Frontal Cerebral Blood Flow Research Articles

Volumetric cerebral perfusion imaging in healthy adults: Regional distribution, laterality, and repeatability of pulsed continuous arterial spin labeling (PCASL)

The regional distribution, laterality, and reliability of volumetric pulsed continuous arterial spin labeling (PCASL) measurements of cerebral blood flow (CBF) in cortical, subcortical, and cerebellar regions were determined in 10 normal volunteers studied on two occasions separated by 3 to 7days. Regional CBF, normalized for global perfusion, was highly reliable when measured on separate days. Several regions showed significant lateral asymmetry; notably, in frontal regions CBF was greater in the right than left hemisphere, whereas left was greater than right in posterior regions. There was considerable regional variability across the brain, whereby the posterior cingulate and central and posterior precuneus cortices had the highest perfusion and the globus pallidus the lowest gray matter perfusion. The latter may be due to iron-induced T1 shortening affecting labeled spins and computed CBF signal. High CBF in the posterior cingulate and posterior and central precuneus cortices in this task-free acquisition suggests high activity in these principal nodes of the “default mode network.”

Frontal Cerebral Blood Flow Changes after Hormone Replacement Therapy in Depressed Postmenopausal Women

We investigated the effects of hormone replacement therapy (HRT) on frontal cerebral blood flow (CBF), depressive symptoms, and cognitive function in depressed postmenopausal women. Fourteen postmenopausal women with depressive symptoms underwent HRT, and seven controls not undergoing HRT were studied. We evaluated frontal CBF, expressed as frontal/cerebellum (F/C) ratio, using Tc-99m hexamethyl propylene amine oxime single photon emission computed tomography (Tc-99m HMPAO SPECT), cognitive function using the Mini-Mental Status Examination (MMSE), and depression using the HAD (Hospital Anxiety and Depression) scale. All studies were carried out at initial status and after 9 months. Single photon emission computed tomography was performed at rest and at activation during the Wisconsin Card Sorting Test (WCST). Initial frontal CBF was not different between groups. After 9 months, resting frontal CBF was similar between groups. However, activated frontal CBF was significantly higher in the HRT group than in controls (F/C ratio: 0.924+/-0.04 versus 0.853+/-0.05, P=0.007). Furthermore, the increase in the activated F/C ratio was inversely associated with years since menopause. Mini-Mental Status Examination scores improved after HRT, but depression scores did not. Hormone replacement therapy improved frontal CBF and cognitive function but not depression in postmenopausal women. The changes in frontal CBF were detected only during WCST activation and were most apparent during early postmenopausal years.

Tomographic measurements of regional cerebral blood flow in progressive supranuclear palsy and Parkinson's disease.

Intellectual changes observed in progressive supranuclear palsy (PSP) are sometimes seen with lesser intensity in Parkinson's disease (PD). Cognitive impairment of PSP has been attributed to a frontal lobe dysfunction explaining the frontal cortex hypometabolism detected by PET. To establish whether this frontal hypometabolism is more pronounced in PSP than in PD, we compared frontal and temporo-parietal cerebral blood flow (CBF) indexes studied by SPECT using Tc99m HmPAO in 18 PSP, 18 PD and 8 control subjects. For each patient neuropsychological performances were also assessed. A significant left frontal hypoperfusion was observed in PSP (mean index value: 0.78 +/- 0.03, p < 0.01) and PD (0.78 +/- 0.04, p < 0.05) as compared to controls (0.84 +/- 0.03), whereas there was no difference between PSP and PD. No correlation was discovered between neuropsychological performances and frontal cortical index changes. This frontal uptake reduction of Tc99m HmPAO in PSP and PD could result from a disconnection phenomenon secondary to subcortical lesions. In both groups mean frontal indexes showed only a left frontal hypoperfusion suggesting that subcortical structures might be asymmetrically involved in early stages of the diseases. The lack of difference for indexe values between PSP and PD might be explained by the difference between the mean disease duration: 4.3 years for the PSP and 7.8 years for the PD. It might also suggest that frontal CBF reduction exists in the same proportions in PD and PSP, but at a later stage in the former case.

Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety

BackgroundMany studies have reported beneficial effects from the application of near-infrared (NIR) light photobiomodulation (PBM) to the body, and one group has reported beneficial effects applying it to the brain in stroke patients. We have reported that the measurement of a patient's left and right hemispheric emotional valence (HEV) may clarify data and guide lateralized treatments. We sought to test whether a NIR treatment could 1. improve the psychological status of patients, 2. show a relationship between immediate psychological improvements when HEV was taken into account, and 3. show an increase in frontal pole regional cerebral blood flow (rCBF), and 4. be applied without side effects.MethodsWe gave 10 patients, (5 M/5 F) with major depression, including 9 with anxiety, 7 with a past history of substance abuse (6 with an opiate abuse and 1 with an alcohol abuse history), and 3 with post traumatic stress disorder, a baseline standard diagnostic interview, a Hamilton Depression Rating Scale (HAM-D), a Hamilton Anxiety Rating Scale (HAM-A), and a Positive and Negative Affect Scale (PANAS). We then gave four 4-minute treatments in a random order: NIR to left forehead at F3, to right forehead at F4, and placebo treatments (light off) at the same sites. Immediately following each treatment we repeated the PANAS, and at 2-weeks and at 4-weeks post treatment we repeated all 3 rating scales. During all treatments we recorded total hemoglobin (cHb), as a measure of rCBF with a commercial NIR spectroscopy device over the left and the right frontal poles of the brain.ResultsAt 2-weeks post treatment 6 of 10 patients had a remission (a score ≤ 10) on the HAM-D and 7 of 10 achieved this on the HAM-A. Patients experienced highly significant reductions in both HAM-D and HAM-A scores following treatment, with the greatest reductions occurring at 2 weeks. Mean rCBF across hemispheres increased from 0.011 units in the off condition to 0.043 units in the on condition, for a difference of 0.032 (95% CI: -0.016, 0.080) units, though this result did not reach statistical significance. Immediately after treatment the PANAS improved to a significantly greater extent with NIR "on" relative to NIR "off" when a hemisphere with more positive HEV was treated than when one with more negative HEV was treated. We observed no side effects.ConclusionThis small feasibility study suggests that NIR-PBM may have utility for the treatment of depression and other psychiatric disorders and that double blind randomized placebo-controlled trials are indicated.Trial registrationClinicalTrials.gov Identifier: NCT00961454

“Resting” CBF in the epileptic baboon: Correlation with ketamine dose and interictal epileptic discharges

Photosensitive epileptic (SZ) baboons demonstrate different cerebral blood flow (CBF) activation patterns from asymptomatic controls (CTL) during intermittent light stimulation (ILS). This study compares "resting" CBF between PS and CTL animals, and CBF correlations with ketamine dose and interictal epileptic discharges (IEDs) between PS and CTL animals. Continuous intravenous ketamine was administered to eight PS and eight CTL baboons (matched for gender and weight), and maintained at subanesthetic doses (4.8-14.6 mg/kg/hr). Three resting H(2)(15)O-PET studies were attempted in each animal (CTI/Siemens HR+ scanner). Images were acquired in 3D mode (63 contiguous slices, 2.4mm thickness). PET images were co-registered with MRI images (3T Siemens Trio, T1-weighted 3D Turboflash sequence, TE/TR/TI=3.04/2100/785 ms, flip angle=13 degrees ). EEG was used to monitor depth of sedation and for quantification of IED rates. Regional CBF was compared between PS and CTL groups and correlations were analyzed for ketamine dose and IED rates. When subsets of animals of either group, receiving similar doses of ketamine were compared, PS animals demonstrated relative CBF increases in the occipital lobes and decreases in the frontal lobes. Correlation analyses with ketamine dose confirmed the frontal and occipital lobe changes in the PS animals. The negative correlations of CBF with ketamine dose and IED rate overlapped frontally. While frontal lobe CBF was also negatively correlated with IED rate, positive correlations were found in the parietal lobe. "Resting" CBF differs between PS and CTL baboons. Correlation analyses of CBF and ketamine dose reveal that occipital lobe CBF increases and frontal lobe in PS animals are driven by ketamine. While frontal lobe CBF decreases may be related to ketamine's propensity to activate IEDs, positive CBF correlations with IED rate suggest involvement of the parietal lobes in their generation.

