Itt írjon a(z) SubcorticalAsymmetries-ról/ről

Asymmetries in the subcortical region of the Brain

Introduction

The subcortical region of the brain primarily functions to control and deliver psychological processes which in turn pre-determine behaviours and mood dispositions. This area of the brain controls coordination of movement, learning, memory, language, and cognitive functions – hence it is a very significant and important region. The subcortical structures receive a wide array of different input signals from the cerebrum, peripheral sense organs and stretch receptors. These structures process these inputs and through the use of recurrent feedback loops, information is interpreted and integrated and a response is formulated. The response is known as an output. These output signals contribute to sequencing, timing and preciseness of motor and non-motor movements, learning, language development, and automation of cognitive functioning.

Extra asymmetries or disturbed asymmetries of the subcortical region can cause impairments to the above functions and can lead to a disruption of ‘normal’ behaviours and ultimately to the development of conditions such as schizophrenia. The role of asymmetrics of the subcortical region is the focus of this paper. It is important to understand that asymmetries exist and can serve very important but differing functions. Important too is an understanding of what can happen when there are abnormalities to the asymmetries. As an example of an abnormal asymmetry, this paper briefly examines the condition of Schizophrenia. Schizophrenia is strongly associated with volumetric alterations within the cortical region. As a result features such as smaller bilateral hippocampus, amygdale, thalamus and accumbens can be observed. Similarly the opposite occurs regarding the bilateral caudate and putamen, which are seen to increase.

The focus of this paper is to examine in detail the abnormal levels of asymmetries which occur in the subcortical region and how these impact normal functioning and contribute to the development of the condition.

Studies of asymmetries in the subcortical region of the brain is primarily concerned with the ratio of white matter to grey matter in the anatomical structures. These structures are primarily comprised of the Basal Ganglia, Planum Temporale, Thalamus and the Limbic System. Grey matter is comprised of the cell bodies of the neurons, while the white matter is comprised of the tendrils, known as dendrites and axons, that spread out from the cell bodies to connect the cell to other neurons. Signals pass between these tendrils through the release and capture of neurotransmitter and neuromodulator chemicals such as, for example, glutamate, dopamine, acetylcholine, noradrenalin, serotonin and endorphins.

This paper will review the literature to provide an understanding of asymmetry of the subcortical system. It will focus on examining the role of the hypothalamic, limbic and the production of hormones

Asymmetry of the Subcortical System

Firstly we need to understand what exactly lateralization is, by scientific terms lateralization refers to ’how neural functions or cognitive function tend to be dominant in one hemisphere of the brain’. There is evidence to show that lateralization occurs in the hypothalamic, limbic, and other brain structures. These structures were also identified as physiological structures which are all directly or indirectly involved in the control of the endocrine glands, as a result asymmetries in the brain can have an effect on the endocrine system. Data suggest predominance of the right half of brain structures in controlling gonadal function. (Gerendai, Halász.,2001.)

1.Hypothalamus

The hypothalamus is a section responsible for the production of many of the body’s essential hormones (thyrotropin-releasing, gonadotropin-releasing, growth hormone-releasing, corticotrophin-releasing, somatostatin, and dopamine) that help control different cells and organs.

Experimental observations supporting the view regarding the hypothalamus asymmetries were conducted and a special experiment was designed: brain lesion on either the right or left side of the brain, was performed in animals subjected to removal of the right or the left endocrine gland, following this changes in biochemical parameters were measured in the right and left halves of the hypothalamus following right- or left-sided complete removal of the ovary. The results of the experiment, were the gonadotropic hormone-releasing hormone (GnRH) content of the hypothalamus halves, studied in hemi-ovariectomized rats, indicated that in intact control animals the GnRH content is significantly higher in the right half of the hypothalamus than in the left half (Gerendai et al.,1978.)

Further studies, similar to the previously mentioned, indicated that in the male rat the right side of the hypothalamus also contains significantly more GnRH than the left (Bakalkin GY et al.,1984.)

