MMPI-2 profiles of patients with intractable epilepsy.

MMPI-2 profiles of 93 presurgical intractable epilepsy patients were examined using Ward's method of cluster analysis. Three clusters were identified. The means of each cluster suggest that 45% of the sample had minimal psychological complaints, 30% presented with generalized clinical elevations, and 25% of the patients had profiles of intermediate elevations with a tendency to emphasize somatic complaints and/or depression. Gender, age of seizure onset, and seizure laterality were not found to be uniquely associated with the cluster profiles. Further examination of correlates of group membership is warranted to provide information for treatment planning.

Verbal encoding deficits in a patient with a left retrosplenial lesion.

Over the past decade, memory impairments associated with retrosplenial damage have received increased attention among neuroscientists, although the exact role of the retrosplenial region in memory has not been clearly defined. Evidence from lesion studies and functional neuroimaging has implicated the retrosplenial region in verbal episodic memory, temporal ordering of information, and topographical memory. In addition, recent positron emission tomography studies have shown increased activation of the retrosplenial cortex during tasks involving both the encoding and retrieval of episodic information. The objective of this study was to define more clearly the nature of memory impairments observed in retrosplenial amnesia. A 47-year-old amnesic male with a left retrosplenial arteriovenous malformation was examined on neurocognitive tasks of automatic and directed encoding, temporal ordering of information, and remote memory. Despite normal performance on frontal cognitive tasks, intact memory for remote information, and a superior IQ, this individual exhibited a profound deficit in the encoding of information, evidenced by poor release from proactive interference, poor category clustering on word list recall, poor semantic encoding on a levels of processing task, and mild impairments in temporal ordering. These results imply that the retrosplenial region plays a role in the verbal encoding of information, which contributes to the profound verbal memory impairment reported in previous case studies of patients with retrosplenial damage.

Basal ganglia dysfunction, working memory, and sentence comprehension in patients with Parkinson's disease.

To investigate the role of the basal ganglia in working memory and sentence comprehension, 14 patients with Parkinson's disease (PD) were administered experimental measures of semantic and phonological working memory, and a measure of sentence comprehension, while receiving dopaminergic medications and after a period of withdrawal from these medications. An age- and education- matched control group (N=14) received the same measures. Comparison with control subjects revealed deficits in patients with PD in sentence processing regardless of medication status, but no deficits in working memory. In contrast to previous studies, withdrawal of dopaminergic medications had no significant impact on task- related working memory functions or on sentence comprehension. Results suggest that basal ganglia dysfunction does not solely account for sentence comprehension deficits seen in PD.

Relative shift in activity from medial to lateral frontal cortex during internally versus externally guided word generation.

Goldberg (1985) hypothesized that as language output changes from internally to externally guided production, activity shifts from supplementary motor area (SMA) to lateral premotor areas, including Broca's area. To test this hypothesis, 15 right-handed native English speakers performed three word generation tasks varying in the amount of internal guidance and a repetition task during functional magnetic resonance imaging (fMRI). Volumes of significant activity for each task versus a resting state were derived using voxel-by-voxel repeated-measures t tests (p <.001) across subjects. Changes in the size of activity volumes for left medial frontal regions (SMA and pre-SMA/BA 32) versus left lateral frontal regions (Broca's area, inferior frontal sulcus) were assessed as internal guidance of word generation decreased and external guidance increased. Comparing SMA to Broca's area, Goldberg's hypothesis was not verified. However, pre-SMA/BA 32 activity volumes decreased significantly and inferior frontal sulcus activity volumes increased significantly as word generation tasks moved from internally to externally guided.

Conceptual apraxia in probable Alzheimer's disease as demonstrated by the Florida Action Recall Test.

