Human Lesion Studies Research Articles

Time to get rid of the ‘Modular’ in neuropsychology: A unified theory of anosognosia as aberrant predictive coding

Cognitive neuroscience, being more inclusive and ambitious in scope than cognitive neuropsychology, seems to have taken the place of the latter within the modern neurosciences. Nevertheless, recent advances in the neurosciences afford neuropsychology with epistemic possibilities that simply did not exist even 15 years ago. Human lesion studies still have an important role to play in shaping such possibilities, particularly when combined with other methods of enquiry. I first outline theoretical and methodological advances within the neurosciences that can inform and shape the rebirth of a dynamic, non-modular neuropsychology. I then use an influential computational theory of brain function, the free energy principle, to suggest an unified account of anosognosia for hemiplegia as a research example of the potential for transition from a modular, cognitive neuropsychology to a dynamic, computational and even restorative neuropsychology. These and many other adjectives that can flexibly, take the place of 'cognitive' next to 'neuropsychology' will hopefully designate the much needed rebirth and demarcation of a field, neuropsychology itself, that has somehow lost its place within the modern neurosciences and yet seems to have a unique and important role to play in the future understanding of the brain.

The parietal cortex and saccade planning: lessons from human lesion studies.

The parietal cortex is a critical interface for attention and integration of multiple sensory signals that can be used for the implementation of motor plans. Many neurons in this region exhibit strong attention-, reach-, grasp- or saccade-related activity. Here, we review human lesion studies supporting the critical role of the parietal cortex in saccade planning. Studies of patients with unilateral parietal damage and spatial neglect reveal characteristic spatially lateralized deficits of saccade programming when multiple stimuli compete for attention. However, these patients also show bilateral impairments of saccade initiation and control that are difficult to explain in the context of their lateralized deficits of visual attention. These findings are reminiscent of the deficits of oculomotor control observed in patients with Bálint's syndrome consecutive to bilateral parietal damage. We propose that some oculomotor deficits following parietal damage are compatible with a decisive role of the parietal cortex in saccade planning under conditions of sensory competition, while other deficits reflect disinhibition of low-level structures of the oculomotor network in the absence of top-down parietal modulation.

Functional topography of human corpus callosum: an FMRI mapping study.

The concept of a topographical map of the corpus callosum (CC) has emerged from human lesion studies and from electrophysiological and anatomical tracing investigations in other mammals. Over the last few years a rising number of researchers have been reporting functional magnetic resonance imaging (fMRI) activation in white matter, particularly the CC. In this study the scope for describing CC topography with fMRI was explored by evoking activation through simple sensory stimulation and motor tasks. We reviewed our published and unpublished fMRI and diffusion tensor imaging data on the cortical representation of tactile, gustatory, auditory, and visual sensitivity and of motor activation, obtained in 36 normal volunteers and in 6 patients with partial callosotomy. Activation foci were consistently detected in discrete CC regions: anterior (taste stimuli), central (motor tasks), central and posterior (tactile stimuli), and splenium (auditory and visual stimuli). Reconstruction of callosal fibers connecting activated primary gustatory, motor, somatosensory, auditory, and visual cortices by diffusion tensor tracking showed bundles crossing, respectively, through the genu, anterior and posterior body, and splenium, at sites harboring fMRI foci. These data confirm that the CC commissure has a topographical organization and demonstrate that its functional topography can be explored with fMRI.

Empathic Deficits in Combat Veterans with Traumatic Brain Injury

To understand better which brain regions support emotional empathy. Emotional empathy, the ability to interpret and share the affective states of others, is a key component in human social interaction. Previous research has suggested that emotional empathy relies on several distinct brain regions, although further evidence from human lesion studies is needed to determine which regions are critical. We studied 192 male Vietnam combat veterans who had sustained focal penetrating traumatic brain injuries, and 54 non-brain-injured veterans. We used voxel-based lesion-symptom mapping on computed tomographic scans to elucidate the neural bases of self-reported emotional empathy as measured by the Balanced Emotional Empathy Scale. Damage in several brain regions, particularly the ventrolateral prefrontal cortex, left and right posterior temporal lobes, and insula, was associated with diminished emotional empathy. These findings provide further insight into the neural substrates of emotional empathy, and are consistent with the notion that emotional empathy is supported by a distributed network of brain regions. Additional work may advance our understanding of the empathic deficits commonly observed in patients with neurologic and psychiatric disorders.

Can cerebellar transcranial direct current stimulation become a valuable neurorehabilitation intervention?

Can cerebellar transcranial direct current stimulation become a valuable neurorehabilitation intervention?

