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Where does damage lead to enhanced food aversion: the ventral pallidum/substantia innominata or lateral hypothalamus?

It is well known that lesions of the lateral hypothalamus (LH) produce aphagia. Several previous studies have reported that lateral hypothalamus damage produces food aversion in addition to aphagia. However, damage to other regions near the LH also produce aphagia and enhanced aversion. The purpose of this study was to resolve where the site or sites for aversion-inducing lesions is/are located. Small, bilateral excitotoxin lesions (QUIN, 10 micrograms in 1 microliter or IBO, 15 micrograms in 1 microliter) or bilateral sham injections of vehicle were made into the globus pallidus (GP), the ventral pallidum/substantia innominata (VP/SI) or the lateral hypothalamus (LH). Affective reactions to taste were elicited by infusing sucrose solutions (1 M) into the mouth via chronic oral cannulae. The number of aversive responses (gapes, chin-rubbing, head-shaking and forelimb flails) emitted was tallied. Individual lesions were mapped and a single 'necessary and sufficient' site for damage-induced aversion was identified (the area of overlapping damage common to all rats that showed enhanced aversive reactions). To identify the lesions, two lesion-mapping techniques were used: (1) a conventional neuron-counting procedure in which an attempt is made to count all neurons within a brain region, and (2) a new modified 'fractionator' procedure consisting of exhaustive 400 x magnification counts at point locations within a brain region. Results indicated that aversive reactions to food are enhanced only following bilateral neuron loss (> 70%) from the caudal ventromedial VP/SI alone. This shared site has a lateral diameter of 1.0 mm, a dorsoventral diameter of 0.5 mm and a rostrocaudal diameter of 1.0 mm. Damage restricted to the LH never produced enhanced aversion even when it produced aphagia. The crucial region for aversion is located ventral and medial to the globus pallidus and dorsal and lateral to the lateral hypothalamus.

Animals↗

Consonant-vowel lateralization in dyslexic children: deficit or compensatory development?

Two studies with the same subjects examined dyslexic children's puzzling superiority in forced left ear (LE) dichotic recall with consonant-vowel (CV) combinations. Thirty dysphonemic dyslexics were compared to 30 age-matched and 30 younger reading-matched normal readers. The children were tested in directed attention dichotic listening and in pseudoword decoding, word recognition, reading comprehension, spelling, arithmetic, and general intelligence (IQ). Failure to replicate the LE effect in the first experiment or in free-recall trials suggests its probable origin in aberrant attention/arousal rather than in deviant verbal lateralization. Experiment two replicated the superior LE effect in comparison to both control groups but also found the dyslexics poorer at the right ear (RE). Laterality coefficients confirmed that the dyslexics were more weakly lateralized. Corrections for stimulus dominance revealed that the uncorrected scores (1) concealed the extreme difficulty of the task and (2) obscured floor effects in the LE performance of the normals. Correlations suggest cautiously that CV lateralization may be associated inversely with reading comprehension and word decoding in the dyslexics and normal readers. The results provide mild support for the hypothesis that weak attentional lateralization for CVs in dyslexia may result from the precocious development of posterior right hemisphere attentional systems in compensation for presumed posterior left hemisphere lesions. No support was found for the competing hypothesis that such weak lateralization may be a component of the dyslexics' primary, correlated, or secondary deficit symptomatology.

Brain↗

The concept of transcortical cell assemblies: a key to the understanding of cortical lateralization and interhemispheric interaction.