Patients with probable Alzheimer's disease (AD) often have difficulties associated with semantic knowledge. Therefore, conceptual apraxia, a defect of action semantics and mechanical knowledge, may be an early sign of this disease. The Florida Action Recall Test (FLART), developed to assess conceptual apraxia, consists of 45 line drawings of objects or scenes. The subject must imagine the proper tool to apply to each pictured object or scene and then pantomime its use. Twelve participants with Alzheimer's disease (NINCDS-ADRDA criteria) and 21 age- and education-matched controls were tested. Nine Alzheimer's disease participants scored below a 2-standard-deviation cutoff on conceptual accuracy, and the three who scored above the cutoff were beyond a 2-standard-deviation cutoff on completion time. The FLART appears to be a sensitive measure of conceptual apraxia in the early stages of Alzheimer's disease.

LOFA: software for individualized localization of functional MRI activity.

Although PET, SPECT, and fMRI studies have led to significant advances in functional mapping of the human brain, precise localization and quantification of activity in individual brains require additional procedures. Difficulties to be addressed by a localization strategy are: resolution of individual anatomic differences, differentiation of functional activity in closely juxtaposed brain regions, and management of multiple intricately shaped 3D anatomic structures. In this paper, we describe a localization tool, LOFA, which addresses these problems by forming ROIs with a user-driven interface. Using LOFA, complex 3D anatomy can be defined through open or closed loops and anatomic landmarks. Resulting partitions can be overlaid on top of each other to form multiple regions of interest (ROIs), and functional activity in these ROIs can be extracted individually, one after the other. LOFA introduces important paradigmatic advances over the other ROI analysis methods. The toolbox is interactive, fully compatible with AFNI (MCW), and requires Pv-Wave (VNI Inc.) license to run.

Left-hemisphere processing of emotional connotation during word generation.

Areas of the brain's left hemisphere involved in retrieving words with emotional connotations were studied with fMRI. Participants silently generated words from different semantic categories which evoked either words with emotional connotations or emotionally neutral words. Participants repeated emotionally neutral words as a control task. Compared with generation of emotionally neutral words, generation of words with emotional connotations engaged cortices near the left frontal and temporal poles which are connected to the limbic system. Thus, emotional connotations of words are processed in or near cortices with access to emotional experience.

Conduction aphasia and the arcuate fasciculus: A reexamination of the Wernicke-Geschwind model.

Wernicke, and later Geschwind, posited that the critical lesion in conduction aphasia is in the dominant hemisphere's arcuate fasciculus. This white matter pathway was thought to connect the anterior language production areas with the posterior language areas that contain auditory memories of words (a phonological lexicon). Alternatively, conduction aphasia might be induced by cortical dysfunction, which impairs the phonological output lexicon. We observed an epileptic patient who, during cortical stimulation of her posterior superior temporal gyrus, demonstrated frequent phonemic paraphasias, decreased repetition of words, and yet had intact semantic knowledge, a pattern consistent with conduction aphasia. These findings suggest that cortical dysfunction alone may induce conduction aphasia.

Activity in the paracingulate and cingulate sulci during word generation: an fMRI study of functional anatomy.

The supracallosal medial frontal cortex can be divided into three functional domains: a ventral region with connections to the limbic system, an anterior dorsal region with connections to lateral prefrontal systems, and a posterior dorsal region with connections to lateral motor systems. Lesion and functional imaging studies implicate this medial frontal cortex in speech and language generation. The current functional magnetic resonance imaging (fMRI) study of word generation was designed to determine which of these three functional domains was substantially involved by mapping individual subjects' functional activity onto structural images of their left medial frontal cortex. Of 28 neurologically normal right-handed participants, 21 demonstrated a prominent paracingu- late sulcus (PCS), which lies in the anterior dorsal region with connections to lateral prefrontal systems. Activity increases for word generation centered in the PCS in 18 of these 21 cases. The posterior dorsal region also demonstrated significant activity in a majority of participants (16/28 cases). Activity rarely extended into the cingulate sulcus (CS) (3/21 cases) when there was a prominent PCS. If there was no prominent PCS, however, activity did extend into the CS (6/7 cases). In no case was activity present on the crest of the cingulate gyrus, which is heavily connected to the limbic system. Thus, current findings suggest that medial frontal activity during word generation reflects cognitive and motor rather than limbic system participation. The current study demonstrates that suitably designed fMRI studies can be used to determine the functional significance of anatomic variants in human cortex.

