**1. Introduction**

Ensuring coordination of the nervous system functioning, communication between various structures, adjusting the functions to the changes in internal and external environment depends on processing of substantial amount of information (Groenewegen, 2007; Groenewegen & van Dongen, 2007).

The concept of cortico-subcortical loops is one of the explanations of the physiological control of the majority of motor, emotional and cognitive functions.

The most important elements are striatum and cerebral cortex. Especially in the pyramidal cells of the cerebral cortex and medium spiny neurons of the striatum there is capacity for plastic changes relating to the control of broadly defined mental functions (motor, emotional, cognitive).

The cerebral cortex is linked to the striatum via cortico-subcortical pathways, from where information is transmitted to the globus pallidus pars internalis or the substantia nigra pars reticulata (which physiologically and anatomically constitute one structure) or via the ventral globus pallidus reach the thalamus and the cerebral cortex subsequently.

The evidence of the anatomical and physiological brain research supported by clinical data and theoretical models suggests there are at least five loops (also called circuits) related to motor, emotional and cognitive functioning control (Alexander et all., 1986; DeLong et all., 1998). The loops division as well as the control of functions assigned to these loops has more model and didactic character rather than it reflects the real character and complexity of the functions controlling these loops.

The following cortico-subcortical loops have been described: 1. motor - between additional motor area of the cerebral cortex and the lateral part of dorsal striatum – putamen; 2. oculomotor - between the frontal visual eye field of the cerebral cortex and the corpus of the caudate (nucleus caudatus) belonging to the medial part of dorsal striatum; 3. prefrontal (associative) - between dorso-lateral prefrontal cortex and the dorso-lateral part of the head of caudate (nucleus caudatus) (the frontal part of the medial part of dorsal striatum); 4. latero-orbito-frontal - between lateral orbito-frontal cerebral cortex and the ventromedial part of the head of caudate (medial part of the dorsal striatum); 5. limbic (circuit of the anterior part of the cingular gyrus) - between the anterior part of the anterior cingulate gyrus and the ventral striatum (of which the main part is the nucleus accumbens).

According to the classic description (Alexander et all., 1986) these circuits pass through various areas of cerebral cortex and subcortical structures and they have similar principles

Functional Anatomy, Physiology and Clinical Aspects of Basal Ganglia 91

Fig. 2. The circuits connecting the basal ganglia with the cerebral cortex (Stahl, 2008).

animals (Thorpe et all., 1983) and people (Drewe, 1975; Bunzeck et all., 2011).

The basal ganglia are connected not only with the motor areas of the cerebral cortex but they also influence the areas that are responsible for operating memory and executive functions (dorso-lateral prefrontal cortex and the anterior part of the gyrus cinguli) (Alexander et all., 1986; Middleton & Strick, 1994; Smith & Jonides, 1999; Hartley & Speer, 2000; Elliott, 2003). Prefrontal (associative), latero-orbito-frontal and limbic loops are particularly essential in the control of executive functions (Alexander et all., 1986; Royall et all., 2002; Haber, 2003). Impairment of prefrontal loop functioning causes disturbances of verbal and spatial operating memory and executive functions (the choice of the aim, planning, accepting and changing of cognitive attitude, self-control and metacognition), involve, in particular, difficulties in executing tests such as Wisconsin Card Sorting Test, WCST) (Fuster, 1980; Cummings, 1995; Fuster, 1995; Goldman-Rakic, 1995a; Milner, 1995; Truelle et all., 1995). The orbito-frontal circuit is most probably responsible for socially adjusted behaviour and hampering not socially accepted one (Cummings, 1995; Truelle et all., 1995). Efficient functioning of this circuit is of importance for the estimation of the risk of the behaviour chosen (Rogers et all., 1999; Schiffer & Schubotz, 2011). The choice between behaviour in which the probability of a reward is large though the reward is small and behaviour in which the probability of a reward is small but the reward is significant depends on the activity of the inferior and preorbital areas of the prefrontal cortex. The damage to the orbital areas of the prefrontal cortex impairs "*go/do not go"* type tasks execution of in

