Neuronal activity of human caudate nucleus and prefrontal cortex in cognitive tasks
Introduction
The caudate nuclei are symmetrical nuclei in the left and right subcortical regions of the brain considered anatomically as a part of basal ganglia. Functions of the basal ganglia were classically associated with various aspects of motor control. Recent reviews illustrate considerable functional distinctions among different regions of basal ganglia 6, 32, 46, each region receiving input from several functionally related cortical areas.
There are several reasons to believe that the head of the caudate nucleus seems to function similarly to the prefrontal cortex and may share with prefrontal regions a relation to certain cognitive functions. Prefrontal lesions acquired during prenatal development result in a bilateral increase of the caudate nuclei in volume with normal neuronal density [75]. Although dopaminergic innervation is widely distributed in the human neocortex [39], major accumulations of dopamine in the human brain demonstrated by positron emission tomography (PET) are in striatum, lateral frontal cortex and anterior cingulate [54]. Recent successes in voltammetric in vivo recording of neurotransmitter levels in different brain regions of behaving animals have demonstrated that the dopamine release in frontal cortex and in striatum may be correlated [90]. Depletion of dopamine in the prefrontal cortex has the same effect on delayed alternation performance in non-human primates as do lesions and this effect is reversible by dopamine agonists [24]. Experimental lesions of the anterior dorsolateral frontal cortex and the caudate nucleus in monkeys may produce strikingly similar behavioral deficits in delayed alternation and delayed response tasks leaving performance on simple visual discrimination tasks unaffected 12, 43, 108. The caudate nucleus receives a visual input with early onset latency 28, 65, 68, 69, 107which appears important for memory functions 66, 91. Studies of the caudate and frontal neuronal activity of animals in identical behavioral tasks reveal cells which demonstrate significant task-related responses, but do not respond to the same stimuli or movements when they occur independently of the task [107]. However, beyond this general tendency, the detailed comparisons of the neuronal responses in the anterior caudate and frontal regions in identical tasks have led to different results. Some studies have 13, 59, 118and some have not [86], found cellular responses in the caudate nucleus with similar functional roles to frontal regions. In some studies the main difference between the anterior caudate and frontal regions appeared to be in the proportion of task-related neurons to all recorded cells 107, 113.
The caudate nucleus largely receives anatomical input from frontal and temporo-parietal cortical areas 63, 64, 72, 85, 102and sends output fibers to globus pallidus and other regions of the basal ganglia, forming anatomical loops with these structures [6]. Anatomically, the caudate consists of separate histochemically distinct compartments which appear somewhat similar to cortical columns [56]. The cortical areas project to the caudate nucleus in a highly organized way; different cortical regions project principally to different compartments of the caudate nucleus [102]. Part of the fronto-caudate loop returns back to Brodmann area 46 in prefrontal cortex [83]. Another part projects to Brodmann area 6 of the premotor cortex [60].
Pathology of caudate nucleus in human patients after hemorrhagic stroke produces cognitive changes among other symptoms 21, 22, 29, 80, 120, 124. Schizophreniform psychoses have been associated with a familial (or idiopathic) basal ganglia calcification [51]. Dementia in patients with Huntington disease has been correlated with the caudate glucose hypometabolism [71]. It was also found that schizophrenic patients have higher D2 dopamine receptor densities in the caudate nucleus as compared to normal subjects [125]. Magnetic resonance imaging (MRI) abnormalities of the caudate nucleus have been reported in schizophrenia [23]and depression 70, 117. Neuroimaging studies of children with attention-deficit hyperactivity disorder reveal a reduced size with a reversed abnormal asymmetry [62]and hypoperfusion [76]of the caudate nuclei. These children are normal in rapid automatic covert shifts of attention controlled by posterior, parietal attention system. However, where the covert shifts of attention are slower and more likely to be controlled by the anterior, frontal attention system, children with attention-deficit hyperactivity disorder are significantly worse than their normal counterparts [121]. Abnormally high glucose metabolism and local blood flow are found in the caudate and anterior frontal regions in patients with obsessive-compulsive disorder 14, 15, 20, 105, which decrease toward a normal range in those patients who respond well to either a drug or behavioral therapy 15, 20. These findings suggest that the anterior attention deficit and obsessive-compulsive disorder may depend on fronto-caudate circuitry as well.
