Anna Barnes

Caudate nucleus: influence of dopaminergic input on sequence learning and brain activation in Parkinsonism

In this study, we tested the hypotheses that (1) the acquisition of sequential information is related to the integrity of dopaminergic input to the caudate nucleus; and (2) the integrity of dopaminergic input to the caudate nucleus correlates significantly with brain activation during sequence acquisition. Twelve early stage Parkinsons disease (PD) patients and six age-matched healthy volunteers were scanned using a dual tracer PET imaging design. All subjects were scanned with [(18)F]fluoropropyl-betaCIT (FPCIT) to measure striatal dopamine transporter (DAT) binding and with [(15)O]water to assess activation during a sequence learning task where movements were made to a repeating sequence of eight targets. Caudate and putamen DAT binding in the PD cohort was reduced by 15% and 43%, respectively. In PD, caudate DAT binding correlated with target acquisition (R = 0.57, P < 0.05), while putamen DAT binding did not correlate with performance. In volunteers, caudate DAT binding correlated with learning-related activation (P < 0.05, corrected for multiple comparisons) in the left dorsolateral and ventral prefrontal cortices, the anterior cingulate and premotor regions, and the right cerebellum. A significant correlation with caudate DAT binding was additionally detected in the right anteromedial thalamus, extending into the rostral midbrain. By contrast, in the PD cohort, most of these regional relationships were lost: Only ventral and dorsolateral prefrontal cortex activation correlated with caudate dopaminergic tone. Our findings suggest that sequence learning is normally associated with tight coupling between dopaminergic input to the caudate and thalamo-cortical functional activity. Despite minimal reductions in nigro-caudate input, PD patients demonstrate a loss of this coupling early in the disease.

Associative encoding of pictures activates the medial temporal lobes

It remains unresolved whether the medial temporal lobe activations found in recent neuroimaging studies are mediated by novelty detection alone, by specific kinds of encoding or consolidation operations, or both. This study attempted to see whether associative encoding or consolidation is sufficient to cause such activation by matching for novelty across conditions. Using single‐photon emission computer tomography (SPECT) (with Tc99mHMPAO), we compared the activation patterns produced by the associative encoding and the perceptual matching of novel complex scenes in 10 normal subjects using both statistical parametric mapping (SPM) and a regions‐of‐interest (ROI) approach. During the encoding condition, significant activations were detected in the left hippocampal/parahippocampal region, the left cingulate cortex, and the right prefrontal cortex, using both statistical techniques. Additionally, activation was found in the right cingulate cortex, and a trend towards activation was found in the right hippocampal/parahippocampal region using the ROI approach. In contrast, no medial temporal activations were found during the matching condition, which produced bilateral occipito‐parietal and right posterior inferior parietal (supramarginal gyrus) activations. These results not only confirm that the associative encoding and/or consolidation of complex scenes is partially mediated by medial temporal lobe structures, but also demonstrate, for the first time, that associative encoding/consolidation is sufficient to produce such an activation. The implications of the high degree of consistency revealed by the results of the SPM and ROI comparison are discussed. Hum. Brain Mapping 6:85–104, 1998.

The Camino Intracranial Pressure Sensor: Is it Optimal Technology? An Internal Audit with a Review of Current Intracranial Pressure Monitoring Technologies

OBJECTIVETo audit the reliability of the Camino intracranial pressure (ICP) sensor (Camino Laboratories, San Diego, CA) in our clinical practice as part of a continuing quality assurance program, and to assess its relative usefulness as compared with currently available ICP monitoring technologies that we reviewed. DESIGNProspective audit of ICP device reliability and function in 50 patients with head injuries. METHODSZero drift was recorded immediately after the ICP device was removed from the patient. Dynamic frequency response bench testing of each functioning catheter from 0 to 30 Hz and static calibration testing from 0 to 100 mm Hg during environmental temperature variation from 22 to 40°C were carried out. RESULTSZero drift (range, −13 to 22 mm Hg; median, −1 mm Hg) was recorded immediately after the devices were removed from patients. Seventeen (50%) of the devices tested for zero drift had absolute drifts of at least 3 mm Hg. There was no correlation between recorded zero drift and duration of monitoring (r = 0.154, P = 0.207). Five sensors (10% of those tested) failed during patient monitoring and were replaced. Static and dynamic calibration tests of the functioning sensors were within the manufacturer’s specifications. However, the sensitivity of the devices to environmental temperature remains a problem. CONCLUSIONThe Camino ICP sensor remains one of the most popular ICP monitoring devices for use in patients with traumatic brain injuries. However, our recent in-house assessment demonstrated the robustness of the device to be less than adequate during routine practice. In this study, more than 50% exhibited zero drift greater than 3 mm Hg, which is unacceptable in a catheter tip ICP monitoring device in which zero drift and calibration cannot be checked in vivo. A review of the literature revealed that other available ICP monitoring devices may prove to be more reliable and thus more appropriate for routine clinical measurement of ICP.

