Voluntary enhancement of neural signatures of affiliative emotion using FMRI neurofeedback.

In Ridley Scott's film "Blade Runner", empathy-detection devices are employed to measure affiliative emotions. Despite recent neurocomputational advances, it is unknown whether brain signatures of affiliative emotions, such as tenderness/affection, can be decoded and voluntarily modulated. Here, we employed multivariate voxel pattern analysis and real-time fMRI to address this question. We found that participants were able to use visual feedback based on decoded fMRI patterns as a neurofeedback signal to increase brain activation characteristic of tenderness/affection relative to pride, an equally complex control emotion. Such improvement was not observed in a control group performing the same fMRI task without neurofeedback. Furthermore, the neurofeedback-driven enhancement of tenderness/affection-related distributed patterns was associated with local fMRI responses in the septohypothalamic area and frontopolar cortex, regions previously implicated in affiliative emotion. This demonstrates that humans can voluntarily enhance brain signatures of tenderness/affection, unlocking new possibilities for promoting prosocial emotions and countering antisocial behavior.

The medial forebrain bundle mediates cardiovascular responses to electrical stimulation of the medial prefrontal cortex.

The medial prefrontal cortex (MPFC) is involved in cardiovascular control. MPFC electrical stimulation has been reported to cause depressor and bradycardic responses in anesthetized rats. Although the pathway involved is yet unknown, there is evidence indicating the existence of a relay in the lateral hypothalamus (LH). The medial forebrain bundle (MFB) that courses in the lateral portion of the LH carries the vast majority of telencephalic afferent as well efferent projections, including those from the MPFC. To evaluate if the hypotensive pathway originating in the MPFC courses the MFB, we studied the effect of coronal or sagittal knife cuts through the LH and other brain areas on the cardiovascular responses to MPFC electrical stimulation. Knife cuts were performed using blades 1 to 6 mm wide. Results indicate that the neural pathway descending from the MFB decussates early in the vicinity of MPFC, crossing the midline within the corpus callosum and yielding two descending pathways that travel rostro-caudally in the lateral portion of the LH, within the MFB. The decussation was confirmed by histological analysis of brain sections processed after the injection of biotinilated dextran amine in the site of the stimulation in the MPFC. Because knife cuts through the LH ipsilateral had minimal effects on the cardiovascular responses and knife cuts performed contralateral to the stimulated MPFC had no effect on the response to MPFC stimulation, data indicate that the contralateral limb of the pathway may be only activated as an alternative pathway when the ipsilateral pathway is blocked.

The role of histamine on cognition.

Histamine was intensively studied at the beginning of the 20th century because of its important role in allergic and inflammation processes. In those days it was very difficult that researchers could envisage another impacting function for the imidazolamine in the living systems. Once the imidazolamine was found located in neuron compartment in the brain, increasing evidence supported many regulatory functions including its possible role in memory and learning. The specific participation of histamine in cognitive functions followed a slow and unclear pathway because the many different experimental learning models, pharmacologic approaches, systemic and localized applications of the histamine active compounds into the brain used by researchers showed facilitating or inhibitory effects on learning, generating an active issue that has extended up to present time. In this review, all these aspects are analyzed and discussed considering the many intracellular different mechanisms discovered for histamine, the specific histamine receptors and the compartmentalizing proprieties of the brain that might explain the apparent inconsistent effects of the imidazolamine in learning. In addition, a hypothetical physiologic role for histamine in memory is proposed under the standard theories of learning in experimental animals and humans.

Ingestive effects of NMDA and AMPA-kainate receptor antagonists microinjections into the lateral hypothalamus of the pigeon (Columba livia).

This study examined the ingestive and behavioral effects of NMDA- and AMPA/kainate glutamatergic receptor blockade in the lateral hypothalamic area (LHy) of free-feeding pigeons (Columba livia). Injections of MK-801 (NMDA receptor antagonist; 6 nmol) or CNQX (AMPA/kainate receptor antagonist; 25.8 nmol) into the LHy of free-feeding pigeons induced significant increases in food intake and in feeding duration, as well as reductions in the latency to start feeding. Duration, latency and volume of water intake, as well as duration of sleep-like behavior, alert immobility, locomotion and preening were not changed by these treatments in the LHy. These results indicate that glutamatergic inputs to cells containing NMDA and/or AMPA receptors located in the LHy could modify both the beginning of a feeding bout (or the end of a period of satiety) and its duration (satiation). Our data also suggest that these inhibitory glutamatergic influences on feeding behavior are tonically active in the LHy.

Cardiovascular responses to the injection of L-glutamate in the lateral hypothalamus of unanesthetized or anesthetized rats.

The present experiment was designed to compare the cardiovascular effects of injections of 0.1 M L-glutamate (50, 100 or 500 nL) into the anterior (LHa), tuberal (LHt) or posterior (LHp) regions of the lateral hypothalamus (LH) of either unanesthetized or anesthetized male Wistar rats. In unanesthetized rats, L-glutamate caused significant depressor responses without significant heart rate (HR) effects. L-Glutamate caused similar depressor responses when injected into the different LH subregions. A positive trend was observed between depressor response intensity and injected volume. In urethane-anesthetized rats, L-glutamate caused either depressor responses or biphasic responses, characterized by a significant initial depressor component followed by a secondary pressor response which was significant only after the injection of L-glutamate in 500 nL. The depressor component was accompanied by significant bradycardia only when the LHa or LHt were stimulated. Similar depressor responses were observed after L-glutamate microinjection into the different LH subregions. A positive trend was observed between depressor response intensity and injected volume. The present results suggest that: 1) lateral hypothalamic L-glutamate-sensitive neurons are involved in cardiovascular control and may have a wide and homogeneous distribution throughout the LH; 2) these neurons are mainly associated to the expression of hypotensive responses in unanesthetized rats; and 3) bradycardiac responses are evidenced when L-glutamate is microinjected into the LHa and the LHt in urethane-anesthetized rats.