of connections (Royall et all., 2002). As shown in Fig. 1, it was conventionally assumed that individual circuits pass through particular areas of the cerebral cortex, dorsal and abdominal striatum and thalamic nuclei, from where the information reaches the cerebral cortex. Moreover, structurally and functionally related areas of the anterior cerebral cortex and striatum are linked to the posterior parts of the cerebral cortex, e. g. the associative circuit processes information from the dorso-lateral prefrontal cortex and from premotor and posterior part of the parietal cerebral cortex (ibid.) (the areas responsible for the control of motor and spatial functions (ibid.). The fronto-subcortical loops leaving various, distantly located from one other, regions of the cerebral cortex converge in relatively small, limited areas of the target basal ganglia, thalamic nuclei and frontal cerebral cortex (ibid.). Classic hypothesis that individual cortico-subcortical circuits are functionally separated and act simultaneously and independently (Alexander et all., 1986), does not explain the complexity of the nervous system functioning and is not confirmed by the results of investigations and clinical observations of the nervous system damages and disturbances in the loop functioning caused by mental disorders. The complex nature of cortico-subcortical loops functioning is most likely the result of functional connections between the loops. This would explain the control of functions related to integration and convergence of the information processed (Percheron & Filion, 1991; Joel & Weiner, 1994; Parent & Hazrati, 1995).

Fig. 1. General scheme of cortico-subcortical loops.

of connections (Royall et all., 2002). As shown in Fig. 1, it was conventionally assumed that individual circuits pass through particular areas of the cerebral cortex, dorsal and abdominal striatum and thalamic nuclei, from where the information reaches the cerebral cortex. Moreover, structurally and functionally related areas of the anterior cerebral cortex and striatum are linked to the posterior parts of the cerebral cortex, e. g. the associative circuit processes information from the dorso-lateral prefrontal cortex and from premotor and posterior part of the parietal cerebral cortex (ibid.) (the areas responsible for the control of motor and spatial functions (ibid.). The fronto-subcortical loops leaving various, distantly located from one other, regions of the cerebral cortex converge in relatively small, limited areas of the target basal ganglia, thalamic nuclei and frontal cerebral cortex (ibid.). Classic hypothesis that individual cortico-subcortical circuits are functionally separated and act simultaneously and independently (Alexander et all., 1986), does not explain the complexity of the nervous system functioning and is not confirmed by the results of investigations and clinical observations of the nervous system damages and disturbances in the loop functioning caused by mental disorders. The complex nature of cortico-subcortical loops functioning is most likely the result of functional connections between the loops. This would explain the control of functions related to integration and convergence of the information

processed (Percheron & Filion, 1991; Joel & Weiner, 1994; Parent & Hazrati, 1995).

Fig. 1. General scheme of cortico-subcortical loops.

Fig. 2. The circuits connecting the basal ganglia with the cerebral cortex (Stahl, 2008).

The basal ganglia are connected not only with the motor areas of the cerebral cortex but they also influence the areas that are responsible for operating memory and executive functions (dorso-lateral prefrontal cortex and the anterior part of the gyrus cinguli) (Alexander et all., 1986; Middleton & Strick, 1994; Smith & Jonides, 1999; Hartley & Speer, 2000; Elliott, 2003). Prefrontal (associative), latero-orbito-frontal and limbic loops are particularly essential in the control of executive functions (Alexander et all., 1986; Royall et all., 2002; Haber, 2003).

Impairment of prefrontal loop functioning causes disturbances of verbal and spatial operating memory and executive functions (the choice of the aim, planning, accepting and changing of cognitive attitude, self-control and metacognition), involve, in particular, difficulties in executing tests such as Wisconsin Card Sorting Test, WCST) (Fuster, 1980; Cummings, 1995; Fuster, 1995; Goldman-Rakic, 1995a; Milner, 1995; Truelle et all., 1995).