According to Hebb, elements of higher cognitive processes, such as concepts, words and mental images, are realized in the brain as cortical cell assemblies, i.e. large and strongly connected neuron populations that form functional units. Neurons belonging to such assemblies may be scattered over wide cortical areas, and some cell assemblies may even comprise neurons of both hemispheres (transcortical assemblies). If full activation (ignition) of an assembly leads to fast circulation of neuronal activity in the assembly, this process should be visible in high-frequency cortical responses. Some evidence will be reviewed that cell assembly ignition indeed leads to changes in high-frequency cortical responses which can be recorded in the EEG and MEG. Within the cell assembly-framework, the question of cortical laterality translates into the question of how neurons of transcortical assemblies are balanced between the hemispheres. This approach allows for different degrees of laterality. Recent evidence is summarized that the degree of laterality indeed differs between language units. For example, the cortical representation of certain words appears to be strongly lateralized to the left hemisphere while those of others are less lateralized. If neurons of both hemispheres are part of one assembly bihemispheric processing should lead to a processing advantage compared to processing in the dominant hemisphere alone. The latter appears to be the case for lexical processing, as revealed by recent behavioral studies. In conclusion, the cell assembly-framework suggests a more fine-grained description of the issue of cortical laterality; it is not appropriate to ask whether "modules" supporting higher cortical functions are located either in the left or right hemisphere. Rather, it appears fruitful to ask how the neurons of transcortical cell assemblies are balanced between the hemispheres.

Brain Mapping↗

Lateralized rhythms of the central and autonomic nervous systems.

This paper reviews lateralized ultradian rhythms in the nervous system and their unique place in evolutionary development. The rhythmic lateralization of neural activity in paired internal structures and the two sides of the central and autonomic nervous system is discussed as a new view for the temporal and spatial organization of higher vertebrates. These lateralized neural rhythms are integral to the hypothesis of the basic rest-activity cycle. Rhythms of alternating cerebral hemispheric dominance are postulated to be coupled to oscillations of the ergotrophic and trophotrophic states. The nasal cycle is coupled to this cerebral rhythm. This lateralized central and autonomic rhythm is discussed in relationship to ultradian rhythms of neuroendocrine activity, REM and NREM sleep, lateralized rhythms of plasma catecholamines, and other lateralized neural events. The relationship of this phenomenon to stress and adaptation is postulated. The effects of unilateral forced nostril breathing is reviewed as a method to alter cerebral activity, cognition, and other autonomic dependent phenomena.

Activity Cycles↗

Abnormal lateralization in finger tapping and overt aggressive behavior.

1. The relationship between abnormal cerebral lateralization and overt aggressive behavior was examined in 41 violent psychiatric patients in a maximum-security hospital. 2. Cerebral lateralization was measured using the Finger Oscillation Test from the Halstead-Reitan Neuropsychological Battery, and aggressive behavior was measured during a six-month period of hospitalization using the Overt Aggression Scale. 3. Patients with the most abnormal pattern of lateralization exhibited the highest frequency as well as the highest severity of overt aggressive behavior. This pattern could not be explained by the influence of age, race, IQ, history of head trauma, brain damage, or psychiatric diagnosis. History of seizures, alcohol abuse, and drug abuse, however, were found to be intervening variables in the lateralization-aggression link. Once their influence was removed using analysis of covariance, there was no relationship between lateralization and aggression. 4. The results suggest that it is unlikely that there is a direct causal relationship between abnormal lateralization and aggressive behavior.

Adult↗

Localization of lateral hypothalamic neurons projecting to the medial part of the parabrachial area of the rat.

We recently showed that electrical self-stimulation registered in the medial part of the parabrachial area, as well as the preference-aversion threshold to saccharin solutions were both significantly altered following ibotenic acid lesion of the lateral hypothalamic neurons. In order to identify the location of the neurons in the lateral hypothalamus directly projecting to the parabrachial area, we injected in the medial part of this area the retrograde tracer wheat germ agglutinin-inactive horseradish peroxidase coupled to colloidal gold. In the lateral hypothalamus a large number of labeled cells was constantly observed. This cluster of cells was located in the middle and posterior parts of the lateral hypothalamic area between the frontal plane corresponding to the posterior third of the ventromedial hypothalamic nucleus and the plane corresponding to the premammillary nuclei. In contrast, the anterior part of the lateral hypothalamus was unlabeled. Since the labeled neurons are located in the same region as those destroyed by our ibotenic acid lesions, the present results strongly suggest that these descending projections, originating in the posterior lateral hypothalamus, are implicated in reward mechanisms elicited from the parabrachial area.