Subcortical mechanisms in language: lexical-semantic mechanisms and the thalamus.

Four previously published cases of dominant thalamic lesion in which the author has participated are reviewed to gain a better understanding of thalamic participation in lexical-semantic functions. Naming deficits in two cases support Nadeau and Crosson's (1997) hypothesis of a selective engagement mechanism involving the frontal lobes, inferior thalamic peduncle, nucleus reticularis, and other thalamic nuclei, possibly the centromedian nucleus. This mechanism selectively engages those cortical areas required to perform a cognitive task, while maintaining other areas in a state of relative disengagement. Deficits in selective engagement disproportionately affect lexical retrieval based on semantic input, as opposed to lexical and sublexical processes, because the former is more dependent upon this attentional system. The concept of selective engagement is also useful in understanding thalamic participation in working memory, as supported by data from one recent functional neuroimaging study. Other processes also may be compromised in more posterior thalamic lesions which damage the pulvinar but not other components of this selective engagement system. A third case with aphasia after a more superior and posterior thalamic lesion also had oral reading errors similar to those in neglect dyslexia. The pattern of deficits suggested a visual processing problem in the early stages of reading. The fourth case had a category-specific naming deficit after posterior thalamic lesion. Taken together, the latter two cases indicate that the nature of language functions in more posterior regions of the dominant thalamus depends upon the cortical connectivity of the thalamic region. Together, findings from the four cases suggest that thalamic nuclei and systems are involved in multiple processes which directly or indirectly support cortical language functions.

Mapping of semantic, phonological, and orthographic verbal working memory in normal adults with functional magnetic resonance imaging.

Twelve neurologically normal participants (4 men and 8 women) performed semantic, phonological, and orthographic working memory tasks and a control task during functional magnetic resonance imaging. Divergent regions of the posterior left hemisphere used for decoding and storage of information emerged in each working memory versus control task comparison. These regions were consistent with previous literature on processing mechanisms for semantic, phonological, and orthographic information. Further, working memory versus control task differences extended into the left frontal lobe, including premotor cortex, and even into subcortical structures. Findings were consistent with R. C. Martin and C. Romani's (1994) contention that different forms of verbal working memory exist and further suggest that a reconceptualization of premotor cortex functions is needed.

Functional imaging: heterogeneity in task strategy and functional anatomy and the case for individual analysis.

To learn more about the functional anatomy of language, the authors used [99mTc]HMPAO single photon emission computed tomography (SPECT) functional imaging to study nonword rhyming, lexical-semantics and syntax. The authors did not find any task-related differences in cerebral blood flow using region-by-region analysis of variance. This led them to examine individual subject's task-related patterns of cerebral blood flow. This analysis revealed regions of interest with little or no change but also regions with changes as great as 30%. There was marked subject-to-subject variability in the pattern of blood flow, which precluded statistically significant results using analysis of variance. An alternative analytic strategy based on numbers of subjects exceeding a minimum threshold task-related change in cerebral blood flow was tested and shows promise in identifying commonalities and differences in individual task-related blood flow patterns. The authors conclude that the complex and difficult to interpret pattern of blood flow changes observed in this study reflect in considerable part the combined effects of variability in task strategy, owing in part to insufficiently constrained task performance, and variability in functional anatomy. The authors also tested the differences in results achieved with simple normalization and analysis of covariance approaches and found them to be insignificant.

Treatment of a case of phonological alexia with agraphia using the Auditory Discrimination in Depth (ADD) program.