Reduced frontal perfusion in depressed postmenopausal women: A SPECT study with WCST

Objectives To investigate frontal cerebral blood flow (CBF) in depressed postmenopausal women and its relation to cognitive function and the severity of depressive symptoms. Methods Regional CBF of 20 unmedicated depressed postmenopausal women was measured using Tc-99m HMPAO SPECT, both at rest and during frontal activation using the Wisconsin card sorting test (WCST). Frontal CBF was semi-quantified by comparing the radioactivity in the prefrontal region to the cerebellum (F/C ratio). We measured the severity of the symptoms of depression using the hospital anxiety and depression scale (HADS) and cognitive function using the mini-mental status examination (MMSE). Results At rest, there was no difference in frontal CBF between patients with moderate or severe (HADS ≥ 11) and patients with mild depressive symptoms (HADS < 11). During the WCST, however, the HADS ≥ 11 group did not score as well as the HADS < 11 group ( P = 0.03). The changes in F/C ratios were inversely correlated with HADS scores ( r = −0.43, P = 0.05) and positively correlated with MMSE scores ( r = 0.58, P = 0.004). After adjusting for age, F/C ratios were significantly correlated with MMSE ( P = 0.002), but not with HADS scores. Conclusions Frontal CBF did not increase in postmenopausal women with moderate/severe symptoms of depression during the WCST activation task, and reduced frontal CBF was related to the impairment of cognitive function. The combination of the functional activation test and SPECT imaging powerfully revealed this functional disease, which remains undetectable using more common baseline measurements.

Accuracy of single-photon emission computed tomography in differentiating frontotemporal dementia from Alzheimer’s disease

Background: Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are the commonest causes of presenile dementia. In the absence of a biological marker, diagnosis is reliant on clinical evaluation. Confirmation is...

Frontal cerebral blood flow change associated with infant-directed speech

Objective: To examine the auditory perception of maternal utterances by neonates using near-infrared spectroscopy (NIRS). Methods: Twenty full-term, healthy neonates were included in this study. The neonates were tested in...

Blood Flow Imaging of the Brain: 50 Years Experience

Blood Flow Imaging of the Brain: 50 Years Experience

Neuropsychological Disturbances and Cerebral Blood Flow in Bipolar Disorder

To determine and correlate alterations in neuropsychological function and cerebral blood flow in bipolar patients. Assessments included the Positive and Negative Symptom Scale, Global Assessment Functioning, Wechsler Adult Intelligence Scale (WAIS), Wisconsin Card Sorting Test (WCST), Stroop test, Trail Making Test (TMT), California Verbal Learning Test (CVLT), Wechsler Memory Scale (WMS) and phonetic verbal fluency/controlled oral word association tests. Single photon emission computed tomography (SPECT) was carried out with the administration of 99mTc-HMPAO. Forty-three outpatients out of 85 fulfilling RDC diagnostic criteria for bipolar disorder and six healthy subjects were included in the study. SPECT and neuropsychological assessments were performed in 30 patients in manic (n = 7), hypomanic (n = 8), depressed (n = 12) or euthymic (n = 3) states. All assessments were carried out before starting treatment. Several corrected correlations between neuropsychological function and cerebral blood flow (CBF) were identified: executive function (WCST) and striatal, frontal, temporal, cerebellum, parietal and cingulate CBF; memory (WMS, WAIS-Digits) and striatal, frontal, temporal and parietal CBF; attentional tasks (Stroop) and striatal, temporo-medial and parietal CBF; verbal learning (CVLT) and frontal, posterior temporal, cingulate and occipital CBF; psychomotor disturbances (TMT) and anterior temporal CBF; poorer intelligence performance scores (WAIS-Vocabulary) and cerebellum and parietal CBF. This study confirms the presence of functional disturbances in fronto-subcortical structures, the cerebellum and limbic system in bipolar patients.

