The relationship between Neuropathology, Neuropsychology and Basil ganglia dysfunction in Parkinson’s disease.

Darragh Scully

114632

Behavioral Neuroscience 1

PSY 208

Tutor: Debbie Rankins

The relationship between the Neuropsychology and Neuropathology of Parkinson’s disease shows how the symptoms of Parkinson’s disease and the explanations for the disorder can be validated with psychometric analysis.

According to Pinel (1993) Neuropathology refers to “the study of nervous system disorders”, (Pinel, p 24, 1993) and Neuropsychology refers to the “study of behavioral deficits produced in humans by brain damage” (Pinel, p 24, 1993). Neuropsychology refers to the examination of the theories of Neuropathology through the use of methodological research methods, however it can be defined to mean; the combination of  neurology and psychology which aims to show a relationship between the effects of neural disorders and behavior or mental experience.  The neuropsychology experiments aim to validate and explain the effects of nervous system disorders and mental experience. For example Neuropsychology would refer to a combination of Neurology testing equipment to measure the effects of neural activity during a cognitive test or during a test of a drug that may be used to treat a neurological disorder. For example a group of non Parkinson patients undergoing similar experimental conditions as parkinsons patients to show the possible differences in neural functioning. 

Parkinson’s disease refers to a number of physical and psychiatric conditions that involve the loss of control over movement. Ridneur & Dean (1999) states that neuropsychological assessment has shown more than traditional symptoms of Parkinson’s disease (such as tremors, see chart 1) are present including “cognitive and emotional symptoms”(Ridneur & Dean, p.1, 1999). The Substantia Nigra has been localized as the area in the Basil ganglia that is damaged, which results in Parkinsons disease emerging (Ridneur and Dean, 1999). From this discovery it has been found that

the use of dopamine facilitators may be used to correct the problems in the Substantia Nigra (Ridneur and Dean, 1999). Hallet (1993) demonstrates the effects of damage in the Substantia Nigra pars compacta. The use of L-dopa, which reacts with methyl-p-tyrosine and becomes Dompamine, is used because dopamine can not cross the blood barrier. Deprynil/Slegiline is also used as it inhibits  Monomine oxidase which destroys Dopamine and converts MPTP into MPP+, which destroys dopaminergeinc neurons in Substantia Nigra (Ridneur and Dean, 1999). As can be seen Parkinsons disease may consist of either Dopamine depletion or Dopamine receptor cell depletion.

            Blanchet, Marie, Davillier, Londrea, Benali, Eustach & Chauvoix (2000) have conducted a correlational experiment to test for cognitive deficits in Parkinson’s disease patients (non demented type). The Parkinsons disease patients consisted of 13 individuals with a mean age of 63.4 years of age. The control group consisted of 12 individuals of similar age (m = 57.8 years old). The experiment consisted of two tests which were correlated against one another. The first test consisted of a Battery of neuropsychology tests. This battery consisted of attention, initiation/preservation, construction, conceptualization and memory components. The second component in the experiment was a visual recognition of memory test, known as the delayed non-matching-to-sample performance scale. The participants were shown single pictures then the same picture was presented in a group of 4 pictures. In the latter display the individuals were instructed to identify the original picture with in a time interval of 1 to 4 seconds.

            The behaviour the experimenters wished to observe was cognitive ability differences between Parkinsons Disease Patients in relation to controls for the purpose of displaying the extent of cognitve defecits that may be present in Parkinsons Disease Patients. Previous research has shown that “short term memory, long term memory and interference” (Asso, 1969; Tweedy, Langer & McDougal 1982, cited in Blanchet et al, p. 473, 2001) is impaired in Parkinson’s patients where as the Parkinson’s disease patients in other research performed equally as well as controls in recognition of “verbal and visual stimuli” (Lee’s & Smith, 1983; Breen, 1983, cited in blanchet et al, p. 473, 2000). The results in the Blanchet et al (2001) study demonstrate how Parkinson’s patients performed substantially worse in all tests than controls and that the cause of the weaker performance was due to executive dysfunction in working memory that results from damage to the Substantia Nigra.

