuli might be related to abnormalities in orienting, attention, and memory processes. METHODS: Behavioral responses and functional magnetic resonance imaging data were collected while 18 patients with schizophrenia and 18 matched healthy control subjects performed a three-stimulus auditory oddball task. RESULTS: Target detection by healthy participants was associated with significant activation in all 38 regions of interest embracing distributed cortical and subcortical systems. Similar reproducibility was observed in healthy participants for processing novel stimuli. Schizophrenia patients, relative to control subjects, showed diffuse cortical and subcortical hypofunctioning during target detection and novelty processing, including bilateral frontal, temporal, and parietal cortices and amygdala, thalamus, and cerebellum. CONCLUSIONS: These data replicate and extend imaging studies of target detection in schizophrenia and present new insights regarding novelty processing in the disorder. The results are consistent with the hypothesis that schizophrenia is characterized by a widespread pathologic process affecting many cerebral areas, including cortical, subcortical, and cerebellar circuits.     

Evidence of interhemispheric transmission in laterality effects

The study was aimed at testing various models that can explain visual lateral asymmetries due to hemispheric specialization. In Experiments 1-3 the subjects had to perform a lateralized "go-no go" discrimination of words (primary task) either alone or in association with secondary tasks that interfered with the processing of the left hemisphere (ordered tapping) or the right hemisphere (finger flexion). In Experiment 4 the primary task was one of lateralized "go-no go" discrimination of faces while the secondary tasks were again those of ordered tapping and finger flexion. The results showed that in the case of word discrimination the advantage in speed of response in favour of the right visual field/left hemisphere (RVF/LH), which was observed for the primary task alone, did not change when the secondary task was added. This held true irrespective of whether the secondary task loaded the left or right hemisphere. The advantage for the left visual field/right hemisphere (LVF/RH) observed for face discrimination alone, disappeared when the secondary task interfered with the processing of the right hemisphere and did not change when the secondary task concerned the left hemisphere. It was concluded that each hemisphere is able to elaborate in parallel the incoming information, but, in normal conditions, interhemispheric transmission is responsible for the lateral asymmetries in perception (conditional interhemispheric transmission model).     

"Pusher syndrome" following cortical lesions that spare the thalamus

Stroke patients with "pusher syndrome" show severe misperception of their own upright body orientation although visualvestibular processing is almost intact. This dissociation argues for a second graviceptive system in humans for the perception of body orientation. Recent studies revealed that the posterior thalamus is an important part of this system. The present investigation aimed to study the cortical representation of this system beyond the thalamus. We evaluated 45 acute patients with and without contraversive pushing following left–or right–sided cortical lesions sparing the thalamus. In both hemispheres, the simple lesion overlap associated with contraversive pushing typically centered on the insular cortex and parts of the postcentral gyrus. The comparison between pusher patients and controls who were matched with respect to age, lesion size, and the frequency of spatial neglect, aphasia and visual field defects revealed only very small regions that were specific for the pusher patients with cortical damage sparing the thalamus. Obviously, the cortical structures representing our control of upright body orientation are in close anatomical proximity to those areas that induce aphasia in the left hemisphere and spatial neglect in the right hemisphere when lesioned. We conclude that in addition to the subcortical area previously identified in the posterior thalamus, parts of the insula and postcentral gyrus appear to contribute at cortical level to the processing of the afferent signals mediating the graviceptive information about upright body orientation.     

Changes of blood flow in the cerebral cortex after subcortical ischemic infarction

The two-dimensional xenon-133 inhalation method was used to measure cortical blood flow in 16 patients with small subcortical ischemic infarcts and in 10 patients with larger cortical infarcts in the chronic phase of stroke. An abnormal hemispheric asymmetry of blood flow was seen, not only in patients with cortical infarcts, but also in those with subcortical infarcts. In the patients with subcortical infarcts, focal areas of reduced cortical blood flow were seen in the symptomatic hemisphere remote from the tissue destruction, usually including part of the noninfarcted frontoparietal cortex. The cortical dysfunction may have contributed to the clinical manifestations including aphasia, which was present in 14 of the 16 patients with subcortical lesions.     

The memory that's right and the memory that's left: event-related potentials reveal hemispheric asymmetries in the encoding and retention of verbal information

We examined the nature and timecourse of hemispheric asymmetries in verbal memory by recording event-related potentials (ERPs) in a continuous recognition task. Participants made overt recognition judgments to test words presented in central vision that were either novel (new words) or had been previously presented in the left or right visual field (old words). An ERP memory effect linked to explicit retrieval revealed no asymmetries for words repeated at short and medium retention intervals, but at longer repetition lags (20-50 intervening words) this 'old/new effect' was more pronounced for words whose study presentation had been biased to the right hemisphere (RH). Additionally, a repetition effect linked to more implicit recognition processes (P2 amplitude changes) was observed at all lags for words preferentially encoded by the RH but was not observed for left hemisphere (LH)-encoded words. These results are consistent with theories that the RH encodes verbal stimuli more veridically whereas the LH encodes in a more abstract manner. The current findings provide a critical link between prior work on memory asymmetries, which has emphasized general LH advantages for verbal material, and on language comprehension, which has pointed to an important role for the RH in language processes that require the retention and integration of verbal information over long time spans.     