Phonological alexia and agraphia are acquired disorders characterized by an impaired ability to convert graphemes to phonemes (alexia) or phonemes to graphemes (agraphia). These disorders result in phonological errors typified by adding, omitting, shifting, or repeating phonemes in words during reading or graphemes when spelling. In developmental dyslexia, similar phonological errors are believed to result from deficient phonological awareness, an oral language skill that manifests itself in the ability to notice, think about, or manipulate the individual sounds in words. The Auditory Discrimination in Depth (ADD) program has been reported to train phonological awareness in developmental dyslexia and dysgraphia. We used a multiple-probe design to evaluate the ADD program's effectiveness with a patient with a mild phonological alexia and mixed agraphia following a left hemisphere infarction. Large gains in phonological awareness, reading and spelling nonwords, and reading and spelling real words were demonstrated. A follow-up reassessment, 2 months posttreatment, found the patient had maintained treatment gains in phonological awareness and reading, and attained additional improvement in real word reading.

Category-specific naming deficit for medical terms after dominant thalamic/capsular hemorrhage.

Postmortem, retrograde degeneration, and electrical stimulation studies have implicated the anterior pulvinar in language processing. We examined a patient who, after a hemorrhage affecting the dominant pulvinar and internal capsule, exhibited a circumscribed anomia for medical items and conditions. No other language disturbance was noted. Five category-specific word lists, matched for word frequency, were administered in a naming-to-definition format. Results indicated that the patient exhibited a significant category-specific naming deficit for medical items and conditions compared to matched control subjects. Although medical item lists were found to differ from nonmedical item lists in imageability and abstractness, B.C.'s category-specific deficit did not seem to be caused by word frequency, concept familiarity, imageability, or abstractness. Nor could the patient's performance be explained on the basis of deficits in broader semantic classifications (i.e., animate vs inanimate or man-made vs natural). The patient was unable to retrieve medical items even when given phonemic cues for those he could not name. Findings indicate that subtotal damage in the dominant pulvinar may create category-specific deficits.

Subcortical aphasia.

We critically review the literature on subcortical aphasia, suggest that a number of traditional concepts regarding mechanisms of aphasia are inconsistent with now abundant data, and propose several new hypotheses. The absence of aphasia in 17 reported cases of dominant hemisphere striatocapsular infarction and the finding of nearly every conceivable pattern of language impairment in 33 different reported cases of striatocapsular infarction provide strong evidence against a major direct role of the basal ganglia in language and against disconnection or diaschisis as mechanisms of nonthalamic subcortical aphasia. However, detailed consideration of the vascular events leading to striatocapsular infarction strongly suggests that associated linguistic deficits are predominantly related to sustained cortical hypoperfusion and infarction not visible on structural imaging studies. Thalamic disconnection, as may occur with striatocapsular infarcts with extension to the temporal stem and putamenal hemorrhages, may also contribute to the language deficits in some patients. Review of the literature on thalamic infarction, in conjunction with previously unreported anatomic details of four cases, suggests that what infarcts in the tuberothalamic artery territory and the occasional infarcts in the paramedian artery territory associated with aphasia have in common is damage to the frontal lobe-inferior thalamic peduncle-nucleus reticularis-center median system that may be involved in regulating the thalamic gate in attentional processes. Disruption of attentional gating in the pulvinar and lateral posterior nuclei resulting from such lesions may impair selection of specific neuronal networks in the projection field of these nuclei that serve as the substrate for lexical-semantic function, which is in effect a disruption of a type of working memory, as defined by Goldman-Rakic. We define this as a defect of selective engagement.

Resting and stimulated states in functional imaging studies: evidence of differences in attentional and intentional set.