The orbito-frontal circuit is most probably responsible for socially adjusted behaviour and hampering not socially accepted one (Cummings, 1995; Truelle et all., 1995). Efficient functioning of this circuit is of importance for the estimation of the risk of the behaviour chosen (Rogers et all., 1999; Schiffer & Schubotz, 2011). The choice between behaviour in which the probability of a reward is large though the reward is small and behaviour in which the probability of a reward is small but the reward is significant depends on the activity of the inferior and preorbital areas of the prefrontal cortex. The damage to the orbital areas of the prefrontal cortex impairs "*go/do not go"* type tasks execution of in animals (Thorpe et all., 1983) and people (Drewe, 1975; Bunzeck et all., 2011).

Functional Anatomy, Physiology and Clinical Aspects of Basal Ganglia 93

It was shown that the anterior cingulate loop is responsible for correcting behaviour following a mistake (Peterson et all., 1999). During the Stroop Interference Color Test, which consists of inhibition of answers learned while choosing opposing answers, the activity of the anterior part of cingulate gyrus and its connections with the central part of the frontal

Motor, emotional and cognitive functions are controlled by two neuronal pathways, being the part of cortico-subcortical loops: direct and indirect (Fig 1). These pathways are under control of connections of the nigrostriatal system of zona compacta nigra (Mandir & Lenz, 1998). The striatum is connected with the thalamus by pathways going through the internal part of the globus pallidus and the reticular part of the substantia nigra. The direct pathway runs from the striatum through the medial part of the globus pallidus, the reticular part of the substantia nigra and the ventral part of the globus pallidus to the thalamus (this causes activation of inhibitory neurons of the thalamus and in consequence activates the cerebral cortex) and further to the cortex of the brain (Longstaff, 2003; Morgane et all., 2005). The indirect pathway runs through the lateral part of the globus pallidus and reaches the subthalamic nucleus (inhibiting glutaminergic transmission of the subthalamic nucleus), from where axons reach the medial part of the globus pallidus and further the thalamus and the brain cortex (ibid.). Control of the stimulation of the cerebral cortex is held, among the others, by striatal neurons (medium spiny neurons) (ibid.). The axons of glutaminergic neurons from the cerebral cortex reach the medium spiny neurons (cortico-striatal pathway) (ibid.). The axons of striatal medium spiny neurons release gamma-aminobutyric acid (GABA) inhibiting activity of the globus pallidus (both: internal and external). Striatal spiny neurons, which are morphologically indistinguishable, can be divided into two populations: 1) medium spiny neurons with D1 receptors containing P substance (SP) and dynorphin (DYN) (GABA/D1/SP/DYN), reach the internal part of the globus pallidus (direct pathway) (Mink, 1999; Longstaff, 2003). 2) medium spiny neurons with D2 containing enkephalin (ENK) (GABA/D2/ENK), reach the external part of the globus pallidus (indirect pathway). Stimuli from the substantia nigra pars compacta neurons of nigrostriatal pathway are transmitted to both populations of the striatal medium spiny neurons. The nigro-striatal pathway increases the activity of the direct pathway and inhibits the activity of the indirect pathway (Mink, 1999; Groenewegen, 2003; Longstaff, 2003; Morgane et all., 2005). Dopamine released in the axon terminals of the nigro-striatal pathway causes in GABA /D1/SP/ DYN striatal medium spiny cells an increase, and in GABA/D2/ENK cells a decrease, in the concentration of the second transmitter: 3'5' - cyclic adenosine monophosphate (cAMP) (ibid.). The activity of the cerebral