The Blanchet et al (2001) experiment incorporated both motor functions and cognitive functions in the overall experiment. The movement fucyions in Parkinson’s patients is known to be impaired during non-movement time periods and the results did show that the longer a delay in a given task the less well the Parkinson’s individuals performed. With minimal delay however the groups were much more equally matched (Blanchet et al, 2001). A critic of certain tests in the neuropsychological battery however may be that the tests may not measure true cognitive ability in Parkinson’s patients. One group of researchers (Bostantjopaulou, et al 2001) whom have recognized the problem of using motor oriented tests for cognitive functioning have suggested that the Toni-2 test, which incorporates a language free measure of cognitive ability may be effective for finding more reliable results in Parkinsons patients than more physically orientated tests. The reason presented for this was that the Toni-2 incorporated “a motor reduction factor” (Bostantjopaulou, et al, p. 206, 2001).

            Youngjhon, Beck, Joungst and Cain (cited in Kail and Cavanaugy, 1999) have stated that it is unknown why a large portion of PD patients suffer cognitive impairment. The Blanchet (et al, 2000) study however has attempted to correlate visuospatial tests with neuropsychological cognitive tests that has shown a reliable difference is present in memory functions between Parkinsons patients and controls. That is that Parkinson patients display a working memory defecit that can be seen in the devienacy in recall with increasing delay intervals which are not as pronounced in controls (Blanchet et al 2001).

            Grossman (et al, 2000) have taken a group of Parkinsons patients (non demented) whom are only mildly affected and conducted a cognitive language experiment. The Parkinson group was compared against an education and age matched control group in a cognitive test for sentence comprehension abilities.

All participants attempted the tasks with a primary and secondary condition applied to the task. The primary task consisted of one of three kinds of action words, which were to be identified by each participant as a sentence was read aloud. These were “active declarative (simple)…subject-reactive centre embedded (subject and object-relative centre embedded” (Grossman et al, p. 11, 2000). The secondry task consisted of “baseline (no secondry task)…, finger tapping… and recognition span” (Grossman et al, p. 11, 2000).

While testing for participants level of grammatical ability in a pre experiment test Grossman , et al (2000) identified a subgroup amongst the Parkinson patients. The subgroup showed an impairment on the primary tasks when the secondry task was the most difficult (recognition span). The subgroup was impaired in the primary task when it was simple or subject though only when the secondary task was the most difficult (see chart 1- compare baseline and tap with span). The more difficult task took longer in parkinsons patients than in controls (Grossman  et al, 2000)

Grossman et al (2000) have thus suggested that all individuals have a determined  level of cognitive resources that is less easily accessed with a concurrent task of increasing difficulty. The blocking of this channel however it is more pronounced in Parkinsons Disease patients. Grossman et al (2000) state that Parkinsons patients are “sensitive to cognitive resource limitations” (Grossman, p 11, 2000). Further more individual assessments of the application of primary (grammatical tasks) task difficulty controlled for confounding functions, such as “lexical comprehension and motor reaction contingent on decision measure” (Grossman, p 11, 2000). Overall however the results show how the decrease in cellular funcition in the basil ganglia negatively affects the ability of Parkinson’s patients to access multiple parts of the brain at a level similar to non impaired individuals( see chart 1).

Hallet (1993) states that there are two pathways in movement, one for voluntary movement and one for synergist and assistor muscle movement functions, which are controlled through a direct or indirect pathway form the Substantia Nigra pars compacta and the internal division of the Globus Padilus in the Basil Gangli. Parkinson’s sufferers however have a loss of dopaminergic neurons in the Substantia Nigra pars compacta which Hallet (1993) states causes a “loss of facilitation in both pathways…and increased activity in the subthalamic nucleus of the GPi”.(Hallet , p 1, 1993). The Substantia Nigra pars compacta has an inhibitory and a excitory conection to the putamen.

