The role of the frontal cortex in the use of advance information in a mental rotation paradigm.

The present study explored the ability of patients with unilateral frontal or temporal lobe excisions to use advance information in a choice-reaction-time task that required the discrimination of alphanumeric characters on the basis of their form of presentation, normal or mirror-image. The response time of the subjects in all the groups depended upon the target's angular orientation, when no information regarding the orientation and the identity of the impending target was provided (No Information condition). In the Advance Information condition, reaction time did not vary greatly with changes in the target's orientation except for the subjects with left or right frontal lobe excisions. These findings provide evidence of the importance of the frontal cortex in the use of advance information.

Functional activation of the human brain during mental rotation.

Regional cerebral blood flow was measured with positron emission tomography during the performance of tasks that required cognitive spatial transformations of alphanumeric stimuli. In the mirror image task, the subjects were required to discriminate between the normal and the mirror images of alphanumeric stimuli presented in the upright orientation. In the mental rotation task, the same judgement was required, but now the stimuli were presented in various orientations other than the upright one. The subjects therefore had to rotate the stimuli, in mind, into the upright position before making their decision. In relation to the control task, which involved discrimination of these same stimuli but not any form of mental transformation, there were significant increases in the right postero-superior parietal cortex and the left inferior parietal cortex in both experimental tasks. For mental rotation, specific activity was seen only within the left inferior parietal region and the right head of the caudate nucleus. These results specified the parietal areas involved in a purely cognitive spatial process and demonstrated a close interaction between these areas and the anterior neostriatum and certain lateral frontal cortical areas in the discrimination of rotated forms of stimuli.

Effects of frontal or temporal lobectomy on the use of advance information in a choice reaction time task.

The ability to make use of directional cues presented to subjects before they are asked to make a specific response was studied in 69 patients who had undergone a unilateral frontal or temporal lobe excision, and in 24 normal control subjects. Choice reaction time was measured in two conditions: (1) informative, where a centrally presented cue indicated in advance the target's location, and (2) neutral, where the cue was a symbol carrying no directional information. Patients with excisions from the left or right frontal lobe did not benefit from the available information to the same extent as patients with either left or right temporal lobe excisions or normal control subjects.

Stability of regional cerebral glucose metabolism in the normal brain measured by positron emission tomography.

Cerebral glucose utilization (LCMRGI) was measured using the [18F]fluorodeoxyglucose method with PET in two groups of ten healthy young volunteers, each scanned in a resting state under different methodological conditions. In addition, five subjects had a second scan within 48 hr. Mean hemispheric values averaged 45.8 +/- 3.3 mumol/100 g/min in the right cerebral hemisphere and 47.0 +/- 3.7 mumol/100 g/min in the left hemisphere. A four-way analysis of variance (group, sex, region, hemisphere) was carried out on the results using three different methods of data manipulation: (a) the raw values of glucose utilization, (b) LCMRGI values "normalized" by the mean hemispheric gray matter LCMRGI value, and (c) log transformed LCMRGI values. For all analysis techniques, significantly higher LCMRGI values were consistently seen in the left mid and posterior temporal area and caudate nucleus relative to the right, and in the right occipital region relative to the left. The coefficient of variation of intrasubject regional differences (9.9%) was significantly smaller than the coefficient of variation for regions between subjects (16.5%). No differences were noted between the sexes and no effect of repeat procedures was seen in subjects having multiple scans. In addition, inter-regional LCMRGI correlations were examined both in values from the 20 normal subjects, as well as in a set of hypothetical "abnormal" values. Results were compared with those reported from other PET centers; despite certain methodological differences, the intersubject and inter-regional variation of LCMRGI is fairly constant.

Localization and lateralization of stereoscopic processing in the human brain.

Positron emission tomography was used to investigate the neural substrate of stereopsis. Changes in cerebral blood flow were measured in nine volunteers while they judged the orientation of a rectangular cyclopean shape in random dot stereograms. This experimental condition was compared with two control conditions, one having a two-dimensional shape but no cyclopean stimulus, the other having neither shape nor cyclopean stimulus. Blood flow increases were observed in areas 17 and 18 in the right hemisphere when comparing experimental with control conditions; blood flow decreases occurred in the right inferotemporal cortex. Results indicate that stereopsis begins in posterior visual areas in the right cerebral hemisphere. Under ambiguous stereoscopic conditions, participation of more anterior areas in the temporal lobe may be elicited.

Localization of cerebral activity during simple singing.

Cerebral blood flow (CBF) was measured with PET during rudimentary singing of a single pitch and vowel, contrasted to passive listening to complex tones. CBF increases in cortical areas related to motor control were seen in the supplementary motor area, anterior cingulate cortex, precentral gyri, anterior insula (and the adjacent inner face of the precentral operculum) and cerebellum, replicating most previously seen during speech. Increases in auditory cortex were seen within right Heschl's gyrus, and in the posterior superior temporal plane (and the immediately overlying parietal cortex). Since cortex near right Heschl's has been linked to complex pitch perception, its asymmetric activation here may be related to analyzing the fundamental frequency of one's own voice for feedback-guided modulation.