Antinociceptive effects of stimulation of discrete sites in the rat hypothalamus: evidence for the participation of the lateral hypothalamus area in descending pain suppression mechanisms.

The sites in the rat hypothalamus where microinjection of morphine (5 micrograms/0.5 microliters) or electrical stimulation depresses the tail withdrawal reflex to noxious heating of the skin were examined. Among other hypothalamic sites found to be sensitive to morphine or to an electrical stimulus, the posterior part of the lateral hypothalamic area (LHA) was the only portion of the hypothalamus that was strongly sensitive to both manipulations. A 15-sec period of 35 microA sine-wave stimulation of the LHA significantly increased the latency of the tail reflex for periods up to 30 min. The effects of intraperitoneal administration of antagonists to opioids (naloxone), 5-hydroxytryptamine (methysergide), noradrenaline (phenoxybenzamine), dopamine (haloperidol), and acetylcholine (atropine and mecamylamine) on the antinociceptive effects of LHA stimulation were also examined. Naloxone, methysergide, and atropine (all given at doses of 0.5 and 1.0 mg/kg) attenuated the effects of LHA stimulation in a dose-dependent manner. Phenoxybenzamine but not haloperidol (both at the dose of 1.0 mg/kg), was also effective but dose-dependent curves could not be constructed. Mecamylamine (1.0 mg/kg) reduced the duration but not the peak effect of stimulating the LHA. We conclude that antagonism at the level of opioid, serotonergic, adrenergic, and muscarinic cholinergic receptors, but not dopamine or nicotinic cholinergic receptors, reduces the antinociceptive effects of LHA stimulation. This may imply that antinociception evoked from the LHA depends on the activation of descending pathways that relay in the mesencephalic periaqueductal gray matter and then in the nucleus raphe magnus and/or nucleus reticularis paragigantocellularis.

Antinociceptive effects of stimulation of discrete sites in the rat hypothalamus: evidence for the participation of the lateral hypothalamus area in descending pain suppression mechanisms

The sites in the rat hypothalamus where microinjection of morphine 5 mug/0.5 mul) or electrical stimulation depresses the tail withdrawal reflex to noxious heating of the skin were examined. Among other hypothalamic sites found to be sensitive to morphine or to an electrical stimulus, the posterior part of the lateral hypothalamic area (LHA) was the only portion of the hypothalamus that was strongly sensitive to both manipulations. A 15-sec period of 35-muA sine-wave stimulation of the LHA significantly increased the latency of the tail reflex for periods up to 30 min. The effects of intraperitoneal administration of antagonists to opioids (naloxone), 5-hydroxytryptamine (methysergide), noradrenaline (phenoxybenzarnine), dopamine (haloperidol and acetylcholine (atropine and mecamylamine) on the antinociceptive effects of LHA stimulation were also examined. Naloxone, methysergide, and atropine (all given at doses of 0.5 and 1.0 mg/kg attenuated the effects of LHA stimulation in a dose-dependent manner. Phenoxybenzamine, but not haloperidol (both at the dose of 1.0 mg/kg), was also effective but dose-dependent curves could not be constructed. Mecamylamine (1.0 mg/kg) reduced the duration but no the peak effect of stimulating the LHA. We conclude that antagonism at the level of opioid, serotonergic, adrenergic, and muscarinic cholinergic receptors, but not dopamine or nicotinic cholinergic receptors reduces the antinociceptive effects of LHA stimulation. This may imply that antinociception evoked from the LHA depends on the activation of descending pathways that relay in the mesencephalic periaqueductal gray matter and then in the nucleus raphe magnus and/or nucleus reticularis paragigantocellularis.

Ventromedial hypothalamus vs. lateral hypothalamic D2 satiety receptors in the body weight increase induced by systemic sulpiride.

Two experiments were conducted in order to see if dopamine satiety receptors in the lateral hypothalamus or satiety mechanisms in the ventromedial hypothalamus were involved in the hyperphagia and body weight increase induced by systemic sulpiride. In the first experiment, it was shown that systemic sulpiride (20 mg/kg) does not block the anorexia caused by intraperifornical injections of amphetamine. In the second experiment, sulpiride (20 mg/kg during 18 days) did not produce an additional increase in body weight in previously VMH-lesioned female rats. This last fact cannot be explained by a ceiling effect since insulin (5 U/day during 7 days) increased body weight in the same VMH rats in which sulpiride was not effective. These results do not support the hypothesis that systemic sulpiride reaches the perifornical dopamine D2 receptors to disinhibit feeding, but suggest instead an involvement of the ventromedial hypothalamus. This last suggestion is more in agreement with the hypothesis that sulpiride alters feeding and body weight gain through the induction of a functional gonadectomy.