In a [99mTc]-hexamethylpropyleneamine oxime single photon emission computed tomography study of cerebral blood flow (CBF) in a visual activation paradigm (awake, eyes closed versus eyes open viewing a reversing checkerboard pattern), the authors systematically measured previously observed qualitative alterations in frontal blood flow associated with visual stimulation (experiment 1). They confirmed a trend toward reductions in CBF throughout precentral cortex that approached significance in areas 9 and 46, in conjunction with significant increases in CBF in postcentral cortices, including visual association area PO, and areas 3-1-2, 22, and 23. The authors posited that these changes may be related to differences in attentional and intentional state in the eyes-closed and eyes-open conditions. Such differences should be associated with alterations in motor preparedness, leading to changes in response times and to alterations in thalamocortical gating of somatosensory information, which in turn lead to changes in somatosensory-evoked potential amplitudes. In experiment 2, the authors measured simple motor response times to a 1500-Hz tone stimulus and early components of somatosensory-evoked potentials under the same experimental conditions. In the visual stimulation condition, there was a significant increase in the evoked potential amplitude (t = 2.686, p = 0.021), and a significant decrease in response time (t = -2.464, p = 0.031). These observations provided tentative support for their hypothesis. The authors also demonstrated the major effect of normalization assumptions on regional blood flow measurements.

Gaze related enhancement of hemispheric blood flow in a stroke patient.

OBJECTIVE: A patient with a right posterior cerebral artery territory infarction and a left superior quadrantanopia exhibited improvement on various visual tasks including Goldmann perimetry during extreme right gaze. The phenomenon was investigated by functional imaging of cerebral blood flow. METHODS: [(99m)Tc]HMPAO SPECT was carried out while the patient gazed to the right and to the left at an 8 Hz flash stimulus. RESULTS: When compared with left gaze, photic stimulation during right gaze was associated with an up to 39.8% increase in regional cerebral blood flow in the damaged right hemisphere, including Brodmann's areas 3-1-2, 7, 21, 22, 39, and 40. CONCLUSIONS: These gaze related alterations in function and synaptic activity suggest the engagement of a novel arousal-like mechanism that may account in part for comparable findings in patients with neglect and other disorders, and may have relevance to rehabilitation.

Tapping, talking and the thalamus: possible influence of the intralaminar nuclei on basal ganglia function.

A patient with a discrete lesion of the left, intralaminar thalamic, nuclei exhibited a paradoxical finding with regard to finger-tapping. Normal subjects typically reduce their tapping rate when performing simultaneous verbal activity. Tapping was impaired in our patient's contralesional hand on baseline trials; however, performing the controlled oral word association (COWA) task, while finger-tapping, normalized her deficit. Subsequent experiments showed that motoric tasks rather than cognitive aspects of the COWA task were critical in potentiating finger-tapping performance. A SPECT study performed at rest revealed focal perfusion asymmetries in motor and premotor cortices. Because the caudal intralaminar nuclei project heavily to the striatum, striatal deafferentiation may account for these asymmetries. These observations provide some insight into the influences of the caudal intralaminar thalamic nuclei on basal ganglia function and the basal ganglia's influence on motor gating.

Lexical-semantic deficits in two patients with dominant thalamic infarction.

Two patients with dominant thalamic infarction, one in the tuberothalamic artery territory, the other in the paramedian artery territory, demonstrated language impairment limited to word retrieval difficulties in spontaneous language and structured naming tasks. Using a cognitive neuropsychological model of lexical processing developed in the study of patients with cortical lesions. We carried out a detailed investigation of their lexical abilities. Both patients demonstrated impairment restricted to oral and written picture naming and oral naming to definition and spared performance on tasks of lexical comprehension, oral word reading, and writing to dictation, as well as syntactic comprehension and production. Naming impairment disproportionately affected lower frequency words, and word substitutions often corresponded to objects that were semantically-related to target words. We propose that our patients' word retrieval impairments reflect a failure of thalamic input to effectively engage the cortical networks subserving lexical semantic processing, leading to degraded levels of activation as the semantic system interfaces with subsequent stages of lexical processing.