Localization of cerebral activity during simple singing.

Cerebral blood flow (CBF) was measured with PET during rudimentary singing of a single pitch and vowel, contrasted to passive listening to complex tones. CBF increases in cortical areas related to motor control were seen in the supplementary motor area, anterior cingulate cortex, precentral gyri, anterior insula (and the adjacent inner face of the precentral operculum) and cerebellum, replicating most previously seen during speech. Increases in auditory cortex were seen within right Heschl's gyrus, and in the posterior superior temporal plane (and the immediately overlying parietal cortex). Since cortex near right Heschl's has been linked to complex pitch perception, its asymmetric activation here may be related to analyzing the fundamental frequency of one's own voice for feedback-guided modulation.

Hemispheric differences in matching Stroop-type letter stimuli.

Two experiments are reported in which normal right-handed males and females had to match two Stroop-type letter stimuli, according to either their global level (Experiment 1) or their local level (Experiment 2). Stimulus presentation was sequential with the first letter presented foveally and the second letter presented to either the right visual field (RVF) or the left visual field (LVF). A manual "Same-Different" response was required. In Experiment 1, the left hemisphere (RVF) showed interference from the irrelevant local level features, supporting an analytic processing mechanism, while the right hemisphere (LVF) showed no such effect, supporting a holistic matching mechanism. In Experiment 2, both hemispheres showed interference from the irrelevant global features, with the right showing a non-significant tendency towards a larger Stroop effect.

Sequential chemo-immunotherapy treatment of metastatic malignant melanoma.

Twelve patients with recurring metastatic inoperable malignant melanoma (performance status ECOG 0-1), received the following chemotherapy: tamoxifen p.o., carmustine i.v., dacarbazine i.v., and cisplatin i.v., followed by immunotherapy: interleukin-2 s.c. and interferon-alpha s.c. The treatment cycle was repeated every 6 weeks. Total response rate was 66.6%, with 25% (3 patients) achieving complete cure that has persisted for a period of 17.75 months (mean). In addition, different responses to treatment were observed between the local recurrence lesions and the metastatic lesions. Medium to severe side effects were observed, all but one of them being reversible (neurotoxicity), such as fever, anemia, leukopenia: nephrotoxicity, neurotoxicity, and dyspnea.

Dissociation of human mid-dorsolateral from posterior dorsolateral frontal cortex in memory processing.

Work with non-human primates had previously demonstrated that the mid-dorsolateral frontal cortex, which comprises cytoarchitectonic areas 46 and 9, plays a critical role in the performance of non-spatial self-ordered working memory tasks, whereas the immediately adjacent posterior dorsolateral frontal cortex (area 8) is critical for the learning and performance of visual conditional associative tasks. The present study used positron emission tomography with magnetic resonance imaging to demonstrate the existence, within the human brain, of these two functionally distinct subdivisions of the lateral frontal cortex. These findings provide direct evidence that, just as the monkey brain, the human lateral frontal cortex is functionally heterogeneous and that comparable anatomical areas underlie similar functions in the two species.

Functional activation of the human frontal cortex during the performance of verbal working memory tasks.

Regional cerebral blood flow was measured with positron emission tomography during the performance of verbal working memory tasks. The same type of verbal response (i.e., reciting numbers) was required in the control and the two experimental tasks. In the control task, the subjects were required to count aloud. In the two experimental tasks, the subjects were required to maintain within working memory the numbers they generated (self-ordered task) or the numbers generated by the experimenter (externally ordered task). Examination of the difference in activation between these conditions revealed strong bilateral activation within the mid-dorsolateral frontal cortex during both experimental tasks. There was, however, no evidence of additional activation within the mid-dorsolateral frontal cortex when monitoring self-generated responses as compared with the monitoring of externally generated responses. These results provide evidence regarding the role of the mid-dorsolateral frontal cortex in mnemonic processing that are in agreement with recent findings from work with non-human primates.

Functional activation of the human ventrolateral frontal cortex during mnemonic retrieval of verbal information.

Regional cerebral blood flow was measured with positron emission tomography during the performance of a verbal free recall task, a verbal paired associate task, and tasks that required the production of verbal responses either by speaking or writing. Examination of the differences in regional cerebral blood flow between these conditions demonstrated that the left ventrolateral frontal cortical area 45 is involved in the recall of verbal information from long-term memory, in addition to its contribution to speech. The act of writing activated a network of areas involving posterior parietal cortex and sensorimotor areas but not ventrolateral frontal cortex.

Attention modulates somatosensory cerebral blood flow response to vibrotactile stimulation as measured by positron emission tomography.

In human primary somatosensory cortex, the cerebral blood flow response to vibrotactile stimulation of the fingers (110 Hz), as measured by positron emission tomography and H2(15)O, was 13% higher (p less than 0.025) when the subjects attended to the stimulus, compared to when they were simultaneously engaged in a distraction task. This suggests that the physiological response of a primary cortical area can be modulated by the attentive behavior of the subject.