Lesions due to non-hemorrhagic stroke strictly localized to the caudate nucleus rarely cause neurological symptoms and their major deficits may be cognitive, including psychiatric symptoms and behavioral problems. The cognitive impairments often have acute onset and may include memory, language or attention disturbances, as well as abulia, disinhibition and deficits in planning, problem solving and personality [82]. These symptoms are similar to the effects produced by prefrontal lesions [77]. The severity of these changes has been shown to correlate with the size and localization of lesion within the caudate nucleus (e.g. dorsolateral versus ventromedial caudate) but not with the lateralization [82]. Bilateral lesions tend to cause more severe cognitive deficits than do unilateral lesions 82, 106.
Electrical stimulations [122]and depth recordings [17]of patients demonstrated the caudate’s relation to language and verbal memory. Lesions involving caudate nucleus may produce aphasia with semantic or phonemic paraphasia and disturbances of naming, oral reading, aural and reading comprehension of words, word associations, spelling, articulation and other aphasic symptoms with clustering different from classical cortical, thalamic or putaminal aphasic syndromes 25, 33, 34, 36.
Thus, the present brief review of anatomical input and output of the caudate nucleus and behavioral effects of its lesions suggests that the circuitry of multiple cortical areas may involve the caudate region. Most relevant to cognitive functions of the head of the caudate nucleus seem to be the dorsolateral prefrontal and the anterior cingulate loops which both involve the caudate nucleus 6, 45, 83.
It is possible to study the activity of neurons in various brain regions during cognitive tasks in certain patients who have depth electrodes for their diagnosis and therapy 16, 18, 61, 88, 89, 110. In our earlier work, we have described the neuronal activity in dorsolateral prefrontal cortex areas 46 and 10 [1]and in Broca’s area including Brodmann’s areas 44 and 9 [19]in visual word processing and object naming tasks. In the present study, we recorded neuronal activity directly from the head of the caudate nucleus in human patients in identical object naming and visual word processing tasks and compared the results to similar cortical studies. Part of these results has been reported recently in an abstract form 4, 5. The goal of the present study is to examine the role that the caudate nucleus plays in language tasks. We start out by showing clear evidence of increased neuronal activity in the caudate specific to visual words as compared to pseudowords. This early activation appeared to relate to semantics and is separate from a later activation related to word sound. Next we show that the early semantic activations occur in these same cells during object naming and that they do not depend upon making a specific response (motor output). The caudate semantic activation is not specific to words, but appears to occur to other stimuli for which a semantic analysis is possible (i.e. objects). Finally, in a section on memory, we show that the increase of neuronal activity to word stimuli does not occur during the task of memory retrieval where no semantic task is required. This suggests the selectivity of firing increase for semantic processing.
Section snippets
Subjects
Subjects were three informed right-handed (by history) Parkinsonism patients (L.N.B.1, woman, 51-year-old; I.P.A., man, 47-year-old; and M.F.S., woman, 50-year-old) with intracerebral electrodes implanted for diagnostic and therapeutic procedures, i.e. solely for clinical purposes unrelated to the present study [16]. All patients gave informed written consent for stereotactic neurosurgical treatment, separate informed consent was obtained for the present cognitive experiments. Bundles of six
Lexical decision
Caudate neuronal responses of subject L.N.B.1 during the lexical decision task are shown in Fig. 3. The localization of this neuronal population is illustrated in Fig. 1a. There was a significant (P<0.001) increase of firing early after the stimulus presentation within 200–700 ms in a delay period of all three task conditions as well as smaller response during a motor output after the response cue (Fig. 3A). Within the delay period, when there was no motor output, the firing rate increase was
Lexical decision
To test the functional role of the caudate neurons in language, we recorded the caudate neuronal activity in a lexical decision task designed to separate elementary component cognitive operations such as semantic and phonological encoding as well as motor output. We have used this task to study the cellular activity in two frontal regions: in anterior inferior prefrontal areas 46 and 10 [1]and in Broca’s area including Brodmann’s areas 44 and 9 [19]. Visual input in this task is identical in
Acknowledgements
We thank S.V. Medvedev, M.I. Posner and A.A. Thompson for invaluable advice.
