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Identification of disabled-1 as a candidate gene for critical period neuroplasticity in cat and mouse visual cortex.

Rearing in darkness slows the time course of the critical period in visual cortex, such that at 5 weeks of age normal cats are more plastic than dark-reared cats, whereas at 20 weeks dark-reared cats are more plastic [G. D. Mower (1991)Dev. Brain Res., 58, 151-158]. Thus, a stringent criterion is that genes that are important for plasticity in visual cortex will show differences in expression between normal and dark-reared visual cortex that are of opposite direction in young vs. older animals. The present study reports the identification by differential display PCR of Dab-1, the mammalian homolog of the drosophila disabled-1 gene, as a candidate gene for critical period neuronal plasticity, expression of which is regulated according to this criterion in cat visual cortex. Evidence for this bidirectional direction regulation is extended to Dab-1 protein in cat and mouse visual cortex and shown to be specific to visual cortex, not occurring in frontal cortex. The Reelin/Dab-1 pathway has well-documented functions in cell migration during prenatal life and increasing evidence indicates that in postnatal brain the pathway plays a role in synaptic plasticity. The present results extend this evidence by directly implicating Dab-1 in postnatal critical period plasticity of visual cortex.

Animals↗

Functional mapping of the insular cortex: clinical implication in temporal lobe epilepsy.

PURPOSE: We report the results of 75 intracortical electrical stimulations of the insular cortex performed in 14 patients during stereo-electroencephalography (SEEG) investigation of drug-resistant partial epilepsy. The insular cortex was investigated on electroclinical arguments suggesting the possibility of a perisylvian spread or a rapid multilobar diffusion of the discharges during video EEG. METHODS: In these 14 patients, 27 stereotactically implanted transopercular electrodes reached the insular cortex (11 the right insula, 16 the left insula). Square pulses of current were applied between the two deepest adjacent contacts of each transopercular electrode using low (1 Hz) or high-frequency (50 Hz) stimulation. Only symptoms evoked in the absence of afterdischarges were analyzed. RESULTS: Clinical responses were evoked in 10 of the 14 patients (in 20 of the 27 insular sites) and showed a clear topographic specificity inside the insular cortex. Viscerosensitive and visceromotor responses, similar to those evoked by temporomesial stimulation, were evoked by anterior insular stimulation and somesthetic sensation, similar to those evoked by opercular cortex stimulation, by posterior insular stimulation. CONCLUSIONS: The topographic organization of the induced responses within the insular cortex suggest that two different cortical networks, a visceral network extending to the temporomesial structures and a somesthetic network reaching the opercular cortex, are disturbed with stimulation of the anterior or the posterior insula, respectively. Thus ictal symptoms associated with the spread of the epileptic discharges to the insular cortex might be difficult to distinguish from those usually reported during temporomesial or opercular discharges.

Adult↗

Origin of dopamine in the rat adrenal cortex.

The hypothesis that dopamine (DA) is involved in the control of aldosterone secretion is given some support by the finding of DA in the adrenal cortex of several species, but the source of this DA is not known. This study showed that the administration of L-dopa to intact rats or medullectomized rats caused a significant DA increase in the adrenal cortex. The DA increase in the cortex was more pronounced than in the medulla, coincident with higher L-dopa uptake by the cortical tissue. Tyrosine administration raised DA levels only in the medulla. Sympathectomy of the rat by 6-hydroxydopamine treatment did not affect DA basal levels in the cortex or the DA increase in this tissue after L-dopa injection. 3,4-Dihydroxyphenylacetic acid (DOPAC) is detectable in the adrenal cortex but not in the adrenal medulla, and DOPAC levels increased significantly after L-dopa, which indicates monoamine oxidase (MAO) activity within the adrenal cortex. Because 6-hydroxydopamine pretreatment did not alter DOPAC levels, cortical MAO may be located outside catecholaminergic neurons. The results established circulating L-dopa as a precursor for DA in the adrenal cortex of the rat. They also showed that tyrosine hydroxylase activity is absent from the adrenal cortex of this species.

3,4-Dihydroxyphenylacetic Acid↗

Spectrotemporal receptive fields in the lemniscal auditory thalamus and cortex.