Animals↗

The regulation of feeding and drinking in rats with lesions of the lateral hypothalamus made by N-methyl-D-aspartate.

Rats bearing excitotoxic lesions of the lateral hypothalamus are hypodipsic and hypophagic, but responses to 24 h food or water deprivation are normal, as are responses to different taste stimuli. The most striking deficit present in lateral hypothalamic-lesioned rats is an inability to respond as controls to dehydrating, dipsogenic or glucoprivic challenges. The present experiments examined the ability of rats bearing bilateral N-methyl-D-aspartate-induced lesions of the lateral hypothalamus to recognize and respond to changes in their internal environments. All of the lesioned rats tested showed mild to moderate hypophagia and hypodipsia, and none responded properly by drinking over 1 h after i.p. injection of hypertonic saline. However, the addition of glucose to the water supply promoted an increase in drinking and a decrease in lab chow consumption to maintain a constant energy intake; the addition of salt to the diet promoted an increase in drinking and no change in eating; 24 h water deprivation induced the same amount of drinking in lateral hypothalamic-lesioned rats as in controls; and injection i.p. of water (but not physiological saline) before drinking water was returned to rats which were 24 h water deprived suppressed drinking. These data suggest that lateral hypothalamic-lesioned rats are in receipt of normal information from their peripheries, and that they can adjust their behaviour over a period of days or minutes to changes in the internal milieu. The most consistent deficit is in responding actively and rapidly to challenging stimuli; the nature of this and the mechanisms which might produce it are discussed. We suggest that the consequences of excitotoxic lesion are better explained by disruption of input to the cortex from the lateral hypothalamus rather than by interference with metabolic processes.

Adaptation, Physiological↗

Lateralized righting behavior in the tortoise (Testudo hermanni).

Lateralization of brain and behaviour at the population level has been documented in all vertebrate classes. Research was mostly carried out on mammalian and avian species, the least investigated class with this regards being the Reptilia, with studies concentrating on lateralized aggressive behaviour in lizards. No research has been carried out on lateralization in the Chelonian order. We investigated the presence of motor asymmetries in the tortoise Testudo hermanni, using the righting response (i.e. the animal is positioned upside-down and the left/right side to which it uprights is observed), a procedure already employed to assess behavioural lateralization in amphibians. The ability of righting has a particularly high adaptive value in tortoises, as in case of overturning, and consequent exposure to sunrays, changes in body temperature and difficulties in respiration could occur leading to serious conditions. Thirty-four tortoises underwent a series of righting tests in a standardized apparatus, 15 tortoises were also retested 10 months later. A bias at the individual as well as at the population level was found for preferentially turning on the right side. Consistency of responses at retest was also observed. The results are discussed with reference to the implications for the evolution of brain lateralization in vertebrates.

Age Factors↗

Foot-use laterality in the Japanese jungle crow (Corvus macrorhynchos).

Laterality of foot-use behaviour was examined in jungle crows (Corvus macrorhynchos). Consistency of laterality was also verified in comparison with two different behaviours. One was beak-scratching, and another was food-holding. Significant bias of foot-use laterality was found in 11 of 13 tested subjects for beak-scratching and in 10 of 12 tested subjects for food-holding. Bias of foot-use laterality was not common among footed subjects, suggesting no population-level bias. However, a significant number of footed subjects (10 of 12) who were tested in both behaviours showed consistent laterality irrespective of behavioural differences. These results suggest that jungle crows have strong individual-level laterality in foot-use behaviour.

Animals↗

The effect of response mode on lateralized lexical decision performance.

