Analogical reasoning and prefrontal cortex: evidence for separable retrieval and integration mechanisms

The present study examined the contributions of prefrontal cortex (PFC) subregions to two component processes underlying verbal analogical reasoning: semantic retrieval and integration. Event-related functional magnetic resonance imaging data were acquired while subjects performed propositional analogy and semantic decision tasks. On each trial, subjects viewed a pair of words (pair 1), followed by an instructional cue and a second word pair (pair 2). On analogy trials, subjects evaluated whether pair 2 was semantically analogous to pair 1. On semantic trials, subjects indicated whether the pair 2 words were semantically related to each other. Thus, analogy--but not semantic--trials required integration across multiple retrieved relations. To identify regions involved in semantic retrieval, we manipulated the associative strength of pair 1 words in both tasks. Anterior left inferior PFC (aLIPC) was modulated by associative strength, consistent with a role in controlled semantic retrieval. Left frontopolar cortex was insensitive to associative strength, but was more sensitive to integration demands than was aLIPC, consistent with a role in integrating the products of semantic retrieval to evaluate whether distinct representations are analogous. Right dorsolateral PFC exhibited a profile consistent with a role in response selection rather than retrieval or integration. These findings indicate that verbal analogical reasoning depends on multiple, PFC-mediated computations.     

Interhemispheric transmission of visuomotor information for motor implementation

Using transcranial magnetic stimulation (TMS), we addressed the contribution of both hemispheres to the visuomotor control of each hand. The subjects had to press one of two buttons as quickly as possible after the go-signal. A precue preceding this conveyed full, partial or no advance information (hand and/or button), such that reaction time (RT) shortened with increasing amount of information. We gave TMS over each hemisphere at various time intervals (100-350 ms) after the go-signal and before the expected onset of response, and measured its effect on RT, movement time (MT) and error rate. At short intervals (100-200 ms), left hemisphere TMS delayed RT and prolonged MT of both hands, while right hemisphere TMS delayed RT only of the right hand, without affecting error rates. At long intervals (250-350 ms), TMS produced slightly more pronounced RT delays of the contralateral hand. RT was delayed more if the precues were less informative. The results suggest the importance of interhemispheric transmission of visuomotor information for motor implementation. The right hemisphere may play a role mainly in calculating target and effector information, determining RT, while the left hemisphere may play a role in elaborating the motor program and determining MT.     

Brain state-dependent functional hemispheric specialization in men but not in women

Hemispheric specialization is reliably demonstrated in patients with unilateral lesions or disconnected hemispheres, but is inconsistent in healthy populations. The reason for this paradox is unclear. We propose that functional hemispheric specialization in healthy participants depends upon functional brain states at stimulus arrival (FBS). Brain activity was recorded from 123 surface electrodes while 22 participants (11 women) performed lateralized lexical decisions (left hemisphere processing) on neutral and emotional (right hemisphere processing) words. We determined two classes of stable FBS, one with right anterior-left posterior orientations (RA-LP maps) and one with left anterior-right posterior orientations (LA-RP maps). Results show that functional hemispheric specialization is dependent upon the class of FBS and gender. Of those with LA-RP maps, only men showed a strong emotional word advantage (EWA) after left visual field (right hemisphere) presentation, but no EWA after right visual field (left hemisphere) presentation. Subsequent to all other brain states, there was an almost equal EWA after presentation to either visual field. Only about half of the FBS in men led to the pattern of functional hemispheric specialization. We suggest that 'split-brain' research may be marginally describable by a model, but only in exceptional situations, while in connected brains this functional hemispheric specialization is only one of many dynamic states.     

