Studies Of Brain-damaged Patients Research Articles

Individual EEG profiling of attention deficits in left spatial neglect: A pilot study

Electrophysiological group studies in brain-damaged patients can be run to capture the EEG correlates of specific cognitive impairments. Nonetheless, this procedure is not adequate to characterize the inter-individual variability present in major neuropsychological syndromes. We tested the possibility of getting a reliable individual EEG characterization of deficits of endogenous orienting of spatial attention in right-brain damaged (RBD) patients with left spatial neglect (N+). We used a single-trial topographical analysis (STTA; [39] of individual scalp EEG topographies recorded during leftward and rightward orienting of attention with central cues in RBD patients with and without (N−) neglect and in healthy controls (HC). We found that the STTA successfully decoded EEG signals related to leftward and rightward orienting in five out of the six N+, five out of the six N− patients and in all the six HC. In agreement with findings from conventional average-group studies, successful classifications of EEG signals in N+ were observed during the 400–800 ms period post-cue-onset, which reflects preserved voluntary engagement of attention resources (ADAN component). These results suggest the possibility of acquiring reliable individual EEG profiles of neglect patients.

Case of Asperger's Syndrome and Lesion of the Right Amygdala: Deficits in Implicit and Explicit Fearful Face Recognition.

Introduction: Studies of brain-damaged patients revealed that amygdala lesions cause deficits in the processing and recognition of emotional faces. Patients with autism spectrum disorders (ASD) have similar deficits also related to dysfunctions of the limbic system including the amygdala.Methods: We investigated a male patient who had been diagnosed with Asperger's syndrome. He also presented with a lesion of the right mesial temporal cortex, including the amygdala. We used functional magnetic resonance imaging (fMRI) to investigate neuronal processing during a passive viewing task of implicit and explicit emotional faces. Clinical assessment included a facial emotion recognition task.Results: There was no amygdala activation on both sides during the presentation of masked emotional faces compared to the no-face control condition. Presentation of unmasked happy and angry faces activated the left amygdala compared to the no-face control condition. There was no amygdala activation in response to unmasked fearful faces on both sides. In the facial emotion recognition task, the patient biased positive and neutral expressions as negative.Conclusions: This case report describes a male patient with right amygdala damage and an ASD. He displayed a non-response of the amygdala to fearful faces and tended to misinterpret fearful expressions. Moreover, a non-reactivity of both amygdalae to emotional facial expressions at an implicit processing level was revealed. It is discussed whether the deficient implicit processing of facial emotional information and abnormalities in fear processing could contribute and aggravate the patient's impairments in social behavior and interaction.

Musical and verbal short-term memory: insights from neurodevelopmental and neurological disorders.

Auditory short-term memory (STM) is a fundamental ability to make sense of auditory information as it unfolds over time. Whether separate STM systems exist for different types of auditory information (music and speech, in particular) is a matter of debate. The present paper reviews studies that have investigated both musical and verbal STM in healthy individuals and in participants with neurodevelopmental and neurological disorders. Overall, the results are in favor of only partly shared networks for musical and verbal STM. Evidence for a distinction in STM for the two materials stems from (1) behavioral studies in healthy participants, in particular from the comparison between nonmusicians and musicians; (2) behavioral studies in congenital amusia, where a selective pitch STM deficit is observed; and (3) studies in brain-damaged patients with cases of double dissociation. In this review we highlight the need for future studies comparing STM for the same perceptual dimension (e.g., pitch) in different materials (e.g., music and speech), as well as for studies aiming at a more insightful characterization of shared and distinct mechanisms for speech and music in the different components of STM, namely encoding, retention, and retrieval.

The cognitive and neural bases of human tool use.

The cognitive and neural bases of human tool use.

P184: Activity and functional connectivity of the premotor-parietal network modulate intrinsic power changes of mu rhythms: an EEG-fMRI study