This simple experiment proved the presence of asymmetries in the Hypothamlic system, it also displayed how asymmetries on either the left or right has an effect on the gonads on the opposite side of the body.

2.Hypophysis/ Pituitary gland

The pituitary gland is a pea-sized structure located at the base of the brain, just below the hypothalamus, to which it is attached via nerve fibers. It is part of the endocrine system and produces critical hormones (LH, TSH, FSH, ACTH). So far little studies have been conducted on the pituitary to prove asymmetries however it is highly likely to be true there also.

3.Hippocampus

The hippocampus is a small region of the brain that forms part of the limbic system and is primarily associated with memory and spatial navigation. two detailed experiments were conducted and very nicely prove asymmetries existing in this region.

3.A. Left-right asymmetry of the hippocampal synapses with differential subunit allocation of glutamate receptors

Left-right asymmetry of the brain has been studied primarily concerning the viewpoint of psychological examination and functional imaging in primates, leaving its molecular and synaptic aspects largely unaddressed and largely remaining unknown.

studies have found that there are two key areas regarding in the hippocampus focused on for their role in asymmetries. They are known as areas CA1 and CA3 of the dorsal hippocampus. Among inotropic (ligand-gated ion channel) glutamate receptor subunits, six major glutamate receptor subunits (GluR1, GluR2, GluR3, NR1, NR2A, and NR2B) are expressed in the hippocampal CA1 pyramidal cell synapses.

Throughout the studies of Shinohara et al. (PNAS.,2008.), they show that hippocampus CA1 pyramidal cell synapses differ in size, shape, and glutamate receptor expression depending on the laterality of presynaptic origin. CA1 synapses receiving neuronal input from the right, CA3 pyramidal cells are larger and have more perforated GluR1 expression level twice as high as those receiving input from the left CA3.

It was also found that the synaptic density of GluR1 increases as the size of a synapse increases, whereas that of NR2B decreases because of the relatively constant NR2B expression in CA1 regardless of synapse size. Densities of other major glutamate receptor subunits show no correlation with synapse size, thus resulting in higher net expression in synapses having right input.

Overall and in relation to the asymmetries their study demonstrates universal left-right asymmetry of hippocampal synapses with a fundamental relationship between synaptic area and the expression of glutamate receptor subunits.

Findings from the report also observed asymmetrical distributions of NR2B subunits of NMDA receptors in the mouse hippocampus. Ipsilateral CA3-CA1 pyramidal cell synapses in the stratum radiatum in the left CA1, were 1.5 times more sensitive to NR2B subunit specific antagonist than those in the right CA1. The contralateral CA3-CA1 pyramidal synapses had the opposite asymmetry.

Rearrangement of these glutamate receptor subunit compositions serves as a molecular switch for synaptic plasticity. When synaptic activity is elevated upon the induction of long-term potentiation (LTP), GluR1-containing AMPA receptors are inserted into postsynaptic sites. Such synaptic insertion of GluR1 is necessary for an enlargement of spines, which accompanies LTP induction. The experiment then found that the synaptic sizes differed between CA1 pyramidal cell synapses receiving input from the left and the right CA3 pyramidal cells.

This report identifies morphological left-right asymmetry at the synaptic level. The study found that the size of a synapse had a significant correlation with the laterality of the presynaptic innervations in the apical dendrite of hippocampal CA1 pyramidal cells. In addition, individual expression of ionotropic glutamate receptor subunits exhibited a close relation to the size of a synapse. The report therefore concluded by propose a simple principle in which asymmetrical distributions of glutamate receptors in CA1 pyramidal cells can be explained by the relationship between sizes of glutamatergic synapses and the levels of ionotropic glutamate receptor subunits in individual synapses.

3.B. Brain asymmetries have been demonstrated in neurotransmitter metabolism and neuroendocrine modulation.

