Changes in cerebral blood oxygenation of the frontal lobe induced by direct electrical stimulation of thalamus and globus pallidus: a near infrared spectroscopy study

OBJECTIVE: Blood oxygenation level dependent (BOLD) contrast functional MRI images show activated cortical areas by detecting a reduced concentration of deoxyhaemoglobin (deoxy-Hb) during neuronal activity; however, near infrared spectroscopy (NIRS) has shown various patterns of cerebral blood oxygenation (CBO) changes in the frontal lobe during cognitive tasks. To determine if various patterns of CBO changes occur in the frontal lobe when the brain is directly stimulated, changes in CBO in the frontal lobe induced by deep brain stimulation in patients with implanted electrodes were evaluated. METHODS: Six patients were studied, including five with Parkinson's disease and one with essential tremor. To reduce tremor or rigidity, the electrodes were implanted at the thalamic nucleus ventralis intermedius (VIM: three Parkinson's disease and one essential tremor) or the globus pallidus internus (GPi: two Parkinson's disease). Using NIRS, changes of deoxy-Hb, oxyhaemoglobin (oxy-Hb) and total haemoglobin (total Hb) were measured in the bilateral frontal lobes during various stimulus conditions. RESULTS: High frequency (120 Hz) GPi stimulation consistently increased oxy-Hb and total Hb with a decrease of deoxy-Hb in an intensity and time dependent manner. Oxy-Hb and total Hb increased immediately after the onset of stimulation and then gradually decreased when stimulation was continued. By contrast, high frequency (120 Hz) VIM stimulation decreased oxy-Hb, deoxy Hb and total Hb in an intensity dependent manner. In the severe tremor patient with VIM stimulation, frequency response was examined by decreasing stimulus frequencies; deoxy-Hb increased at high frequencies (70-40 Hz), and then decreased below the control level at low frequencies (30-0 Hz), whereas oxy-Hb and total Hb increased consistently at high and low frequencies. CONCLUSION: The electrical stimulation of GPi and VIM caused various CBO changes in the frontal lobe, which were similar to those found during cognitive tasks. Such a multiplicity of CBO changes in the frontal lobe may be caused by complex neuronal circuits in the frontal lobe which has many neuronal connections to other cortical areas or the basal ganglia.     

Activation of the prefrontal cortex during the Wisconsin Card Sorting Test as measured by multichannel near-infrared spectroscopy

BACKGROUND: The Wisconsin Card Sorting Test (WCST) is a neuropsychological test to evaluate the function of the prefrontal cortex (PFC). However, inconsistent results have been reported concerning whether this task activates the PFC symmetrically or asymmetrically. OBJECTIVES: To investigate the brain activation in the PFC during the WCST, we examined blood oxygenation changes of healthy subjects by using multichannel near-infrared spectroscopy (NIRS). METHODS: Subjects were 32 healthy volunteers, 18 males and 14 females. The WCST was administered using a computerized version, and the hemodynamic changes of the PFC during the WCST were measured by a 24-channel NIRS system. RESULTS: A bilateral increase in oxygenated hemoglobin (oxyHb) was observed in the PFC in 20 subjects during the WCST. However, 5 subjects showed predominant activation on the left side and 3 subjects one on the right side. No oxyHb change was observed in 4 subjects, although they had good performances in the WCST. CONCLUSIONS: These results directly confirmed that the PFC was activated during the WCST in vivo by using the optical technique and suggested that the distribution of the activation in the PFC is different among healthy individuals.     

Reduced frontal functional asymmetry in schizophrenia during a cued continuous performance test assessed with near-infrared spectroscopy

Near-infrared spectroscopy (NIRS) allows noninvasive, in vivo measurement of changes in the concentrations of oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) in brain tissue based on their distinctive optical properties. A previous NIRS investigation on healthy subjects (Fallgatter and Strik 1997) found indications of right frontal activation during a Continuous Performance Test (CPT) that are consistent with results from positron emission tomography (PET) and event-related potentials studies. The indications consisted of right frontal blood oxygenation changes, consistent with a hemodynamic response, along with a significant left frontal increase in HHb. The current study investigated whether this characteristic lateralized frontal NIRS activation pattern was present in a group of nine schizophrenia patients during the execution of a CPT. In contrast to the previous study, no overall or hemispheric activation effects were found in the schizophrenia subjects. Direct comparison of the results of the two studies confirmed group differences, with a lack of lateralized activation in schizophrenia patients. Furthermore, a trend of higher left/right HHb ratios at rest and during activation was found in patients with schizophrenia. The finding is interpreted as a sign of reduced specific lateralized frontal reactivity, possibly based on a left hemisphere functional deficit.     