Increased reliance on a right hemispheric mechanism during idiom processing in adults with dyslexia

Previous studies on adults with dyslexia (DYS) have indicated difficulties in the comprehension of figurative language. Using the divided visual field paradigm, the present study investigated the hemispheric processing of idioms among 22 adults with DYS and 21 regular reader (RR) adults. Participants performed a lexical decision task for a target word related to either a literal or a figurative interpretation of an idiom. The results show that whereas the RR group demonstrated a bilateral pattern of hemispheric processing of idiomatic meanings, the DYS group showed a right hemisphere (RH) advantage. Furthermore, both groups demonstrated the typical RH advantage in processing the literal meanings of idioms. Our findings indicate increased recruitment of the RH in dyslexia, probably due to differences in cerebral language areas or weaker LH semantic processing.     

The human cerebro-cerebellar system: its computing, cognitive, and language skills.

In this review of the human cerebro-cerebellar system, the focus is on the possible contributions of the cerebellum to cognitive and language functions. The role of the cerebellum in these human functions has tended to be obscured by the traditional preoccupation with the motor functions of the cerebellum, which have been widely observed in other vertebrates as well. In the human brain, some phylogenetically new parts evolved and enlarged in the cerebellum, concomitantly with the enlargement of association areas in the cerebral cortex. Anatomical evidence and behavioral evidence combine to suggest that this enlarged cerebellum contributes not only to motor function but also to some sensory, cognitive, linguistic, and emotional aspects of behavior. The anatomical evidence derives from the modularity of the cerebellum, whose cortical nerve cells are organized into longitudinal micro-modules, which are arrayed perpendicular to the cortical surface and parallel to each other. The number of these micro-modules increased when the cerebellum enlarged, which enlarged the computing capabilities of the network. (From principles underlying the processing of information, it is known that when modules with modest processing capabilities are assembled in large numbers in parallel, the resulting network can achieve remarkably powerful computing capabilities.) Such cerebellar computing capabilities can be utilized in the different areas of the cerebral cortex to which the cerebellum sends signals. The cerebellar output connections convey signals through the thalamus to the cerebral cortex in segregated channels of communication, which preserve the modularity of the cerebellum. Through these channels, modules in the lateral cerebellum can send signals to new cognitive and language areas of the cerebral cortex, such as Broca's area in the prefrontal cortex. The anatomy of the human cerebro-cerebellar system therefore suggests that the cerebellum can contribute to the learning not only of motor skills but also of some cognitive and language skills. Supporting this anatomical evidence is the mounting behavioral evidence, obtained both in normal brains and in clinical studies, which indicates that the lateral cerebellum is indeed involved in some cognitive and language functions.     

Cerebral cortex: an MRI-based study of volume and variance with age and sex.

The aim of the present study was to examine quantitative differences in lobar cerebral cortical volumes in a healthy adult population. Quantitative volumetric MRI of whole brain, cerebral and cerebellar volumes was performed in a cross-sectional analysis of 97 normal volunteers, with segmented frontal, temporal, parietal and occipital cortical volumes measured in a subgroup of 60 subjects, 30 male and 30 female, matched for age and sex. The right cerebral hemisphere was larger than the left across the study group with a small (<1%) but significant difference in symmetry (P<0.001). No difference was found between volumes of right and left cerebellar hemispheres. Rightward cerebral cortical asymmetry (right larger than left) was found to be significant across all lobes except parietal. Males had greater cerebral, cerebellar and cerebral cortical lobar volumes than females. Larger male cerebral cortical volumes were seen in all lobes except for left parietal. Females had greater left parietal to left cerebral hemisphere and smaller left temporal to left cerebral hemisphere ratios. There was a mild reduction in cerebral volumes with age, more marked in males. This study confirms and augments past work indicating underlying structural asymmetries in the human brain, and provides further evidence that brain structures in humans are differentially sensitive to the effects of both age and sex.     

Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems

Disconnection syndromes were originally conceptualized as a disruption of communication between different cerebral cortical areas. Two developments mandate a re-evaluation of this notion. First, we present a synopsis of our anatomical studies in monkey elucidating principles of organization of cerebral cortex. Efferent fibers emanate from every cortical area, and are directed with topographic precision via association fibers to ipsilateral cortical areas, commissural fibers to contralateral cerebral regions, striatal fibers to basal ganglia, and projection subcortical bundles to thalamus, brainstem and/or pontocerebellar system. We note that cortical areas can be defined by their patterns of subcortical and cortical connections. Second, we consider motor, cognitive and neuropsychiatric disorders in patients with lesions restricted to basal ganglia, thalamus, or cerebellum, and recognize that these lesions mimic deficits resulting from cortical lesions, with qualitative differences between the manifestations of lesions in functionally related areas of cortical and subcortical nodes. We consider these findings on the basis of anatomical observations from tract tracing studies in monkey, viewing them as disconnection syndromes reflecting loss of the contribution of subcortical nodes to the distributed neural circuits. We introduce a new theoretical framework for the distributed neural circuits, based on general, and specific, principles of anatomical organization, and on the architecture of the nodes that comprise these systems. We propose that neural architecture determines function, i.e., each architectonically distinct cortical and subcortical area contributes a unique transform, or computation, to information processing; anatomically precise and segregated connections between nodes define behavior; and association fiber tracts that link cerebral cortical areas with each other enable the cross-modal integration required for evolved complex behaviors. This model enables the formulation and testing of future hypotheses in investigations using evolving magnetic resonance imaging techniques in humans, and in clinical studies in patients with cortical and subcortical lesions.