Investigation into the mechanisms of vagus nerve stimulation for the treatment of intractable epilepsy, using 99mTc-HMPAO SPET brain images

Abstract. Vagus nerve stimulation (VNS) has gained recognition as a treatment for refractory epilepsies where surgical treatment is not possible. While it appears that this treatment is effective in some patients, the mechanism of action is not clearly understood. The purpose of this study was to clarify findings of other positron emission tomography and single-photon emission tomography (SPET) investigations by measuring the acute effect of VNS on patients who have normal cerebral anatomy on magnetic resonance imaging and who have not previously been exposed to VNS. We investigated six subjects (two males and four females, mean age 29.5 years, range 21–39 years) with intractable epilepsy. One patient had primary generalised epilepsy causing generalised tonic-clonic seizures; the remaining five patients had localisation-related epilepsy causing complex partial seizures. SPET imaging was performed using 250xa0MBq of 99mTc-HMPAO and a four-scan paradigm – two with and two without stimulation. The stimulation began at VNS current levels of 0.25xa0mA and was increased according to the limit of patients tolerance, usually defined by coughing or discomfort. The stimulating waveform was of continuous square wave pulses of 500xa0µs duration at 30xa0Hz. Image analysis was by SPM99. Reduced perfusion during stimulation was observed in the ipsilateral brain stem, cingulate, amygdala and hippocampus and contralateral thalamus and cingulate. The study provides further evidence of the involvement of the limbic system in the action of vagal nerve stimulation.

Cingulate Abnormalities Associated with PANSS Negative Scores in First Episode Schizophrenia

There is evidence for the involvement of the cingulate gyrus in schizophrenia. We present details of a Statistical Parametric Mapping (SPM) analysis of SPECT data from the largest study (N = 39) of drug naive schizophrenic patients. The main findings are that there is decreased perfusion in the anterior cingulate during verbal fluency when patients are compared to controls (matched individually by age, gender and father’s social class as determined by occupation) and also that PANSS negative scores correlate negatively with regional cerebral blood flow in the cingulate gyrus (Pearson’s Correlation coefficient of r = − 0.49 and significance p < 0.005). This suggests that measurement of change of perfusion in this region could be a useful biological marker in assessing the effect of neuroleptics on negative symptoms.

The Use of Statistical Parametric Mapping (SPM96) as a Decision Aid in the Differential Diagnosis of Dementia Using 99mTc-HMPAO SPECT

In this study standard patterns of cerebral perfusion based on classifications described in the literature have been chosen and the ability of experienced imaging specialists to categorise the 99m Tc HMPAO SPECT scans of patients referred to the department for investigation of dementia has been compared before and after the calculation of Statistical Parametric Maps (SPM - Wellcome Dept of Cognitive Neurology). The primary aim was to investigate whether SPM is an effective decision aid and whether it impacts on the confidence of image reporting. The secondary aim was to examine the influence of SPM on the agreement between image reporting and clinical diagnosis. The results showed that there was a slight decrease in agreement between the imaging specialists after the introduction of additional information from SPM (K=0.57 to K=0.5) and that agreement between imaging reporting (including information from SPM) and clinical diagnosis was moderate (K=0.28). This study was able to confirm that SPM is capable of producing meaningful significance maps of individual patients in a routine clinical environment. However, there was no overwhelming evidence that SPM was able to resolve many of the dilemmas associated with the use of SPECT for the differential diagnosis of dementia. In particular, interpretation of SPECT perfusion patterns in dementia is a bigger problem than the initial identification of abnormalities.