We examined the effect of manipulations of response programming, i.e. post-lexical decision making requirements, on lateralized lexical decision. Although response hand manipulations tend to elicit weaker laterality effects than those involving visual field of presentation, the implementation of different lateralized response strategies remains relatively unexplored. Four different response conditions were compared in a between-subjects design: (1) unimanual, (2) bimanual, (3) congruent visual field/response hand, and (4) confounded response hand/target lexicality response. It was observed that hemispheric specialization and interaction effects during the lexical decision task remained unchanged despite the very different response requirements. However, a priori examination of each condition revealed that some manipulations yielded a reduced power to detect laterality effects. The consistent observation of left hemisphere specialization, and both left and right hemisphere lexicality priming effects (interhemispheric transfer), indicate that these effects are relatively robust and unaffected by late occurring processes in the lexical decision task. It appears that the lateralized response mode neither determines nor reflects the laterality of decision processes. In contrast, the target visual half-field is critical for determining the deciding hemisphere and is a sensitive index of hemispheric specialization, as well as of directional interhemispheric transfer.

Adult↗

Electrophysiologic changes in the lateral and basal amygdaloid nuclei in temporal lobe epilepsy: an in vitro study in epileptic rats.

The functional consequences of neuronal loss during epileptogenesis in the lateral and basal amygdaloid nuclei are poorly understood. The present study tested the hypothesis that electrical responsiveness varies in different amygdaloid nuclei in the chronically epileptic amygdala. Further, we examined the amygdaloid region most prone to seizure initiation. Epileptogenesis was triggered in 20 rats by inducing status epilepticus (SE) with electrical stimulation of the lateral nucleus of the amygdala. Electrode-implanted non-stimulated rats served as controls. The occurrence and duration of spontaneous seizures were monitored with video-electroencephalography (EEG) at 8-9 weeks after SE. Thereafter, animals were killed and extracellular recordings were made from slices of both amygdalas. In the lateral nucleus of epileptic animals, the frequency of spontaneous responses was reduced compared with controls (P < 0.05). The amplitudes of evoked field responses were reduced (P < 0.01), whereas paired pulse (PP) facilitation was enhanced (P < or = 0.05). In the basal nucleus of the epileptic animals, PP facilitation was enhanced (P < 0.05) and sensitivity to 4-aminopyridine (4-AP)-induced epileptiform activity was increased compared with controls (P < 0.05). In the epileptic animals, the basal nucleus was also more sensitive than the lateral nucleus to 4-AP-induced epileptiform activity (P < 0.05). Correlation analysis indicated that longer SE duration was associated with longer half widths (P = 0.001) and smaller slopes (P < 0.05) of evoked responses as well as with attenuated PP facilitation (P<0.01). Moreover, a higher frequency of spontaneous seizures was associated with longer half widths (P < 0.05) and smaller slopes (P < 0.05) of evoked responses as well as with enhanced PP facilitation (P < 0.05). These data suggest that there is a reduced release of glutamate and reduced inhibition in the lateral and basal amygdaloid nuclei in epileptic animals. Further, the basal nucleus is more prone to epileptic activity than the lateral nucleus. Finally, the severity of SE and spontaneous seizures in vivo is associated with electrophysiologic alterations in vitro.

4-Aminopyridine↗

Activation of lateral hypothalamic neurons stimulates brown adipose tissue thermogenesis.