P185 – Figure 1. A. Brain regions more activated when using tools compared to neutral objects (bars) in fMRI study with healthy controls. B. Statistical map of the voxels associated with tool use scoring in LBD patients in lesion analyse study using VLSM. acquired brain activity from fifteen healthy participants (age range 21-35), by combining 32-channel MRI-compatible EEG and Siemens 3T-MRI systems. During data acquisition, the participants were awake and not engaged in any tasks with their eyes closed. BOLD-based fMRI signals and surface EEG data were recorded simultaneously for 20 min. Power of mu rhythms was calculated from EEG data at C3 and C4 electrodes within a 3-second time bin, corresponding to a single scan of MRI data (400 data points in total). Using SPM software, voxel-based general linear model analyses were performed in the whole brain to find regions correlated with spontaneous fluctuations of mu rhythm power physically at rest. We found that greater BOLD activities in the IPL and PMv were linked with suppression of mu rhythm power. Furthermore, we discovered that the functional connectivity between IPL and PMv was decreased when the power of mu rhythms was suppressed. We did not find any brain regions showing greater activities or functional connectivity in association with increases of mu rhythm power. We conclude that greater activity but reduced functional connectivity of IPL and PMv are correlated with spontaneous suppression of mu rhythm amplitudes at rest. Our results may provide new insight into mechanisms of spontaneous fluctuations of brain activity or connectivity in a resting state. P185 Investigation of the neural correlates of tool use with activation studies in healthy subjects and lesion studies in brain damaged patients E. Salazar-Lopez1, M.L. Brandi1, G. Goldenberg2, A. Wohlschlaeger3, L. Johannsen1, J. Hermsdoerfer1 1Technische Universitaet Muenchen, Lehrstuhl fuer Bewegungswissenschaft, Muenchen, Germany; 2Klinikum Bogenhausen, Klinik fuer Neuropsychologie, Muenchen, Germany; 3Technische Universitaet Muenchen, Klinikum rechts der Isar, Diagnostische und Interventionelle Neuroradiologie. Neuro-Kopf-Zentrum, Muenchen, Germany Question: Results from brain activation studies in healthy subjects and lesion analyses in brain damage patients are expected to reveal a correspondence between areas activated by task performance with lesioned areas in case of deficits. We are planning to directly compare both approaches to study the neural network of tool use in as similar as possible and as realistic as possible conditions: On the other hand we examined tool use in healthy elderly subjects, during the realization of fMRI. On the other hand we plan to correlate the execution in this task in chronic stroke patients – with apraxia – with their damaged brain areas. Methods: Both experiments used a tool carousel for controlled tool presentation (12 tools of daily life). The fMRI-data was analyzed with SPM8 in a factorial design (object and task) during the planningand action-phase. In the lesion analyze study we score the execution according to an apraxic errors scale and use the voxel based lesion symptom mapping (VLSM), a method that includes mapping the lesion manually, normalizing brain image using cost function masking with SPM8 and making a voxelwise statistical analysis of neurological lesions to define the relationship between tissue damaged and behavior. Results: Besides a clear left-sided lateralization, a wide spread network can be identified with the fMRI analysis (see figure). This is specific to planning tool use and includes parietal cortex (superior and inferior parietal lobule and intraparietal sulcus), frontal cortex (dorsal and ventral premotor cortex

P185: Investigation of the neural correlates of tool use with activation studies in healthy subjects and lesion studies in brain damaged patients

P185: Investigation of the neural correlates of tool use with activation studies in healthy subjects and lesion studies in brain damaged patients

Music and speech prosody: a common rhythm

Disorders of music and speech perception, known as amusia and aphasia, have traditionally been regarded as dissociated deficits based on studies of brain damaged patients. This has been taken as evidence that music and speech are perceived by largely separate and independent networks in the brain. However, recent studies of congenital amusia have broadened this view by showing that the deficit is associated with problems in perceiving speech prosody, especially intonation and emotional prosody. In the present study the association between the perception of music and speech prosody was investigated with healthy Finnish adults (n = 61) using an on-line music perception test including the Scale subtest of Montreal Battery of Evaluation of Amusia (MBEA) and Off-Beat and Out-of-key tasks as well as a prosodic verbal task that measures the perception of word stress. Regression analyses showed that there was a clear association between prosody perception and music perception, especially in the domain of rhythm perception. This association was evident after controlling for music education, age, pitch perception, visuospatial perception, and working memory. Pitch perception was significantly associated with music perception but not with prosody perception. The association between music perception and visuospatial perception (measured using analogous tasks) was less clear. Overall, the pattern of results indicates that there is a robust link between music and speech perception and that this link can be mediated by rhythmic cues (time and stress).