Hallet (1993) explains the indirect pathway as follows. The inhibitory connection facilitates “Gaba and Enkaplactin” then the Putamen has an inhibitory connection with the external division of the Globus Palidus internal division which has a inhibitory connection with the Subthalmic Nucleus. The Subthatlamic Nucleus has an exciatory connection to the internal division of the Globus pallidus. This is the indirect pathway and Hallet (1993) states that reflexes are inhibited through this negative feedback-loop.

Hallet (1993) also explains the direct pathway as follows. The direct path, which relates to voluntary movement, involves the Substantia Nigra pars compacta which has a connection with the Putaman. The Putaman then has a direct connection to the internal division of the Globus Pallidus. The internal division of the Globus Pallidus has an inhibitory connection with the Pars Oralis portion of the Ventrolateral Thalamus which has an excitatory effect on the cortex. The cortex then creates a positive feedback loop to the Putaman with which there is an excitatory connection. Damage to the Substantia Nigra globus pallidus causes the direct pathway to become ineffective and Hallet (1993) states that the symptoms are associated to poor initiation of voluntary movement known as Bradykinesia ( see table 1).

Pramstra and Plat (2001) conducted an experiment with Parkinson’s patients examining the automatic activation of motor responses in Parkinson’s disease. The Parkinson’s individuals and the control group, whom were matched by age and education, undertook the “Simon test”(Simon cited in Pramstra and Plat, 2001). Measurements were recorded via event related potentials from scalp electrodes which were aiming to record motor responses involved in the direct and indirect pathways (Hallet, 1993). This choice-reaction task supposes that direct and indirect routes are taken when either compatible or incompatible spatial positioning of stimuli occurs (Pramstra and Plat 2001). The indirect path will occour when stimulus and response is incompatible. In the Simon test this occurs when spatial positions of a stimulus does not match with a response (Dejong, Liang & Lauber, 1994; Kornblum, Hasbroucq & Osman, 1990; Faith & Done, 1986., cited in Pramstra and Plat, 2001) and inhibitory motor functions are activated. The direct route occours when spatial positions of a stimulus matches a response (Dejong, Liang & Lauber, 1994; Kornblum, Hasbroucq & Osman, 1990; Faith & Done, 1986., cited in Pramstra and Plat, 2001) and movements can occour automatically. Praamstra and Plat (2001) hypothesized that when the indirect path is taken by an individual during a incompatible sequence an individual will inhibit automatic stimulus response tendencies and would result in slower reaction times in the Simon test.

The results of the Simon test taken from the scalp electrodes showed that force signals were faster for individuals with Parkinsons disease however the time form force to onset of peak force was double that of controls for Parkinson’ patients, which Pramsta and Prat (2001) state is evidential of motor skill deficits resulting form basil ganglia dysfunction. A reaction time analysis took sequential dependencies between successive trials into account whereby each trial was preceeded by a compatible or incompatible stimulus response location (Praamstra and Plat, 2001). From this analysis it was found that when an incompatible stimulus response location preceded a trial, controls adjusted responses where as Parkinson individuals did not. This was evidenced in that there was a 21 millisecond difference between response times with incompatible stimuli where controls scores were 2 milliseconds where as Parkinson individuals scored 23 milliseconds however Control and Parkinson individuals recorded 52.5 millisecond responses for the compatible stimulus response times. Parkinson individuals also made more errors in the Simon test than control groups however the error rates were more pronounced when the trial was preceded by an incompatible stimulus-response task. Parkinson’s patients take loger to react and there reactions often produce innocorrect choices with incompatible stimuli which is a result of a loss of inhibitory motor functions (Pramstra and Platt, 2001).

These Results states Pramstra and Plat (2001) confirm the facts that Parkinson individuals fail to inhibit automatic response activations. This is further evidenced through response-locked-lateralized potential (see figure 2). It can be seen that the control subjects produce effective negative feedback loops on the incompatible conditions (indicated by an arrow in chart 2) however the negative feed back which controls the inhibition of movements in Parkinson patients is not being produced which Praamsta and Plat (2001) state is evidence of the deficit in the basil ganglia of Parkinson patients that is responsible for the inhibition of movements.