The effects of clozapine on cognitive function and regional cerebral blood flow in the negative symptom profile schizophrenia

OBJECTIVE: Cognitive function and regional cerebral blood flow (rCBF) were studied in negative symptom profile schizophrenic patients by using WCST and SPECT. METHODS: Twenty-one schizophrenic patients who matched the criteria of Andreason's negative symptom profile received SPECT and WCST, and then were treated with clozapine for 8 consecutive weeks. There were 28 and 12 normal subjects as the control groups of WCST and SPECT, respectively. RESULTS: Compared with controls, significantly poorer performance on total trials of category (TT), persevering errors (PE), and non-persevering errors (NPE) of WCST were found in schizophrenia (p < 0.05). The total score of the scale for assessment negative symptoms (SANS) was significantly related with poor TT (r = 0.45, p < 0.01) and PE performance (r = 0.45, p < 0.01). The poor TT, PE, and NPE tasks of WCST and SANS scores in the negative schizophrenic patients were significantly improved through clozapine treatment (p < 0.05). The schizophrenic patients had a significantly lower rCBF in bilateral frontal and temporal lobes and lower change rate of rCBF in bilateral frontal lobes during WCST compared to normal controls (p < 0.05). CONCLUSIONS: Negative symptom profile schizophrenia has cognitive deficits and lower rCBF in bilateral frontal and temporal lobes, which suggests that negative symptom profile schizophrenic patients have hypofrontality. Clozapine can improve negative symptoms and improve cognitive dysfunction, although it cannot improve reduced rCBF in the frontal lobes.     

Wisconsin Card Sorting Test Performance Following Head Injury: Dorsolateral Fronto-Striatal Circuit Activity Predicts Perseveration

The Wisconsin Card Sorting Test (WCST) has been argued to be a sensitive indicator of frontal lobe function. However, several recent studies have failed to find a consistent relationship between structural damage to this cortical area and perseveration on the test. In the present study, positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose was used to examine the relationship of regional brain metabolism to perseverative responding on the WCST in patients with a history of closed-head injury. An inverse relationship was found between perseverative responses and metabolism in the right, but not the left, dorsolateral prefrontal cortex and caudate nucleus. Perseverative responding was not related to metabolism in several other regions of the frontal lobes and basal ganglia, including the putamen and the frontal poles bilaterally. These data suggest that the functional integrity of the right dorsolateral frontal-subcortical circuit is critical for WCST performance.     

Frontal and temporal cortical functional recovery after electroconvulsive therapy for depression: A longitudinal functional near-infrared spectroscopy study

While the efficacy and tolerability of electroconvulsive therapy (ECT) for depression has been well established, the acute effects of ECT on brain function remain unclear. Particularly, although cognitive dysfunction has been consistently observed after ECT, little is known about the extent and time course of ECT-induced brain functional changes, as observed during cognitive tasks. Considering the acute antidepressant effects of ECT on depression, aberrant brain functional responses during cognitive tasks in patients with depression may improve immediately after this treatment. To clarify changes in cortical functional responses to cognitive tasks following ECT, we used task-related functional near-infrared spectroscopy (NIRS) to assess 30 patients with major depressive disorder or bipolar depression before and after an ECT series, as well as 108 healthy controls. Prior to ECT, patients exhibited significantly smaller [oxy-Hb] values in the bilateral frontal cortex during a letter verbal fluency task (VFT) compared with healthy controls. We found a significant increase in [oxy-Hb] values in the bilateral frontal cortex during the VFT after ECT in the patient group. A decrease in depression severity was significantly correlated with an increase in [oxy-Hb] values in the right ventrolateral prefrontal cortex following ECT. This is the first NIRS study to evaluate brain functional changes before vs. after ECT. Impaired functional responses, observed during the cognitive task in depressed patients, were normalized after ECT. Thus, recovery from abnormal functional responses to cognitive tasks in the frontal brain regions may be associated with the acute therapeutic effects of ECT for depression.     