Postcallosotomy language impairments in patients with crossed cerebral dominance

Language impairments were reviewed retrospectively in patients who underwent partial or total corpus callosum section for medically refractory secondary generalized epilepsy. Postoperatively, four of 32 patients had clinically significant language impairments that were not present prior to the operation. All involved primarily verbal output (speech and writing) and spared verbal comprehension. Written language skills (reading and spelling), verbal memory, and verbal reasoning abilities were impaired to varying degrees. These impairments were associated with crossed cerebral dominance. Three patients with severe difficulties after surgery were right hemisphere-dominant for speech and were right-handed. One left hemisphere speech-dominant, left-handed patient was agraphic after surgery, but spoke normally. It is concluded from these data and from other reports in the literature that three syndromes of language disturbance may follow callosotomy. The first, involving speech difficulty but but sparing writing, is attributable to buccofacial apraxia. The second involves speech and writing difficulties and occurs in right hemisphere-dominant right-handed patients. The third involves dysgraphia with intact speech and occurs in left hemisphere-dominant left-handed patients.     

Anatomical physiology of spatial extinction

Neurologically intact volunteers participated in a functional magnetic resonance imaging experiment that simulated the unilateral (focal) and bilateral (global) stimulations used to elicit extinction in patients with hemispatial neglect. In peristriate areas, attentional modulations were selectively sensitive to contralaterally directed attention. A higher level of mapping was observed in the intraparietal sulcus (IPS), inferior parietal lobule (IPL), and inferior frontal gyrus (IFG). In these areas, there was no distinction between contralateral and ipsilateral focal attention, and the need to distribute attention globally led to greater activity than either focal condition. These physiological characteristics were symmetrically distributed in the IPS and IFG, suggesting that the effects of unilateral lesions in these 2 areas can be compensated by the contralateral hemisphere. In the IPL, the greater activation by the bilateral attentional mode was seen only in the right hemisphere. Its contralateral counterpart displayed equivalent activations when attention was distributed to the right, to the left, or bilaterally. Within the context of this experiment, the IPL of the right hemisphere emerged as the one area where unilateral lesions can cause the most uncompensated and selective impairment of global attention (without interfering with unilateral attention to either side), giving rise to the phenomenon of extinction.     

Noninvasive determination of speech dominance by single magnetic stimulation of the bilateral hand motor cortex

Magnetic stimulation of the hand area of the motor cortex in both hemispheres was performed at rest and during reading aloud to observe modulated facilitation of hand muscle motor potentials in 6 right-handed patients, with supratentorial lesions but no motor impairment or aphasia, who had undergone the Wada test to determine speech dominance, showing that 5 were left hemisphere dominant and one was bilateral hemisphere dominant. Motor potentials were facilitated during reading aloud in only the right hand in 3 patients, all left hemisphere dominant, greater in the right hand in one, left hemisphere dominant, and greater in the left hand in one patient, bilateral hemisphere dominant. Based on these results we defined a laterality index which was consistent with the Wada test results. Magnetic stimulation may prove useful for determining cerebral dominance, as our method correlates well with the Wada test, and is safe, convenient, and inexpensive.     

Functional specializations in lateral prefrontal cortex associated with the integration and segregation of information in working memory

Control processes are thought to play an important role in working memory (WM), by enabling the coordination, transformation, and integration of stored information. Yet little is known about the neural mechanisms that subserve such control processes. This study examined whether integration operations within WM involve the activation of distinct neural mechanisms within lateral prefrontal cortex (PFC). Event-related functional magnetic resonance imaging was used to monitor brain activity while participants performed a mental arithmetic task. In the integration (IN) condition, a WM preload item had to be mentally inserted into the last step of the math problem. This contrasted with the segregation (SG) condition, which also required maintenance of the WM preload while performing mental arithmetic but had no integration requirement. Two additional control conditions involved either ignoring the preload (math only condition) or ignoring the math problem (recall only condition). Left anterior PFC (Brodmann's Area [BA] 46/10) was selectively engaged by integration demands, with activation increasing prior to, as well as during the integration period. A homologous right anterior PFC region showed selectively increased activity in the SG condition during the period in which the math problem and preload digit were reported. Left middorsolateral PFC regions (BA 9/46) showed increased, but equivalent, activity in both the SG and IN conditions relative to both control conditions. These results provide support for the selective role of lateral PFC in cognitive control over WM and suggest more specific hypotheses regarding dissociable PFC mechanisms involved during the integration and segregation of stored WM items.     