As the hippocampus modulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis in stress and basal conditions, it was though perhaps the hippocampal corticoid receptors may be asymmetrically distributed and that asymmetry may differ according to behavioural lateralization of animals. In order to answer these questions, binding capacity of mineralocorticoid (MR) and glucocorticoid (GR) receptors was determined in right and left hippocampi of mice previously selected for paw preference. The results show that regardless of behavioural lateralization, there was a tendency for a right dominance in MR binding capacity in the hippocampus. The affinity of MRs did not depend on behavioural lateralization. GR binding capacity was similar in each hemisphere and no relationship was found between GR binding capacity and paw preference scores. These results suggest that hippocampal receptors for corticoids may play an important role in the asymmetrical brain control of immune reactivity. (Neveu PJ1 et al., 1998.).

4. Brain Stem

At the beginning of asymmetrical studies it was thought Lateralization of neural function is generally localized only at the level of the cerebral cortex and perhaps the thalamus. Levine and McGaffigan (EEG Clin. Neurophysiol.,1983.) challenged this view by identifying a neural asymmetry at the level of the brainstem. They analysed brainstem auditory evoked potentials (BAEPs) and found that peak III (+) amplitude was significantly larger in response to right than to left ear stimulation. This brainstem asymmetry finding may represent the general and often noticeable tendency of humans to orient right and/or may be a precursor of higher level asymmetries. (Robert Aaron Levine et al,,1988.).

In research by Dieterich, M., Kirsch, V. & Brandt, (T. J Neurol.,2017). Three structural types of right–left fiber distributions could be delineated:

1.Evenly distributed pathways at the lower pontine level from the vestibular nuclei to the pontine crossing.

2.A moderate, ponto-mesencephalic right-sided lateralization between the pontine and mesencephalic crossings.

3.A further increase of the right-sided lateralization above the mesencephalic crossing leading to the thalamic vestibular sub nuclei.

The increasing lateralization along the brainstem was the result of an asymmetric number of pontine and mesencephalic crossing fibers which was higher for left-to-right crossings. The dominance of the right vestibular meso-diencephalic circuitry in right-handers corresponds to the right-hemispheric dominance of the vestibular cortical network.

5. Amygdala

”The amygdala has historically been strongly implicated in the neurobiology of emotion” (Gallagher & Chibe,1996; Kluver & Bucy,1939; Meunier et al,1999; Weiskrantz, 1956; Zola-Morgan et al.,1991), and an extensive amount of research has established the amygdala as being critical for a variety of social and emotion-related processes. For example, the amygdala is important for the detection and recognition of emotional facial expressions (Adolphs., 2002, 2003; Anderson et al., 2003; Vuilleumier et al., 2001), for the processing of social information more generally (Hariri et al., 2002; Norris et al., 2004), and for the enhancement of memory by emotion (Buchanan & Adolphs., 2004; Buchanan et al., 2006; LaBar & Cabeza, 2006; LaBar & Phelps., 1998; McGaugh et al., 1996; Phelps, 2004).” (Tranel and Bechara., 2009).

An example of the amygdala’s role is the management of associated learning through fear. “Gastrin-releasing peptide (GRP) is produced in the amygdala and excites local interneurons via the gastrin-releasing peptide receptor (GRPR). Mice deficient in GRPR show greater and more persistent fear memory after single-trial associative learning and it has been proposed that agonists may be developed as therapies for fear-related disorders. GRPR also has a role in the regulation of immune function” (Chaperon et al, 2012).

It has been shown that amygdala activation during the encoding of emotionally arousing material correlates with subsequent memory for the material (Cahill et al,,1996; Canli et al., 1999, 2000; Hamann et al., 1999), and in men, this relationship is most robust for the right amygdala, whereas in women, the relationship is most robust for the left amygdala (Cahill et al., 2001, 2004; Canli & Gabrieli, 2004; Canli et al., 2002; Mackiewicz et al., 2006). Cahill (2003, 2006) has interpreted these findings to suggest that emotional arousal enhances memory in men via activation of the right amygdala, whereas emotional arousal enhances memory in women via activation of the left amygdala. (Tranel and Bechara., 2009).

