A test-retest study of cerebral blood flow during somatosensory stimulation in depressed patients with schizophrenia and major depression

Six depressed patients with schizophrenia and 6 depressed patients with major depression were investigated before and during somatosensory stimulation (SS) with Tc-99m HMPAO SPECT. 8 controls were investigated only under resting conditions. The results can be summarized as follows: 1. Both psychiatric patient groups were hypofrontal (dorsolateral prefrontal cortex) compared to controls. 2. Hypofrontality was further enhanced by SS, significantly only in affective psychoses in the right inferior frontal lobe and in the right frontal hemisphere in total, in schizophrenia in the left dorsolateral prefrontal cortex. 3. Within the frontal lobes different regions were affected by SS in the two diagnostic groups. 4. In the right inferior parietal lobe SS response was significantly different in the two illnesses with schizophrenia showing a relative decrease, affective psychoses showing a relative increase of activity. 5. SS produced an increase of cerebral blood flow in subcortical regions (statistically significant contralateral to SS in thalamus and basal ganglia, ipsilateral to SS in cerebellum), a pattern which was common to all psychiatric patients. 6. Somatosensory cortex flow was not changed by SS. In conclusion, we could not fully confirm our hypotheses that similar blood flow abnormalities in different illnesses during SS are only caused by similarities in depressive psychopathology. Instead, depressed patients with schizophrenia were different from depressed patients with major depression in showing decreased activity in interrelating brain regions participating in an attentional network.     

Measurement of nitric oxide in the rat cerebral cortex during hypercapnoea

Changes in nitric oxide (NO) concentration and cerebral blood flow (CBF) in the parietal cortex during hypercapnoea were investigated in anaesthetized rats, using a NO-selective electrode and laser Doppler flowmetry. When hypercapnoea was induced by inhalation of 5% CO2 for 10 min, both the NO concentration and CBF increased. After administration of 7-nitroindazole, a neuronal NO synthase (nNOS) inhibitor, both the basal NO and CBF decreased, and responses to hypercapnoea were also significantly suppressed by 70.1% and 73.2%, respectively, compared with the control state. These results suggest that NO derived from nNOS is involved not only in maintaining resting cerebral circulation but also in regulating CBF response during hypercapnoea.     

Neuron discharges in the rat auditory cortex during electrical intracortical stimulation

Cocaine and cocaine-associated cues elicit craving in addicts and reinstate cocaine-seeking behavior in rats. Craving and cocaine-seeking behavior may be mediated by withdrawal-induced changes in dopamine (DA) neurotransmission in the amygdala. To examine whether there are concomittant changes in cocaine-seeking behavior and extracellular DA levels during withdrawal, experimental rats were trained to self-administer cocaine (0.75 mg/kg i.v.). After 14 daily 3-hour training sessions, animals underwent either a 1-day, 1-week, or 1-month withdrawal period. Extracellular DA levels were assessed during baseline, extinction, cue reinstatement, and cocaine (15 mg/kg i.p.) reinstatement of cocaine-seeking behavior (i.e., defined as the difference in nonreinforced lever presses on an active minus inactive lever). Cocaine-seeking behavior became more intense during the course of cocaine withdrawal. Additionally, basal and cocaine-induced extracellular DA levels were enhanced after the 1-month withdrawal period. We suggest that the former may reflect a persistent elevation in tonic extracellular DA levels in the amygdala, whereas the latter may reflect a persistent elevation in phasic extracellular DA levels.     

EEG evidence of stimulus-directed response dynamics in human somatosensory cortex

Dense multichannel recordings of scalp electroencephalogram (EEG) were obtained in the vicinity of primary somatosensory cortex, time-locked to repetitive vibrotactile stimulation of sites on the right index finger of a single human subject. Frequency-domain analysis of cross-trial averages revealed prominent 'driving' responses in the EEG at the frequency of stimulation, which under specific stimulus conditions displayed pronounced changes in amplitude and topographic organization over brief (4 s) durations of stimulus exposure. The changes were systematic and physiologically coherent, evolving toward driving-response topographies observed in the same subject in conjunction with periodic microstimulation of single mechanoreceptive afferents whose receptive fields occupied corresponding positions on the digit. This dynamic process was orderly and reproducible, and could be controlled by manipulating factors such as the amplitude, frequency, and temporal spacing of the stimuli. The results are tentatively interpreted in light of a previously proposed neurophysiological model of stimulus-driven response plasticity in mammalian somatosensory cortex.     