Selective impairment of action-verb naming and comprehension in progressive supranuclear palsy

Some previous studies in brain-damaged patients suggested that neural systems in the left temporal lobe might be crucial in the production and comprehension of nouns, while analogous systems in posterior frontal cortical areas might be involved in the production and comprehension of verbs. We assessed performance on neuropsychological tasks of production and comprehension of nouns and action-verbs in 10 patients with progressive supranuclear palsy (PSP) and in 10 age-matched healthy controls. PSP patients also underwent measurements of regional cerebral blood flow by means of single photon emission computed tomography (SPECT), using 99mTc-Ethyl Cysteinate Dimer. In all PSP patients, SPECT showed a significant hypoperfusion in the inferior frontal gyrus (IFG). PSP patients performed significantly worse than controls on all lexical–semantic tasks, except for the auditory lexical decision task on nouns. Within PSP patients, however, a significantly lower performance was observed on action-verbs as compared to nouns on various lexical–semantic tasks (oral and written confrontation naming, auditory and visual single-word comprehension). Analysis of individual performance revealed heterogeneous patterns of neuropsychological impairment in different PSP patients. Despite some difficulty in drawing clear-cut conclusions about the locus of functional damage, we hypothesise that in most of our PSP patients such selective impairment in the production and in the comprehension of action-verbs could be due to semantic deficits affecting the conceptual category of actions. These findings are consistent with the hypothesis that in PSP a dysfunction of neural systems in posterior frontal cortical areas (mainly involving the IFG) critical for processing the conceptual category of actions might result in a selective impairment of production and comprehension of action-verbs.

Listening to White Noise Counteracts Visual and Haptic Pseudoneglect

Neurologically intact individuals usually show a leftward bias in line bisection, a tendency known as "pseudoneglect", likely reflecting a right-hemisphere dominance in controlling the allocation of spatial attention. Studies in brain-damaged patients with left visuospatial neglect have reported that auditory stimulation may reduce the deficit, both in a spatially dependent and in a spatially independent way. Here we show for the first time that the concurrent binaural presentation of auditory white noise affects healthy individuals' performance in both visual and haptic bisection, reducing their leftward error. We suggest that this effect depends on the noise boosting alertness and restoring the hemispheric activation balance. Our data clearly show that task-irrelevant auditory noise crossmodally affects the allocation of spatial resources in both the haptic and the visual space; future research may clarify whether these effects are specific for the type of auditory stimulation.

Disentangling visual imagery and perception of real-world objects

During mental imagery, visual representations can be evoked in the absence of "bottom-up" sensory input. Prior studies have reported similar neural substrates for imagery and perception, but studies of brain-damaged patients have revealed a double dissociation with some patients showing preserved imagery in spite of impaired perception and others vice versa. Here, we used fMRI and multi-voxel pattern analysis to investigate the specificity, distribution, and similarity of information for individual seen and imagined objects to try and resolve this apparent contradiction. In an event-related design, participants either viewed or imagined individual named object images on which they had been trained prior to the scan. We found that the identity of both seen and imagined objects could be decoded from the pattern of activity throughout the ventral visual processing stream. Further, there was enough correspondence between imagery and perception to allow discrimination of individual imagined objects based on the response during perception. However, the distribution of object information across visual areas was strikingly different during imagery and perception. While there was an obvious posterior-anterior gradient along the ventral visual stream for seen objects, there was an opposite gradient for imagined objects. Moreover, the structure of representations (i.e. the pattern of similarity between responses to all objects) was more similar during imagery than perception in all regions along the visual stream. These results suggest that while imagery and perception have similar neural substrates, they involve different network dynamics, resolving the tension between previous imaging and neuropsychological studies.

Language-invariant verb processing regions in Spanish-English bilinguals.

Nouns and verbs are fundamental grammatical building blocks of all languages. Studies of brain-damaged patients and healthy individuals have demonstrated that verb processing can be dissociated from noun processing at a neuroanatomical level. In cases where bilingual patients have a noun or verb deficit, the deficit has been observed in both languages. This suggests that the noun-verb distinction may be based on neural components that are common across languages. Here we investigated the cortical organization of grammatical categories in healthy, early Spanish-English bilinguals using functional magnetic resonance imaging (fMRI) in a morphophonological alternation task. Four regions showed greater activity for verbs than for nouns in both languages: left posterior middle temporal gyrus (LMTG), left middle frontal gyrus (LMFG), pre-supplementary motor area (pre-SMA), and right middle occipital gyrus (RMOG); no regions showed greater activation for nouns. Multi-voxel pattern analysis within verb-specific regions showed indistinguishable activity patterns for English and Spanish, indicating language-invariant bilingual processing. In LMTG and LMFG, patterns were more similar within than across grammatical category, both within and across languages, indicating language-invariant grammatical class information. These results suggest that the neural substrates underlying verb-specific processing are largely independent of language in bilinguals, both at the macroscopic neuroanatomical level and at the level of voxel activity patterns.