Receptive fields have been characterized independently in the lemniscal auditory thalamus and cortex, usually with spectrotemporally simple sounds tailored to a specific task. No studies have employed naturalistic stimuli to investigate the thalamocortical transformation in temporal, spectral, and aural domains simultaneously and under identical conditions. We recorded simultaneously in the ventral division of the medial geniculate body (MGBv) and in primary auditory cortex (AI) of the ketamine-anesthetized cat. Spectrotemporal receptive fields (STRFs) of single units (n = 387) were derived by reverse-correlation with a broadband and dynamically varying stimulus, the dynamic ripple. Spectral integration, as measured by excitatory bandwidth and spectral modulation preference, was similar across both stations (mean Q(1/e) thalamus = 5.8, cortex = 5.4; upper cutoff of spectral modulation transfer function, thalamus = 1.30 cycles/octave, cortex = 1.37 cycles/octave). Temporal modulation rates slowed by a factor of two from thalamus to cortex (mean preferred rate, thalamus = 32.4 Hz, cortex = 16.6 Hz; upper cutoff of temporal modulation transfer function, thalamus = 62.9 Hz, cortex = 37.4 Hz). We found no correlation between spectral and temporal integration properties, suggesting that the excitatory-inhibitory interactions underlying preference in each domain are largely independent. A small number of neurons in each station had highly asymmetric STRFs, evidence of frequency sweep selectivity, but the population showed no directional bias. Binaural preferences differed in their relative proportions, most notably an increased prevalence of excitatory contralateral-only cells in cortex (40%) versus thalamus (23%), indicating a reorganization of this parameter. By comparing simultaneously along multiple stimulus dimensions in both stations, these observations establish the global characteristics of the thalamocortical receptive field transformation.

Acoustic Stimulation↗

Enhancement of visual responses in monkey striate cortex and frontal eye fields.

1. We have studied the visual enhancement effect in two areas of the cerebral cortex of monkeys. The response of the cells to a visual stimulus was determined both when the monkey used the visual stimulus as the target for a saccadic eye movement and when he did not. 2. In striate cortex cells with nonoriented, simple, complex, and hypercomplex receptive-field types were studied. Clear enhancement of the response to the appropriate visual stimulus was seldom seen when the monkey used the stimulus as a target for a saccade. In addition, any enhancement effect seen was nonselective; it occurred whether the monkey made a saccade to the receptive-field stimulus or some other stimulus at a point distant from the receptive field. The enhancement also occurred whether the monkey made a saccade to the stimulus or just released the bar when the stimulus dimmed. 3. This nonselective enhancement in striate cortex is in striking contrast to the selective enhancement of the visual response seen in the superior colliculus. The different characteristics of the enhancement in striate cortex and the observation of enhancement in the colliculus following ablation of striate cortex suggest that this cortical area is an unlikely source of the collicular enhancement. 4. These observations reinforce the distinction between striate cortex and superior colliculus. Striate cortex is an excellent analyzer of stimulus characteristics but a poor evaluator of stimulus significance. The superior colliculus is an excellent evaluator but a poor analyzer. 5. The area of frontal eye fields in which cells have clear visual responses has been better localized. Enhancement of the visual response of these cells also occurs and, at least for some cells, the response enhancement is selective. The response enhancement, like the visual properties of these frontal eye field cells, appears to be more closely related to the properties of superior colliculus cells than to striate cortex cells.

Animals↗

Effects of cooling somatosensory cortex on response properties of tactile cells in the superior colliculus.

The corticotectal influences of somatosensory cortex were investigated by using reversible deactivation of cortex by cooling. More than half of the somatosensory superior colliculus (SC) cells studied exhibited a response depression (often not apparent qualitatively) or an elimination of responses to somatosensory stimuli during the period in which cortex was rendered inactive. Responses were restored to their initial levels by cortical rewarming. Hyperresponsiveness was never observed as a consequence of cortical cooling. Susceptibility to cooling-induced depression was not invariably linked to a specific cell type, location in the SC, or receptive-field size. Yet cells that had small receptive fields and were activated by hair displacement had the highest probability of being affected by this procedure. In some cells a contraction of the receptive field was induced by cortical cooling. This observation is consistent with previous experiments that showed that SC somatosensory receptive fields are constructed by the convergence of ascending and descending inputs and indicates that the responsiveness of specific receptive-field regions may depend on the functional integrity of cortex. Two cortical regions were found to produce cooling-induced effects in somatosensory SC cells: 1) SIV (and para-SIV), located in the anterior ectosylvian sulcus, and 2) the cortex within the rostral suprasylvian sulcus. These results indicate that somatosensory cortex, like visual cortex, plays a critical role in modulating the responses of SC cells. Apparently, the ability of both somatosensory and visual SC cells to code the presence of peripheral stimuli depends largely on the functional influences of their respective cortices. However, in contrast to previous observations on visual corticotectal influences, no specific receptive-field properties could be shown to be impressed on SC cells by somatosensory cortex.