Direct visualization of cerebellar nuclei in patients with focal cerebellar lesions and its application for lesion-symptom mapping

As yet, human cerebellar lesion studies have not taken advantage of direct magnetic resonance imaging (MRI) of the cerebellar nuclei in individual patients. In the present study, susceptibility weighted imaging (SWI) was used to visualize lesions of the dentate nuclei in patients with chronic focal lesions. Fifteen patients with cerebellar lesions either due to stroke or tumor surgery underwent SWI imaging using a 1.5T MRI scanner. Dentate nuclei were seen as hypointensities in all patients. Three of the patients underwent additional SWI imaging at 3T and 7T. Compared to 1.5T, corrugation of the dentate wall was seen with greater precision and the dorsal, iron-poorer part was seen more fully. Lesion-symptom mapping was performed based on the 1.5T MR images. Patients were divided into two groups with and without upper limb ataxia. A region-of-interest-(ROI)-driven normalization technique was used which had initially been developed by Diedrichsen et al. (2011) for functional MRI (fMRI) of the dentate nuclei. Compared to conventional normalization of the cerebellum, overlap of dentate lesions improved and lead to increased sensitivity of lesion-symptom maps. Subtraction analysis revealed that the more dorsal and rostral parts of the dentate nuclei were related to upper limb ataxia. Findings were in good accordance with the dentate hand area shown in recent fMRI studies. These data provide evidence that direct identification of dentate lesions together with the ROI-driven normalization technique allows for improved lesion-symptom mapping at the level of the cerebellar nuclei already at conventional 1.5T MRI field strength.

Induction of visual dream reports after transcranial direct current stimulation (tDCs) during Stage 2 sleep

REM sleep is a unique brain state characterized by frontal deactivation alongside activation of the posterior association and limbic cortices. Human brain lesion studies have found that the loss of dreaming is characterized by damage to the frontal and posterior parieto-temporo-occipital association cortex. Therefore, it is reasonable to assume that the function of these brain regions might encapsulate the neural processes of dreaming. The aim of the following two experiments was to investigate the effect of transcranial direct current stimulation (tDCs), applied simultaneously to the frontal and right posterior parietal cortex during Stage 2 sleep, on dreaming. In Experiment 1, 17 healthy participants received tDCs (cathodal-frontal, anodal-parietal) and low-intensity tDCs as well as no tDCs (blank control) during Stage 2 sleep in a counterbalanced order across the night. Dream reports were collected upon awakening after each of the three conditions. In Experiment 2, 10 participants received tDCs (cathodal-frontal, anodal-parietal), no tDCs (blank control) and two additional control conditions (reversed polarity and other-cephalic tDCs). In both experiments a significantly greater number of imagery reports were found on awakening after tDCs (cathodal-frontal, anodal-parietal), compared to the blank control conditions. However, in Experiment 2 the frequency of imagery reports from the tDCs (cathodal-frontal, anodal-parietal) was not significantly different from the other two tDC conditions, suggesting a non-specific effect of tDCs. Overall, it was concluded that tDCs (cathodal-frontal, anodal-parietal) increased the frequency of dream reports with visual imagery, possibly via a general arousing effect and/or recreating specific cortical neural activity involved in dreaming.

Kognitive Funktionen des Kleinhirns

The role of the cerebellum in motor control and motor learning is well-recognised. Patients with cerebellar disease consult a doctor because of their motor dysfunction (ataxia). For nearly three decades intense research has been addressing the question to what extent the cerebellum may support cognitive functions. Neuroanatomic findings support the notion that posterolateral parts of the cerebellum contribute to cognition. Although there is a huge number of neuropsychological studies in patients with cerebellar disease, interpretation of findings is frequently hampered by the accompanying motor disorders and extracerebellar lesions. This review summarises the anatomic findings and attempts to give a critical evaluation of findings in human lesion studies. There are good reasons to believe that cerebellar disorders, both cerebellar degeneration and focal cerebellar lesions, may lead to certain cognitive dysfunctions. Disorders in executive function, in particular working memory, and certain higher language tasks are best documented. However, disorders in adults with chronic diseases tend to be mild. Dysfunction appears to be more prominent in patients with acute disease.

