7.4. “New Discoveries”
Semyonova states,
“Research implicates the frontal cortex, subcortical structures, and lowered activity of the serotonergic system in impulsive aggression in both dogs and humans. Impulsive aggressive behavior in dogs seems to have a different biological basis than appropriate aggressive behavior.
Kathelijne Peremans, DVM discovered this by studying two different populations of impulsively aggressive dogs.”
This was not “discovered” by Peremans: it was known prior to Peremans’ study. See the following citation. Additionally, “lowered activity of the serotonergic system in impulsive aggression in both dogs and humans” has NOT been implicated by research. It has been “hypothesized” and “expected”.
At http://lib.ugent.be/fulltxt/RUG01/000/471/809/RUG01-000471809_2010_0001_AC.pdf, beginning on Page 14 of Functional Brain Imaging in the Dog – Single Photon Emission Tomography as a Research and Clinical Tool for the Investigation of Canine Brain Physiology and Pathophysiology Dr. Kathelijne Peremans states,
“Impulsive behaviour, for animals defined as “incapacity to wait or to delay response” 39 and for humans as “acts related to inadequate self-control, impaired impulse control” 39, result in reactions that are “sudden” and “unpremeditated” 40. This impulsive behaviour is often aggressive in nature and therefore, has large impact on the victim and on the perpetrator.
It is important to define this “impulsive” behaviour in contrast to “normal” aggressive behaviour in animals. Indeed, several types of aggression, such as maternal, intermale, territorial and predatory aggression are described in animals, depending on different neuronal circuits and hormonal mechanisms. 41, 42 These behavioural patterns are in-born and instinctive in nature and as such, considered as normal coping activities to a set of environmental stimulus conditions. Therefore, they are not pathological, although they can become beyond control, influenced by previous experiences or situational determinants. Most of these reactions have been accepted by humans during domestication of animals, as long as these reactions are appropriate in relation to the stimuli and as long as they can be foreseen. 43
Moreover, impulsive, aggressive behaviour can be of advantage under certain circumstances, such as in a dangerous environment where quick reactions and high levels of arousal coupled to a high degree of aggressivity are necessary as coping mechanisms. But, in safer habitats this behaviour will result in unnecessary attacks leading to injury. 44 Extensive research has been performed on impulsivity, pointing at the frontal cortex and subcortical structures as the structural anatomical substrate and at lowered activity of the serotonergic system as the biochemical substrate for impulsive behaviour.
First, studies on the anatomical and structural substrate of these impulsive disinhibited disorders were based on acquired brain damage in humans and on ablation studies in animals. Phineas Gage was one of the first clinical proves that the frontal cortex played an important, if not major role in the expression of this abnormal, disinhibited behaviour. 45”
At http://medical-dictionary.thefreedictionary.com/ablation, “ablation” is defined as,
“an amputation or excision of any part of the body, or a removal of a growth or harmful substance.”
At http://lib.ugent.be/fulltxt/RUG01/000/471/809/RUG01-000471809_2010_0001_AC.pdf, beginning on Page 14 of Functional Brain Imaging in the Dog – Single Photon Emission Tomography as a Research and Clinical Tool for the Investigation of Canine Brain Physiology and Pathophysiology, Dr. Kathelijne Peremans continues,
“This previously conscientious railway worker turned into an impulsive, aggressive drunk after an accident with a metal rod that perforated his left frontal-cortical lobe. This was later confirmed with frontal ablation studies in several animal species, demonstrating that the frontal cortex exerted control over limbic drives of hunger and aggression. 46 Summarized, the frontal cortex will generate an adequate, premeditated response based on the association of the limbic and sensoric information guided by possible previous experiences, thereby permitting acceptable or “in-context” necessary reactions or inhibiting certain inappropriate reactions.
In humans disturbed frontal perfusion and metabolism was demonstrated in murderers and aggressive individuals with SPET 47, 48 and altered metabolism was found with PET 49-51. It is important to notice that in these cases disturbed frontal perfusion patterns were present without concurring structural anatomical brain abnormalities, as was proven with CT or MRI and therefore represented true functional perfusion and metabolism deficits.
No comparable functional imaging studies in animals are present at this moment. It can be hypothesized that comparable functional deficits in the frontal brain structures of dogs with impulsive behavioural disorder exist.