Frontal activation during a verbal-fluency task as measured by near-infrared spectroscopy

Near-infrared spectroscopy (NIRS) is an optical method which allows non-invasive in vivo measurements of concentration changes of oxygenated hemoglobin (O(2)Hb) and deoxygenated hemoglobin (HHb) in brain tissue. The present study investigated the blood oxygenation changes that were associated with the execution of the Verbal-Fluency Test (VFT) in left and right prefrontal brain areas of 14 healthy subjects by means of NIRS. During the VFT, subjects were required to pronounce as many nouns as possible beginning with the letters "A," "F," and "S." Compared to a baseline resting condition, we found a significant increase of O2Hb (left hemisphere: baseline, 1.2+/-1.1microm; VFT(letterS), 3.56+/-2.02microm; right hemisphere: baseline, 1.26+/-1.08microm; VFT(letterS), 3.67+/-2.03microm) and a significant decrease of HHb (left hemisphere: baseline, -0.21+/-0.59microm; VFT(letterS), -0.67+/-0.60microm; right hemisphere: baseline, -0.29+/-0.53microm; VFT(letterS), -0.68+/-0.44microm) during the execution of the VFT over both hemispheres. No lateralization effects were observed. The results confirm that NIRS is suitable for the measurement of blood oxygenation changes in frontal brain areas that are associated with cognitive tasks.     

Near-infrared spectroscopy to define cognitive frontal lobe functions.

Near-infrared spectroscopy (NIRS) monitors changes in the regional cerebral oxygenation (rSO) and has been used to study cerebral physiologic functions in normal states and during epileptic seizures. Yet, the limitations and pitfalls of the technique are not fully understood. The authors evaluated NIRS changes over the frontal lobes during language tasks known to be associated with the integrity of the dominant frontal lobe in 17 normal adults (handedness: 14 right, 3 left). Recording protocol involved a baseline (3 minutes) with the subject relaxed and thinking of a blue sky and a second baseline during voluntary mouth movements mimicking speech. Two standardized neuropsychological word-generation tasks (controlled word-association tests: CFL and Animals) were then administered (4 minutes total) followed again by the two baseline procedures. Mouth movement without verbalization increased rSO values in excess of 2 SD of baseline fluctuations in 70% of the subjects. A t-test comparison of these baseline measurements was statistically significant (P < 0.0001). A general linear model repeated-measures procedure was then used to statistically examine NIRS increments during the cognitive tasks above and beyond the contribution produced by mouth movements during the second baseline. Compared to the second baseline, rSO further increased significantly during the word generation tasks (left frontal F value = 21.4, P < 0.0001; right frontal F value = 15.2, P < 0.001), confirming the utility of the technique. There was no apparent difference related to handedness. These findings corroborate the usefulness of NIRS to demonstrate focal cerebral activation during an "executive" language task. However, interpretation of changes can be confounded by extracerebral factors such as mouth movement, a finding of particular relevance in NIRS clinical applications.     

Neurologic validity of the Wisconsin Card Sorting Test with a pediatric population

This study investigated the neurologic validity of the Wisconsin Card Sorting Test (WCST) with a pediatric population; that is, the ability of the test to detect dysfunction in the frontal lobes. Fifty children with diverse etiologies of brain dysfunction were classified via EEG, MRI, or CT as having left hemisphere, right hemisphere, or bilateral frontal, extrafrontal, or multifocal/diffuse regions of brain dysfunction. Findings failed to support the hypotheses that WCST performance is more impaired in frontal lesions than extrafrontal or multifocal/diffuse lesions, or that WCST performance is more impaired in left hemisphere lesions than right. Although the WCST is not helpful in localizing cerebral area of dysfunction, it may still be a clinically useful test for examining processes that children use to solve complex problems.     