Dynamics of evoked potentials at different points in the cat somatosensory cortex during elaboration of conditioned reflexes

In chronic experiments on cats a study was made of the spreading of evoked potentials (EP) in the somatosensory zones S1 and S2 in response to biologically significant tonal stimuli. The formation of conditioned connections enhances the capacity for polysensory reactions in different cortical somatic fields outside the zones of local projection of the unconditioned stimulus. As stable conditioned connections are formed, this capacity diminishes in relation to reinforced and, particularly, easily differentiated sounds: EP are more localized in response to the former, and disappear altogether when the latter are presented. The wide EP spreading in zones S1 and S2 is the longest in response to medium and fine differentiation tones, which points to the involvement of these zones in the integrative analysis of signals by their biological quality.     

Single-cell correlates of a representational boundary in rat somatosensory cortex

In primary somatosensory cortex (S1), the transition from one representation to the next is typically abrupt when assayed physiologically. However, the extent of anatomical projections to and within the cortex do not strictly respect these physiologically defined transitions. Physiological properties, such as synaptic strengths or intracortical inhibition, have been hypothesized to account for the functionally defined precision of these representational borders. Because these representational borders can be translocated across the cortex by manipulations or behaviors that change the activity patterns of inputs to the cortex, understanding the physiological mechanisms that delimit representations is also an important starting point for understanding cortical plasticity. A novel in vivo and in vitro preparation has been developed to examine the cellular and synaptic mechanisms that underlie representational borders in the rat. In vivo, a short segment of the border between the forepaw-lower jaw representations in rat S1 was mapped using standard electrophysiological methods and was visibly marked using iontophoresis of pontamine sky blue dye. Slices were then obtained from this marked region and maintained in vitro. Intracellularly recorded responses to electrical stimulation of supragranular cortex were obtained from single neurons near the border in response to stimulation within the representational zone or across the border. Both excitatory and inhibitory responses were smaller when evoked by stimuli that activated projections that crossed borders, as compared with stimuli to projections that did not. These findings indicate that intracortical network properties are contributing to the expressions of representational discontinuities in the cortex.     

Optical intrinsic signal imaging responses are modulated in rodent somatosensory cortex during simultaneous whisker and forelimb stimulation

Optical intrinsic signal imaging (OIS) was used to investigate physiologic interactions between spatially and functionally distinct cortical somatosensory systems. The OIS response magnitude was evaluated after simultaneous stimulation of single whiskers and forelimb digits. Whisker C1 was deflected at a frequency of 10 Hz for 2 seconds while low- or high-intensity vibratory stimuli were applied to forelimb digits. The OIS responses to simultaneous whisker and forelimb stimulation were compared with lone whisker stimulated controls. Overall, addition of a second stimulus caused decreases in barrel cortex response magnitude. Three different response patterns were detected within individual trial sets. Modulation of barrel cortex evoked potentials provided evidence that changes in OIS responses observed here may be partially influenced by vascular responses to changes in neuronal activity. However, OIS responses in the barrel region during lone forelimb stimulation that were unaccompanied by evoked potentials suggested the possibility of independent vascular dynamic influences on response modulation. This study demonstrates that cortical responses at the level of primary sensory processing may be significantly influenced by activity in adjacent regions. Furthermore, it reveals that vascular and neuronal characteristics of interregional modulation do not co-localize and may produce responses in which one component increases while the other decreases.     

Restoration of oxygen uptake and blood flow in the rat cerebral cortex after halothane anaesthesia

The thoracic and lumbar curvatures of 105 Nigerian adults have been measured with a flexible rule (flexicurve). The lumbar curvature is relatively greater in women. Compared with a previous survey of Europeans, the curvatures in both men and women appear to be about 20 per cent greater in Nigerians. This is likely to be a genetic difference but the Nigerian practice of carrying heavy loads on the head may be a contributory factor.     