Glutaminergic neurons of the subthalamic nucleus (indirect pathway) stimulate the external part of the globus pallidus, simultaneously reducing activity of the thalamus and cerebral cortex neurons. The striatum inhibits the neurons of the lateral part of the globus pallidus, what leads to disinhibition of glutaminergic cells of the subthalamic nucleus and stimulation of the globus pallidus pars interna. Dynamic changes of the activity of direct and indirect pathway make it possible to stimulate well defined areas of the cerebral cortex with simultaneous inhibition of the areas, which do not take part in execution of particular

The damage of various structures of basalo-thalamo-cortical loop can manifest with symptoms related to a definite loop (Alexander, 1986; Royall et all., 2002). According to this argumentation it can be assumed that pathology of the basal ganglia can cause symptoms

cerebral cortex increases (ibid.).

cortex is proportional to the concentration of cAMP (ibid.).

movement or mental action (Mink, 1999; Groenewegen; 2003).


1(nucleus ventralis lateralis) = (nucleus ventralis intermedius) 2(nucleus ventralis anterior) = (nucleus ventralis anteromedialis) 3(nucleus medialis dorsalis) = (nucleus medialis)

4(nucleus ventralis lateralis (medial part (rostral) = (nucleus ventrolateralis pars oralis) 5(nucleus ventralis lateralis - medial part) = (nucleus ventrodorsalis pars medialis) 6(nucleus ventralis anterior pars magnocellularis) = (nucleus anterior pars magnocellularis)

7(nucleus medialis dorsalis pars paralamellaris (most lateral) = (nucleus medialis dorsalis pars paralamellaris)

Table 1. Five basalo-thalamo-cortical loop (Mink 1999; Smith et all., 2004; Bochenek & Reicher 2006; Laskowska et all., 2008, Laskowska & Gorzelańczyk, 2009).

striatum PUTAMEN body head ventral

middle part dorso-lateral

(posterior part)

pars magnocellularis (lateral part)6

pars paralamellaris7

4(nucleus ventralis lateralis (medial part (rostral) = (nucleus ventrolateralis pars oralis) 5(nucleus ventralis lateralis - medial part) = (nucleus ventrodorsalis pars medialis) 6(nucleus ventralis anterior pars magnocellularis) = (nucleus anterior pars magnocellularis)

7(nucleus medialis dorsalis pars paralamellaris (most lateral) = (nucleus medialis dorsalis pars

Table 1. Five basalo-thalamo-cortical loop (Mink 1999; Smith et all., 2004; Bochenek &

Reicher 2006; Laskowska et all., 2008, Laskowska & Gorzelańczyk, 2009).

dorsolateral prefrontal cortex posterior parietal cortex frontal oculomotor area

DORSO-LATERAL PREFRONTAL

posterior parietal cortex premotor area dorsolateral prefrontal cortex

CAUDATE (caudate nucleus)

part

dorso-medial (lateral part)

postero-lateral ventro-lateral anterio-lateral anterior-medial anterio-

pars parvocellularis

pars parvocellularis

LATERAL ORBITO-FRONTAL

superior and inferior temporal gyrus anterior part of the gyrus cinguli lateral orbitofrontal cortex

ventro-medial part

dorso-medial (middle part)

pars magnocellularis (medial part)

pars magnocellularis

LIMBIC (anterior cingulate)

hippocampal cortex entorhinal cortex superior and interior temporal gyrus

striatum

anteriolateral

lateral

ventral globus pallidus

posteromedial part

LOOPS

ventro-lateral dorso-medial

anterior part (rostral)4 medial part5

1(nucleus ventralis lateralis) = (nucleus ventralis intermedius) 2(nucleus ventralis anterior) = (nucleus ventralis anteromedialis) 3(nucleus medialis dorsalis) = (nucleus medialis)

loop unit MOTOR OCULOMOTOR

premotor area primary motor cortex somatosensory cortex additional motor area

cerebral cortex

globus pallidus pars internalis

> substantia nigra pars reticularis

ventral globus pallidus

nucleus nucleus ventralis anterior 2

nucleus ventralis lateralis 1

anteriors (group) nucleus medialis dorsalis 3

palliadum

thalamus

paralamellaris)

It was shown that the anterior cingulate loop is responsible for correcting behaviour following a mistake (Peterson et all., 1999). During the Stroop Interference Color Test, which consists of inhibition of answers learned while choosing opposing answers, the activity of the anterior part of cingulate gyrus and its connections with the central part of the frontal cerebral cortex increases (ibid.).