Neurologic Validity of the Wisconsin Card Sorting Test with a Pediatric Population

This study investigated the neurologic validity of the Wisconsin Card Sorting Test (WCST) with a pediatric population; that is, the ability of the test to detect dysfunction in the frontal lobes. Fifty children with diverse etiologies of brain dysfunction were classified via EEG, MRI, or CT as having left hemisphere, right hemisphere, or bilateral frontal, extrafrontal, or multifocal/diffuse regions of brain dysfunction. Findings failed to support the hypotheses that WCST performance is more impaired in frontal lesions than extrafrontal or multifocal/diffuse lesions, or that WCST performance is more impaired in left hemisphere lesions than right. Although the WCST is not helpful in localizing cerebral area of dysfunction, it may still be a clinically useful test for examining processes that children use to solve complex problems.     

Wisconsin Card Sorting Test Performance as a Measure of Frontal Lobe Damage

Abstract

We examined the sensitivity and specificity of the Wisconsin Card Sorting Test (WCST) as a measure of frontal lobe damage in 91 subjects with stable focal brain lesions. Anatomical information about the location and extent of brain damage was obtained from MR and CT transparencies. No significant differences in WCST performance were found between subjects with frontal vs. nonfrontal damage. Some subjects with extensive frontal lobe damage performed well on the WCST, and some subjects with damage outside of the frontal lobes failed. The optimal cutoff scores for discriminating frontal from nonfrontal subjects correctly classified only 62% of the subjects. Further analysis of WCST performances associated with damage to various subregions of the frontal lobes also failed to reveal any reliable relationships. These findings indicate that performance on the WCST cannot be interpreted in isolation as an index of frontal lobe damage.     

Evaluation of two patients with SCA2 with frontal lobe dysfunction using brain SPECT with three-dimensional stereotactic surface projections (3D-SSP)]

We evaluated the cognitive impairment of two patients with genetically confirmed spinocerebellar ataxia type 2 (SCA2). Neurological examination revealed ignorance of his illness and Gegenhalten phenomenon in patient 1, and emotional incontinence in patient 2. Although their mental status evaluated by HDS-R or Mini-Mental State Examination (MMSE) was almost normal, the results of WAIS-R and Wisconsin Card Sorting Test (WCST) revealed the existence of intellectual decline and executive dysfunction. 3D-SSP SPECT demonstrated distinct hypoperfusion in bilateral frontal lobes, whereas brain MRI revealed no apparent cerebral atrophy in both patients. These results raise the possibility that frontal lobe dysfunction was observed in the early stages of SCA2, and that 3D-SSP SPECT is useful for evaluating the involvement of frontal lobe dysfunction in SCA2.     

Prefrontal brain activation during stop-signal response inhibition: an event-related functional near-infrared spectroscopy study

Previous lesion and neuroimaging studies have shown that the frontal lobes play an important role in response inhibition. In the present study event-related functional near-infrared spectroscopy (NIRS) was applied to investigate cerebral blood oxygenation in the right and left prefrontal cortex (PFC) in 15 male participants during the performance of a stop-change paradigm. Data analysis showed stronger brain activation in the left and right PFC during successful and failed stopping of initiated responses in comparison to a condition without stopping. Changes in cerebral blood oxygenation were more pronounced in the right than in the left PFC. No substantial activation changes were found during successful or failed changing of initiated responses (response inhibition and subsequent response re-engagement). The findings indicate that NIRS is suitable for the functional identification of prefrontal activation during the inhibition of initiated responses and provide further support for the contribution of the PFC to response inhibition.     