道德判断的认知机制：研究现状与展望<br>The Neural Mechanism of Moral Judgment: Research Status and Future Directions

道德判断是个体判定他人或自己行为正当与否的认识活动，是人们进行道德选择和道德评价的一个关键环节。道德判断中的情绪直觉与认知推理及其作用机制一直存在争议。近年来主要围绕社会直觉论与双过程加工论，对正常人和脑损伤个体进行了关于道德两难问题的系列脑机制研究。未来研究应借助标准化的情境材料，在整合道德能力评估范式、提高生态效度并控制文化效应的基础上更加细致地探讨道德判断的神经机制。 Moral judgment, which was the key link of moral choice and evaluation, referred to individual’s cognitive activity about judging others’ or himself/herself’s behavior proper or not. However, there’s an argu- ment about the affective intuition, deliberate reasoning, as well as their neural mechanisms in moral judgment. Thus, a series of human brain lesion and imaging studies on moral dilemma had been discussed focusing on the Social Intuition theory and the Dual-process theory in recent years. Future studies on the neural me- chanism of the moral judgment should concern of the following factors: using standardized situational ma- terials, integrating different experiment paradigms, improving the ecological validity and controlling the cul- tural effect.

Impaired Representation of Geometric Relationships in Humans with Damage to the Hippocampal Formation

The pivotal role of the hippocampus for spatial memory is well-established. However, while neurophysiological and imaging studies suggest a specialization of the hippocampus for viewpoint-independent or allocentric memory, results from human lesion studies have been less conclusive. It is currently unclear whether disproportionate impairment in allocentric memory tasks reflects impairment of cognitive functions that are not sufficiently supported by regions outside the medial temporal lobe or whether the deficits observed in some studies are due to experimental factors. Here, we have investigated whether hippocampal contributions to spatial memory depend on the spatial references that are available in a certain behavioral context. Patients with medial temporal lobe lesions affecting systematically the right hippocampal formation performed a series of three oculomotor tasks that required memory of a spatial cue either in retinal coordinates or relative to a single environmental reference across a delay of 5000 ms. Stimulus displays varied the availability of spatial references and contained no complex visuo-spatial associations. Patients showed a selective impairment in a condition that critically depended on memory of the geometric relationship between spatial cue and environmental reference. We infer that regions of the medial temporal lobe, most likely the hippocampal formation, contribute to behavior in conditions that exceed the potential of viewpoint-dependent or egocentric representations. Apparently, this already applies to short-term memory of simple geometric relationships and does not necessarily depend on task difficulty or integration of landmarks into more complex representations. Deficient memory of basic geometric relationships may represent a core deficit that contributes to impaired performance in allocentric spatial memory tasks.

Functional neuroimaging studies of prospective memory: What have we learnt so far?

The complexity of the behaviour described by the term “prospective memory” meant that it was not at all clear, when the earliest studies were conducted, that this would prove a fruitful area for neuroimaging study. However, a consistent relation rapidly emerged between activation in rostral prefrontal cortex (approximating Brodmann Area 10) and performance of prospective memory paradigms. This consistency has greatly increased the accumulation of findings, since each study has offered perspectives on the previous ones. Considerable help too has come from broad agreement between functional neuroimaging findings and those from other methods (e.g. human lesion studies, electrophysiology). The result has been a quite startling degree of advance given the relatively few studies that have been conducted. These findings are summarised, along with those from other brain regions, and new directions suggested. Key points are that there is a medial–lateral dissociation within rostral PFC. Some (but not all) regions of medial rostral PFC are typically more active during performance of the ongoing task only, and lateral aspects are relatively more active during conditions involving delayed intentions. Some of these rostral PFC activations seem remarkably insensitive to the form of stimulus material presented, the nature of the ongoing task, the specifics of the intention, how easy or hard the PM cue is to detect, or the intended action is to recall. However there are other regions within rostral PFC where haemodynamic changes vary with alterations in these, and other, aspects of prospective memory paradigms. It is concluded that rostral PFC most likely plays a super-ordinate role during many stages of creating, maintaining and enacting delayed intentions, which in some cases may be linked to recent evidence showing that this brain region is involved in the control of stimulus-oriented vs. stimulus-independent attending. Other key brain regions activated during prospective memory paradigms appear to be the parietal lobe, especially Brodmann Area (BA) 40 and precuneus (BA 7), and the anterior cingulate (BA 32). These regions are often co-activated with lateral rostral PFC across a wide range of tasks, not just those involving prospective memory.

Topographical organization of human corpus callosum: An fMRI mapping study

The concept of a topographical map of the corpus callosum (CC) has emerged from human lesion studies and from anatomical tracing investigations in other mammals. Over the last few years, a rising number of researchers have been reporting functional magnetic resonance imaging (fMRI) activation in white matter, particularly the CC. In this study, the scope for describing CC topography with fMRI was explored by evoking activation through simple sensory stimulation and motor tasks. We reviewed our published and unpublished fMRI data on the cortical representation of tactile, gustatory, and visual sensitivity and of motor activation, obtained in 36 volunteers. Activation foci were consistently detected in discrete CC regions: anterior (taste stimuli), central (motor tasks), central and posterior (tactile stimuli), and splenium (visual stimuli). These findings demonstrate that the functional topography of the CC can be explored with fMRI.