Cognitive and functional neuroimaging correlate for anosognosia in Mild Cognitive Impairment and Alzheimer's disease

To investigate the correlation between anosognosia and behavioural symptoms, performance on executive tests, and frontal cortex regional cerebral blood flow (rCBF) in patients with 'amnestic mild cognitive impairment' (MCI) and mild Alzheimer's disease (AD). From a prospective Memory Clinic cohort including consecutively referred patients, age 60 years or above, and with MMSE score 20 or above, 36 patients with AD and 30 with MCI were included in this study. Anosognosia was assessed using a categorical scale and discrepancy scores between patients' and relatives' reports on a 20-item Memory Questionnaire (MQ). Behavioural symptoms were assessed with Frontal Behavioural Inventory (FBI). Executive functions were examined with a range of neuropsychological tests. Tc99m-HMPAO SPECT was obtained in an unselected sample of 55 of the 66 patients, and rCBF was analysed in six cortical frontal regions. Insight was equally impaired in the two patient groups. A significant correlation was found between impaired awareness and dementia severity (MMSE). Discrepancy-scores on the MQ were significantly correlated to scores on FBI and to rCBF in the right inferior frontal gyrus, but not to executive tests. The groups classified by the categorical ratings 'full', 'shallow' and 'no' awareness were not characterized by differences in behavioural symptoms, executive performance or frontal rCBF. Impaired awareness is associated with behavioural symptoms and may reflect functional impairment in the right inferior frontal cortex.

Brain single photon emission computed tomographic evaluation of patients with childhood absence epilepsy.

This study was performed to determine the utility of 99mTc-hexamethylpropylenamine oxime (HMPAO) brain single photon emission computed tomography (SPECT) in evaluating patients with childhood absence epilepsy. Twenty-three patients (13 female, 10 male), aged 7 to 15 years (mean age 10.3 +/- 2.2), were studied. All patients underwent a detailed neurologic examination, interictal and ictal electroencephalography (EEG), computed tomography, and/or magnetic resonance imaging, and SPECT. The baseline study was performed during the interictal period and the activation study was performed on a separate day while the patients were having seizures provoked by hyperventilation. Their EEGs were monitored at the same time. Transaxial, sagittal, and coronal slices were obtained for both studies. The mean counts per pixel were calculated on 11 regions of interest on three representative transaxial slices. Count density was calculated for each region. Region-to-occipital cortex ratios were obtained. For each region, normalized ratios were used to obtain a side-to-side percent asymmetry index between baseline and activation studies. Visual interpretation of the baseline study showed that 10 of the 23 patients had a detectable abnormality in regional cerebral blood flow during the interictal period. These abnormalities consisted of relative hypoperfusion in the frontal lobes that could involve neighboring parietal and temporal regions. The activation study revealed that 13 of 23 patients had relative hyperperfusion in these brain regions that were relatively hypoperfused in the baseline study. These hyperperfused regions occupied larger areas than baseline hypoperfused regions. All patients had global increased perfusion in the ictal study. The side-to-side asymmetry indexes for these visually interpreted regional cerebral blood flow abnormalities ranged from 2 to 6%. The relatively consistent pattern of frontal regional cerebral blood flow alterations suggests that altered frontal lobe functions can be implicated in patients with childhood absence epilepsy.

Frontal cerebral blood flow is impaired in patients with heart transplantation

Frontal cerebral blood flow is impaired in patients with heart transplantation

Contribution of frontal cerebral blood flow measured by (99m)Tc-Bicisate spect and executive function deficits to predicting treatment outcome in alcohol-dependent patients.