Motor, emotional and cognitive functions are controlled by two neuronal pathways, being the part of cortico-subcortical loops: direct and indirect (Fig 1). These pathways are under control of connections of the nigrostriatal system of zona compacta nigra (Mandir & Lenz, 1998). The striatum is connected with the thalamus by pathways going through the internal part of the globus pallidus and the reticular part of the substantia nigra. The direct pathway runs from the striatum through the medial part of the globus pallidus, the reticular part of the substantia nigra and the ventral part of the globus pallidus to the thalamus (this causes activation of inhibitory neurons of the thalamus and in consequence activates the cerebral cortex) and further to the cortex of the brain (Longstaff, 2003; Morgane et all., 2005). The indirect pathway runs through the lateral part of the globus pallidus and reaches the subthalamic nucleus (inhibiting glutaminergic transmission of the subthalamic nucleus), from where axons reach the medial part of the globus pallidus and further the thalamus and the brain cortex (ibid.). Control of the stimulation of the cerebral cortex is held, among the others, by striatal neurons (medium spiny neurons) (ibid.). The axons of glutaminergic neurons from the cerebral cortex reach the medium spiny neurons (cortico-striatal pathway) (ibid.). The axons of striatal medium spiny neurons release gamma-aminobutyric acid (GABA) inhibiting activity of the globus pallidus (both: internal and external). Striatal spiny neurons, which are morphologically indistinguishable, can be divided into two populations: 1) medium spiny neurons with D1 receptors containing P substance (SP) and dynorphin (DYN) (GABA/D1/SP/DYN), reach the internal part of the globus pallidus (direct pathway) (Mink, 1999; Longstaff, 2003). 2) medium spiny neurons with D2 containing enkephalin (ENK) (GABA/D2/ENK), reach the external part of the globus pallidus (indirect pathway). Stimuli from the substantia nigra pars compacta neurons of nigrostriatal pathway are transmitted to both populations of the striatal medium spiny neurons. The nigro-striatal pathway increases the activity of the direct pathway and inhibits the activity of the indirect pathway (Mink, 1999; Groenewegen, 2003; Longstaff, 2003; Morgane et all., 2005). Dopamine released in the axon terminals of the nigro-striatal pathway causes in GABA /D1/SP/ DYN striatal medium spiny cells an increase, and in GABA/D2/ENK cells a decrease, in the concentration of the second transmitter: 3'5' - cyclic adenosine monophosphate (cAMP) (ibid.). The activity of the cerebral cortex is proportional to the concentration of cAMP (ibid.).

Glutaminergic neurons of the subthalamic nucleus (indirect pathway) stimulate the external part of the globus pallidus, simultaneously reducing activity of the thalamus and cerebral cortex neurons. The striatum inhibits the neurons of the lateral part of the globus pallidus, what leads to disinhibition of glutaminergic cells of the subthalamic nucleus and stimulation of the globus pallidus pars interna. Dynamic changes of the activity of direct and indirect pathway make it possible to stimulate well defined areas of the cerebral cortex with simultaneous inhibition of the areas, which do not take part in execution of particular movement or mental action (Mink, 1999; Groenewegen; 2003).