A unified framework for the functional organization of the medial temporal lobes and the phenomenology of episodic memory

There is currently an intense debate about the nature of recognition memory and about the roles of medial temporal lobe subregions in recognition memory processes. At a larger level, this debate has been about whether it is appropriate to propose unified theories to explain memory at neural, functional, and phenomenological levels of analysis. Here, I review findings from physiology, functional imaging, and lesion studies in humans, monkeys, and rodents relevant to the roles of medial temporal lobe subregions in recognition memory, as well as in short-term memory and perception. The results from these studies are consistent with the idea that there is functional heterogeneity in the medial temporal lobes, although the differences among medial temporal lobe subregions do not precisely correspond to different types of memory tasks, cognitive processes, or states of awareness. Instead, the evidence is consistent with the idea that medial temporal lobe subregions differ in terms of the kind of information they process and represent, and that these regions collectively support episodic memory by binding item and context information.

007 Mild cognitive impairment

: Mild cognitive impairment (MCI) is a syndromic label for people with informant-corroborated memory problems and evidence of memory impairment on formal testing in the absence of more pervasive deficits...

Structural and Functional Magnetic Resonance Imaging of the Human Cerebellar Nuclei

The present review focuses on recent developments in structural and functional magnetic resonance imaging (MRI) of the deep cerebellar nuclei (DCN), the main output structure of the cerebellum. The high iron content in the DCN allows for their visibility in T2*-weighted images. Spatial resolution has improved allowing the identification of DCN in individual cerebellar patients and healthy subjects. Based on findings in larger groups of healthy subjects, probabilistic MRI-based atlases of the deep cerebellar nuclei have been developed, which are important tools in human lesion and functional imaging studies. High iron content in the DCN, on the other hand, decreases the blood oxygenation level dependent-signal making functional imaging a difficult challenge. Compared to the vast amount of studies reporting activation of the cerebellar cortex, the number of studies demonstrating activation of the DCN is much less. Most studies report activation of the dentate nucleus. Dentate activations appear to be more reliable in more complex tasks for reasons currently unknown. As yet, few studies tried to show activations of functional subunits of the dentate nucleus. Increased signal-to-noise ratio and better spatial resolution using higher MR field strength together with recent progress in dentate normalization methods will allow identification of functional subunits and their interactions with the cerebellar cortex in future studies.

Human Medial Temporal Lobe Damage Can Disrupt the Perception of Single Objects

The idea that the medial temporal lobe (MTL), traditionally viewed as an exclusive memory system, may also subserve higher-order perception has been debated fiercely. To support this suggestion, monkey and human lesion studies have demonstrated that perirhinal cortex damage impairs complex object discrimination. The interpretation of these findings has, however, been disputed because these impairments may reflect a primary deficit in MTL-mediated working memory processes or, in the case of human patients, undetected damage to visual processing regions beyond the MTL. To address these issues, this study investigated object perception in two human amnesic patients who were chosen on the basis of their lesion locations and suitability for detailed neuroimaging investigation. A neuropsychological task with minimal working memory demands was administered in which participants assessed the structural coherency of single novel objects. Critically, only the patient with perirhinal atrophy was impaired. Moreover, volumetric and functional neuroimaging data demonstrated that this deficit cannot be attributed to the dysfunction of visual cortical areas. Additional analyses of eye-movement patterns during the perceptual task revealed an inability of this patient to detect structural incoherency consistently. This study uses a combination of techniques to provide strong evidence that the perirhinal cortex subserves perception and suggests that the MTL perceptual-mnemonic debate cannot be dismissed on the basis of anatomy or a working memory impairment.

Organisation topographique du corps calleux chez l’homme. Étude cartographique en imagerie par résonance magnétique fonctionnelle (f-IRM)

The concept of a topographical map of the corpus callosum (CC) has emerged from lesion studies in humans and from anatomical tracing investigations in other mammals. We conducted the first in vivo study aimed at outlining the topographical organization of the normal human CC, using non-invasive functional magnetic resonance imaging (fMRI). We tested cortical and callosal activation by the BOLD effect during simple sensory stimulation (tactile, gustatory and visual) and simple motor tasks in 38 volunteers. The axonal organization of callosal white matter was also studied in 16/38 subjects, using diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT). Activation foci evoked by taste stimuli were detected in most subjects in the anterior part of the CC, those elicited by motor tasks lay in the central portion of the body of the CC, and those elicited by tactile stimulation of different body regions lay in the posterior part of the body. Activation foci evoked by visual stimulation were seen in the splenium of the CC. Callosal fibers interconnecting the primary cortical areas activated by taste stimulation, motor tasks, and tactile and visual stimuli were shown by DTT. Anatomical correlates of the BOLD activation foci were demonstrated in the CC, with fibers crossing it at the level of the genu, anterior and posterior body, and splenium, respectively. This study demonstrates for the first time that the functional topographical organization of the human CC can be explored by fMRI in vivo. Our findings may have clinical implications, especially for neurosurgical planning.