Representing actions through their sound

Since the discovery of 'mirror neurons' in the monkey premotor and parietal cortex, an increasing body of evidence in animals and humans alike has supported the notion of the inextricable link between action execution and action perception. Although research originally focused on the relationship between performed and viewed actions, more recent studies highlight the importance of representing the actions of others through audition. In the first part of this article, we discuss animal studies, which provide direct evidence that action is inherently linked to multi-sensory cues, as well as the studies carried out on healthy subjects by using state-of-the-art cognitive neuroscience techniques such as functional magnetic resonance imaging (fMRI), event-related potentials (ERP), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS). In the second section, we review the lesion analysis studies in brain-damaged patients demonstrating the link between 'resonant' fronto-parieto-temporal networks and the ability to represent an action by hearing its sound. Moreover, we examine the evidence in favour of somatotopy as a possible representational rule underlying the auditory mapping of actions and consider the links between language and audio-motor action mapping. We conclude with a discussion of some outstanding questions for future research on the link between actions and the sounds they produce.

Identifying abnormal connectivity in patients using Dynamic Causal Modelling of fMRI responses

Functional imaging studies of brain damaged patients offer a unique opportunity to understand how sensorimotor and cognitive tasks can be carried out when parts of the neural system that support normal performance are no longer available. In addition to knowing which regions a patient activates, we also need to know how these regions interact with one another, and how these inter-regional interactions deviate from normal. Dynamic causal modeling (DCM) offers the opportunity to assess task-dependent interactions within a set of regions. Here we review its use in patients when the question of interest concerns the characterization of abnormal connectivity for a given pathology. We describe the currently available implementations of DCM for fMRI responses, varying from the deterministic bilinear models with one-state equation to the stochastic non-linear models with two-state equations. We also highlight the importance of the new Bayesian model selection and averaging tools that allow different plausible models to be compared at the single subject and group level. These procedures allow inferences to be made at different levels of model selection, from features (model families) to connectivity parameters. Following a critical review of previous DCM studies that investigated abnormal connectivity we propose a systematic procedure that will ensure more flexibility and efficiency when using DCM in patients. Finally, some practical and methodological issues crucial for interpreting or generalizing DCM findings in patients are discussed.

Parietal versus temporal lobe components in spatial cognition: Setting the mid‐point of a horizontal line

Recent anatomo-clinical correlation studies have extended to the superior temporal gyrus, the right hemisphere lesion sites associated with the left unilateral spatial neglect, in addition to the traditional posterior-inferior-parietal localization of the responsible lesion (supramarginal gyrus, at the temporo-parietal junction). The study aimed at teasing apart, by means of repetitive transcranial magnetic stimulation (rTMS), the contribution of the inferior parietal lobule (angular gyrus versus supramarginal gyrus) and of the superior temporal gyrus of the right hemisphere, in making judgments about the mid-point of a horizontal line, a widely used task for detecting and investigating spatial neglect. rTMS trains at 25 Hz frequency were delivered over the inferior parietal lobule (angular gyrus and supramarginal gyrus), the superior temporal gyrus and the anterior parietal lobe of the right hemisphere, in 10 neurologically unimpaired participants, performing a line bisection judgment task. rTMS of the inferior parietal lobule at the level of the supramarginal gyrus brought about a rightward error in the bisection judgment, ipsilateral to the side of the rTMS, with stimulation over the other sites being ineffective. The neural correlates of computing the mid-point of a horizontal segment include the right supramarginal gyrus in the inferior parietal lobule and do not extend to the angular gyrus and the superior temporal gyrus. These rTMS data in unimpaired subjects constrain the evidence from lesion studies in brain-damaged patients, emphasizing the major role of a subset of relevant regions.

Language Processing: The Neural Basis of Nouns and Verbs

A new study of the functional anatomy of noun and verb production suggests an important role for semantic representations in the cortical processing of these two distinct grammatical classes.