Animals↗

Visual response latencies in striate cortex of the macaque monkey.

1. Many lines of evidence suggest that signals relayed by the magnocellular and parvocellular subdivisions of the primate lateral geniculate nucleus (LGN) maintain their segregation in cortical processing. We have examined two response properties of units in the striate cortex of macaque monkeys, latency and transience, with the goal of assessing whether they might be used to infer specific geniculate contributions. Recordings were made from 298 isolated units and 1,129 multiunit sites in the striate cortex in four monkeys. Excitotoxin lesions that selectively affected one or the other LGN subdivision were made in three animals to demonstrate directly the magnocellular and parvocellular contributions. An additional 435 single units and 551 multiunit sites were recorded after the ablations. 2. Most units in striate cortex had visual response latencies in the range of 30-50 ms under the stimulus conditions used. The earliest neuronal responses in striate cortex differed appreciably between individuals. The shortest latency recorded in the four animals ranged from 20 to 31 ms. Comparable values were obtained from both single unit and multiunit sites. After lesions were made in the magnocellular subdivision of the LGN in two animals, the shortest response latencies were 7 and 10 ms later than before the ablations. A larger lesion in the parvocellular subdivision of another animal produced no such shift. Thus it appears that the first 7-10 ms of cortical activation can be attributed to activation relayed by the magnocellular layers of the LGN. 3. The units with the shortest latencies were all found in layers 4C or 6 and their responses were among the most transient in striate cortex. Furthermore, their responses all showed a pronounced periodicity at a frequency of 50-100 Hz. This periodicity was stimulus locked, and the responses of all short-latency units oscillated in phase. 4. An index of response transience was computed for the units recorded in striate cortex. The distribution of this index was unimodal and gave no suggestion of distinct contributions from the geniculate subdivisions. Magnocellular and the parvocellular lesions affected the overall transience of responses in striate cortex. The changes, however, were very small; extremely transient responses and extremely sustained responses survived both types of lesions. 5. A characteristic profile was observed in the response latencies in superficial layers. Latencies appeared to increase monotonically from layer 4 toward the surface of cortex, with the most superficial neurons not becoming active until 15 ms after responses were observed in layer 4C.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Comparison of cerebellar and motor cortex activity during reaching: directional tuning and response variability.

1. The responses of 262 motor cortex cells and 223 cerebellar neurons were recorded during whole-arm reaching movements toward targets lights in eight evenly distributed directions radiating from a common central starting position. The reaching movements were followed by a 2-s target hold period where a fixed arm posture was actively maintained to stabilize the hand over the target light. 2. Cerebellar neurons had a higher mean tonic discharge rate while holding over the starting position (22.9 imp/s) than did motor cortex cells (12.5 imp/s). The mean population response curve describing the changes in activities with movement direction was likewise shifted toward higher frequencies in the cerebellum compared with the motor cortex, but the amplitude of the two curves was about equal. Therefore, the baseline discharges of cerebellar neurons were higher, but their changes in activity during movement were similar to those of motor cortical cells. 3. Motor cortex neurons were more strongly related to active maintenance of different arm postures than were cerebellar units. This was shown by a larger posture-related population response curve in the motor cortex (half-wave amplitude of cosine function was 11.2 imp/s, compared with 7.0 imp/s for cerebellar neurons), which represented the average response curve calculated from all the cells of the population. Furthermore, the motor cortex population had a higher percentage of single cells with tonic responses while the hand was held over different targets (tonic and phasic-tonic cells composed 57% of motor cortex population, compared with 38% of cerebellar population). Proportionately more cerebellar cells were phasically related to the movements. 4. The majority of motor cortex cells (58%) showed reciprocal changes relative to the center-hold time activity where the activity increased for movements in the preferred direction and decreased for movements in the opposite direction. Most of the remaining cells (40%) showed graded changes where the activity increased gradually as reaching was directed closer to the preferred direction. In contrast, the most common cerebellar response pattern was graded (38%). Only 26% were reciprocal and 18% were non-directional. The remaining 2% of motor cortical cells and 18% of cerebellar neurons could not be readily assigned to any of these three response classes. 5. Sector widths were calculated to measure the dispersion of individual cerebellar and motor cortical cell activities about the eight movement directions. Sector widths calculated from the absolute activities were always broader for cerebellar neurons (i.e., the cells were more broadly tuned).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Oscillatory activity in sensorimotor cortex of awake monkeys: synchronization of local field potentials and relation to behavior.