Activation of Human Prefrontal Cortex during Spatial and Nonspatial Working Memory Tasks Measured by Functional MRI

Separate working memory domains for spatial location, and forobjects, faces, and patterns, have been identified in the prefrontalcortex (PFC) of nonhuman primates. We have used functional magneticresonance imaging to examine whether spatial and nonspatialvisual working memory processes are similarly dissociable inhuman PFC. Subjects performed tasks which required them to remembereither the location or shape of successive visual stimuli. Wefound that the mnemonic component of the working memory tasksaffected the hemispheric pattern of PFC activation. The spatial(LOCATION) working memory task preferentially activated themiddle frontal gyrus (MFG) in the right hemisphere, while thenonspatial (SHAPE) working memory task activated the NIFG inboth hemispheres. Furthermore, the area of activation in theleft hemisphere extended into the inferior frontal gyrus forthe nonspatial SHAPE task. A perceptual target (DOT) detectiontask also activated the MFG bilaterally, but at a level approximatelyhalf that of the working memory tasks. The activation in theMFG occurred within 3–6 s of task onset and declined followingtask offset. Time-course analysis revealed a different patternfor the cingulate gyrus, in which activation occurred upon taskcompletion. Cingulate activation was greatest following theSHAPE task and was greater in the left hemisphere. The presentresults support the prominent role of the PFC and, specifically,the MFG in working memory, and indicate that the mnemonic contentof the task affects the relative weighting of hemispheric activation.     

Evidence-Based Medicine for Dermatologic Surgeons: Concepts in Critical Appraisal of Information

BACKGROUND: The term evidence-based medicine (EBM) is increasingly being used. Physicians, journal editors, insurance companies, and patients are applying its tenets to clinical decision making. Although there are concerns about the overly zealous application of EBM to clinical situations, many of the basic concepts are important in improving decision making. OBJECTIVE: To define evidence-based medicine and to review potential problems in basing decision making entirely on less-than-ideal evidence. METHODS: We reviewed the EBM literature and looked for examples in dermatology of pitfalls in decision making based on poor evidence. RESULTS: Following a definition of EBM, we review problems inherent in anecdotes and uncontrolled trials, including the placebo effect. Examples of medical practice that have been altered by doing more rigorous studies are provided. CONCLUSIONS: Concepts of EBM as currently defined should be considered by dermatologic surgeons in assessing the available information for clinical decision making.     

Language hemispheric dominance in patients with congenital lesions of eloquent brain

OBJECTIVE: In 90% of normal subjects, the left hemisphere is dominant for language function. We investigated whether congenital lesions of the left perisylvian regions altered cortical language representation in right-handed individuals. METHODS: Using functional magnetic resonance imaging, we studied language hemispheric dominance in five right-handed adult patients with congenitally acquired arteriovenous malformations (AVMs) originating from left hemispheric cortical language regions. The AVMs had not caused neurological symptoms during early development, but patients presented as adults with migraine, seizure, or minor hemorrhage. Results obtained from the AVM patients were contrasted to those from right-handed brain-injured stroke patients recovering from aphasia and to those from right-handed normal subjects. RESULTS: During silent picture naming and verb generation tasks, cortical language networks lateralized primarily to the right hemisphere in the AVM group, compared with the left hemisphere in the normal group. This right hemisphere-shifted language network in the AVM group exceeded the shifts toward right hemispheric dominance found in the stroke group. CONCLUSION: Patients with AVMs affecting the left perisylvian regions recruited the right hemisphere into language processing networks during early development, presumably in response to congenitally aberrant circulation. This early right hemisphere recruitment in the AVM patients exceeded the similar process in the brains of stroke patients whose left cortical language networks were damaged in adulthood. Our data provide evidence of effective plasticity in the developing human brain compared with the mature brain response to injury. Knowledge of cortical language representation should assist presurgical planning in patients with developmental anomalies affecting apparently language-dominant brain regions.     