Through Tranel’s and Bechara’s 2009 experiment it was seen that there was an inherent difference between men and women and asymmetry in the functioning of the Amygdala. In regards to women right-sided damage did not develop significant changes in social status, employment status, or interpersonal functioning, whereas left-sided damage evidenced severe changes and impairments in these domains. In regards to men, right-sided damage had severe changes and impairments in said domains, whereas left-sided damage did not lead such changes or impairments. A similar pattern was seen for the outcomes on emotional functioning, personality, and complex decision-making (Tranel and Bechara,, 2009).

Tranel and Bechara (2009) suggest this asymmetry by stating the fact that women bear children and men do not. This biological reality surely has implications for the neurobiology of social and emotional processing, and could prompt sex-related differences in the manner in which men and women apprehend, process, and execute emotional information and solve social problems. As another perspective, consider the fact that mothering and fathering usually do not entail identical sets of parenting activities.” Another example of brain asymmetries is Sadler et al experiment in 2017; “The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA.” (Sadler et al., 2017)

Therefore, we can conclude that there is much scientific evidence of ’natural’ asymmetries in the subcorietal region of the brain. The following section will examine the condition of Schizophernia as an example of how disturbed asymmetries can lead to changes in ’normal’ behaviours and the development of abnormal behaviours.

Extra Asymmetries or disturbed asymmetries.

Schizophrenia

Schizophrenia is a severe illness that affects about 1% of the population (Jablensky, 2000) Schizophrenia presents with a diversity of symptoms that represent multiple psychological domains, for example, perception, inference, concept formation, language, volition, motor activity, social interaction, and emotion.

In the sense of the word ‘cognition’ the condition involves some type of abnormality in receiving and processing information from the external world, relating it to information that has already been processed and stored previously and acting on that information to produce some type of reaction or response. The disturbance encompasses not just executive functions, but several forms of memory, attention, emotion, and motor activity. Its underlying neural network is not only cortical, but also subcortical.

To express the diversity of the disturbance we refer to it as "cognitive dysmetria." As a neurological symptom, dysmetria expresses itself in the coordination of motor activity. Slowing of reaction times is one of the most consistent features. Studies have also documented the presence of motor system "soft signs" in first-episode neuroleptic naive patients (Gupta et al. 1995). These soft signs include the classical indices of motor dysmetria e.g., dysdiadokokinesia.

Schizophrenia has been genetically studied also and it has been linked to the NOTCH-4 gene, which is a neurogenic locus notch homolog protein-4 located on chromosome 6p. This gene is then thought to be involved with type-1 transmembrane protein which in turn is thought to be involved with developmental processes by controlling cell fate decisions. (Su, L. et al.,2013.)

The majority of studies of schizophrenia have focused on the cerebral cortex, in particular on temporal lobe regions such as the hippocampus. The thalamus is conventionally divided into relay and diffuse projection nuclei (Kandel et al.,1991). The relay nuclei project to sensory and motor cortical regions and receive projections from the same cortical areas. These recurrent connections may allow the thalamus to modulate sensory and motor input. The diffuse projection nuclei are believed to be part of a system that governs the level of arousal of the brain. The thalamus clearly must have a fundamental and important function in human cognition because of its extensive connections to the rest of the brain (Jones., 1985). Several neuropathological studies have reported abnormalities of the thalamus (Stevens 1982; Pakkenberg 1990, 1992; Bogerts 1993). In particular, Pakkenberg (1990) has described substantial cell loss in the medial dorsal nucleus of the thalamus, the nucleus that serves as the major relay station to the prefrontal cortex

Another abnormality leading to schizophrenic symptoms is connected to the brain stem. Källstrand et al. (1999) talks of abnormal laterization, or asymmetry, in subcortical regions such as the brain stem. Friston specifically speaks of the lack of asymmetry between relation between the Nucleus Oliva and the cochlear nuclei “It has been reported that schizophrenic patients lack the functional medial olivocochlear asymmetry found in healthy individuals, and show increased evoked otoacoustic emission intensity in the right ear (Veuillet et al, 2001).” (Källstrand et al. 2011). Which means that the lack of medial asymmetry lead to an increase of intensity of otoacoustic emissions, most probably causing the patient to hear sounds that are not from their environment. The diverse symptoms of schizophrenia reflect abnormalities in connectivity in the circuitry that links prefrontal and thalamic regions and where cerebro-cerebellar connectivity may also be disrupted.