1. Oscillations of 20-40 Hz were observed in local field potentials (LFPs) and unit activity in sensorimotor cortices of three awake monkeys while the monkeys performed trained wrist movements and untrained exploratory arm movements. The mean frequency of LFP oscillations was 25.9 +/- 1.4 (SD) Hz and the number of cycles of oscillations per episode was variable, with a mean of 4.2 +/- 0.5 (mean +/- SE). 2. Oscillatory episodes occurred most often when the monkeys retrieved raisins from a Klüver board (0.59 +/- 0.23 episodes per s, mean +/- SD) or from unseen locations with the use of somatosensory feedback (0.62 +/- 0.12 episodes per s); they occurred less often when the monkeys performed repetitive wrist flexion and extension movements (0.22 +/- 0.04 episodes per s) or sat quietly at rest (0.23 +/- 0.17 episodes per s). 3. The amplitude of LFP oscillations increased with depth in cortex, reaching a maximum between 1 and 2 mm. LFP oscillations at the surface of the cortex were 180 degrees out of phase with oscillations in the deep cortical layers. The phase shift (with respect to the deep layers) decreased with depth in the cortex and disappeared at depths of > 1 mm. 4. LFPs were recorded simultaneously at multiple sites in the sensorimotor cortex when monkeys retrieved raisins from a Klüver board or from unseen locations. Cross-correlation of LFPs recorded at different sites indicated that oscillations in the 20- to 40-Hz range could become synchronized at sites separated by up to > or = 14 mm in the precentral cortex. 5. The probability of occurrence of significant correlations between LFP oscillations at paired sites and the average correlation amplitude decreased with increasing horizontal separation of sites in precentral cortex. The phase shift between LFP oscillations recorded at paired sites did not change significantly with increasing horizontal separation. 6. For paired sites in precentral cortex, the average strength of correlations and the proportion of oscillations that were significantly correlated were greater during exploratory behaviors such as retrieving raisins from slots of the Klüver board than during periods of rest or overtrained wrist movements. 7. Oscillations could become synchronized with small phase shifts (0.5 +/- 1.6 ms) between pre- and postcentral cortical sites. Average strength and probability of occurrence of significant correlations between pre- and postcentral LFPs increased during exploratory behaviors. 8. Oscillations occurred simultaneously in the left and right motor cortex and could become synchronized with negligible phase shifts when the monkey performed bimanual manipulations. However, synchronization occurred as often and as strongly for unimanual as for bimanual manipulations. 9. These results indicate that episodes of 20- to 40-Hz oscillations occur often and become synchronized over a large cortical area during exploratory forelimb movements. However, they have no reliable relation to particular components of the movement and therefore seem unlikely to be involved directly in movement execution; instead, they may represent a neural correlate of attention during demanding sensorimotor behaviors.

Animals↗

Functional double dissociation between two inferior temporal cortical areas: perirhinal cortex versus middle temporal gyrus.

There is both anatomic and cytoarchitectural evidence for dorsal-ventral subdivisions of the inferior temporal cortex. Despite this, there has been only limited evidence of corresponding functional subdivisions and no evidence that two adjacent cortical areas within the inferior temporal cortex, namely area TE and the perirhinal cortex, have distinctly different roles in vision and memory. We assessed the color discrimination abilities of cynomolgus monkeys with either bilateral ablation of the perirhinal cortex or bilateral ablation of the middle temporal gyrus. The stimuli were isoluminant colored squares presented on a touch screen. In each trial the subject had to learn to discriminate and select the correct choice (green) from among a maximum of eight other foils, each varying in either hue or saturation. Relative to unoperated controls, monkeys with middle temporal gyrus lesions were severely impaired in the color discrimination task, whereas monkeys with perirhinal lesions were unimpaired on this task. We also assessed the visual recognition abilities, as measured by a basic delayed nonmatching-to-sample task with trial-unique objects presented in a Wisconsin General Test Apparatus, of rhesus monkeys with bilateral middle temporal gyrus lesions. We then tested the monkeys' postoperative performance on a delayed nonmatching-to-sample task with delays and extended list lengths. The results from this experiment were compared with those from two other groups of rhesus monkeys, an unoperated control group and a group with bilateral perirhinal cortex lesions, both of which had performed the identical tasks in a previous experiment. Relative to unoperated controls, monkeys with perirhinal cortex lesions were severely impaired both in relearning the basic delayed nonmatching-to-sample task and on the postoperative performance test. In contrast, monkeys with middle temporal gyrus lesions were only mildly affected in relearning the basic nonmatching task and were unimpaired on the postoperative performance test. Thus our data demonstrate a clear functional double dissociation between the perirhinal cortex and the middle temporal gyrus. This result gives strong support to the hypothesis that the perirhinal cortex and the adjacent area TE have distinctly different roles in visual learning and memory.