Combining Lesion and Functional Imaging Approaches to Explore Prefrontal Functions

Event Abstract Back to Event Combining Lesion and Functional Imaging Approaches to Explore Prefrontal Functions Emmanuelle Volle1* 1 Institute of Cognitive Neuroscience , United Kingdom Understanding the functional organization of the prefrontal cortex and the specific roles of its distinct subregions (e.g., dorsolateral or rostral areas) is an essential issue in cognitive neuroscience. Functional neuroimaging has provided a large amount of data and influential theories regarding these questions. In order to draw stronger inferences, human lesion studies, which indicate the critical regions within the activated networks, are crucial to complement activation approaches. Recently, the development of voxel-based lesion-deficit mapping techniques allows better integration of lesion studies with functional imaging ones, and can also provide data that functional imaging cannot. Accordingly, we have developed a voxel-based lesion method, called Anatomo-Clinical Overlapping Maps (AnaCOM), specifically to assess frontal functions. We have performed several studies using this new method (AnaCOM), to explore the functional organization and the role of specific areas of the prefrontal cortex in human behavioral adaptation. In a first study [1], functional and lesion methods were combined, using the same working memory tasks across both. AnaCOM identified different critical sub-regions for distinct aspects of working memory within the networks activated during neuroimaging. These converging data argue in favor of a hybrid model of organization of the prefrontal cortex in which domain-oriented and cross-domain executive-dependent regions co-exist, reconciling previously divergent data. In addition, voxel-based lesion mapping methods may be especially useful to understand the crucial role of the rostral prefrontal cortex, which is activated by a wide range of tasks, even simple ones, in functional imaging. In further studies using specific cognitive tests, AnaCOM allowed us to determine distinct and critical aspects of behavioral adaptation for which an intact rostral prefrontal region is necessary [2]. In addition to the advance in cognitive neuroscience knowledge, voxel-based lesion mapping techniques provide more precise information to neurologists and neurosurgeons about the expected cognitive consequences following particular prefrontal lesions or their removal.

How Consistent are Cognitive Impairments in Patients with Cerebellar Disorders?

Many human lesion und functional brain imaging studies suggest involvement of the cerebellum in cognitive functions. However, negative and inconsistent findings are rarely discussed. It is still an open question as to which areas of cognition the cerebellum contributes, as well as how, and to what extent. Frequently cited earlier findings in one area of cognition have been challenged in more recent studies, that is the cerebellum may not be directly involved in attention. Furthermore, disorders in patients with acquired cerebellar disease are frequently mild and less severe compared to lesions of the corresponding areas of the cerebral cortex. Patients with cerebellar disease often perform within the normal range of neuropsychological test norms. This pattern is illustrated based on general intelligence and verbal working memory, which have been assessed by a large number of authors using comparable tests. Findings, however, appear to be more pronounced in individual cases with acute onset cerebellar disorders and in children, in particular with congenital disease. The review suggests that the inconsistencies in cognitive impairments may offer clues as to the nature of cerebellar cognitive involvement.

How consistent are cognitive impairments in patients with cerebellar disorders?

Many human lesion und functional brain imaging studies suggest involvement of the cerebellum in cognitive functions. However, negative and inconsistent findings are rarely discussed. It is still an open question as to which areas of cognition the cerebellum contributes, as well as how, and to what extent. Frequently cited earlier findings in one area of cognition have been challenged in more recent studies, that is the cerebellum may not be directly involved in attention. Furthermore, disorders in patients with acquired cerebellar disease are frequently mild and less severe compared to lesions of the corresponding areas of the cerebral cortex. Patients with cerebellar disease often perform within the normal range of neuropsychological test norms. This pattern is illustrated based on general intelligence and verbal working memory, which have been assessed by a large number of authors using comparable tests. Findings, however, appear to be more pronounced in individual cases with acute onset cerebellar disorders and in children, in particular with congenital disease. The review suggests that the inconsistencies in cognitive impairments may offer clues as to the nature of cerebellar cognitive involvement.