References (126)
- et al.
Neuronal correlate of the higher-order semantic code in human prefrontal cortex in language tasks
Int J Psychophysiol
(1993) - et al.
Event-related brain potential imaging of semantic encoding during processing single words
Neuroimage
(1998) - et al.
Abnormal pattern of cerebral glucose metabolic rates involving language areas in young adults with Down syndrome
Brain Lang
(1994) - et al.
Neurophysiological codes of words in subcortical structures of the human brain
Brain Lang
(1979) - et al.
Psychophysiological micromapping of the human brain
Int J Psychophysiol
(1989) - et al.
Neuronal activity in frontal speech area 44 of the human cerebral cortex during word recognition
Neurosci Lett
(1991) - et al.
Basal ganglia participation in language pathology
Brain Lang
(1982) - et al.
Responses of striatal neurons in the behaving monkey. 2. Visual processing in the caudal neostriatum
Brain Res
(1984) - et al.
Evidence for a widespread dopaminergic innervation of the human cerebral neocortex
Neurosci Lett
(1989) - et al.
Differential activation of right and left posterior sylvian regions by semantic and phonological tasks: a positron emission tomography study in normal human subjects
Neurosci Lett
(1994)
Delayed alternation in cats with lesions of the prefrontal cortex and the caudate nucleus
Physiol Behav
Behavioral correlates of activity in basal ganglia neurons
Trends Neurosci
The crossed cortico-caudate projection in the rhesus monkey
Neurosci Lett
Interhemispheric organization of corticocaudate projections in the cat: a retrograde double-labelling study
Neurosci Lett
Subcortical crossed axonal projections to the caudate nucleus of the cat: a double-labelling study
Neurosci Lett
Error’ potentials in limbic cortex (anterior cingulate area 24) of monkeys during motor learning
Neurosci Lett
A detailed anatomical analysis of neurotransmitter receptors in the putamen and caudate in Parkinson’s disease and Alzheimer’s disease
Neurosci Lett
Memory consolidation: brain region and neurotransmitter specificity
Neurosci Lett
Increase in size of the caudate nucleus of the cat after a prenatal neocortical lesion
Dev Brain Res
The programming of constructive activity in local brain injuries
Neuropsychologia
Striatal dopamine distribution in Parkinsonian patients during life
J Neurol Sci
Delayed alternation performance and unit activity of the caudate head and medial orbitofrontal gyrus in the monkey
Brain Res
Brain mechanisms of cognitive skills
Conscious Cogn
Regional response differences within the human auditory cortex when listening to words
Neurosci Lett
Time course of activating brain areas in generating verbal associations
Psychol Sci
Aspects of language processing by neurons in the human caudate nucleus
Neuroimage
Parallel organization of functionally segregated circuits linking basal ganglia and cortex
Annu Rev Neurosci
Effect of the nigrostriatal dopamine system on acquired neural responses in the striatum of behaving monkeys
Science
Working memory
Comparison of the effects of frontal and caudate lesions on delayed response and alternation in monkeys
J Comp Physiol Psychol
Cerebral glucose metabolic rates in non-depressed patients with obsessive-compulsive disorder
Am J Psychiatry
Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder
Arch Gen Psychiatry
Local cerebral glucose metabolic rates in obsessive-compulsive disorder
Arch Gen Psychiatry
The behavioural and motor consequences of focal lesions of the basal ganglia in man
Brain
Long-term cognitive impairment associated with caudate stroke
Stroke
Brain morphology and schizophrenia: a magnetic resonance imaging study of limbic, prefrontal cortex and caudate structures
Arch Gen Psychiatry
Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey
Science
Neural circuits in schizophrenia and positron emission tomography
Hum Brain Mapping
Detection of cortical activation during averaged single trials of a cognitive task using functional magnetic resonance imaging
Proc Natl Acad Sci USA
Caudate infarcts
Arch Neurol
Description and scanographic study of Leborgne’s brain: Broca’s discovery
Rev Neurol (Paris)
Lexical access in simple reading tasks
Frontal-subcortical circuits and human behavior
Arch Neurol
Aphasia with non-hemorrhagic lesions in the basal ganglia and internal capsule
Arch Neurol
Language and the basal ganglia
Trends Neurosci
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