The lateral hypothalamic area, containing orexin neurons, is involved in several aspects of autonomic regulation, including thermoregulation and energy expenditure. To determine if activation of lateral hypothalamic area neurons influences sympathetically-regulated thermogenesis in brown adipose tissue, we microinjected bicuculline (120 pmol, 60 nl, unilateral) into the lateral hypothalamic area in urethane/chloralose-anesthetized, artificially-ventilated rats. Disinhibition of neurons in lateral hypothalamic area evoked a significant increase (+1309%) in brown adipose tissue sympathetic nerve activity accompanied by parallel increases in brown adipose tissue temperature (+2.0 degrees C), in expired CO2 (+0.6%), in heart rate (+88 bpm) and in mean arterial pressure (+11 mm Hg). Subsequent microinjections of glycine (30 nmol, 60 nl) to inhibit local neurons in raphe pallidus or in dorsomedial hypothalamus or of glutamate receptor antagonists into dorsomedial hypothalamus promptly reversed the increases in brown adipose tissue sympathetic nerve activity, brown adipose tissue temperature and heart rate evoked by disinhibition of neurons in lateral hypothalamic area. We conclude that neurons in the lateral hypothalamic area can influence brown adipose tissue sympathetic nerve activity, brown adipose tissue thermogenesis and heart rate through pathways that are dependent on the activation of neurons in dorsomedial hypothalamus and raphe pallidus.

2-Amino-5-phosphonovalerate↗

Lateralization of verbal ability in pre-psychotic children.

Deficits in lateralization have been reported in handedness, language and anatomical asymmetry in schizophrenia, but the relationship between these anomalies has been unclear. Extending earlier work demonstrating that degrees of lateralization are related to verbal ability in the general population, we here investigate the relationship in children who later developed psychosis. Using data from a box-marking test and an index of receptive verbal ability in the UK National Child Development study, we constructed three-dimensional plots of verbal ability in relation to left- and right-hand skill at the age of 11 years, and compared the performance of 34 children who by age 28 had developed schizophrenia and 21 who had developed affective psychosis with 12,782 in the total population. In the total population, verbal skill is decreased in those who are close to the L=R line. Children premorbid for schizophrenia are less lateralized and their verbal skill is lower than predicted by their hand skill, with a similar trend in children premorbid for affective psychosis. Thus pre-psychotic children deviate from the general population in the trajectory of lateralization of words. The findings are consistent with the concept that in psychosis at some critical stage in development there is a failure of lateralization of the components of language.

Adult↗

Sex difference and laterality in the volume of mouse dentate gyrus granule cell layer.

Sex differences in spatial learning have been reported in both humans and rodents. Correspondingly, there have been reports of sexual dimorphism in the morphology of the hippocampal formation (HF), a brain structure implicated in spatial cognition. In Experiment 1, we confirmed earlier reports that the overall volume of the granule cell layer (GCL) of the dentate gyrus (DG) of A/J mice is larger in males than in females. We also found that male A/J mice have a larger GCL volume in the right hemisphere than the left. Female A/J mice displayed no such laterality. A similar pattern of laterality, favoring the right HF, had been reported previously in male, but not female, rats. In Experiment 2, we examined mice with a defective structural gene for androgen receptors (testicular feminization mutant, or tfm mice) on a C57/BL6J background. The C57/J strain had not previously been examined for hippocampal sexual dimorphism. We found no sexual dimorphism in the left, right, or total volume of the GCL in C57/BL6J mice whether they were wildtype or tfm. However, the right GCL volume was greater than the left in wildtype C57/BL6J mice of either sex. No lateralization of GCL volume was found in the androgen-insensitive tfm-affected males or the partially androgen-insensitive tfm-carrier females. These findings confirm earlier reports that sexual dimorphism in mouse HF is found in some inbred strains but not others, and indicate for the first time that mouse HF structures are lateralized. The absence of lateralization in partially or wholly androgen-insensitive mice suggests that androgen receptors may play a role in development of laterality in the GCL independently of any sexual dimorphism in this structure.

Androgen-Insensitivity Syndrome↗

Cortical language lateralization in right handed normal subjects using functional magnetic resonance imaging.