Dissociating the roles of right ventral lateral and dorsal lateral prefrontal cortex in generation and maintenance of hypotheses in set-shift problems

Although patient data have traditionally implicated the left prefrontal cortex (PFC) in hypothesis generation, recent lesion data implicate right PFC in hypothesis generation tasks that involve set shifts (lateral transformations). To test the involvement of the right prefrontal cortex in a hypothesis generation task involving set shifts, we scanned 13 normal subjects with fMRI as they completed Match Problems (a classic divergent thinking task) and a baseline task. In Match Problems subjects determined the number of possible solutions for each trial. Successful solutions are indicative of set shifts. In the baseline condition subjects evaluated the accuracy of hypothetical solutions to match problems. A comparison of Match Problems versus baseline trials revealed activation in right ventral lateral PFC (BA 47) and left dorsal lateral PFC (BA 46). A further comparison of successfully versus unsuccessfully completed Match Problems revealed activation in right ventral lateral PFC (BA 47), left middle frontal gyrus (BA 9) and left frontal pole (BA 10), thus identifying the former as a critical component of the neural mechanisms of set-shift transformation. By contrast, activation in right dorsal lateral PFC (BA 46) covaried as a function of the number of solutions generated in Match Problems, possibly due to increased working memory demands to maintain multiple solutions 'on-line', conflict resolution, or progress monitoring. These results go beyond the patient data by identifying the ventral lateral (BA 47) aspect of right PFC as being a critical component of the neural systems underlying lateral transformations, and demonstrate a dissociation between right VLPFC and DLPFC in hypotheses generation and maintenance.     

Subclavian artery to internal carotid artery bypass with saphenous vein graft in the treatment of bilateral common carotid artery occlusion; a case report]

A case of left common carotid artery occlusion, which was treated by a saphenous vein graft, is reported. A 49-year-old right handed male was admitted to the hospital because of right hemiparesis and aphasia. These symptoms disappeared spontaneously two weeks after admission. However, visual acuity remained impaired on the left side due to occlusion of the central retinal artery. Angiography revealed complete occlusion of the common carotid arteries as well as patency of the internal carotid arteries on both sides. PET and 123I-IMP-SPECT studies showed hypoperfusion in the left cerebral hemisphere. To restore the blood flow as well as to remove the source of the emboli, endarterectomy was performed on the left internal carotid artery. This was followed by a saphenous vein graft between the left subclavian and the internal carotid artery. Postoperative angiography revealed patency of the bypass, and a SPECT study revealed increased blood flow in the left cerebral hemisphere. The patient has remained in stable condition during the following 30 months with no neurological problems. We conclude that in the treatment of complete occlusion of the common carotid artery and subsequent cerebral hypoperfusion, a bypass graft between the internal carotid and the subclavian artery is quite effective, and that the site of the bypass graft should carefully be sought for by using preoperative angiographic studies.     

New Evidence for Distinct Right and Left Brain Systems for Deductive versus Probabilistic Reasoning.

Deductive and probabilistic reasoning are central to cognition but the functional neuroanatomy underlying them is poorly understood. The present study contrasted these two kinds of reasoning via positron emission tomography. Relying on changes in instruction and psychological 'set', deductive versus probabilistic reasoning was induced using identical stimuli. The stimuli were arguments in propositional calculus not readily solved via mental diagrams. Probabilistic reasoning activated mostly left brain areas whereas deductive activated mostly right. Deduction activated areas near right brain homologues of left language areas in middle temporal lobe, inferior frontal cortex and basal ganglia, as well as right amygdala, but not spatial-visual areas. Right hemisphere activations in the deduction task cannot be explained by spill-over from overtaxed, left language areas. Probabilistic reasoning was mostly associated with left hemispheric areas in inferior frontal, posterior cingulate, parahippocampal, medial temporal, and superior and medial prefrontal cortices. The foregoing regions are implicated in recalling and evaluating a range of world knowledge, operations required during probabilistic thought. The findings confirm that deduction and induction are distinct processes, consistent with psychological theories enforcing their partial separation. The results also suggest that, except for statement decoding, deduction is largely independent of language, and that some forms of logical thinking are non-diagrammatic.     