Schizophrenia and performance on the Wisconsin Card Sorting Test (WCST): deficits and rehabilitation]

In recent years, there has been a sustained interest in the so-called "frontal hypothesis" of schizophrenia: the idea that clinical symptoms and cognitive deficits characteristic of schizophrenia might be explained by defective function of the frontal lobes. Several studies have attempted to test this hypothesis by examining the performance of schizophrenic subjects on the Wisconsin Card Sorting Test (WCST), a neuropsychological evaluation widely believed to reflect the functional capacity of frontal lobes. A typical finding is that schizophrenic patients demonstrate a tendency to perseverate in producing an inappropriate response in spite of negative feedback. This perseverative tendency resembles the perseveration often seen in patients with frontal brain damage. This article proposes a critical examination of the available evidence linking frontal deficits with schizophrenia via the WCST. As we will show, in most of these studies, only a relatively small number of the available measures on the WCST are made, and consequently many interesting cognitive capacities in schizophrenic subjects have not been adequately examined with this test. These "non-classical" measures will be described and critically examined with respect to their pertinence for further work on schizophrenic subjects. Of particular interest are the "failure to maintain set", which measures cognitive instability, "conceptual responses", which can indicate a certain conceptual capacity even in subjects who show perseveration, and "learning to learn", which can demonstrate a capacity to profit from experience on the test. A second objective will be to critically examine the evidence concerning the capacity of schizophrenic patients to improve their performance on the WCST. To the extent that performance on the WCST reflects the functional level of cognitive capacities important for everyday life, any capacity in schizophrenic patients to improve their performance could have important implications for therapeutic intervention and re-education.     

Wisconsin Card Sorting Test performance in patients with focal frontal and posterior brain damage: effects of lesion location and test structure on separable cognitive processes

Forty-six patients with single focal lesions (35 frontal, 11 nonfrontal) were administered the Wisconsin Card Sorting Test (WCST) under three conditions of test administration. The three conditions varied in the amount of external support provided via specificity of instructions. The WCST, while a multifactorial test, is specifically sensitive to the effects of frontal lobe damage if deficits in language comprehension and visual-spatial search are controlled. There is also specificity of functioning within the frontal lobes: patients with inferior medial frontal lesions, unilateral or bilateral, were not impaired on the standard measures although they had increased loss of set when informed of the sorting categories. Verbal instructions may provide a probe to improve diagnosis and prognosis, assessment of the potential efficacy of treatment, and the time frame of plasticity of specific cognitive operations.     

Wisconsin Card Sorting Test performance as a measure of frontal lobe damage.

We examined the sensitivity and specificity of the Wisconsin Card Sorting Test (WCST) as a measure of frontal lobe damage in 91 subjects with stable focal brain lesions. Anatomical information about the location and extent of brain damage was obtained from MR and CT transparencies. No significant differences in WCST performance were found between subjects with frontal vs. nonfrontal damage. Some subjects with extensive frontal lobe damage performed well on the WCST, and some subjects with damage outside of the frontal lobes failed. The optimal cutoff scores for discriminating frontal from nonfrontal subjects correctly classified only 62% of the subjects. Further analysis of WCST performances associated with damage to various subregions of the frontal lobes also failed to reveal any reliable relationships. These findings indicate that performance on the WCST cannot be interpreted in isolation as an index of frontal lobe damage.     

Impairment of autonomic emotional response for executive function in children with ADHD: A multi-modal fNIRS and pupillometric study during the Wisconsin Card Sorting Test

ObjectiveChildren with attention deficit hyperactivity disorder (ADHD) often experience difficulties with emotional control and a consequent inability to perform tasks. To clarify the effects of emotional behavior on cognitive functions, we aimed to determine the association between emotional changes and executive functions in children with ADHD by measuring the pupil diameter changes associated with emotional changes.Participants and methodsThis study included 14 children with ADHD and 10 typically developing children (TDC) aged between 10 and 16 years. During the Wisconsin Card Sorting Test (WCST), which is related to context formation and task switching among executive functions, changes in pupil diameter and frontal oxygenated hemoglobin (oxy-Hb) using functional near-infrared spectroscopy (fNIRS) were recorded simultaneously. Pupil diameter changes during “cognitive shift” and “consecutive correction” were compared between both groups.ResultsDuring cognitive shift, the pupils of children with ADHD contracted, whereas those of the TDC were mydriatic. During consecutive correction, the pupils of children with ADHD were mydriatic, whereas those of the TDC tended to contract. These results correlated with WCST performance. Moreover, during cognitive shifts, changes in bilateral frontal blood flow were increased in TDC, but not in children with ADHD.ConclusionThe locus coeruleus-norepinephrine (LC-NE) system plays an important role in pupillary diameter response. These results suggest that the LC-NE system may be dysfunctional in children with ADHD, and the system’s abnormality may lead to affective abnormalities in such patients, which results in poor performance on WCST (i.e., impaired executive functions).     