The damage of various structures of basalo-thalamo-cortical loop can manifest with symptoms related to a definite loop (Alexander, 1986; Royall et all., 2002). According to this argumentation it can be assumed that pathology of the basal ganglia can cause symptoms

Functional Anatomy, Physiology and Clinical Aspects of Basal Ganglia 95

Motor control of skeletal muscles relates to the motor loop (motor circuit) and the oculomotor loop (oculomotor circuit) (ibid.). The dorso-medial prefrontal loop, orbitofrontal loop and the anterior part of the cingular gyrus loop are associated with the control

The motor circuit is responsible, inter alia, for automatic motor activity connected with maintenance of body posture and reflexes (Fix, 1997), as well as for the control of muscular tension. The motor loop plays an essential role in initiating and fluent performing of motor actions executed by skeletal muscles especially during will dependent movements. The disorders of this loop can cause muscular stiffness, bradykinesia, akinesia and hipokinesia (e.g. in Parkinson's disease and parkinsonian syndrome) or excessively large and

The oculomotor loop participates in the control of saccadic eyeball movements. Efferent connections to the superior colliculus (Sc) from the cortical areas of the brain and subcortical nuclei, especially the reticular part of substantia nigra (SNr) make it possible to control rapid eyeball movements through the inhibition of movements disturbing the execution of a task (Hikosaka, 2000). Pressumably the neurons of ventro-lateral part of substantia nigra pars reticularis and caudate nucleus play essential role in external eyeball muscles movements, both through the neurons in which information on previously executed movements is remembered (memory-guided saccades), as well as neurons reacting on currently incoming visual stimuli (visually-guided saccades) (ibid.). In the result of oculomotor loop damage visual fixation can be impaired, and unilateral neglect syndrome, as well as attention deficits can be observed especially in the tasks requiring rapid movements targeted at stimuli (Hikosaka, 2000). The shortage of functions of external eyeball muscles caused by damages of basal ganglia (e.g. in Parkinson's disease, Huntington's disease) can impair saccadic movements of eyeballs depending on previously remembered information. In persons with basal ganglia disorders dysfunctions in intentional inhibition of eye movements, triggered

The dorsolateral prefrontal loop is responsible for the choice of aims, planning, programming of the sequence of mental actions and behaviours, switching between sentences (the ability to change attitude flexibly), verbal and spatial working memory, selfcontrol and metacognition (self-consciousness) (Royall et all., 2002). The disorders of the loop functions can lead to incorrect order of linguistic behaviours what results in verbal

The lateral orbitofrontal circuit takes part in initiating social behaviours motivated by an award and in inhibiting behaviours, which can trigger punishment (Royall et all., 2002). Incorrect functioning of this circuit may result in disinhibition of behaviours, personality changes, lack of control and emotional liability, as well as irritability and gaiety (DeLong & Wichmann, 2007). The damage of this loop can cause perseverations, which make it difficult to process information from external environment and adaptation of behaviours to a

uncontrolled movements of limbs (e.g. Huntington's chorea, balism) (Fix, 1997).

**2. Motor loops (motor and oculomotor)** 

of cognitive and emotional functions (ibid.).

by visual stimuli (ibid.), were observed.

fluency reduction (DeLong & Wichmann, 2007).

**3. Dorsolateral prefrontal loop** 

**4. Lateral orbitofrontal loop** 

particular situation (Royall et all., 2002).

typical for the damage of a particular loop or cause typical symptoms for the damage of several of them (ibid.). The symptoms, being the consequence of, definitely localized in the brain, damages of the particular structures of cortico-subcortical loops, can overlap with the symptoms from different areas of encephalon connected with a specific functional system, which is not a part of this system (ibid.). The conceptual model of basalo-thalamo-cortical connections can be helpful in interpretations of the symptoms of mental disorders relating to basal ganglia pathologies, for example in Parkinson's disease (Tröster & Arnett, 2005).

Fig. 3. The original conceptual model of the neuronal loop connecting the internal globus pallidus (GPI), subthalamic nucleus (STN) and thalamus with the cerebral cortex compiled on the basis of the literature (Fix, 1997; Longstaff, 2003; Groenewegen, 2003).