Strategies for Spinal Cord Protection during Descending Thoracic and Thoracoabdominal Aortic Surgery: Up-to-date Experimental and Clinical Results - A review

Abstract

Objectives. Stroke following cardiac surgery may occur either in association with surgery (early) or occur postoperatively (delayed). The hemispheric distribution of lesions may provide information about embolic routes, which was analyzed here. Design. In 10,809 patients undergoing cardiac surgery, early (n = 223) and delayed stroke (n = 116) were explored. Symptoms and computed tomography findings were evaluated to categorize hemispheric distributions. This was compared with pre- and intra-operative characteristics and survival, using logistic regression and Kaplan-Meier statistics. Results. Early stroke had preponderance for the right rather than the left hemisphere (P = 0.009), whereas delayed stroke had a uniform distribution. Several intraoperative variables predicted the development of bilateral stroke compared with its unilateral counterpart. At multivariable analysis, the use of tranexamic acid was associated with bilateral stroke (P = 0.017), but was also associated with right rather than left-hemispheric stroke (P = 0.001). Bilateral lesions dramatically impaired survival versus those with unilateral lesions (P < 0.001). There was no survival difference between left and right-hemispheric stroke. Conclusions. When stroke, after cardiac surgery, is subdivided into early and delayed forms, it becomes evident that early, but not delayed stroke, demonstrates a hemispheric side difference. The preponderance for right-hemispheric lesions may indicate embolic mechanisms routed via the brachiocephalic trunk.     

The right hemisphere: neuropsychological functions

In the past two to three decades, clinicians and neuroscientists have been studying the functions of the right hemisphere. Neither hemisphere seems to be dominant in the absolute sense. Each appears to be specialized and is dominant for different functions. However, most functions require the cooperation of both hemispheres. When one is damaged, the other can often compensate for the damaged one. Lesions of the left hemisphere are associated with language (speech, reading, and writing) and praxic disorders, and lesions of the right hemisphere can result in visuospatial, attentional, and emotional disorders. The authors review some of the major behavior disorders associated with right hemisphere dysfunction and concentrate on three major types of disorders--visuospatial, attentional, and emotional. Although not all the behavioral defects associated with right hemisphere damage can be subgrouped under these three types, they are the ones most often associated with right hemisphere lesions.     

FMRI evidence for an organization of prefrontal cortex by both type of process and type of information

Neuroimaging evidence is conflicting regarding whether human prefrontal cortex (PFC) shows functional organization by type of processes engaged or type of information processed. Most studies use complex working or long-term memory tasks requiring multiple processes and the combinations of processes recruited for different materials may vary. Using functional magnetic resonance imaging (fMRI) and simple tasks suggested by a component process approach, we found activity in left PFC when participants thought about (refreshed) a just-seen item and in right PFC when participants noted whether an item had been presented previously. Furthermore, the distribution of activation in left or right PFC varied with type of information. Thus, at the component process level, PFC shows functional organization by both process and type of information.     

The role of radiotherapy in the management of thymic tumors

Radiotherapy is a major therapeutic modality for thymic malignancies. The exact role of adjuvant radiotherapy after complete resection is still debated for stage II through III tumors. Histology or size, capsular invasion, and even molecular data may be included in the decision making. Radiotherapy may be recommended for stage III thymomas, thymic carcinoma, or after incomplete surgical resection. Combination with chemotherapy may be useful, and must be further evaluated using validated end points, including 5- and 10-year time-to-progression and overall survival. Several initiatives have been taken worldwide to launch collaborative studies in the field, including prospective trials specifically readdressing the role of radiotherapy for thymic malignancies.     