PET findings and neuropsychological deficits in a case of Fahr's disease.

In a case of Fahr's disease with frontal lobe type dementia and hyperkinetic-hypotone syndrome, functional changes were investigated using positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) as a tracer. Computed tomography showed bilateral calcifications in the putamen and globus pallidus consistent with the diagnosis of Fahr's disease and a frontally pronounced brain atrophy. In contrast, reduced glucose uptake in PET was not only confined to the areas mentioned above, but extended to the temporal and parietal cortices, bilaterally. These functional changes corresponded to the neuropsychological deficits observed, i.e. disturbed selective attention and cognitive flexibility, verbal perseverations, and declarative memory deficits. It is suggested that functional changes may precede cerebral atrophy in Fahr's disease and may reflect deficits in functional circuits, which involve both the basal ganglia and the frontal, parietal, and temporal lobes.     

Characteristics of oxygenated hemoglobin concentration change during pleasant and unpleasant image‐recall tasks in patients with depression: Comparison with healthy subjects

Aim

Patients with major depressive disorder (MDD) have been reported to show cognitive impairment in attention, cognition control, and motivation. The prefrontal cortex plays an important role in the pathophysiology of depression. Neurophysiological abnormalities have been examined in MDD patients by several neuroimaging studies. However, the underlying neural mechanism is still unclear. We evaluated brain function during pleasant and unpleasant image‐recall tasks using multichannel near‐infrared spectroscopy (NIRS) in MDD patients.

Methods

The subjects were 25 MDD patients and 25 age‐ and sex‐matched healthy controls. Patients were classified according to DSM‐IV‐TR criteria. We measured the oxygenated hemoglobin concentration change (δoxyHb) in the forehead and temporal lobe during image‐recall task with pleasant (e.g., puppy) and unpleasant (e.g., snake) images using NIRS. To check whether all subjects understood the task, they were asked to draw pictures of both image tasks after NIRS measurement.

Results

The δoxyHb in the healthy group was significantly higher than that in the MDD group in the bilateral frontal region during the unpleasant condition. A significant negative correlation between the Hamilton Rating Scale for Depression score and δoxyHb was observed in the left frontal region during the unpleasant condition.

Conclusion

We suggest that image‐recall tasks related to emotion measured by NIRS might be a visually useful psychophysiological marker to understand the decrease in the frontal lobe function in MDD patients. In particular, we suggest that the decrease in δoxyHb in the left frontal lobe is related to the severity of depression.     

Cortical activation during two verbal fluency tasks in schizophrenic patients and healthy controls as assessed by multi-channel near-infrared spectroscopy

Near-infrared spectroscopy (NIRS) is an optical imaging method that allows non-invasive in-vivo measurements of changes in the concentration of oxygenated (O(2)Hb) and deoxygenated (HHb) hemoglobin in brain tissue. For the present study, we examined 12 schizophrenic patients and 12 age- and gender-matched healthy controls by means of multi-channel NIRS (Optical Topography; ETG-100, Hitachi Medical Co., Japan) during performance of two versions of the Verbal Fluency Test (VFT; letter and category version). The results indicate that the verbal fluency tasks generally led to clear frontal activation in healthy controls, which was significantly reduced in schizophrenic patients. The letter version of the VFT induced overall stronger activation than the category version, the group difference being particularly pronounced for phonological fluency. Moreover, significant positive correlations between task-related activation effects in prefrontal and temporal NIRS channels were found in both schizophrenic patients and healthy controls. The results confirm functional deficits within the frontal lobe in patients suffering from schizophrenic illnesses, but do not confirm previous findings on abnormal fronto-temporal correlations or increased temporal activation in this group of patients. The data furthermore underline the usefulness of functional NIRS in monitoring hemodynamic responses associated with cognitive processes in healthy controls and patients with neuro-psychiatric disorders.