Analysis of Variance↗

Handedness and asymmetry of hand representation in human motor cortex.

The cortical representation of five simple hand and finger movements in the human motor cortex was determined in left- and right-handed people with whole-head magnetoencephalography. Different movements were found to be represented by spatially segregated dipolar sources in primary motor cortex. The spatial arrangement of neuronal sources for digit and wrist movements was nonsomatotopic and varied greatly between subjects. As an estimator of hand area size in primary motor cortex, we determined the smallest cuboid volume enclosing the five dipole sources within the left and right hemisphere of each subject. Interhemispheric comparison revealed a significant increase of this volume in primary motor cortex opposite to the preferred hand. This asymmetry was due to a greater spatial segregation of neuronal dipole generators subserving different hand and finger actions in the dominant hemisphere. Mean Euclidean distances between dipole sources for different movements were 10.7 +/- 3.5 mm in the dominant and 9.4 +/- 3.5 mm in the nondominant hemisphere (mean +/- SD; P = 0. 01, two-tailed t-test). The expansion of hand representation in primary motor cortex could not simply be attributed to a greater number of pyramidal cells devoted to each particular movement as inferred from current source amplitudes. The degree of hemispheric asymmetry of hand area size in the primary motor cortex was correlated highly with the asymmetry of hand performance in a standardized handedness test (r = -0.76, P < 0.01). These results demonstrate for the first time a biological correlate of handedness in human motor cortex. The expansion of hand motor cortex in the dominant hemisphere may provide extra space for the cortical encoding of a greater motor skill repertoire of the preferred hand.

Adult↗

Role of mammalian auditory cortex in the perception of elementary sound properties.

Studies in several mammalian species have demonstrated that bilateral ablations of the auditory cortex have little effect on simple sound intensity and frequency-based behaviors. In the rat, for example, early experiments have shown that auditory ablations result in virtually no effect on the rat's ability to either detect tones or discriminate frequencies. Such lesion experiments, however, typically examine an animal's performance some time after recovery from ablation surgery. As such, they demonstrate that the cortex is not essential for simple auditory behaviors in the long run. Our study further explores the role of cortex in basic auditory perception by examining whether the cortex is normally involved in these behaviors. In these experiments we reversibly inactivated the rat primary auditory cortex (AI) using the GABA agonist muscimol, while the animals performed a simple auditory task. At the same time we monitored the rat's auditory activity by recording auditory evoked potentials (AEP) from the cortical surface. In contrast to lesion studies, the rapid time course of these experimental conditions preclude reorganization of the auditory system that might otherwise compensate for the loss of cortical processing. Soon after bilateral muscimol application to their AI region, our rats exhibited an acute and profound inability to detect tones. After a few hours this state was followed by a gradual recovery of normal hearing, first of tone detection and, much later, of the ability to discriminate frequencies. Surface muscimol application, at the same time, drastically altered the normal rat AEP. Some of the normal AEP components vanished nearly instantaneously to unveil an underlying waveform, whose size was related to the severity of accompanying behavioral deficits. These results strongly suggest that the cortex is directly involved in basic acoustic processing. Along with observations from accompanying multiunit experiments that related the AEP to AI neuronal activity, our results suggest that a critical amount of activity in the auditory cortex is necessary for normal hearing. It is likely that the involvement of the cortex in simple auditory perceptions has hitherto not been clearly understood because of underlying recovery processes that, in the long-term, safeguard fundamental auditory abilities after cortical injury.