Fast track to the medial prefrontal cortex

Studies of brain-damaged patients have provided remarkable insights into how our memories are organized (1). In particular, these studies have established that memory consolidation is a dynamic process involving gradual (but quite dramatic) reorganization of the circuits supporting memory over time (2, 3). A pioneer in this field was the French psychologist Theodule Ribot. In the late part of the 19th century, Ribot described how memory loss after brain insult tended to be related to the age of the memory: the effect on more recent memories was typically greater than that on older (or more remote) memories (4). Later studies established that damage to the medial temporal lobe (5), and more specifically the hippocampus (1), is responsible for this typical graded amnesia. This Ribot gradient has suggested that the hippocampus is only temporarily involved in the storage and recall of certain types of memory, and that these functions must be subsumed by extrahippocampal structures as memories mature (2, 6). Hippocampal damage in experimental animals also preferentially disrupts recent memory. Such examples, from mice to monkeys, suggest that time-dependent memory reorganization is an evolutionarily conserved process for memory consolidation (3). However, differences do exist between human and experimental animal studies, and these differences have made it difficult to come up with a unified mechanistic account of memory consolidation. For example, the lengths of the gradients vary dramatically from days or weeks (for example, in rodents) to years (in humans), suggesting that the rate of reorganization may vary greatly across species. Second, although studies in experimental animals have begun to successfully identify extrahippocampal brain regions that support remote memory recall, the evidence from human studies of remote memory has been much less consistent, and it has even been suggested that autobiographical memories may never become truly independent of the …

Frontal and Temporo-Parietal Lobe Contributions to Theory of Mind: Neuropsychological Evidence from a False-Belief Task with Reduced Language and Executive Demands

A model of the functional and anatomical basis of belief reasoning is essential for understanding the relationship between belief reasoning and other cognitive processes in both normal development and pathology. Studies of brain-damaged patients can give valuable insights into the nature of belief processing but pose unique methodological problems. The current study addresses these problems by using a nonlinguistic belief-reasoning task with substantially reduced executive demands. A case series of 12 brain-damaged patients is presented. The belief-reasoning errors of four patients with damage to the prefrontal cortex appeared to arise from these patients' executive function problems. The belief-reasoning errors of three patients with damage to the temporo-parietal junction could not easily be accounted for in this way, raising the possibility that this brain region has a necessary role in representing beliefs, rather than handling the executive demands of belief-reasoning tasks. We discuss the importance of gaining empirical evidence about the scope of ''theory of mind'' impairments, and the important role for neuropsychological studies in this project.

Representing arithmetic table facts in memory: Evidence from acquired impairments

In this article we explore how arithmetic table facts (e.g., 6 × 9 = 54) are stored in memory and evaluate the possibility that arithmetic facts are exclusively stored in a phonological or sound-based form. We present two single-case studies of brain-damaged patients who suffer specific number processing impairments. Both patients often retrieve the correct answer to simple arithmetic problems from memory when unable to generate the phonological representation of either the arithmetic problem or the answer to that problem. We argue that this pattern of performance is incompatible with the hypothesis that arithmetic facts are stored and retrieved from memory exclusively in a phonological form. Accounts consistent with out findings are proposed.

Craniotopic updating of visual space across saccades in the human posterior parietal cortex.

The neural mechanisms underlying the craniotopic updating of visual space across saccadic eye movements are poorly understood. Previous single-unit recording studies in primates and clinical studies in brain-damaged patients have shown that the posterior parietal cortex (PPC) has a key role in this process. In the present study, we used single-pulse transcranial magnetic stimulation (TMS) to disrupt the processing within the PPC during a task that requires craniotopic updating: double saccades. In this task, two targets are presented in quick succession and the subject is required to make a saccade to each location as accurately as possible. We show here that TMS delivered to the PPC just prior to the second saccade effectively disrupts the craniotopic coding normally observed in this task. This causes subjects to revert to saccades more consistent with a representation of the targets based on their positions relative to one another. By contrast, stimulation at earlier times between the two saccades did not disrupt performance. These results suggest that extraretinal information generated during the first perisaccadic period is not put into functional use until just prior to the second saccade.

What Can Studies of Brain-Damaged Patients Tell Us That Other Methods Can't?

Patient-based studies have played a pivotal role in developing theories of brain and cognitive functioning. In the 19th century, patient-based studies championed the notion that mental functions could be localized and in the last 30 years or so they have been used to uncover the fine-grained structure of cognition. Farah and Feinberg have assembled an impressive review of this literature covering topics from traditional neuropsychological areas such as aphasia, agnosia, and amnesia through less-studied areas such as acalculia, disorders of body representation, and amusia. The aim of this review is to evaluate critically the assumptions behind the patient-based approach, contrasting it with other approaches and drawing on evidence presented in the various chapters in the book. Times have changed: Functional imaging and other methods have become the darling of cognitive neuroscientists. It is, therefore, worthwhile to speculate as to how patient-based studies will sit alongside such methods and whether patient-based studies will, in fact, be supplanted by them.