Second, studies on the functional biochemical deficits in the brain of impulsive subjects pointed at the involvement of a deficient serotonergic system in impulsive behaviour. 6, 39, 52-66 This is one of the most replicated findings in biological psychiatry in human medicine. But also studies in other species demonstrated a prominent role of serotonin in social adequate and inadequate behaviour. 67-75 The cell bodies of the serotonergic neurons are located in the raphe nucleus, with widespread projections to the limbic system, hypothalamus and the cortical regions, explaining their link with mood and behavioural disorders. The influence of the serotonergic system on behaviour in animals and man has been investigated with direct and indirect studies. A decreased metabolism, demonstrated by decreased amounts of 5-hydroxy indolic acetic acid (5-HIAA, the principal metabolite of 5-HT) incerebrospinal fluid (CSF) was found both in humans as in animals with impulsive, aggressive and self-injurious behaviour. 6, 60, 61, 69-72, 77-80 Dietary tryptophan depletion increased aggressiveness and tryptophan supplementation decreased aggressiveness in both animals and humans. 57, 63, 68, 81 Using pharmacological probes, affecting the serotonin transporter mechanism and/or the receptor, aggressive behaviour both in animals and humans could be influenced. 67,82-88 More specific studies on the 5-HT2A receptor, using measurements of 5-HT2A receptors density on platelets, demonstrated increases in binding index in suicidal patients and in patients with aggressive personality disorders. 54, 66, 89-92 Direct autoradiographic studies showed increased density of 5-HT2A receptors in patients, committed suicide. 73, 93, 94
Since the development of specific receptor radioligands for functional imaging, using SPET or PET, these methods have received increasing attention in research on the serotonergic system in vivo, under physiological and pathological conditions, with and without pharmacological interventions. Concerning SPET imaging, a relatively new radioligand 123 I-5-I-R91160 has been used to investigate the serotonin-2A receptor status in normal volunteers. 26, 95 Recently, the Ghent Molecular Imaging Group investigated human patients with recent suicide attempts 8 and patients with eating disorders and found a decreased cortical serotonin-2a binding index. No comparable functional imaging studies on the serotonin-2A receptor in animals are present at this moment. One could expect comparable functional deficits in the cortical brain structures of dogs with impulsive behavioural disorder.”
The cited Peremans’ study sought to confirm that a new method of imaging could produce similar results as previous methods, but was faster and cheaper: it was not research related to “heritability”.
At http://lib.ugent.be/fulltxt/RUG01/000/471/809/RUG01-000471809_2010_0001_AC.pdf, on Page 3 of Functional Brain Imaging in the Dog – Single Photon Emission Tomography as a Research and Clinical Tool for the Investigation of Canina Brain Physiology and Pathophysiology, Dr. Kathelijne Peremans states,
“This thesis evaluates the use of single photon emission tomography (SPET) as functional imaging modality in the study of canine brain and its relation to behavioural pathology.
First, the use of SPET in the study of in vivo brain perfusion was assessed.
Second, in vivo measurement of the serotonin-2A (5-HT2A) receptor binding in the dog brain was evaluated with SPET. The clinical applications of these techniques in aged and in impulsive, aggressive dogs were evaluated.”
On Page 25, Peremans states,
“Research on the pathophysiology of abnormal canine behaviour in vivo is scarce due to the fact that objective measurement of behaviour is difficult. The only available way to investigate the disordered animal is by means of behavioural testing and elaborated questionnaires, which are no doubt of significant importance but remain subjective (operator/owner dependent). It was the aim of this study to evaluate the applicability of functional imaging of the brain in the dog, i.e. to evaluate this technique as a tool to visualize and measure perfusion and the 5-HT2A receptor in normal dogs, aging dogs and in dogs showing impulsive aggressive behaviour.
In this work we tried to address the following questions:
1. Can we measure canine brain perfusion with functional brain imaging, using the SPET modality, and what is the normal distribution pattern in dogs without neurological or behavioural disorders?
2. What are the technical issues to consider when performing receptor radioligand imaging studies, using the SPET modality?
3. Is it possible to use the radioligand, 123 I-5-I-R91150 to image and quantify the 5-HT2A receptor in canine brain?
4. What is the normal distribution pattern of this receptor in the brain of dogs without neurological or behavioural disorders?
5. What is the influence of age on brain perfusion and binding characteristics of the specific serotonin-2A radioligand 123 I-5-I-R91150 in normal aging canine brain?
6. Can we include impulsive aggressive behaviour in dogs as a clinical behavioural disorder to investigation with this imaging modality?
7. Is it possible to demonstrate differences in brain perfusion and/or serotonin-2A radioligand binding using SPET, between normal dogs and dogs showing impulsive, aggressive behaviour?”
On Page 31, Peremans states,
“Hence, the aim of this study was to determine the scintigraphic regional perfusion pattern of the normal canine brain. Ten healthy shepherd type dogs were injected with 925 MBq Technetium-99m ethyl cysteinate (ECD) 20 minutes prior to the examination.”
On Page 11, Peremans states,
“Under impulse of Egas Moniz, frontal lobotomy was widely used for patients with uncontrollable aggression. Paradoxically, Moniz was killed by one of his own lobotomized patients. In that era, the neurosurgeon travelling between mental institutions and “treating fourteen patients in one morning”, was a reality.
Only in the 1960s, with the emergence and the introduction of the first brain-dedicated pharmaceuticals, a reasonable alternative was offered for lobotomy and electro-convulsion therapy. Initially, serendipity lead to the awareness that certain neurotransmitters were involved in behavioural and psychiatric disorders. Huge scientific efforts, often supported by pharmaceutical industry, lead to the development of neuroleptics such as chlorpromazine, haloperidol and risperidone and anti-depressants such as imipramine and fluoxetine. Paradoxically, it was the application of these psychotropics in the treatment of behavioural disorders, that finally offered a better insight in neuroreceptor functioning and pathophysiology of behavioural and psychiatric disorders.”