In 95% of right handed individuals the left hemisphere is dominant for speech and language function. The evidence for this is accumulated primarily from clinical populations. We investigated cortical topography of language function and lateralization in a sample of the right handed population using functional magnetic resonance imaging and two lexical-semantic paradigms. Activated cortical language networks were assessed topographically and quantitatively by using a lateralization index. As a group, we observed left hemispheric language dominance. Individually, the lateralization index varied continuously from left hemisphere dominant to bilateral representation. In males, language primarily lateralized to left, and in females, approximately half had left lateralization and the other half had bilateral representation. Our data indicate that a previous view of female bilateral hemispheric dominance for language (McGlone, 1980. Sex differences in human brain asymmetry: a critical survey. Behav Brain Sci 3:215-263; Shaywitz et al., 1995. Sex differences in the functional organization of the brain for language. Nature 373:607-609) simplifies the complexity of cortical language distribution in this population. Analysis of the distribution of the lateralization index in our study allowed us to make this difference in females apparent.

Adult↗

Hemispheric lateralization of the processing of consonant-vowel syllables (formant transitions): effects of stimulus characteristics and attentional demands on evoked magnetic fields.

It is still unsettled in how far temporal resolution of dynamic acoustic events (formant transitions) or phonetic/linguistic processes contribute to predominant left-hemisphere encoding of consonant-vowel syllables. To further elucidate the underlying mechanisms, evoked magnetic fields in response to consonant-vowel events (synthetic versus spoken) were recorded (oddball design: standards=binaural/ba/, deviants=dichotic/ba/-/da/; 20 right-handed subjects) under different attentional conditions (visual distraction versus stimulus identification). Spoken events yielded a left-lateralized peak phase of the mismatch field (MMF; 150-200ms post-stimulus onset) in response to right-ear deviants during distraction. By contrast, pre-attentive processing of synthetic items gave rise to a left-enhanced MMF onset (100ms), but failed to elicit later lateralization effects. In case of directed attention, synthetic deviants elicited a left-pronounced MMF peak resembling the pre-attentive response to natural syllables. These interactions of MMF asymmetry with signal structure and attentional load indicate two distinct successive left-lateralization effects: signal-related operations and representation of 'phonetic traces'. Furthermore, a right-lateralized early MMF component (100ms) emerged in response to natural syllables during pre-attentive processing and to synthetic stimuli in case of directed attention. Conceivably, these effects indicate right hemisphere operations prior to phonetic evaluation such as periodicity representation. Two distinct time windows showed correlations between dichotic listening performance and ear effects on magnetic responses reflecting early gain factors (ca. 75ms post-stimulus onset) and binaural fusion strategies (ca. 200ms), respectively. Finally, gender interacted with MMF lateralization, indicating different processing strategies in case of artificial speech signals.

Adult↗

Laterality effects in the processing of melody and timbre.

Laterality for the processing of melody and timbre was investigated in 64 right-handed non-musicians. In one block of dichotic-listening trials, participants listened for a prespecified target melody, and in a second block they listened for a prespecified target instrument. Females were more accurate on the left ear in the melody task (whereas males tended to show no ear advantage), but there were no significant ear differences in the timbre task for either sex. This supports the idea of a complementary sex-based pattern of lateralization, with males more strongly lateralized for verbal stimuli and females more strongly lateralized for non-verbal stimuli. No relation was observed between lambda measures for the two tasks, suggesting that laterality for melody processing is independent of laterality for timbre processing.

Adolescent↗

Differential bilingual laterality: mythical monster found in Wales.

Paradis (1992) likens studies of bilingual laterality to reported sightings of the Loch Ness Monster, in that although some studies claim differential laterality much conflicting research evidence does not-and like the mythical Scottish monster, what reason have we to suspect that any such phenomenon might exist? This study reexamines differential bilingual laterality using four groups of English-Welsh bilinguals which differ in their age of acquisition and in their environment of acquisition. Using a split visual field paradigm we present evidence which, supports the notion of greater right hemisphere processing in a later learned language. Our findings also suggest the pattern of lateralization in bilinguals is strongly affected by the specific language environment during development such that the shift toward greater right hemisphere involvement for the later learned language will be more pronounced in individuals which are brought up in areas where that language is not regularly heard.

Adolescent↗