Animals↗

Frequency potentiation in the medial cortex of young turtle brains in vitro.

Turtle brains have a relatively primitive cortex. Glutamate receptors in the cortex of turtles include N-methyl-D-aspartate (NMDA) and DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA). Our aim was to determine whether the medial cortex in turtles, like the cortex and hippocampus in mammals exhibits frequency potentiation, a non-lasting form of synaptic plasticity, and, if so, to identify the involved receptors. Our results indicate that (1) the medial cortex exhibits this phenomenon with septal stimulation at 2 Hz, the frequency with maximum power spectral density in the electrocorticogram of turtles, showing an increase in both the excitatory postsynaptic potential and the evoked potential amplitudes; (2) the frequency potentiation of the medial cortex in turtles is mediated by AMPA type glutamate receptors; (3) the dynamics of frequency potentiation development in turtles show a number of differences from that in mammals. In summary, the cortex in this group of reptiles exhibits a functional trait of the cortex in mammals that is related to learning and memory; this trait, frequency potentiation, may have appeared as an independent specialization in both groups.

Animals↗

Arterial supply of the feline motor cortex.

The arterial supply of the feline motor cortex is derived from both the anterior and middle cerebral arteries. The anterior cerebral artery supplies most of cortical area 6 (premotor cortex), the intrafundal cruciate and medial postcruciate cortex, (hindlimb motor cortex), and the midline and medial portions of the sensory areas 3a-7. The middle cerebral artery supplies the lateral prorean cortex, (lateral premotor cortex), precruciate and lateral sigmoid cortex, (forelimb motor cortex), and the remainder of the coronal and Sylvian cortical areas.

Animals↗

Incomplete brain infarction of reperfused cortex may be quantitated with iomazenil.

BACKGROUND AND PURPOSE: [123I]Iomazenil is a specific radioligand for the central benzodiazepine receptor that may be useful as an indicator of the intactness of cortical neurons after focal cerebral ischemia. We evaluated the binding of this receptor in reperfused cortex among patients with ischemic stroke to detect viable neurons in cortex that appeared structurally intact on conventional neuroimaging studies. METHODS: Fourteen patients were selected by (1) angiography within 24 hours of onset showing embolic occlusion of an intracranial artery, (2) cerebral blood flow showing ischemia of moderate severity in 12 cases and spontaneous reflow in 2 cases, and (3) thrombolysis with reperfusion within 24 hours in most cases. Thirty reperfused cortical areas that remained structurally intact, 7 infarcted cortical areas, and 6 contralateral cerebellar areas with reduced blood flow were selected as regions of interest to estimate receptor binding 5 days to 23 months after the stroke. A two-compartment model was used to compute the distribution volume (Vd) of iomazenil in relative units, with Vd proportional to benzodiazepine receptor concentration. The side-to-side asymmetry ratio of Vd was calculated. RESULTS: The mean asymmetry ratio was 0.89 +/- 0.11 (range, 0.64 to 1.05), 0.50 +/- 0.15 (range, 0.23 to 0.67), and 0.97 +/- 0.05 (range, 0.90 to 1.04) in reperfused cortex, infarcted cortex, and contralateral cerebellum, respectively. Compared with unity, both reperfused cortex and infarcted cortex showed significant decrease of Vd (P < .001). Contralateral cerebellum showing diaschisis had no reduction of Vd. On MRI, obtained 3 or 6 months after the stroke, mild cortical atrophy was observed in two reperfused areas where the asymmetry ratio was moderately reduced (0.64 and 0.80). CONCLUSIONS: The reduction of benzodiazepine receptor concentration in reperfused cortex that remained structurally intact is likely to be the result of injury involving only a limited number of neurons (ie, incomplete infarction). Our data suggest that the degree of viability of ischemic cortex apparently salvaged by early reperfusion can be quantified by iomazenil.

Aged↗

Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: an MRI-based parcellation of the prefrontal cortex.