To determine whether inhibition and working memory deficits, and reduced regional cerebral blood flow (rCBF) (previously shown to be related), measured at the end of a detoxification programme, predict alcoholic relapse 2 months later. Twenty uncomplicated alcoholic inpatients were investigated at the end of detoxification, at least 7 days since the last dose of diazepam, and a mean of 18.8 days since the last drink. Their performance was assessed on the inhibition (Hayling) test, working memory (Alpha-span task), episodic memory (California Verbal Learning Test) and abstract reasoning (Progressive Matrices). Frontal CBF was assessed at the same time with a semiquantitative (99m)Tc-Bicisate SPECT procedure. Patients were contacted 2 months later. Patients who abstained (n = 9) did not differ from those who relapsed (n = 11) on age, gender, smoking, duration of alcohol misuse, number of previous detoxifications, amount of ethanol consumed the month prior to admission to the detoxification programme, state anxiety, trait anxiety, or depression. Relapsed subjects had shown a lower uptake of (99m)Tc-Bicisate in the bilateral medial frontal gyrus (n = 9; mean ratio +/- SD = 0.69 +/- 0.006) than abstainers (n = 11; 0.85 +/- 0.19), and poorer performance on the Alpha-span task and the Hayling test. The other tests were not different. Inhibition and working memory deficits, associated with low levels of CBF in the medial frontal gyrus, are related to the difficulty of maintaining short-term abstinence from alcohol.

Surgical Treatment of Mental Illness: Impact of Imaging

Surgical Treatment of Mental Illness: Impact of Imaging

Reduced regional cerebral blood flow in non-psychotic violent offenders

The present study was designed to replicate previously reported findings of abnormal frontal and/or temporal cerebral blood flow in violent offenders and to control for the influence of major mental disorder (MMD), substance abuse, and current medication. HMPAO-SPECT-CBF and MRI scans from pretrial forensic psychiatric investigations of 21 subjects convicted of impulsive violent crimes were retrospectively re-evaluated. In 16/21 subjects, visual assessment of SPECT scans showed some hypoperfusion in the temporal and/or frontal lobes. MRI showed no corresponding structural damage. Quantified regional cerebral blood flow (rCBF) in defined regions of interest was compared between index cases and 11 healthy control subjects. Index subjects had significant reductions in the right angular gyrus and the right medial temporal gyrus, bilaterally in the hippocampus, and in the left white frontal matter, but they had significantly increased rCBF in the parietal association cortex bilaterally. The aberrations were as frequent and severe among the subjects without MMD, substance abuse, and current medication ( n=7) as in the entire group of index subjects.

Regional cerebral blood flow in down syndrome adults during the Wisconsin card sorting test: exploring cognitive activation in the context of poor performance

Background: Prior studies have indicated abnormal frontal lobes in Down syndrome (DS). The Wisconsin Card Sorting Test (WCST) has been used during functional brain imaging studies to activate the prefrontal cortex. Whether this activation is dependent on successful performance remains unclear. To determine frontal lobe regional cerebral blood flow (rCBF) response in DS and to further understand the effect of performance on rCBF during the WCST, we studied DS adults who perform poorly on this task. Methods: Initial slope (IS), an rCBF index, was measured with the 133Xe inhalation technique during a Numbers Matching Control Task and the WCST. Ten healthy DS subjects (mean age 28.3 years) and 20 sex-matched healthy volunteers (mean age 28.7 years) were examined. Results: Performance of DS subjects was markedly impaired compared to controls. Both DS and control subjects significantly increased prefrontal IS indices compared to the control task during the WCST. Conclusions: Prefrontal activation in DS during the WCST was not related to performance of that task, but may reflect engagement of some components involved in the task, such as effort. Further, these results show that failure to activate prefrontal cortex during WCST in schizophrenia is unlikely to be due to poor performance alone.