45Ca metabolism in slices of rat cerebral cortex during long-term potentiation

Ca45 kinetics was studied in 5, 15 and 30 min after potentiation. In the induction phase (1-5 min), the potentiation decreased the fraction of intracellular bound Ca. The 15-25 min potentiation the intra- and extracellular Ca levels was equal to the control ones. In 30 min, a considerable redistribution of Ca in the cells occurred.     

Developmental changes in intracellular calcium regulation in rat cerebral cortex during hypoxia

During the first weeks of life, injury to the central nervous system caused by brief periods of oxygen deprivation greatly increases. To investigate possible causes for this change, the effects of hypoxia or application of the excitatory neurotransmitter glutamate on intracellular calcium ([Ca2+]i) and ATP were studied in rat cerebrocortical brain slices. [Ca2+]i was measured fluorometrically with the indicator Fura-2. Hypoxia (95% N2/5% CO2) or 100 microM sodium cyanide produced gradual elevations in [Ca2+]i and ATP depletion in slices from rats < 2 weeks old, but rapid changes in older rats. After 20 min, [Ca2+]i in adult slices exposed to cyanide was 1,980 +/- 310 nM; in day 1-14 animals, it was 796 +/- 181 nM (p < 0.05). Combination of cyanide and a glycolytic inhibitor (iodoacetate) rapidly elevated [Ca2+]i and depleted ATP in all age groups. Energy utilization during anoxia, assessed by measuring ATP fall in cyanide/iodoacetate-treated brain slices, increased with age. Elevations in [Ca2+]i caused by application of 500 microM glutamate increased 240% from days 1-2 to day 28, but ATP loss caused by glutamate did not change with age. The N-methyl-D-aspartate antagonist MK-801 delayed calcium entry during the initial 5-7 min of hypoxia or cyanide in rats < 2 weeks old. We conclude that anaerobic ATP production, conservation of energy by reduced ATP consumption, and reduced sensitivity to glutamate contribute to delaying elevation in [Ca2+]i in neonatal rat brain during hypoxia.     

Effect of neuronal NO synthase inhibition on the cerebral vasodilatory response to somatosensory stimulation

Whether nitric oxide (NO) mediates--or not--the local cerebral blood flow (CBF) increases occurring during functional brain activation is still a controversial issue. In the present study, we sought to determine whether neuronal NO synthase is involved in the cerebrovascular response to activation of the trigeminal pathway in the rat. Local CBF was measured using the autoradiographic [14C]iodoantipyrine technique in control alpha-chloralose anesthetized rats and 30 min following administration of 7-nitroindazole (7-NI), an inhibitor of the neuronal NO synthase. Unilateral whiskers stroking increased local CBF in all six regions of the trigeminal pathway. Under 7-NI, CBF was slightly decreased and the vasodilatatory response to whisker stimulation was unaltered in the four trigeminal nuclei studied. In contrast, no significant vasodilatation was noted in the ventral posteromedial thalamic nucleus and somatosensory cortex. These results suggest that the neuronal NO synthase mediates the hyperemia associated with somatosensory activation in second order relay stations but not in the site of termination of primary afferents.     

The cerebral control of the somatosensory and auditory afferent projections to the cerebral cortex in man and animals

The main purpose of the present paper was consisted in studying of topology (spreading) of the somatosensory and auditory projections in cortex of both brain hemispheres in humans under different functional states conditions: during quiet walking state and during realization of the meditative programme. At the same time for the purpose of verification these steering mechanisms a number of experiments were realized in animals with neurosurgical cutting of brainstem ascending projections, which control the transfer of somatosensory and auditory sensibility. Experimental study was realized with two groups of subjects--8 subjects (age from 25 to 35 years old) and 25 (age from 25 to 40 years old) subjects practicing technique of Transcendental Meditation (TM). In addition to the mentioned above group some groups of animals were used in the experiments. Among them there were used the groups of monkeys (8 macaque rhesus and macaque nemestrina) and cats (10 animals) in conditions of acute experiment, under tiopenthal anesthesia. Two experimental methods were used in the study: electrophysiological for subjects and neurosurgical, additionally for animals. For evaluation of the brain reactivity in subjects registration of the somatosensory, to median nerve stimulation, and auditory, to bilateral application of auditory clicks, evoked potentials (EPs) in the symmetrical cortical structures of the brain was used. Registration of the somatosensory and auditory evoked potentials in animals was realized not only from the cortex, but from the brainstem somatosensory and auditory structures. SSEP in subjects-meditators were registered before and during meditation programme. In animals SSEP and AEP registration on the corresponding stimuli realized before and after neurosurgical operation--section of the midbrain tegmentum. Specific alterations of the early (up to 80 ms) and late components SSEP and AEP complexes in forms of topology spreading and diminution of registration areas of these components were obtained during the meditation. Origins of these functional reorganization are discussed from the positions of internal 'feed-back' inhibition.     