Ischemic events due to intraoperative microemboli developing in the cerebral hemisphere contralateral to carotid endarterectomy in a patient with preoperative cerebral hemodynamic impairment

A 74-year-old man with a history of asymptomatic right internal carotid artery (ICA) occlusion experienced amaurosis fugax in the left eye. Angiography showed left cervical ICA stenosis in addition to right cervical ICA occlusion. The right anterior and middle cerebral artery (MCA) territories were perfused from the left ICA via the anterior communicating artery. Brain perfusion single-photon emission computed tomography revealed reduced cerebral blood flow and reduced cerebrovascular reactivity to acetazolamide only in the right cerebral hemisphere. The patient underwent left carotid endarterectomy (CEA). Transcranial Doppler monitoring showed microembolic signals in the left MCA during dissection of the left ICA, but intraoperative monitoring suggested absence of global hypoperfusion or ischemia in the bilateral cerebral hemispheres during left ICA clamping. Transient and slight motor weakness of the left upper extremity was noted on recovery from anesthesia. Diffusion-weighted magnetic resonance imaging demonstrated the development of new spotty ischemic lesions only in the right cerebral hemisphere. The present case suggests that intraoperative cerebral embolism causing postoperative neurological deficits can develop exclusively in the cerebral hemisphere contralateral to CEA if the hemisphere has preoperative hemodynamic impairment and collateral circulation via the anterior communicating artery from the ICA ipsilateral to CEA.     

Discrepancy between [18F]fluorodeoxyglucose and 11C-methionine positron emission tomography findings in Sturge-Weber syndrome--case report

Cerebral blood flow and metabolism were evaluated in an adult with symptomatic intractable epilepsy and Sturge-Weber syndrome (SWS) manifesting as angiomas in the left cerebral hemisphere. 99mTc-ethylcysteinate dimer single photon emission computed tomography detected reduced blood flow in the entire left cerebral hemisphere, and [18F]fluorodeoxyglucose positron emission tomography (PET) showed decreased glucose metabolism in the left cerebral hemisphere. These findings indicated hypofunction of the left cerebral hemisphere, which caused the right hemiparesis. 11C-methionine (11C-Met) PET revealed high 11C-Met accumulation in the angiomas in the left cerebral hemisphere. Immunostaining for glial fibrillary acidic protein showed positive reaction in the lesions. Gliosis is a likely mechanism for the 11C-Met accumulation, which is possibly associated with progressive calcification in the angiomas and retarded growth of patients with SWS occurring over many years.     

The effects of aging on material-independent and material-dependent neural correlates of source memory retrieval

Age-related declines in source memory have been observed for various stimuli and associated details. These impairments may be related to alterations in brain regions contributing to source memory via material-independent processes and/or regions specialized for processing specific materials. Using event-related functional magnetic resonance imaging, we investigate the effects of aging on source memory and associated neural activity for words and objects. Source accuracy was equally impaired in older adults for both materials. Imaging data revealed both groups recruited similar networks of regions to support source memory accuracy irrespective of material, including parietal and prefrontal cortices (PFC) and the hippocampus. Age-related decreases in material-independent activity linked to postretrieval monitoring were observed in right lateral PFC. Additionally, age-related increases in source accuracy effects were shown in perirhinal cortex, which were positively correlated with performance in older adults, potentially reflecting functional compensation. In addition to group differences in material-independent regions, age-related crossover interactions for material-dependent source memory effects were observed in regions selectively engaged by objects. These results suggest that older adults' source memory impairments reflect alterations in regions making material-independent contributions to source memory retrieval, primarily the lateral PFC, but may be further impacted by changes in regions sensitive to particular materials.