CONCLUSION

This paper has sought to review the literature to establish the nature and type of work undertaken to date relating to scientific evidence of asymmetries in the subcortical region of the brain. Research has undoubtedly proven that asymmetries do exist and has highlighted the importance of understanding the role and function of the asymmetries in the various component modules of the right side of the brain.

Bibliography

• •Ida Gerendai and Béla Halász: Asymmetry of the Neuroendocrine System, 2001 Vol. 16 no. 2, 92-95. •Gerendai I, Rotsztejn W, Marchetti B, Kordon C, and Scapagnini U. Unilateral ovariectomy-induced luteinizing hormone-releasing hormone content changes in the two halves of the mediobasal hypothalamus. Neurosci Lett 9: 333–336, 1978.) •Bakalkin GY, Tsibezov VV, Sjutkin EA, Veselova SP, Novikov ID, and Krivosheev OG. Lateralization of LHRH in rat hypothalamus. Brain Res 296: 361–364, 1984. •PNAS December 9, vol. 105 no. 49 2008. •Neveu PJ1, Liège S, Sarrieau A. Asymmetrical distribution of hippocampal mineralocorticoid receptors depends on lateralization in mice. 1998;5(1-2):16-21). •EEG Clin. Neurophysiol. 55, 532–537, 1983) •Robert Aaron Levine, Jacqueline Liederman, Pamela Riley. The Brainstem auditory evoked potential asymmetry is replicable and reliable. Volume 26, Issue 4, 1988, 603–614. •T. J Neurol.,2017.

  •Gallagher & Chibe, 1996; Kluver & Bucy, 1939; Meunier et al., 1999; Weiskrantz, 1956; Zola-Morgan et al., 1991. •Adolphs, 2002, 2003; Anderson et al., 2003; Vuilleumier et al., 2001. •Hariri et al., 2002; Norris et al., 2004.

  •Buchanan & Adolphs, 2004; Buchanan et al., 2006; LaBar & Cabeza, 2006; LaBar & Phelps, 1998; McGaugh et al., 1996; Phelps, 2004).” (Tranel and Bechara, 2009). •Chaperon et al, 2012. •Cahill et al,,1996; Canli et al., 1999, 2000; Hamann et al., 1999. •Su, L., Long, J., Liang, B., Gu, L., Pan, R., Li, L.Wei, B. (2014). Association between the NOTCH4 gene rs3131296 polymorphism with schizophrenia risk in the Chinese Zhuang population and Chinese Han population. Acta Neuropsychiatrica,(4), 240-245. 2013.66. •Tranel D., Bechara A., 2009. Sex-Related Functional Asymmetry of the Amygdala: Preliminary Evidence Using a Case-Matched Lesion Approach. Neurocase, 15(3): 217–234.

  •Chaperon F., Frendt M., Kelly P. H., Lingenhoehl K., Mosbacher J., Olpe H. R., Schmid P., Sturchler C., McAllister K. H., Van der Putten P. H., Gee C. H., Gatrin -Releasing Peptide Signaling Plays a Limited and Subtle Role in Amygdala Physiology and Aversive Memorym, 2012..

  •Sadler K.E., McQuaid N.A., Cox A.C., Behun M.N., Trouten A.M., Kolber B.J., 2017. Divergent functions of the left and right central amygdala in visceral nociception. •Kandel et al., 1991. •Jones., 1985. •Stevens 1982; Pakkenberg 1990, 1992; Bogerts 1993. •Källstrand J., Nehlstedt S. F., Sköld M. L., Nielzén S., 2011. Lateral asymmetry and reduced forward making effect in early brainstem auditory evoked responses in schizophrenia. Phychiatry Research: Volume 196, Issues 2-3, 30 April 2012, Pages 188-193.