Action of L-acetylcarnitine on different cerebral mitochondrial populations from cerebral cortex

The maximum rate (Vmax) of some mitochondrial enzymatic activities related to the energy transduction (citrate synthase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase, glutamate-pyruvate-transaminase, glutamate-oxaloacetate-transaminase) was evaluated in non-synaptic (free) and intra-synaptic mitochondria from rat brain cerebral cortex. Three types of mitochondria were isolated from rats subjected to i.p. treatment with L-acetylcarnitine at two different doses (30 and 60 mg.kg-1, 28 days, 5 days/week). In control (vehicle-treated) animals, enzyme activities are differently expressed in non-synaptic mitochondria respect to intra-synaptic "light" and "heavy" ones. In fact, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, glutamate-pyruvate-transaminase and glutamate-oxaloacetate-transaminase are lower, while citrate synthase, cytochrome oxidase and glutamate dehydrogenase are higher in intra-synaptic mitochondria than in non-synaptic ones. This confirms that in various types of brain mitochondria a different metabolic machinery exists, due to their location in vivo. Treatment with L-acetylcarnitine decreased citrate synthase and glutamate dehydrogenase activities, while increased cytochrome oxidase and alpha-ketoglutarate dehydrogenase activities only in intra-synaptic mitochondria. Therefore in vivo administration of L-acetylcarnitine mainly affects some specific enzyme activities, suggesting a specific molecular trigger mode of action and only of the intra-synaptic mitochondria, suggesting a specific subcellular trigger site of action.     

Blood flow in different adipose tissue depots during prolonged exercise in dogs

Adipose tissue blood flow was measured by the microsphere technique in all major adipose tissue depots in dogs during exercise. The measurements were done during rest, after 1 and 2 h of exercise and after a postexercise rest period. It was found that the blood flow to the inguinal, subcutaneous adipose tissue increased from about 6 ml/(100 g . min) during rest to about 10 ml/(100 g.min) during exercise. This increase in flow was significantly smaller than the increase found in the perirenal, the mesenteric and the pericardial depots. In these depots the resting blood flow was about 10 ml/(100 g . min) increasing to about 30 ml/(100 g . min) during exercise. It is concluded that the increase in adipose tissue blood flow during exercise is a general phenomenon for all major adipose tissue depots. The increase in flow in the inguinal, subcutaneous fat pad was comparable to the previously described increase in flow in abdominal, subcutaneous tissue in man. Blood flow to abdominal skin was constant during exercise, while the flow in tissues from the gastrointestinal canal and in the kidneys decreased. The flow in the tongue and in the Achilles tendon significantly increased during exercise.     

Decreased heterogeneity of capillary plasma flow in the rat whisker-barrel cortex during functional hyperemia

The pattern of capillary plasma perfusion was investigated in the rat brain during functional activation. Functional hyperemia was induced in the left whisker-barrel cortex by deflection of the right mystacial vibrissae for 2 min at frequencies of 1-7 Hz. Rats were decapitated under anesthesia 3-4 s after i.v. bolus injection of Evans blue dye. The steep increase of the arterial dye concentration ensures that divergent capillary plasma transit times result in unequal intracapillary dye concentrations. Plasma perfusion heterogeneity was determined from the coefficient of variation (CV) of Evans blue concentrations measured in numerous single capillaries of the whisker-barrel cortex. Functional hyperemia was quantified from measurements of CBF using the [14C]-iodoantipyrine technique in a second experimental group. CBF in the left whisker-barrel cortex increased with the stimulation frequency and was maximal at 5 Hz compared to the right side. Conversely, plasma perfusion heterogeneity decreased with stimulation frequency in a reciprocal way, being minimal at 5 Hz. Results indicate a decrease in the microcirculatory flow heterogeneity during functional hyperemia in the brain.     

Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex

Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex. J. Neurophysiol. 80: 2882-2892, 1998. Whole cell recordings of synaptic responses evoked by deflection of individual vibrissa were obtained from neurons within adult rat primary somatosensory cortex. To define the spatial and temporal properties of subthreshold receptive fields, the spread, amplitude, latency to onset, rise time to half peak amplitude, and the balance of excitation and inhibition of subthreshold input were quantified. The convergence of information onto single neurons was found to be extensive: inputs were consistently evoked by vibrissa one- and two-away from the vibrissa that evoked the largest response (the "primary vibrissa"). Latency to onset, rise time, and the incidence and strength of inhibitory postsynaptic potentials (IPSPs) varied as a function of position within the receptive field and the strength of evoked excitatory input. Nonprimary vibrissae evoked smaller amplitude subthreshold responses [primary vibrissa, 9.1 +/- 0.84 (SE) mV, n = 14; 1-away, 5. 1 +/- 0.5 mV, n = 38; 2-away, 3.7 +/- 0.59 mV, n = 22; 3-away, 1.3 +/- 0.70 mV, n = 8] with longer latencies (primary vibrissa, 10.8 +/- 0.80 ms; 1-away, 15.0 +/- 1.2 ms; 2-away, 15.7 +/- 2.0 ms). Rise times were significantly faster for inputs that could evoke action potential responses (suprathreshold, 4.1 +/- 1.3 ms, n = 8; subthreshold, 12.4 +/- 1.5 ms, n = 61). In a subset of cells, sensory evoked IPSPs were examined by deflecting vibrissa during injection of hyperpolarizing and depolarizing current. The strongest IPSPs were evoked by the primary vibrissa (n = 5/5), but smaller IPSPs also were evoked by nonprimary vibrissae (n = 8/13). Inhibition peaked by 10-20 ms after the onset of the fastest excitatory input to the cortex. This pattern of inhibitory activity led to a functional reversal of the center of the receptive field and to suppression of later-arriving and slower-rising nonprimary inputs. Together, these data demonstrate that subthreshold receptive fields are on average large, and the spatio-temporal dynamics of these receptive fields vary as a function of position within the receptive field and strength of excitatory input. These findings constrain models of suprathreshold receptive field generation, multivibrissa interactions, and cortical plasticity.     

Long-term potentiation of the neuronal activity in the motor cortex induced by simultaneous stimulation of the thalamus and somatosensory cortex in cats

Long-lasting potentiation of the cat motor cortex units induced by tetanic stimulation of the VL + SCx led to an increase of the motor cortex unit discharge rate. The findings suggest that co-activation of cortico-cortical and thalamo-cortical afferents modifies neuronal activity of the motor cortex at the specific site which receives convergent sensory input from the thalamus and the somatosensory cortex.     

Regional cerebral blood flow during and after 2 hours of middle cerebral artery occlusion in the rat

In this study we explored if the secondary bioenergetic failure, which occurs a few hours after recirculation, following transient middle cerebral artery occlusion (MCAO) in rats, is caused by a compromised reflow. We induced 2 hours of MCAO and measured CBF at the end of the ischemia, as well as 15 minutes, 1, 2, and 4 hours after the start of recirculation, using autoradiographic or tissue sampling 14C-iodoantipyrine techniques. After 2 hours of MCAO, the autoradiographically measured CBF in the ischemic core areas was reduced to 3 to 5% of contralateral values. The reduction in CBF was less in neighboring, penumbral areas. After recirculation, flow already normalized in core tissues after 15 minutes, and remained close to normal for the 4 hours recirculation period studied. However, in penumbral tissues, recovery CBF values were usually below normal. The results show that tissues that are heavily compromised by the 2-hour period of ischemia and are destined to incur infarction, show a "relative hyperemia" during recirculation. In fact, some areas of the previously densely ischemic tissue showed overt hyperperfusion. This finding raises the question whether the relative or absolute hyperemia reflects events that are pathogenetically important. Because drugs that clearly ameliorate the final damage incurred fail to alter the relative hyperperfusion of previously ischemic tissues, it is concluded that vascular events in the reperfusion period do not play a major role in causing the final damage.