Effects of level of retrieval success on recall-related frontal and medial temporal lobe activations

Brain dedicated single photon emission computed tomography (SPECT) was used to compare the neuroactivation produced by the cued recall of response words in a set of studied word pairs with that produced by the cued retrieval of words semantically related to unstudied stimulus words. Six of the 12 subjects scanned were extensively trained so as to have good memory of the studied pairs and the remaining six were minimally trained so as to have poor memory. When comparing episodic with semantic retrieval, the well-trained subjects showed significant left medial temporal lobe activation, which was also significantly greater than that shown by the poorly trained subjects, who failed to show significant medial temporal lobe activation. In contrast, the poorly trained subjects showed significant bilateral frontal lobe activation, which was significantly greater than that shown by the well-trained subjects who failed to show significant frontal lobe activation. The frontal activations occurred mainly in the dorsolateral region, but extended into the ventrolateral and, to a lesser extent, the frontal polar regions. It is argued that whereas the medial temporal lobe activation increased as the proportion of response words successfully recalled increased, the bilateral frontal lobe activation increased in proportion to retrieval effort, which was greater when learning had been less good.

Image quality versus statistical power.

We investigated whether SPET studies of neuroactivation might benefit from a similar approach used in PET; that is, increase the number of scans per task and accept poorer individual scan quality. Different study paradigms were simulated by varying the scanning parameters: (1) administered radiation activity per scan, (2) number of scans per task and (3) scan acquisition time. The maximum total dose received by each simulated subject remained the same. Areas of activation of varying signal strength were added to the scans using a customized graphics package. To establish the statistical benefits of a replication paradigm versus a non-replication paradigm, the datasets were analysed using SPM95 statistics software. This simulation was able to show that, when an SPM investigation is used for data analysis, study replication is more important than the individual image quality typically available from a high-performance SPET system.

Perfusion SPECT in cochlear implantation and promontory stimulation.

BackgroundRecent studies of profoundly deaf patients with cochlear implants have demonstrated that these patients are able to process sound in the auditory cortex in a similar way to normal subjects. However, there are large variations in outcome. Various clinical criteria are used for subject selection and the decision as to which ear is to be implanted involves electrical stimulation of the promontory which is used to confirm the persistence of auditory neurones and fibres that can be utilized by the cochlear implant. In this study we have used SPECT with 99mTc-HMPAO to investigate activation of the auditory cortex in cochlear implantees post-surgery. In addition we also investigated whether electrical stimulation of the promontory does produce change in blood flow in the auditory cortex in pre-surgery candidates, which would indicate viable auditory networks that can be utilized by a cochlear implant device. Methods and resultsImage analysis was performed with SPM99. Results of a simple subtraction paradigm indicated bilateral activation of auditory cortex and Wernickes area in the post-implant group during auditory stimulus (speech) and bilateral activation of the ventral lateral posterior thalamus and bilateral auditory association cortex BA21/22/42, in the pre-implant group during electrical stimulus but no activation of the primary auditory cortex. A conjunction analysis used to investigate the common areas of activation across both groups during the stimulus condition showed that there was a common bilateral activation of the primary auditory cortex in both groups (BA22/41/42). In addition, analysis of a subset of the seven post-implant subjects who did not comprehend the speech in our study showed an activation (Pu<0.05, where Pu is the peak voxel threshold, uncorrected for multiple comparisons) in the left auditory cortex that extended into area BA22 synonymous with Wernickes area. This supports the theory that this region has a sensory role.

Cingulate abnormalities associated with PANSS negative scores in first episode schizophrenia

There is evidence for the involvement of the cingulate gyrus in schizophrenia. We present details of a Statistical Parametric Mapping (SPM) analysis of SPECT data from the largest study (N = 39) of drug naive schizophrenic patients. The main findings are that there is decreased perfusion in the anterior cingulate during verbal fluency when patients are compared to controls (matched individually by age, gender and fathers social class as determined by occupation) and also that PANSS negative scores correlate negatively with regional cerebral blood flow in the cingulate gyrus (Pearsons Correlation coefficient of r = - 0.49 and significance p< 0.005). This suggests that measurement of change of perfusion in this region could be a useful biological marker in assessing the effect of neuroleptics on negative symptoms.