OBJECTIVE: To examine structural abnormalities in subregions of the prefrontal cortex in elderly patients with depression, the authors explored differences in gray matter, white matter, and CSF volumes by applying a parcellation method based on magnetic resonance imaging (MRI). METHOD: Twenty-four elderly patients with major depression and 19 group-matched comparison subjects were studied with high-resolution MRI. Cortical surface extraction, tissue segmentation, and cortical parcellation methods were applied to obtain volume measures of gray matter, white matter, and CSF in seven prefrontal subregions: the anterior cingulate, gyrus rectus, orbitofrontal cortex, precentral gyrus, superior frontal cortex, middle frontal cortex, and inferior frontal cortex. RESULTS: Highly significant bilateral volume reductions in gray matter were observed in the anterior cingulate, the gyrus rectus, and the orbitofrontal cortex. Depressed patients also exhibited significant bilateral white matter volume reductions and significant CSF volume increases in the anterior cingulate and the gyrus rectus. Finally, the depressed group showed significant CSF volume reductions in the orbitofrontal cortex relative to the comparison subjects. None of the other regions examined revealed significant structural abnormalities. CONCLUSIONS: The prominent bilateral gray matter deficits in the anterior cingulate and the gyrus rectus as well as the orbitofrontal cortex may reflect disease-specific modifications of elderly depression. The differential pattern of abnormalities detected in the white matter and CSF compartments imply that distinct etiopathological mechanisms might underlie the structural cortical changes in these regions.

Aged↗

Usefulness of MRI measures of entorhinal cortex versus hippocampus in AD.

OBJECTIVE: MRI-based measurements of hippocampal atrophy are a sensitive indicator of the early pathologic degeneration of the medial temporal lobe in AD. However, AD pathology appears first in the transentorhinal/entorhinal cortex, not the hippocampus. The authors tested the hypothesis that MRI-based measurements of the entorhinal cortex are more sensitive than measurements of hippocampal volume in discriminating among three clinical groups; controls, patients with a mild cognitive impairment (MCI), and patients with mild probable AD. METHODS: The authors studied 30 controls, 30 patients with MCI, and 30 patients with AD who were matched among clinical groups on age, gender, and education. All underwent a standardized MRI protocol from which the authors made measurements of hippocampal volume, entorhinal cortex volume, and the cumulative length of the medial border of the entorhinal cortex. RESULTS: Pairwise intergroup differences (p < 0.01) were found for all MRI measurements with the exception of the cumulative length of the entorhinal cortex, which did not differentiate controls from MCI patients. Whereas the hippocampal and entorhinal cortex volume measurements provided slightly better intergroup discrimination than the entorhinal distance measurement, overall differences in discriminating ability among the three MRI measurements were minor. CONCLUSIONS: Despite the theoretical rationale for the superiority of entorhinal measurements in early AD, the authors found MRI measurements of the hippocampus and entorhinal cortex were approximately equivalent at intergroup discrimination. Measurements of the hippocampus may be preferable because MRI depiction of the boundaries of the entorhinal cortex can be obscured by anatomic ambiguity, image artifact, or both.

Aged↗

Double dissociation of exteroceptive and interoceptive feedback systems in the orbital and ventromedial prefrontal cortex of humans.

The primate ventral prefrontal cortex contains two densely interconnected subregions: a lateral/orbital cortex processing primarily sensory/exteroceptive information, and a ventromedial cortex processing primarily visceroappetitive/interoceptive information. These regions have major afferents from and efferents to other associative cortices. The organization of these structures leads to an hypothesized role in feedback processing. We use neuroimaging to test this model, defined so far mostly through anatomical studies. Healthy volunteers were trained operantly on a transitive inference task (A>B, B>C ==> A>C) requiring flexible manipulation of feedback to solve. Two groups of subjects learned an arbitrary face hierarchy, one adjacent face pair at a time; each group received either visual/exteroceptive ("XXXX") or visceroappetitive/interoceptive (fruit juice) feedback for correct responses to adjacent face pairs. After task acquisition, the subjects were tested on novel stimulus pairs (i.e., nonadjacent, TEST) derived from the acquired hierarchy. The TEST condition required transitive inference. No feedback was provided during TEST. Brain activity during TEST in the group trained with visual/exteroceptive feedback increased in the orbital prefrontal cortex and decreased in the ventromedial prefrontal cortex. In contrast, brain activity during TEST in the group trained with visceroappetitive/interoceptive feedback decreased in the orbital prefrontal cortex and increased in the ventromedial prefrontal cortex. These results provide functional evidence, consistent with previous anatomical studies, for two major feedback systems in human ventral prefrontal cortex: a lateral system specialized for exteroceptive information and a medial system specialized for interoceptive information. Although highly interconnected, there is a double dissociation of function between these networks in healthy humans.

Adult↗