Role of the cingulate gyrus during the Wisconsin Card Sorting Test: a single photon emission computed tomography study in normal volunteers

The purpose of this study was to investigate the effect of the Wisconsin Card Sorting Test (WCST) on frontal regional cerebral blood flow (rCBF) in normal subjects, separating the cingulate gyrus from the prefrontal cortex. Two technetium-99m-hexamethyl-propylene-amine-oxime brain single photon emission computed tomography (SPECT) scans, at rest and during WCST performance, were performed in randomized order on 13 right-handed normal volunteers. A statistically significant rCBF increase was found in the left inferior cingulate and the left posterior frontal region, although rCBF ratios in the left and right prefrontal cortex, and in the right inferior cingulate, were slightly higher during WCST performance in nine of the 13 subjects studied. No differences in activation scores (activated-resting rCBF ratios) were found between subjects who had the resting SPECT first and subjects who had the resting condition second. These results suggest that the inferior cingulate cortex, a limbic region that has been implicated in attentional mechanisms, plays a significant role in WCST performance. Furthermore, the motor component of the WCST may account for the activation of the left posterior frontal region. In addition, no order effect was found in this study. These findings illustrate the advantage of independently evaluating the cingulate gyrus and the prefrontal cortex in SPECT studies of frontal cognitive function.

Postural and gait disturbance correlated with decreased frontal cerebral blood flow in Alzheimer disease.

In a group of 45 patients with Alzheimer disease (AD) and 15 control subjects, we studied the relationship between parameters showing postural and gait disturbance and regional cerebral blood flow (rCBF) measured with N-isopropyl-p-[123I]iodoam-phetamine single photon emission computed tomography at different clinical stages. Patients with AD with mild dementia exhibited only increased postural sway associated with a reduced mean value of rCBF in the cortex. At a moderate stage, the reduced mean values of rCBF in the cortex and in the frontal lobe were associated with increased postural sway and stride length variability and with decreased stride length. At a severe stage, reduced rCBF in the basal ganglia and in the frontal lobe additionally were associated with increased postural sway, double support time, and stride length variability, and with decreased walking speed and stride length. In multiple regression analysis, there was a high contribution by rCBF in the frontal lobe to account for postural and gait disturbance in AD. We propose that impaired frontal lobe circulation is an important factor causing postural and gait disturbance as AD progresses.

Vascular dementia of Binswanger's type: clinical, neuroradiological and 99mTc-HMPAO SPET study.

In 24 patients with vascular dementia of Binswanger's type (VDBT) and 14 age-matched neurologically normal volunteers, we investigated the relationship between clinical features, white matter lesions (leuco-araiosis) and cerebral atrophy on computed tomographic (CT) scan, and regional cerebral blood flow. All subjects underwent the Mini-Mental State Examination of Taiwan, version 1 (MMSE-T1), for assessing the severity of cognitive impairment. The patients were subdivided into two groups, one with mild to moderate (group I, MMSE-T1 scores: 11-24, n=11), and the other with severe dementia (group II, MMSE-T1 scores: below 10, n=13). White matter degeneration was evaluated with densitometric methods. Loss of brain parenchyma was estimated with seven linear measurements (Evan's ratio, third ventricle ratio, width of temporal horn tip, anterior-posterior length of temporal horn, anterior-posterior length of Sylvian fissure and width of frontal interhemispheric fissure) by CT scans. Regional cerebral blood flow was determined with technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission tomography (SPET). In neuroimaging studies, subcortical leuco-araiosis was localized at the frontal region in group I patients and scattered diffusely in group II patients. 99mTc-HMPAO SPET analysis revealed reduction of regional cerebral blood flow in the frontal lobe in group I patients and widespread reduction of regional cerebral blood flow in group II patients. A correlation between frontal leuco-araiosis and perfusion defect of the frontal pole was demonstrated in group I patients, showing findings typical of subcortical dementia. There was no difference in frontal atrophic measurements between group I patients and controls. Ratios of volumes of lost brain parenchyma and leuco-araiosis were significantly higher in group II patients than in the age-matched controls, corresponding to a diffuse cerebral perfusion defect. These results suggest that patients with VDBT have early frontal lobe involvement with posterior progression. Patients with mild VDBT are more likely to show reduction of frontal cerebral blood flow and leuco-araiosis, while those with severe VDBT are more likely to have diffuse leuco-araiosis, cerebral hypoperfusion and brain atrophy.